S5: Pharmacology

Topic outline

• 

  General

  • Announcements Forum
  • S5: Pharmacology SB File
  • S5: Pharmacology TG File
• UNIT 2: ANTHELMINTIC (ANTIHELMINTHIC) DRUGS

                  Key Unit Competence

  Utilize appropriate anti-helminthic
  drugs to manage different
  health conditions
  at the primary healthcare settings.
  

               Introductory activity 2.0 
  

  
  

                              

   1) What do you observe on the image above? 

  2) Have you ever seen the same 

  scenario in your community? 

  If yes, which drugs have you seen

   being used in the same scenario?   
  

    2.1. Introduction to anthelmintic 

      drugs and deworming    

                  Learning Activity 2.1

                  Read the scenario below:

   A patient GN presents at your
  health clinic with
  the complaints of severe 
   abdominal pain, vomiting
  and diarrheas'.
  For all physical examination
  performed,
   no signs of abnormalities found.
  All vital signs
  are normal and by history taking, 
   his family lives in a region
  with poor sanitation.
  The laboratory results revealed
   the presence of eggs of Ascaris during
  the direct stool examination. 
  In addition, the patient tells you that
  he was given one year ago the 
  

  drug as a single dose, the treatment                                                                                                                                                                         which was given in mass campaign. 

  1) What is the disease do you think 
  patient GN
  is suffering from? 
  2) Which of the following
  medications may be
  used in mass deworming? 
  a) Tinidazole
   b) Mebendazole
   c) Metronidazole
   d) Amoxicillin
   3) What are the classes of helminthic
   parasites are often
  

   targeted in deworming?

               CONTENT SUMMARY     

  Helminths are a broad range of
  organisms that include
   intestinal parasitic worms. 
   There are three major groups
  of helminths namely:
  nematodes (roundworms), 
   trematodes (flukes) and
   cestodes (tapeworms).
   
  These groups of helminths are
  divided into two phyla;
  nematodes (roundworms) 
  and platyhelminths
  (trematodes and cestodes).
  Infected people excrete helminth
  eggs in their faeces,
  which then contaminate the s
  oil in areas with inadequate sanitation. 
  
   Other people can then be infected
  by ingesting eggs or
   larvae in contaminated food,
   or through penetration
  of the skin by infective
   larvae in the soil (hookworms). 
   Infestation can cause morbidity,
  and sometimes
  death, by compromising
  nutritional status, 
  affecting cognitive processes,
   inducing tissue
  reactions, such as granuloma,
   and provoking
   intestinal obstruction or
  rectal prolapse.
   Control of helminthiasis
   is based on drug
  treatment, 
  improved sanitation and
  health education.
   Over millions of preschool-age children and 
  school-age children live in areas where these
   parasites are intensively transmitted, 
  and are in need of treatment and preventive
   interventions.
  Anthelminthics are a group of antiparasitic
   drugs that expel parasitic worms
   (helminths) and other internal parasites
  from the body by either stunning or
   killing them and without causing significant
   damage to the host. They may also 
  be called vermifuges (those that stun) or
  vermicides (those that kill). Anthelmintics
   are used to treat people who are infected
   by helminths, a condition called helminthiasis.
   Pills containing anthelmintics are used in mass
  deworming campaigns of school
   aged children in many developing countries.
  Anthelmintic are classified based 
   upon their chemical structures.
  i. Piperazines: eg. Diethylcarbamazine
   citrate, Piperazine citrate. 
  ii. Benzimidazoles: eg. Albendazole, 
  

  Mebendazole, Thiabendazole.

  Albendazole Use: 

  It is a new benzimidazole useful in the
  treatment of intestinal nematode infection 
   and echinococcosis. It is effective against
   roundworm, hookworm, whipworm 
  and threadworm infestations. 
  

  It is effective in the treatment of ascariasis. 

  Mebendazole Use:

   It is used in the treatment of hookworm,
  pinworm, and roundworm and
  

   whipworm infestation. 

  iii. Heterocyclics: eg. Oxamniquine,
  Praziquantel. Praziquantel 
  

  Use: It is considered as drug of choice for
  the treatment of Schistosoma japonicum,
  (blood fluke) falciolopsiasis (intestinal flukes)
   clonorchiasis (chinese liver fluke) and 
  

   opisthorchosis (liver fluke) 

  iv. Natural products: 

  eg. Ivermectin, Avermectin. 

  Use: Ivermectin is widely used
   in veterinary practice
   for the control of endoparasite 
   and exoparasite in domestic animals.
  It is also used to treat onchocerciasis                                                                                                                                                                                  in humans. caused by round worm
  Onchocerca volvulus.
   
  

  v. Vinyl pyrimidines : 

  eg. Pyrantel, Oxantel. Pyrantel 

  Use: The anthelmintic choice in the treatment 

  of hookworm, pinworm and  roundworm Infestations. 

  vi. Amide: 

  eg. Niclosamide (Niclosan)

   Use: The anthelmintic of first choice in the 

  treatment of beef tapeworm,  fish tapeworm, 

  pork tapeworm and dwarf tapeworm infestations. 

  vii. Nitro derivative: eg. Niridazole.

   viii. Imidazo thiazole: eg. Levamisole 

  Deworming is the giving of an anthelmintic
   drug to a human to rid them 
   of helminths parasites, such as roundworm,
  flukes and tapeworm. 
  Mass deworming campaigns of school children
   have been used both
   as a preventive as well as a treatment method
  for helminthiasis, which
   includes soil transmitted helminthiasis
   in children. Children can
   be treated by administering, for example,
  mebendazole and albendazole.
   According to the World Health Organization
   (WHO), over 870 million children
   (half of the children in the world)
  are at risk of parasitic worm infection. 
   Worm infections interfere with nutrient
  uptake, can lead to anemia, 
  malnourishment and impaired mental
  and physical development, 
  and pose a serious threat to children’s health,
   education, and productivity.
   Infected children are often too sick or
   tired to concentrate at school, or to attend at all.
                     Self-assessment 2.1
    1) Give the classes of anthelminthic drugs.
    2) The deworming of children usually involves
  the use of mebendazole and coartem. True or False
  3) Worm infections interfere with nutrient uptake,
  and can lead to anemia.  True or False
  
   2.2. Anthelmintic medications
    Learning Activity 2.2    
  

  A patient X was admitted in a clinical health
  facility for intestinal worm infestation. 
  

   After the laboratory investigations done,
  they found the eggs of hookworm in the stool. 
  

  The healthcare providers decide to prescribe
  a drug that would be effective 
   to manage the client’s condition.
   1) Which class of drugs can be used
  to manage the client’s condition? 
  2) What is the mechanism of action
  of mebendazole? 
  3) What are the common side 
  

  effects of albendazole?

  CONTENT SUMMARY 

   Anthelmintic agents are indicated for the
  treatment of infections by certain susceptible 
  worms and are very specific in the worms that
  they affect; they are not interchangeable 
  for treating various worm infections.
  Treatment of a helminthic infection
   entails the use of an anthelmintic drug.
   Another important part of therapy for
  helminthic infections involves
   the prevention of reinfection or spread
  of an existing infection.
  Measures such as thorough
   hand washing after use of the toilet;
   frequent laundering of bed linens
  and underwear in very hot,
   chlorine-treated water; disinfection
  of toilets and bathroom areas
  after each use; and good 
  personal hygiene to wash away 
  ova are important to prevent
  

   the spread of the disease.

  When the infestation is present or associated
  with complications occur, pharmacotherapy
  is initiated. Pharmacotherapy is targeted at killing the
  parasites locally in the intestine and systemically in 
  

  the tissues and organs they have invaded.

                    Table Common anti-helminthic drugs
  

                     

                         Mebendazole (Vermox)

    Mechanism of action Mebendazole is
  the most widely prescribed anthelmintic.
   Mebendazole is available in the form of
  a chewable tablet, and a typical 3-day course 
  can be repeated in 3 weeks if needed.
  Mebendazole interferes with the ability to use
   glucose, leading to an inability to reproduce
  and cell death. It is used in the treatment 
  

  of a wide range of helminth infections, 

  including those caused by roundworm (Ascaris)and

  pinworm (Enterobiasis). As a broadspectrum drug,
  it is particularly valuable in mixed
  

   helminth infections, which is more common
  in regions with poor sanitation. It is effective 
  

  against both the adult and larval stages
   of these parasites. Because very little
  of mebendazole is absorbed systemically,
   it retains high
  concentrations in the intestine where
   it kills the pathogens.
  

   For pinworm infections, a single
  dose is usually sufficient;
  other infections require 3 consecutive 
  days of therapy.
  
  Pharmacokinetics
  Very little of the mebendazole
   is absorbed systemically, 
  so adverse effects are few.
   The drug is not metabolized in the body,
  and most of it is excreted 
  

  unchanged in the feces. 

  A small amount may be excreted in the urine.

               
  

    Administration Alerts 

  – The drug is most effective when chewed
     and taken with a fatty meal.
   – Pregnancy category 
  C. Adverse Effects: Because so little
  of the drug is absorbed, mebendazole does not
  

   generally cause serious systemic side effects.
  As the worms die, some abdominal
  

  l pain, distention, and diarrhea may be experienced.

   Contraindications: 
  The only contraindication is
  hypersensitivity to the drug.
   Interactions: 
  Drug–Drug: Carbamazepine and
  phenytoin can increase the metabolism 
   of mebendazole.
   Lab Tests: Unknown interaction with lab tests.
   Herbal/Food: High-fat foods may increase
   the absorption of the drug. Treatment of Overdose:
   There is no specific  treatment for overdose. 
  Albendazole 
  Albendazole is an anthelmintic
   or anti-worm medication. 
  It prevents newly hatched insect larvae
   (worms) from growing or multiplying in the body.
  
   Mechanism of action
  As a vermicide, albendazole causes
  degenerative alterations in the intestinal cells
   of the worm by binding to the colchicine
  -sensitive site of β-tubulin, 
  thus inhibiting its polymerization or
  assembly into microtubules 
  (it binds much better to the β-tubulin
  of parasites than that of mammals)
   Albendazole leads to impaired uptake
  of glucose by the larval and adult
   stages of the susceptible parasites,
  and depletes their glycogen stores.
   Albendazole also prevents the formation
   of spindle fibers needed for 
  cell division, which in turn blocks egg
  production and development; 
  

   existing eggs are prevented from hatching.

               Pharmacokinetics
  

   Oral absorption of albendazole varies among
  species, with 1–5% of the drug being  successfully
  absorbed in humans,  20–30% in rats, and 50% in cattle.
  
  The absorption also largely depends on gastric pH.
   People have varying gastric 
   pHs on empty stomachs, and
  thus absorption from one person
  to another can
   vary wildly when taken without food.
  Generally, the absorption in the GI tract is 
  poor due to albendazole’s low solubility in water.
  It is, however, better absorbed
   than other benzimidazole carbamates.
   Food stimulates gastric acid secretion, 
  

  lowering the pH and making albendazole 

  more soluble and thus more easily absorbed.

  Oral absorption is especially increased with a fatty meal,
  as albendazole dissolves better 
  in lipids, allowing it to cross the lipid barrier created
   by the mucus surface of the GI tract. 
  To target intestinal parasites, albendazole
   is taken on an empty stomach to stay 
  within the gut. Absorption is also affected
  by how much of the albendazole
  

   is degraded within the small intestine 

  by metabolic enzymes in the villi.

  The pharmacokinetics of albendazole differ
  slightly between men and women:
   women have a lower oral clearance
  and volume of distribution, while men have 
  

  a lower serum peak concentration

  Common side effects

  The most common side effects by albendazole
  are experienced by over 10% 
  of people and include: Headache, neck stiffness,
  increased sensitivity to light, 
  confusion; fever; nausea, vomiting, stomach pain;
   abnormal liver function tests; 
  dizziness, spinning sensation;
  or temporary hair loss. 
  
  Ivermectin (Stromectol)
  Stromectol is a prescription medicine used
  to treat the symptoms of 
  certainparasiteinfections (Strongyloidiasis
  of the Intestinal Tract and River BlindNess 
  [Onchocerciasis]). Stromectol may be used
  alone or with other medications.
  
  Mechanism of action
  Ivermectin is an anti-parasitic medication.
  Ivermectin works by binding to 
  invertebrate muscle and nerve
  cells of parasites,
   causing paralysis and death of 
  parasites. Ivermectin is active against
  the non-adult form of Onchocerca volvulus.
  
  Pharmacokinetics
  Ivermectin is readily absorbed from the GI
  tract and reaches peak plasma levels 
  in 4 hours. It is completely metabolized
  in the liver with a half-life of 16 hours; 
  

  excretion is through the feces. 

  Indications

  STROMECTOL (ivermectin) is indicated for the
   treatment of the following infections: 
  Strongyloidiasis of the intestinal tract.
  Stromectol
   (ivermectin) is indicated for the 
  treatment of intestinal (i.e., nondisseminated)
  strongyloidiasis due to the nematode 
  parasite Strongyloides stercoralis.
  Is indicated for the treatment of onchocerciasis 
  

  due to the nematode parasite Onchocerca volvulus.

  Doses 

  The recommended dosage of STROMECTOL
  for the treatment of onchocerciasis 
  is a single oral dose designed to provide
  approximately 150 mcg of ivermectin per 
  

  kg of body weight. Patients should take

   tablets on an empty stomach with water.

  Side effects

  The most common side effects of Stromectol
   include: Headache, muscle aches, 
  dizziness, nausea, diarrhea, and mild skin rash
  Contraindications / Precautions
  It contraindicated in Asthma, Hepatic disease,
  Human immunodeficiency virus 
  

  (HIV) infection, immunosuppression, 

  Pregnancy, Breast-feeding, Children, infants.

  Praziquantel

  Praziquantel is used to treat infections 

  caused by Schistosoma worms

  Mechanism of action

  The action of praziquantel is limited very
   specifically to trematodes and cestodes; 
  nematodes (including filariae) are not affected.
   Praziquantel works by causing 
  severe spasms and paralysis
  of the worms’ muscles.
   This paralysis is accompanied 
  

  - and probably caused 

  - by a rapid Ca 2+ influx inside the schistosome

  Pharmacokinetics

  The absorption of praziquantel is rapid
  and nearly complete but the systemic 
  bioavailability of praziquantel is low and
  varies considerably between individuals. 
  After the administration of 40 mg/kg to fasted
  healthy adults Oral drugs have a 
  greater pharmacokinetic variability than drugs
  administered by the intravenous 
  route, explained by the blood flow at the
  absorption site, the absorptive surface 
  

  area, the transit time and the gastric pH, 

  factors all influenced by concurrent food uptake

  Dosages of Praziquantel:
   Adult and Pediatric Dosages:
  

  Dosage Considerations 

  – Should be Given as Follows:

  Adult Dosage:
  20 mg/kg orally three times per day for 1 day, every 4-6 hours
  Pediatric Dosage:
  Children under 4 years old:
  safety and efficacy not established
  Children 4 years and older:
  20 mg/kg orally three times daily for 1 day,
  every 4-6 hours
  

  Contraindication 

  BILTRICIDE (praziquantel) is contraindicated
  in patients who previously have shown 
  hypersensitivity to the drug or
  any of the excipients.
  Since parasite destruction 
  within the eye may cause
  irreversible lesions,
  ocular cysticercosis must not be 
  

  treated with this compound.

   Side effects 

  Abdominal pain, allergic reaction,
  cerebrospinal reaction syndrome, diarrhea, 
  dizziness, drowsiness, feeling unwell
  (malaise), fever, headache, hives, itching, 
  mild fever, mild skin rash, nausea, rash,
   sweating, tired feeling, upset stomach, 
  

  vomiting.

                   Self-assessment 2.2

  1) Which of the following drugs
  can be used in the treatment of schistosoma 
  infection?
  a) Praziquantel
  b) Ivermectin
  c) Albendazole
  d) Mebendazole
  2) What is the mechanism of action of albendazole?
  
  3) As a nurse student in the clinical placement,
  you are providing health 
  education to a patient who is taking albendazole.
  Which of the following 
  statements should be included in your teaching?
  
  a) Oral absorption is especially decreased
   with a fatty meal, and it should 
  not never be taken with fatty meal
  
  b) Albendazole dissolves better in water,
  and drinking a lot of water speeds 
  up its absorption
  
  c) Albendazole can never cross the
  lipid barrier created by the mucus 
  surface of the GI tract.
  d) To target intestinal parasites,
  albendazole is taken on an empty stomach 
  

  to stay within the gut.

  2.3. National Guidelines for Deworming and 

  WHO Community Deworming

                 Learning Activity 2.3     

                         

  1) Which activity does the image above indicate?
  2) Which medications and at which doses does
  the WHO recommend for 
  deworming using annual or biannual
  single-dose as a public health 
  intervention for children aged 7 years old? 
  
  3) Deworming of children and
  pregnant women and children through the 
  health services and in schools is well
  established and can help to reduce 
  

  iron deficiency. True or False 

  CONTENT SUMMARY 

  Those living in poverty are most vulnerable to
   infection which can impair nutritional 
  status by causing internal bleeding which
  can lead to loss of iron and anemia; 
  intestinal inflammation and obstruction;
  diarrhea; and impairment of nutrient intake, 
  

  digestion and absorption. 

  Evidence shows that preventive chemotherapy,
  or the periodic large-scale 
  administration of anthelminthic medicines
   to populations at risk, can dramatically 
  

  reduce the burden of worms caused by 

  soil-transmitted helminth infections.

  Preventive chemotherapy is an important
  \ part of a comprehensive package to 
  eliminate morbidity due to soil-transmitted
   helminths in at-risk populations. However, 
  long-term solutions to soil-transmitted helminth
  infections will need to address many 
  factors, including improvements in water, 
  

  sanitation and hygiene.

  The WHO recommends Preventive chemotherapy
  (deworming), using annual or 
  biannual single-dose albendazole (400 mg)
  or mebendazole (500 mg) as a public 
  health intervention for all young children
  12–23 months of age, preschool children 
  

  1–4 years of age, and school-age children 

  5–12 years of age living in areas where

   the baseline prevalence of any soil-transmitted
   infection is 20% or more among 
  

  children, in order to reduce the worm burden 

  of soil-transmitted helminth infection.]

                            Self-assessment 2.3

  1) What is the important part of a
   comprehensive package to eliminate 
  morbidity due to soil-transmitted helminths
   in at-risk populations?
  

  2) Discuss on how deworming is

   being applied in your community?

                          2.4. End unit assessment
  

                           End of unit assessment
  

  1) What are the three major groups
   of helminths?
  2) Which of the following can be
  classified in heterocyclics ?
  a) Piperazine citrate.
  b) Thiabendazole
  c) Mebendazole
  d) Praziquantel
  3) Ivermectin is classified among natural
  products category of anthelminthic 
  drugs. True or False. 
  4) Which of the following are
  the most commonly used medications in 
  deworming?
  a) Mebendazole and albendazole
  b) Mebendazole and tinidazole 
  c) Mebendazole and Ivermictin 
  d) Ivermictin and albendazole
  5) Due to its effectiveness,
  praziquantel is the drug of choice for filariae. 
  True or False
  6) The deworming is the giving
  of an anthelmintic drugs human to help them 
  get rid of:
  a) Roundworms, flukes and protozoa
  b) Roundworms, flukes and tapeworm
  c) Flukes, protozoa and tapeworm
  

  d) Protozoa, tapeworm and roundworms

• UNIT 1: ANTIBIOTICS

                         Key Unit competence: 

   Manage different health conditions at the primary healthcare settings 
  

   by utilizing  antibiotics appropriately.

                 Introductory activity 1.0     

   The images below show different patients with bacterial infections and 
  

  they are being treated with different medications.

                      

  1) Have you even seen such kinds of patients?
  2) If yes, what types of drugs you heard or saw they were taking?
  

  3) Have you ever seen some types of the drugs in these images? 

          1.1. Definition of antibiotics and key concepts

               Learning Activity 1.1

      1) Read the scenario below:
  

   A 37-year-old female patient is on drugs that she takes every eight hours. She 
  was told that she has a disease that requires to be taken for 10 consecutive 
  days. Not all details were provided by the healthcare providers, and she heard 
  from different people that both antimicrobial and antibiotic agents may be used 
  for an extended period of time that can go beyond 10 days. She then doubts 
  whether she is taking an antibiotic or antimicribial, and wants to get your view. 
  
  Answer the questions below:
  a) In details, differentiate antibiotic from antimicrobial agents
  b) Give a difference between broad spectrum and narrow spectrum 
  

  antibiotics

            CONTENT SUMMARY

                  
  

  Antibiotics are medicines that fight bacterial infections in people and animals. They 
  work by killing the bacteria or by making it hard for the bacteria to grow and multiply.
  Examples: Amoxicillin, Gentamicin, Cotrimoxazole.
  
  An antimicrobial is a drug used to treat a microbial infection. “Antimicrobial” is a 
  general term that refers to a group of drugs that includes antibiotics, antifungals, 
  antiprotozoal, and antivirals. The antibiotics belong to the wide class of 
  antimicrobials.
  
  Examples: Ketoconazole (antifungal), Metronidazole (antiprotozoal), and acyclovir 
  (Antiviral).
  

  Antibiotic drugs can be bacteriostatic or bactericidal.

  “Bacteriostatic” refers to the ability of the agent (antibiotic) to prevent the growth of 
  bacteria while “bactericidal” is the ability of the agent to kill bacteria.
  
  However, several antibiotics are both bactericidal and bacteriostatic, depending on 
  the concentration of the particular drug.
  
  There is no perfect antibiotic that is without effect on the human host. Therefore, 
  health personnel try to select an antibiotic with selective toxicity, which is the ability 
  to strike foreign cells with little or no effect on human cells.
  
  Antibiotics may be classified as having broad spectrum of activity or narrow spectrum 
  of activity. Narrow-spectrum antibiotics act against a limited group of bacteria while 
  

  broad-spectrum antibiotics act against a larger group of bacteria.

           Difference between narrow-spectrum and broad-spectrum antibiotics 

                   
  

                      Self-assessment 1.1

  1) A colleague of class tells you that he is swallowing capsules of amoxicillin 
       as an antibiotic after having sustained an injury that developed pus. The 
       colleague wants to know what an antiotic is, and what it is used for. What 
       will you tell your colleague?
  

  2) Is there any relevance in prescribing such drug to your colleague?

             1.2. Ideal antibiotics and Mechanism of action of antibiotics
  

                   Learning Activity 1.2

             1) Read carefully the scenario below:

  A 62-year-old female is admitted at the healthcare facility with features of an 
  infection. The laboratory investigations help to identify the causal agent of 
  the bacterial infection, and an appropriate antibiotic is prescribed basing on 
  the identified agent. The reason to choose the drug was mainly based on the 
  mechanism of action of the prescribed antibiotic against the infectious bacterial 
  agent. In addition, the healthcare provider chose an antibiotic basing on its 
  characteristics. 
  
  a) Describe the qualities of an ideal antibiotic the nurse will consider while 
       prescribing the antibiotic.
  b) List the 5 main mechanisms of action of antibiotics?
  c) Is it required to consider the mechanism of action of an antibiotic during 
       its prescription? Explain your answer.
  
  Guidance: Read the book of pharmacology brought by the teacher in 
  

                         class, on topic of Mechanism of action of antibiotics.

  CONTENT SUMMARY

  An ideal antibiotic is an antibacterial agent that kills or inhibits the growth of all 
  harmful bacteria in a host, regardless of site of infection without affecting beneficial 
  gut microbes (gut flora) or causing undue toxicity to the host. Ideal antibiotics should 
  be toxic to microbes, and not to humans, bactericidal rather than bacteriostatic, 
  effective against broad range of bacteria; active in placenta, and other body fluids; 
  cost effective; and should not cause allergic and hypersensitive reactions, should 
  not give drugs resistance, long shelf life
  ; and desired levels should be reached 
  rapidly and maintained for adequate period of time. 
  
  The antibiotics exert their effects through different mechanisms that alter or damage 
  the bacterial cell. This disruption of the bacterial cell function ends up in the death 
  of the bacteria, which is an expected outcome of the treatment with antibiotics. This 
  is made possible by the fact that bacterial prokaryotic cells have some differences 
  with the human cells, and the former become the target of antibiotic drug action.
  
  Several different classes of antibacterials use a mechanism of “Inhibition of bacterial 
  cell wall synthesis” by blocking steps in the biosynthesis of peptidoglycan, making 
  cells more susceptible to osmotic lysis. Therefore, antibacterials that target cell 
  

  wall biosynthesis are bactericidal in their action. Because human cells do not make

  peptidoglycaa) Write the names of antibiotic drugs observed in the image above.
  b) Put the drugs you identified in their respective classes.
  c) What are the common side effects of antibiotics?n, this mode of action is                                                                                               an excellent example of selective toxicity.
  A small group of antibacterials alter the bacterial cell membranes in their mode of 
  action. They interact with lipopolysaccharide in the outer membrane of gram-negative 
  bacteria, killing the cell through the eventual disruption of the outer membrane and 
  cytoplasmic membrane. For gram-positive bacteria, these antibacterials insert into 
  the cytoplasmic membrane of the bacteria, disrupting the membrane and killing the 
  

  cell.

  Other antibacterials inhibit bacterial protein synthesis. The cytoplasmic ribosomes
  found in animal cells (80S) are structurally distinct from those found in bacterial 
  cells (70S), making protein biosynthesis a good selective target for antibacterial 
  

  drugs. 

  Some synthetic drugs control bacterial infections by functioning as antimetabolites, 
  competitive inhibitors for bacterial metabolic enzymes. In their mechanism of action, 
  these antibiotics may inhibit the enzyme involved in production of dihydrofolic acid, 
  they may inhibit the enzyme involved in the production of tetrahydrofolic acid or 
  

  interfere with the synthesis of mycolic acid.

  Finally, some antibacterial drugs work by inhibiting bacterial nucleic acid synthesis. 
  In this case, these antibiotics inhibit bacterial RNA polymerase activity and blocks 
  transcription, killing the cell. Alternatively, they inhibit the activity of DNA gyrase and 
  

  blocks DNA replication, killing the cell.

               Self-assessment 1.2

               Read the scenario below:
  A 25-year-old female patient comes to the health post where you work. She 
  comes 3 days after starting treatment with antibiotics, complaining of additional 
  symptoms after starting the treatment. She reports severe diarrhea, nausea, 
  vomiting, many skin rashes, and difficult swallowing. The nurse receiving the 
  patient decided to change the antibiotic for the patient, and managed the 
  additional complaints.
  
  The patient recovered after a short period of time. 
  1) In your understanding, was it necessary for the patient to come back to 
  the health post?
  2) Was the first drug ideal antibiotic to the patient?
  3) All of the following are the mechanisms of action of antibiotics, EXCEPT:
  a) Inhibiting bacterial nucleic acid synthesis
  b) Alter the bacterial cell membranes
  c) Inhibit bacterial protein synthesis
  d) Acting as bacterial metabolites
  4) As human cells make peptidoglycan, this prevents the antibiotics from 
  

  exerting their selective toxicity effect. TRUE or FALSE

          1.3. Drug resistance and prevention of antibiotic drug resistance
  

                 Learning Activity 1.3

                1.  Read carefully the scenario below:

  A 17-year-old female adolescent was involved in unprotected sexual intercourse 
  and got infected with sexually transmitted bacteria. She consulted the nearest 
  health post and doxycycline has been prescribed as antibiotics to be taken 
  BID for 14 days. After taking first dose, she complained that the drug tasted 
  badly and refused to continue taking the drug. After 4 days, she felt severe 
  pain in lower abdomen with painful urination. She then took other 3 doses, the 
  symptoms reduced, and she stopped again. After the period of 1 month, she felt 
  again similar severe pain and consulted another health post and she was given 
  the same drug (doxycycline). She decided to take completely and correctly the 
  prescribed drug but after the completion of prescribed doses, the symptoms 
  persisted. She decided to consult the hospital to give sample for culture and 
  sensitivity. The laboratory results showed that doxycycline could not cure the 
  disease because microbes had developed the resistance against doxycycline.
  
  a) According to you, what mistakes did the adolescent commit in taking the 
       initially prescribed drug?
  b) Referring to the scenario above, how can antimicrobial drug resistance 
  develop? Explain your answer?
  c) What type of resistance did this adolescent develop?
  
  Guidance: Read the book on topic of antibiotic resistance provided by the 
  

  teacher, and answer the questions above.

                 CONTENT SUMMARY 
  

  Antimicrobial resistance may develop anytime, when necessary, measures while 
  using antimicrobials are not taken. In nature, microbes are constantly evolving in 
  order to overcome the antimicrobial compounds produced by other microorganisms. 
  Human development of antimicrobial drugs and their widespread clinical use has 
  simply provided another selective pressure that promotes further evolution. Several 
  important factors can accelerate the evolution of drug resistance. These include 
  the overuse and misuse of antimicrobials, inappropriate use of antimicrobials,
  sub therapeutic dosing, and patient noncompliance with the recommended course of 
  

  treatment. Resistance can be natural or acquired. 

  Anti-infectives act on specific enzyme systems or biological processes. 
  On one hand, many microorganisms that do not use that system or process                                                                                                  are not affected
  by a particular anti-infective drug. They are said to have a natural or intrinsic 
  resistance. On the other hand, microorganisms that were once very sensitive to the 
  effects of particular drugs have begun to develop acquired resistance to the agents. 
  

  This is known as acquired resistance.

  With the current use of antibiotics in humans and animals, emergence of resistant 
  strains of microbes is becoming a serious public health problem. Health care 
  providers must work together to prevent this issue, given that exposure to an 
  antimicrobial agent can lead to the development of resistance. It is therefore 
  important to limit the use of antimicrobial agents to the treatment of specific 
  pathogens known to be sensitive to the drug being used. Drug dosing is important 
  in preventing the development of resistance, and doses should be high enough 
  and the duration of drug therapy should be long enough to eradicate even slightly 
  

  resistant microorganisms. 

  Around-the-clock dosing eliminates the peaks and valleys in drug concentration 
  and helps to maintain a constant therapeutic level to prevent the emergence of 
  resistant microbes during times of low concentration. The duration of drug use is 
  critical to ensure that the microbes are completely, not partially, eliminated and are 
  

  not given the chance to grow and develop resistant strains.

  It was identified that it is difficult to convince people who are taking anti-infective 
  drugs that the timing of doses and the length of time they continue to take the 
  drug are important. There is a need to be cautious about the indiscriminate use 
  of anti-infectives, and insist that antibiotics are not effective in the treatment of 
  viral infections or illnesses such as the common cold. However, many patients 
  demand prescriptions for these drugs when they visit practitioners because they 
  

  are convinced that they need to take something to feel better.

  With many serious illnesses, including pneumonias for which the causative organism 
  is suspected, antibiotic therapy may be started as soon as a sample of the bacteria, 
  or culture, is taken and before the results are known. In many cases, it is necessary 
  to perform sensitivity testing on the cultured microbes to evaluate bacteria and 
  determine which drugs are most effective. Health care providers also tend to try 
  newly introduced, more powerful drugs when a more established drug may be just 
  as effective. Use of a powerful drug in this way leads to the rapid emergence of 
  resistant strains to that drug, perhaps limiting its potential usefulness when it might 
  

  be truly necessary.

                  Self-assessment 1.3
  

  1) Differentiate acquired resistance from natural resistance.

  2) List 2 factors that can accelerate the occurrence of antibiotic resistance.

  3) Around-the-clock dosing exposes people to the occurrence of antibiotic 

  resistance. TRUE or FALSE

      1.4. Classification of antibiotics with focus on antibiotics 
  

        available in healthcare settings in Rwanda

            1.4.1 Introduction to antibiotics

                Learning Activity 1.4.1

              1) Observe attentively the image below:

                      
                 

  a) Write the names of antibiotic drugs observed in the image above. 

  b) Put the drugs you identified in their respective classes.

  c) What are the common side effects of antibiotics?     

           CONTENT SUMMARY
  

   Bacteria can invade the human body through many routes. The goal of antibiotic 
  therapy is to decrease the population of invading bacteria to a point at which the 
  human immune system can effectively deal with the invader. To determine which 
  antibiotic will effectively interfere with the specific proteins or enzyme systems for 
  treatment of a specific infection, the causative organism must be identified through 
  a culture. Sensitivity testing is also done to determine the antibiotic to which that 
  particular organism is most sensitive (e.g., which antibiotic best kills or controls 
  

  the bacteria). Drugs with broad spectrum activity are often given at the beginning

   of treatment until the exact organism and sensitivity can be established. Because 
  these antibiotics have such a wide range of effects, they are frequently associated 
  with adverse effects. Human cells have many of the same properties as bacterial 
  cells and can be affected in much the same way, so damage may occur to the 
  human cells, as well as to the bacterial cells. There is no perfect antibiotic that is 
  

  without effect on the human host.

  Certain antibiotics may be contraindicated in some patients because of known 
  adverse effects. Some patients for which antibiotics are contraindicated due to 
  known adverse reactions include: Immunocompromised patients; Patients with 
  

  severe GI disease, and Patients who are debilitated.

  The antibiotic of choice is one that affects the causative organism and leads to the 
  fewest adverse effects for the patient involved. In some cases, antibiotics are given 
  in combination because they are synergistic. Use of synergistic antibiotics also 
  allows the patient to take a lower dose of each antibiotic to achieve the desired 
  effect. This helps to reduce the adverse effects that a particular drug may have. In 
  some situations, antibiotics are used as a means of prophylaxis, or prevention of 
  

  potential infection.

  The most common side effects of antibiotics are: Ocular damage, Superinfections 
  (GI and Genito-urinary tract), Allergic reactions, Bone marrow depression, GI 
  

  effects, Dermatological reactions, Auditory damage and Renal damage.

  There are some pieces of advice, any patient taking antibiotics should follow:
  (1) Do not demand an antibiotic when you come to see your doctor.
  (2) Take your antibiotics 
  as prescribed and use all pills even if you are feeling better. When you stop taking 
  the pills before you have used them all, there’s a likely chance that all of the bacteria 
  have not been killed and the remaining bacteria will become stronger and replicate 
  new bacteria that will be more resistant to the antibiotic next time around.
  (3) There should not be leftovers, and if for some reason there are, do not save                                                                                   them to take at another time.
  (4) Never share your antibiotics with someone else.
  (5) Always take 
  antibiotics with food to prevent stomach upset, except otherwise indicated.
  (6) If the antibiotic is making you feel worse, talk to your doctor about your symptoms.                                                                            You may need a different antibiotic or something that will help with the side effects.
   (7) Diarrhea is a common side effect of antibiotics. As a preventive measure, you can 
  

  take an over-the-counter probiotic to help reduce diarrhea symptoms.

                                

  Antibiotics are classified into the following classes: Aminoglycosides, carbapenems, 
  cephalosporins, fluoroquinolones, penicillins (and penicillinase-resistant drugs), 
  sulfonamides, tetracyclines, disease-specific antimycobacterials (antitubercular and 
  leprostatic drugs), ketolides (E.g.: telithromycin), lincosamides, lipoglycopeptides 
  

  (E.g.: televancin), macrolides, and monobactams (E.g.: aztreonam) 

               Self-assessment 1.4.1   

  1) What is the advantage of using synergistic drugs? 
  

  2) Use of synergistic antibiotics allows the patient to increase the dose                                                                                                                   of each antibiotic to get the desired effect. TRUE or FALSE.

       1.4.2. Class of penicillins and penicillinase resistant antibiotics
  

                   Learning Activity 1.4.2  

                   1) Read the case study below and answer the questions related to it: 

  A 40-year-old female patient consults the health post where you are appointed in 
  the clinical placement. She reports that she had unprotected sex, and developed 
  a painless sore that disappeared after some period. You suspect that the patient 
  suffers from syphilis, and you want to prescribe a drug in the class of penicillins.
  
  a) Is it relevant to treat syphilis with drugs in the class of penicillins?
  b) Give at least 5 drugs in the class of penicillins
  c) Is is advisable to combine penicillins and parenteral aminoglycosides? 
  

  Explain your answer

  CONTENT SUMMARY

  Penicillin was the first antibiotic introduced for clinical use. Penicillins include 
  penicillin G benzathine, penicillin G potassium, penicillin G procaine, penicillin V, 
  

  amoxicillin, and ampicillin.

  With the prolonged use of penicillin, more and more bacterial species have 
  synthesized the enzyme penicillinase to counteract the effects of penicillin. A group 
  of drugs with a resistance to penicillinase was developed, and this allows them to 
  

  remain effective against bacteria that are now resistant to the penicillins.                                                                                             Penicillin resistant antibiotics include nafcillin and oxacillin.

   These antibiotics produce bactericidal effects by interfering with the ability of 
  susceptible bacteria to build their cell walls when they are dividing. Because human 
  cells do not use the biochemical process that the bacteria use to form the cell 
  wall, this effect is a selective toxicity. The penicillins are indicated for the treatment 
  of streptococcal infections, including pharyngitis, tonsillitis, scarlet fever, and 
  endocarditis; pneumococcal infections; staphylococcal infections; fusospirochetal 
  infections; rat-bite fever; diphtheria; anthrax; syphilis; and uncomplicatedgonococcal 
  infections. At high doses, these drugs are also used to treat meningococcal 
  

  meningitis. Most of the penicillins are rapidly absorbed from the GI tract, reaching peak                                                               levels in 1 hour.

  Should be taken on an empty stomach to ensure adequate absorption. 
  Penicillins are excreted unchanged in the urine, and enter breast milk which can 
  

  cause adverse reactions.

  Penicillins are contraindicated in patients with allergies to penicillin or cephalosporins 
  or other allergens. Penicillin sensitivity tests are available if the patient’s history 
  of allergy is unclear and a penicillin is the drug of choice. Use with caution in 
  patients with renal disease, in pregnant and lactating patients because diarrhea 
  and superinfections may occur in the infant. Perform culture and sensitivity before 
  therapy to select the right drug to the causal agent. With the emergence of many 
  

  resistant strains of bacteria, this has become increasingly important.

  GI adverse effects are common and include nausea, vomiting, diarrhea, 
  abdominal pain, glossitis, stomatitis, gastritis, sore of the mouth, and furry tongue. 
  Superinfections, including yeast may also develop. Pain and inflammation at the 
  injection site can occur with injectable forms. Hypersensitivity reactions may include 
  rash, fever, wheezing, and, with repeated exposure, anaphylaxis that can progress 
  

  to anaphylactic shock and death.

  Different drugs may interact with penicillins, and necessary precautions should be 
  taken. If penicillins and penicillinase-resistant antibiotics are taken concurrently 
  with tetracyclines, a decrease in the effectiveness of the penicillins results. This 
  combination should be avoided if at all possible, or the penicillin doses should be 
  raised, which could increase the occurrence of adverse effects. When the parenteral 
  forms of penicillins and penicillinase-resistant drugs are administered in combination 
  with any of the parenteral aminoglycosides, inactivation of the aminoglycosides 
  

  occurs. These combinations should also be avoided whenever possible.

  There is a variety of nursing considerations that need to be taken into account 
  while administering the penicillins: Assess for possible contraindications or 
  cautions; Perform a physical assessment to establish baseline data for evaluating 
  the effectiveness of the drug and the occurrence of any adverse effects associated 
  with drug therapy; Examine skin and mucous membranes for any rashes or lesions 
  and injection sites for abscess formation to provide a baseline for possible adverse 
  effects; Perform culture and sensitivity tests at the site of infection to ensure that this 
  is the drug of choice for this patient; Note respiratory status to provide a baseline 
  for the occurrence of hypersensitivity reactions; Examine the abdomen to monitor 
  

  for adverse effects.

                    Tables 1.4.2.1: Summary of the prototype penicillins
  

                       

                         

                         
                           

                              

                               
  
                               
                                
                                  Self-assessment 1.4.2
  

  1) Which of the following statements describes the mechanism of action of 
  amoxicillin?
  a) Interference with the 50S subunit of bacterial ribosomes
  b) Inhibition of bacterial cell wall synthesis
  c) Interference with the 30S subunit of bacterial ribosomes
  d) Suppression of folate synthesis
  2) One of the following penicillin drugs is effective on infections caused by 
  beta-lactamase producing organisms:
  a) Cloxacillin
  b) Amoxicillin
  c) Ampicillin
  d) Penicillin V
  3) One of the following penicillin antibiotics can be used in the prophylaxis of 
  rheumatic fever and syphilis:
  a) Amoxicillin
  b) Ampicillin
  c) Penicillin V
  d) Penicillin G benzathine
  4) The healthcare professionals need to take necessary caution when 
  

  administering penicillins to people allergic to cephalosporins.                                                                                                                           TRUE or FALSE

       1.4.3 Class of aminoglycosides

                  Learning Activity 1.4.3       

  1) Read the case study below and answer the questions related to it:
  A 50-year-old male patient consults the health post where you are carrying out 
  the clinical placement. He has a serious bacterial infectious disease that requires 
  treatment with an aminoglycoside. You then refer the patient to the nearest district 
  hospital to receive an aminoglycoside through the parenteral route. Answer the 
  following questions related to the scenario above:
  a) Give at least 3 drugs in the class of aminoglycosides
  b) Which mechanism of action do aminoglycosides use to exert their 
  effects?
  Guidance: Read the textbook provided by the teacher, on the topic of 
  

  aminoglycosides, and answer the questions above.         

      CONTENT SUMMARY

  Aminoglycosides are powerful antibiotics used to treat serious infections caused 
  by gram-negative aerobic bacilli. Because most of these drugs have potentially 
  serious adverse effects, newer, less-toxic drugs have replaced aminoglycosides in 
  the treatment of less serious infections. They include amikacin (Amikin), gentamicin 
  (Garamycin), Kanamycin (Kantrex), neomycin (Mycifradin), streptomycin, and 
  tobramycin (TOBI, Tobrex),promomycin and plazomycin.
  
  The aminoglycosides are bactericidal and inhibit protein synthesis in susceptible 
  strains of gram-negative bacteria. These antibiotics are used to treat serious 
  infections caused by Pseudomonas aeruginosa, E. coli, Proteus species, the 
  Klebsiella, Enterobacter, Serratia group, Citrobacter species, and Staphylococcus 
  species such as Staphylococcus aureus. 
  
  Aminoglycosides are indicated for the treatment of serious infections that are 
  susceptible to penicillin when penicillin is contraindicated. They can be used in 
  severe infections before culture and sensitivity tests have been completed. The 
  aminoglycosides are poorly absorbed from the GI tract but rapidly absorbed after 
  intramuscular injection, reaching peak levels within 1 hour. They have an average 
  half-life of 2 to 3 hours. They are widely distributed throughout the body, cross the 
  placenta and enter breast milk, and are excreted unchanged in the urine.
  
  Aminoglycosides are contraindicated in case of known allergy to any of the 
  aminoglycosides. They are also contraindicated in renal or hepatic disease that 
  could be exacerbated by toxic aminoglycoside effects and that could interfere 
  

  with drug metabolism and excretion, leading to higher toxicity. Preexisting hearing 

  loss, which could be intensified by toxic drug effects on the auditory nerve is a 
  contraindication to the use of antibiotics. Ideally, aminoglycosides should be 
  

  avoided in case of lactation.

  Cautions should be taken while using during pregnancy (the benefits of the drug 
  

  must be carefully weighed against potential adverse effects on the fetus).

  Test urine function frequently when these drugs are used because they depend on 
  the kidney for excretion and are toxic to the kidney. The potential for nephrotoxicity 
  and ototoxicity with amikacin is very high with the use of aminoglycosides, and 
  special caution for kanamycin is to ensure it is not used for longer than 7 to 10 days. 
  Streptomycin, once a commonly used drug, is reserved for use in special situations 
  because it is very toxic to the eighth cranial nerve and kidney.
  
  Their main severe side effects may include ototoxicity, nephrotoxicity, and 
  neuromuscular blockade. The interaction of aminoglycoside antibiotics and 
  calcium channel blockers is of clinical significance because when these agents 
  are given concurrently during the perioperative period they may lead to respiratory 
  depression or prolonged apnoea. 
  
  There are some nursing considerations that need to be taken into account while 
  administering aminoglycosides. Assess for possible contraindications or cautions. 
  Perform a physical assessment to establish baseline data for assessing the 
  effectiveness of the drug and the occurrence of any adverse effects associated with 
  drug therapy. Perform culture and sensitivity tests at the site of infection to ensure 
  appropriate use of the drug. Conduct auditory testing to evaluate any CNS effects 
  

  of the drug, perform renal and hepatic function tests, and assess vital signs.

               Tables 1.4.3.1: Summary of the prototype aminoglycosides

                  

                                  

                   

                     

                     

                      

                       

                        

                          Self-assessment 1.4.3

   1) Aminoglycosides are primarily used for infections by what type of 
  pathogen?
  a) Gram negative aerobic bacilli
  b) Both Gram negative and Gram-positive bacteria
  c) Yeast and fungi
  d) Gram positive bacteria only
  2) Which of the following is an example of an aminoglycoside antibiotic?
  a) Azithromycin
  b) Erythromycin
  c) Streptomycin
  d) Clindamycin
  3) The associate nurse considers administration of gentamicin. Which of the 
  following is NOT a side effect of this medication?
  a) Diaphoresis
  b) Ototoxicity
  c) Anorexia
  

  d) Nephrotoxicit

             1.4.4 Class of cephalosporins          

               Learning Activity 1.4.4

               1) Read the scenario below:

  A 18-year-old male patient comes to the health facility with compalins of chronic 
  wound drainage, pain, and exposed bone. On the observation, the patient is 
  suspected to have a chronic osteomyelitis, and he is sheduled for surgery. 
  Postoperatively, the patient is written a third generation cephalosporin for 14 
  days. Answer the following questions related to the case study above
  a) Give at least 2 drugs in the class of third generation cephalosporins
  

  b) Which mechanism of action do cephalosporins use to exert their effects?

  CONTENT SUMMARY

  The cephalosporins are drugs similar to the penicillins in structure and in activity. This 
  means that their mechanism of action is through inhibition of bacterial cell wall 
  

  peptidoglycan synthesis. 

  Over time, different generations of cephalosporins have been introduced, each 
  group with its own spectrum of activity. In this book, only 3 generations will be 
  

  discussed. 

  First-generation cephalosporins are largely effective against the same gram positive                                                                  bacteria that are affected by penicillin G, as well as the gram-negative 
  bacteria P. mirabilis, E. coli, and K. pneumoniae. First-generation drugs include 
  cefadroxil (generic), cefazolin (Zolicef), and cephalex.
  
  Second-generation cephalosporins are effective against the previously mentioned 
  strains, as well as H. influenzae, Enterobacter aerogenes, and Neisseria species. 
  Second-generation drugs are less effective against gram-positive bacteria. These 
  include cefaclor (Ceclor), cefoxitin (generic), cefprozil (generic), and cefuroxime 
  

  (Zinacef).

  Third-generation cephalosporins, which are effective against all of the previously 
  mentioned strains, are weak against gram-positive bacteria but are more potent 
  against the gram-negative bacilli. Third-generation drugs include cefdinir (Omnicef), 
  cefotaxime (Claforan), cefpodoxime (Vantin), ceftazidime (Ceptaz, Tazicef), 
  

  ceftibuten (Cedax), ceftizoxime (Cefi zox), and ceftriaxone (Rocephin).

  The cephalosporins are both bactericidal and bacteriostatic, depending on the dose 
  used and the specific drug involved. In susceptible species, these agents basically 
  interfere with the cell wall–building ability of bacteria when they divide; that is, they 
  

  prevent the bacteria from biosynthesizing the framework of their cell walls.

  Avoid the use of cephalosporins in patients with known allergies to cephalosporins 
  or penicillins because cross-sensitivity is common. Use with caution in patients with 
  hepatic or renal impairment because these drugs are toxic to the kidneys and could 
  interfere with the metabolism and excretion of the drug. In addition, use with caution 
  in pregnant or lactating patients because potential effects on the fetus and infant 
  are not known; use only if the benefits clearly outweigh the potential risk of toxicity 
  

  to the fetus or infant.

  The most common adverse effects of the cephalosporins involve the GI tract and 
  include nausea, vomiting, diarrhea, anorexia, abdominal pain, and flatulence. CNS 
  symptoms include headache, dizziness, lethargy, and paresthesias. Nephrotoxicity 
  is also associated with the use of cephalosporins, most particularly in patients who 
  

  have a predisposing renal insufficiency

  Patients who receive oral anticoagulants in addition to cephalosporins may 

  experience increased bleeding. Instruct the patient receiving cephalosporins 
  to avoid alcohol for up to 72 hours after discontinuation of the drug to prevent a 
  disulfiram-like reaction, which results in unpleasant symptoms such as flushing, 
  throbbing headache, nausea and vomiting, chest pain, palpitations, dyspnea, 
  syncope, vertigo, blurred vision, and, in extreme reactions, cardiovascular collapse, 
  convulsions, or even death. Concurrent administration of cephalosporins with 
  aminoglycosides increases the risk for nephrotoxicity. Frequently monitor patients 
  receiving this combination, and evaluate serum blood urea nitrogen (BUN) and 
  creatinine levels.
  
  There is a variety of nursing considerations that need to be taken into account: 
  Assess for possible contraindications or cautions. Monitor the patient for any signs 
  of superinfection to arrange for treatment if superinfection occurs. Instruct the patient 
  about the appropriate dosage schedule and about possible side effects to enhance 
  patient knowledge about drug therapy and to promote compliance. Take safety 
  precautions, including changing position slowly and avoiding driving and hazardous 
  tasks, if CNS effects occur. Try to drink a lot of fluids and to maintain nutrition (very 
  important) even though nausea, vomiting, and diarrhea may occur. Report difficulty 
  breathing, severe headache, severe diarrhea, dizziness, or weakness. Avoid 
  consuming alcoholic beverages while receiving cephalosporins and for at least 72 
  

  hours after completing the drug course because serious side effects could occur.

          Tables.1.4.4.1 Summary the prototype cephalosporins

            CEPHALOSPORINS OF FIRST GENERATION:
  

                            

                              

                                   CEPHALOSPORINS OF SECOND GENERATION

                                     

                                        

                                        

                                         

                                           Self-assessment 1.4.4

   1) Which of the following antibiotics belongs to the class of cephalosporins? 
        a) Amoxicillin 
        b) Gentamicin 
        c) Cefotaxime 
        d) Bactrim 
  2) Which of the following IS NOT a caution for the use of cephalosporins? 
      a) Allergy to penicillin
      b) Allergy to aspirin
     c) Renal failure
  

     d) Concurrent treatment with aminoglycosides

                            1.4.5. Class of fluoroquinolones

                           Learning Activity 1.4.5
  

   1) Read the scenario below:

  A 30-year-old female patient consults the health post where you allocated 
  during the clinical practice, complaining of recurrent urinary tract infections on a 
  pregnancy of 3 months. The patient reports that he was treated with amoxicillin 
  without success. You then decide to prescribe a fluoroquinolone antibiotic, 
  bearing in mind its effectiveness in urinary tract infections.
  a) List at least 4 fluoroquinolone drugs
  b) Bearing in mind that this patient is pregnant, is it advisable to prescribe 
  fluoroquinolones?
  Guidance: Read the textbook provided by the teacher, on the topic of 
  

  fluoroquinolones, and answer the questions above

  CONTENT SUMMARY

  The fluoroquinolones are a relatively new synthetic class of antibiotics with a broad 
  spectrum of activity. Fluoroquinolones include ciprofloxacin (Cipro), which is the 
  most widely used fluoroquinolone; gemifloxacin (Factive), levofloxacin (Levaquin), 
  

  moxifloxacin (Avelox), norfloxacin (Noroxin), and ofloxacin.

  The fluoroquinolones enter the bacterial cell by passive diffusion through channels 
  in the cell membrane. Once inside, they interfere with the action of DNA enzymes 
  necessary for the growth and reproduction of the bacteria. This leads to cell death 
  because the bacterial DNA is damaged and the cell cannot be maintained. However, 
  misuse of these drugs in the short time the class has been available has led to the 
  

  existence of resistant strains of bacteria.

  The fluoroquinolones are indicated for treating infections caused by susceptible 
  strains of gram-negative bacteria, S. aureus, Staphylococcus epidermidis, some 
  Neisseria gonorrhoeae, and group D streptococci. These infections frequently 
  include urinary tract, respiratory tract, and skin infections. Ciprofloxacin is effective 
  

  against a wide spectrum of gram-negative bacteria.

  Fluoroquinolones are contraindicated in patients with known allergy to any 
  fluoroquinolone and in pregnant or lactating patients because potential effects 
  on the fetus and infant are not known. Use with caution in the presence of renal 
  dysfunction, which could interfere with the metabolism and excretion of the drug, 
  and seizures, which could be exacerbated by the drugs’ effects on cell membrane 
  channels. The use of antacids has been recognized to impair the action of 
  

  fluoroquinolones, therefore, such concomitant use is not recommended.

  These drugs are generally associated with relatively mild adverse reactions. 
  The most common are headache, dizziness, insomnia, and depression related 
  to possible effects on the CNS membranes. GI effects include nausea, vomiting, 
  diarrhea, and dry mouth, related to direct drug effect on the GI tract and possibly to 
  

  stimulation of the chemoreceptor trigger zone in the CNS.

  There are nursing considerations that the nurses ought to bear in mind: Assess for 
  possible contraindications or cautions. Perform physical assessment to establish 
  baseline data for assessing the effectiveness of the drug and the occurrence of 
  any adverse effects associated with drug therapy. Examine the skin for any rash 
  or lesions to provide a baseline for possible adverse effects. Perform culture and 
  sensitivity tests at the site of infection to ensure appropriate use of the drug. Perform 
  renal function tests, including blood urea nitrogen and creatinine clearance, to 
  evaluate the status of renal functioning and to assess necessary changes in dose. 
  Conduct assessment of orientation, affect, and reflexes to establish a baseline for 
  

  any central nervous system (CNS) effects of the drug.

                      Table 1.4.5.1: Summary of the prototype fluoroquinolones

                        

                                   

                   

       Self-assessment 1.4.5

   1) Read the scenario below:

  A 32-year-old female patient consults the health post where you are appointed, 
  complaining of recurrent urinary tract infections. The patient reports that he 
  was treated with amoxicillin without success. You then decide to prescribe a 
  fluoroquinolone antibiotic, bearing in mind its effectiveness in urinary tract 
  infections. 
  a) What are the nursing considerations you would consider before 
  

  prescribing a fluoroquinolone to any patient?

    1.4.6. Class of macrolides

    Learning Activity 1.4.6

  1) Read the scenario below:

  You receive a 60-year-old male patient who consults the health post where you 
  work with complaints of respiratory tract infection. The patient reports that he 
  took amoxicillin in the past, and developed an allergic reaction. He was then 
  warned not to take any penicillin drug again in the past, because of allergy to 
  penicillins. You then decide to prescribe a macrolide antibiotic, as it may replace 
  a penicillin in such infections.
  a) List at least 2 antibiotics that belong to the class of macrolides
  

  b) What is the mechanism of action of a macrolide?

  CONTENT SUMMARY

  The macrolides are antibiotics that interfere with protein synthesis in susceptible 
  bacteria. Macrolides include erythromycin, azithromycin, clarithromycin, and 
  

  dirithromycin.

  The macrolides may be bactericidal or bacteriostatic, exerting their effect by binding 
  to the bacterial cell membrane and changing protein function. This action can 
  prevent the cell from dividing or cause cell death, depending on the sensitivity of 
  

  the bacteria and the concentration of the drug. 

  Macrolides are indicated for treatment of the following conditions: acute infections 
  caused by susceptible strains of S. pneumoniae, M. pneumoniae, Listeria 
  monocytogenes, and Legionella pneumophila; infections caused by group A beta                                                                                hemolytic streptococci; pelvic inflammatory disease caused by N. gonorrhoeae; 
  upper respiratory tract infections caused by H. influenzae (with sulfonamides); 
  infections caused by Corynebacterium diphtheriae and Corynebacterium 
  minutissimum (with antitoxin); intestinal amebiasis; and infections caused by C. 
  

  trachomatis. 

  In addition, macrolides may be used as prophylaxis for endocarditis before dental 
  procedures in high-risk patients with valvular heart disease who are allergic to 
  penicillin. Topical macrolides are indicated for the treatment of ocular infections 
  caused by susceptible organisms and for acne vulgaris, and they may also be used 
  prophylactically against infection in minor skin abrasions and for the treatment of 
  

  skin infections caused by sensitive organisms.

  The macrolides are widely distributed throughout the body; they cross the placenta 
  

  and enter the breast milk. These drugs are absorbed in the GI tract.

  Erythromycin is metabolized in the liver, with excretion mainly in the bile to feces. 
  

  The half-life of erythromycin is 1.6 hours. 

  Azithromycin and clarithromycin are mainly excreted unchanged in the urine, 
  making it necessary to monitor renal function when patients are taking these drugs. 
  The half-life of azithromycin is 68 hours, making it useful for patients who have 
  trouble remembering to take pills because it can be given once a day.                                                                                                              The half life of clarithromycin is 3 to 7 hours. Dirithromycin is converted from the prodrug 
  dirithromycin to erythromycylamine in the intestinal wall. Most of the drug is excreted 
  through the feces. It has a half-life of 2 to 36 hours. It also has the advantage of 
  

  once-a-day dosing, which increases compliance in many cases.

  Macrolides are contraindicated in patients with a known allergy to any macrolide 
  because cross-sensitivity occurs. Use with caution in patients with hepatic 
  dysfunction, which could alter the metabolism of the drug, and in those with renal 
  disease, which could interfere with the excretion of some of the drug. 
  Also use with caution in lactating women because macrolides secreted in breast milk can 
  cause diarrhea and superinfections in the infant and in pregnant women because 
  of potential adverse effects on the developing fetus; use only if the benefit clearly 
  

  outweighs the risk to the fetus.

  Relatively few adverse effects are associated with the macrolides. The most 
  frequent ones, which involve the direct effects of the drug on the GI tract, are 
  often uncomfortable enough to limit the use of the drug. These include abdominal 
  cramping, anorexia, diarrhea, vomiting, and pseudomembranous colitis. Other 
  effects include neurological symptoms such as confusion, abnormal thinking, 
  and uncontrollable emotions, which could be related to drug effects on the CNS 
  membranes; hypersensitivity reactions ranging from rash to anaphylaxis; and 
  

  superinfections related to the loss of normal flora.

  During macrolide administration, there are nursing considerations that nurses need 
  to consider: GI upset is common and patients can be advised to take medication 
  with food. Patients should also be advised to avoid excessive sunlight and to 
  wear protective clothing and use sunscreen when outside, as well as to report any 
  adverse reactions immediately. Advise patients to report symptoms of chest pain, 
  palpitations, or yellowing of eyes or skin. Additionally, patients should be advised 
  

  that these medications can cause drowsiness.

  Assess for possible contraindications or precautions to macrolides. Perform a 
  physical assessment to establish baseline data for assessing the effectiveness of 
  the drug and the occurrence of any adverse effects associated with drug therapy. 
  Examine the skin for any rash or lesions to provide a baseline for possible adverse 
  effects. Obtain specimens for culture and sensitivity testing from the site of infection 
  to ensure appropriate use of the drug. Monitor temperature to detect infection. 
  Conduct assessment of orientation, affect, and reflexes to establish a baseline for 
  any CNS effects of the drug. Assess liver and renal function test values to determine 
  the status of renal and liver functioning and to determine any needed alteration in 
  

  dosage

                   Tables 1.4.6.1 Summarizing of the prototype macrolides

                      

                      

                        

                         Self-assessment 1.4.6

  1) Which of the following antibiotic would be given to a patient with gastritis 
  associated with Helicobacter pylori?
  a) Erythromycin
  b) Clarithromycin
  c) Gentamicin
  d) Doxycycline
  1) All of the following antibiotics are macrolides, EXCEPT:
  a) Erythromycin
  b) Clarithromycin
  c) Azithromycin
  

  d) Streptomycin

       1.4.7. Class of tetracyclines

         Learning Activity 1.4.7

       1) Read the scenario below:

  You receive a 45-year-old female patient who consults the health post 
  where you are doing your clinical placement, with complaints of urinary 
  tract infection. This infection can be treated by a tetracycline antibiotic that 
  is effective against some bacteria that cause urinary tract infection. As a 
  student nurse, you wish to prescribe a tetracycline antibiotic that will help 
  to clear the infection. 
  a) List at least 2 antibiotics that belong to the class of tetracyclines
  

  b) What is the mechanism of action of tetracyclines?

  CONTENT SUMMARY

  The class of tetracyclines has been developed as semisynthetic antibiotics basing 
  on the structure of a common soil mold. They are composed of four rings, which 
  defines how they got their name. Researchers have developed newer tetracyclines 
  to increase absorption and tissue penetration. Their use has been limited in 
  recent years due to their noted widespread resistance. Existing Tetracyclines 
  include tetracycline (Sumycin), demeclocycline (Declomycin), doxycycline (Doryx, 
  

  Periostat), and minocycline (Minocin).

  The tetracyclines work by inhibiting protein synthesis in a wide range of bacteria, 
  leading to the inability of the bacteria to multiply. Because the affected protein is 
  similar to a protein found in human cells, these drugs can be toxic to humans at 
  

  high concentrations. 

  Tetracyclines are indicated for treatment of infections caused by susceptible agents; 
  when penicillin is contraindicated in susceptible infections; and for treatment of 
  acne and uncomplicated GU infections caused by C. trachomatis. Some of the 
  tetracyclines are also used as adjuncts in the treatment of certain protozoal 
  

  infections such as malaria.

  Tetracyclines are absorbed adequately, but not completely, from the GI tract. Their 
  absorption is affected by food, iron, calcium, and other drugs in the stomach. 
  Tetracyclines are concentrated in the liver and excreted unchanged in the urine, 
  with half-lives ranging from 12 to 25 hours. These drugs cross the placenta and 
  pass into breast milk. Tetracycline is available in oral and topical forms, in addition 
  to being available as an ophthalmic agent. Demeclocycline is available in oral form. 
  

  Doxycycline and minocycline are available in IV and oral forms.

  Tetracyclines are contraindicated in patients with known allergy to tetracyclines or 
  to tartrazine (e.g., in specifi c oral preparations that contain tartrazine) and during 
  

  pregnancy and lactation because of effects on developing bones and teeth. 

  The ophthalmic preparation is contraindicated in patients who have fungal, 
  mycobacterial, or viral ocular infections because the drug kills not only the 
  undesired bacteria but also bacteria of the normal flora, which increases the risk 
  for exacerbation of the ocular infection that is being treated. Tetracyclines should 
  be used with caution in children younger than 8 years of age because they can 
  potentially damage developing bones and teeth and in patients with hepatic or renal 
  

  dysfunction because they are concentrated in the bile and excreted in the urine.

  The major adverse effects of tetracycline therapy involve direct irritation of the 
  GI tract and include nausea vomiting, diarrhea, abdominal pain, glossitis, and 
  dysphagia. Fatal hepatotoxicity related to the drug’s irritating effect on the liver 
  

  has also been reported. Skeletal effects involve damage to the teeth and bones. 

  Because tetracyclines have an affinity for teeth and bones, they accumulate there, 
  weakening the structure and causing staining and pitting of teeth and bones. 
  Dermatological effects include photosensitivity and rash. Superinfections, including 
  yeast infections, occur when bacteria of the normal flora are destroyed. Local effects, 
  such as pain and stinging with topical or ocular application, are fairly common. 
  Hematological effects are less frequent, such as hemolytic anemia and bone 
  marrow depression secondary to the effects on bone marrow cells that turn over 
  rapidly. Hypersensitivity reactions reportedly range from urticaria to anaphylaxis 
  

  and also include intracranial hypertension

  When penicillin G and tetracyclines are taken concurrently, the effectiveness of 
  penicillin G decreases. If this combination is used, the dose of the penicillin should be 
  increased. When oral contraceptives are taken with tetracyclines, the effectiveness 
  of the contraceptives decreases, and patients who take oral contraceptives should 
  

  be advised to use an additional form of birth control while receiving the tetracycline.

  Because oral tetracyclines are not absorbed effectively if taken with food or dairy 
  products, they should be administered on an empty stomach 1 hour before or 2 to 
  

  3 hours after any meal or other medication.

  The following nursing considerations should be taken into account as the 
  nurses are providing care to patients receiving tetracyclines: Assess for possible 
  contraindications or cautions. Perform a physical examination to establish baseline 
  data for assessing the effectiveness of the drug and the occurrence of any adverse 
  effects associated with drug therapy. Examine the skin for any rash or lesions to 
  provide a baseline for possible adverse effects. Perform culture and sensitivity tests 
  at the site of infection to ensure that this is the appropriate drug for this patient. 
  Note respiratory status to provide a baseline for the occurrence of hypersensitivity 
  reactions. Evaluate renal and liver function test reports, including blood urea nitrogen 
  and creatinine clearance, to assess the status of renal and liver functioning, which 
  

  helps to determine any needed changes in dose. 

              Tables 1.4.7.1 summarizing the prototype tetracyclines

                 

                 

      Self-assessment 1.4.

  1) Which of the following antibiotics belongs to the class of tetracyclines?
  a) Doxycycline
  b) Erythromycin
  c) Amoxicillin
  d) Azithromycin
  

  2) Why are tetracyclines contraindicated in children aged less than 8 years?

         1.4.8. Class of sulphonamides (sulfonamides)

            Learning Activity 1.4.8         

             1) Read the scenario below:

   You receive a 52-year-old male patient who consults the health post where you 
  are assigned in the clinical placement, with history of HIV infection. The patient 
  says that he takes an antibiotic drug in addition to the antiretroviral drugs. He 
  specifies that he was told that the antibiotic intends is to prevent the pneumonia 
  caused by pneumocystis carinii. As a student nurse, you anticipate that the 
  antibiotic may belong to the class of sulfonamides.
  a) List at least 2 antibiotics that belong to the class of sulfonamides
  

  b) What is the mechanism of action of sulfonamides?

  CONTENT SUMMARY

  The sulfonamides, or sulfa drugs, are drugs that inhibit folic acid synthesis. 
  

  Sulfonamides include sulfadiazine, sulfasalazine, and cotrimoxazole (Bactrim).

  Folic acid is necessary for the synthesis of purines and pyrimidines, which are 
  precursors of RNA and DNA. For cells to grow and reproduce, they require folic acid. 
  Humans cannot synthesize folic acid and depend on the folate in their diet to obtain 
  this essential substance. Bacteria are impermeable to folic acid and must synthesize 
  it inside the cell. The sulfonamides competitively block paraaminobenzoic acid to 
  prevent the synthesis of folic acid in susceptible bacteria that synthesize their own 
  folates for the production of RNA and DNA. This includes gram-negative and gram                                                                                positive bacteria such as Chlamydia trachomatis and Nocardia and some strains of 
  

  H. influenzae, E. coli, and P. mirabilis.

  Because of the emergence of resistant bacterial strains and the development                                                                                           of newer antibiotics, the sulfa drugs are no longer used much. 
  
  However, they remain an inexpensive and effective treatment for UTIs and trachoma, 
  especially in developing countries and when cost is an issue. These drugs are 
  used to treat trachoma (a leading cause of blindness), nocardiosis (which causes 
  pneumonias, as well as brain abscesses and inflammation), UTIs, and sexually 
  transmitted diseases. Sulfasalazine is used in the treatment of ulcerative colitis and 
  

  rheumatoid arthritis.

  The sulfonamides are teratogenic; they are distributed into breast milk. These 
  drugs, given orally, are absorbed from the GI tract, metabolized in the liver, and 
  excreted in the urine. The time to peak level and the half-life of the individual drug 
  vary. Sulfadiazine is an oral agent slowly absorbed from the GI tract, reaching
  peak levels in 3 to 6 hours. Sulfasalazine is a sulfapyridine that is carried by 
  aminosalicylic acids (aspirin), which release the aminosalicylic acid in the colon 
  where is provides direct antiinflammatory effects. In a delayed-release form, this 
  sulfa drug is also used to treat rheumatoid arthritis that does not respond to other 
  treatments. It is rapidly absorbed from the GI tract, reaching peak levels in 2 to 6 
  hours. After being metabolized in the liver, it is excreted in the urine with a half-life of 
  5 to 10 hours. Cotrimoxazole is a combination drug that contains sulfamethoxazole 
  and trimethoprim, another antibacterial drug. It is rapidly absorbed from the GI tract, 
  reaching peak levels in 2 hours. After being metabolized in the liver, it is excreted in 
  

  the urine with a half-life of 7 to 12 hours.

  The sulfonamides are contraindicated with any known allergy to any sulfonamide, 
  to sulfonylureas, or to thiazide diuretics because cross-sensitivities occur; during 
  pregnancy because the drugs can cause birth defects, as well as kernicterus; and 
  during lactation because of a risk of kernicterus, diarrhea, and rash in the infant. 
  They should be used with caution in patients with renal disease or a history of 
  

  kidney stones because of the possibility of increased toxic effects of the drugs.

  Adverse effects associated with sulfonamides include GI effects such as nausea, 
  vomiting, diarrhea, abdominal pain, anorexia, stomatitis, and hepatic injury, which 
  are all related to direct irritation of the GI tract and the death of normal bacteria. 
  Renal effects are related to the filtration of the drug in the glomerulus and include 
  crystalluria, hematuria, and proteinuria, which can progress to a nephrotic 
  syndrome and possible toxic nephrosis. CNS effects include headache, dizziness, 
  vertigo, ataxia, convulsions, and depression (possibly related to drug effects on 
  the nerves). Bone marrow depression may occur and is related to drug effects on 
  the cells that turn over rapidly in the bone marrow. Dermatological effects include 
  photosensitivity and rash related to direct effects on the dermal cells. A wide range 
  

  of hypersensitivity reactions may also occur.

  Nursing considerations: Assess for possible contraindications or cautions. 
  Perform a physical assessment to establish baseline data for assessing the 
  effectiveness of the drug and the occurrence of any adverse effects associated 
  with drug therapy. Examine skin and mucous membranes for any rash or lesions to 
  provide a baseline for possible adverse effects. Obtain specimens for culture and 
  sensitivity tests at the site of infection to ensure that this is the appropriate drug 
  for this patient. Note respiratory status to provide a baseline for the occurrence of 
  hypersensitivity reactions. Conduct assessment of orientation, affect, and reflexes 
  to monitor for adverse drug effects and examination of the abdomen to monitor 
  for adverse effects. Monitor renal function test findings, including blood urea 
  nitrogen and creatinine clearance, to evaluate the status of renal functioning and to 
  determine any needed alteration in dosage. Also perform a complete blood count 
  

  (CBC) to establish a baseline to monitor for adverse effects.

                 Table1.4.8.1 Summarizing the prototype sulfonamide

                  

                     Self-assessment 1.4.8

  1) Which of the following antibiotics belongs to the class of sulphonamides? 
  a) Tetracycline 
  b) Ciprofloxacin
   c) Streptomycin 
  d) Cotrimoxazole 
  

  2) It is advisable to administer sulphonamides to pregnant women when                                                                                                             indicated because they are safe during pregnancy. TRUE or FALSE

        1.5. Medications used in treatment of bacterial sexually 

              transmitted diseases and tuberculosis

       1.5.1. Medications used in treatment of bacterial sexually transmitted 

                            diseases

               Learning Activity 1.5.1

  Read carefully the scenario below and answer the questions related to it:
  1) A 35-year-old-female patient finds you in the consultation room at the 
  health post where you are placed in the clinical practice. She complains 
  of lower abdominal pain and unusual whitish vaginal discharge that 
  occurred two weeks after unprotected sexual intercourse. The patient 
  is not pregnant and the physical assessment revealed that the patient 
  has a tenderness of lower abdomen and the features of the urinary tract 
  infection (UTI) have been excluded.
  a) In which category of syndromic management of STIs would you classify 
       the symptoms of the client in the above scenario?
  b) Name the antibiotics that can be used in the syndromic management of 
  

  this client?

       CONTENT SUMMARY 

  Sexually transmitted infections are infections caused by bacteria, viruses and 
  parasites that are transferred mainly via sexual contact, be it vaginal, anal, and 
  oral or in some instances via non-sexual means, i.e. by means of blood or blood 
  products. Mother-to-child transmission of for example chlamydia, gonorrhea, and 
  syphilis occurs during pregnancy and childbirth. The most common causal agents 
  are Chlamydia, Neisseria gonorrhoeae, treponema pallidum and trichomonas 
  

  vaginalis.

  Treatment of STIs relies on the syndromic approaches by taking note of observable 
  clinical signs and symptoms patients complain of, and by making use of clinical 
  algorithms or flow charts. Examples of observed syndromes include genital ulcers, 
  

  abdominal pain, vaginal discharge and urethral discharge.

  Vaginal discharge syndrome (VDS)

  Vaginal discharge can be due to trichomoniasis, vaginosis (bacterial) and candidiasis 
  

  but may also arise from N. gonorrhoeae and Chlamydia trachomatis infections. 

  Lower abdominal pain (LAP)

  Pain in the lower abdominal region may be the result of pelvic inflammatory disease 
  

  caused by N. gonorrhoeae and C. trachomatis infections.

  Genital ulcer syndrome (GUS) 

  The presence of genital ulcers may be due to H. simplex,                                                                                                                                        T. pallidum and H. ducreyi or a combination of these pathogens. 
  
  Male urethritis syndrome (MUS) and scrotal swelling (SSW)
  N. gonorrhoeae or C. trachomatis or a combination of both                                                                                                                                    may cause urethral discharge and scrotal swelling.
  
         Table 1.5.1.1: COMMON SEXUAL TRANSMITTED DISEASES AND THEIR TREATMENT:
                      
                        
                         
  NOTICE: All the time, the treatment guidelines and protocols are established by 

  Rwanda Biomedical Canter and changed periodically

          Self-assessment 1.5.1   

  Read carefully the scenario below and answer the questions related to it:

  1) Your colleague calls you for advice. He tells you that he receives a client 
  in the consultation room presenting non painful ulcer on the opening of 
  his penis, post unprotected sexual intercourse in the last 2 months. The 
  physical examination reveals that the patient has no inguinal bubo. He 
  also adds that it is the first time he meets with such case and he asks you 
  the following questions:
  a) What is the diagnosis for this client based on the syndromic management 
      of STIs?
  b) What antibiotic that can be used in this case based on the syndromic 
  

  management of STIs?

                  1.5.2. Medications used in treatment of tuberculosis
  

                              Learning Activity 1.5.2

  Read the case study below:

  A 45-year-old female patient, weighing 65 kilos, is admitted to the health facility 
  with cough, nocturnal hyperthermia, anorexia, asthenia, weight loss, and night 
  sweating. She reports that these signs and symptoms have been there for the 
  

  last 4 weeks. 

  She also reports having taken the full course of treatment with amoxicillin for 7 
  days that didn’t help. The healthcare provider took a decision to take the sputum 
  smear which became positive for Mycobacterium tuberculosis. The client is 
  informed that she contracted pulmonary tuberculosis, and she is counselled that 
  she will need to take all the antituberculosis drugs as prescribed. It is the first 
  time for the patient to suffer from tuberculosis, and there is a need to immediately 
  

  institute antituberculosis treatment.

  a) What are the names of antituberculosis drugs that must be used in the 
  treatment of this patient?
  

  b) What are the treatment phases of tuberculosis? 

              CONTENT SUMMARY

  Tuberculosis treatment refers to the medical treatment of tuberculosis (TB) which 
  is an infectious disease that usually affects the lungs, but can affect other parts of 
  the body. The standard “short” course treatment for TB is isoniazid, rifampicin (also 
  known as rifampin in the United States), pyrazinamide, and ethambutol for two 
  months, then isoniazid and rifampicin alone for a further four-month period. The 
  patient is considered cured at six months (although there are still some cases of 
  relapse rate of about 2 to 3%). For latent tuberculosis, the standard treatment is six 
  to nine months of isoniazid alone. If the organism is known to be fully sensitive, then 
  treatment is with isoniazid, rifampicin, and pyrazinamide for two months, followed by 
  isoniazid and rifampicin for four months. Ethambutol needs not be used. However, 
  ethambutol is always part of the initial treatment of tuberculosis in Rwanda. Using 
  the drugs in combination helps to decrease the emergence of resistant strains and 
  

  to affect the bacteria at various phases during their long and slow life cycle.

  First line anti-tuberculous drug names have a standard three-letter and a single                                                                                         letter abbreviation: Ethambutol is EMB or E; Isoniazid is INH or H; Pyrazinamide is 
  PZA or Z and Rifampicin is RMP or R. Drug regimens are similarly abbreviated in 
  a standardized manner. The drugs are listed using their single letter abbreviations 
  (in the order given above, which is roughly the order of introduction into clinical 
  practice). 
  A prefix denotes the number of months the treatment should be given for; a subscript 
  denotes intermittent dosing (so 3 means three times a week) and no subscript 
  

  means daily dosing.

  Most regimens have an initial high-intensity phase, followed by a continuation 
  phase (also called a consolidation phase or eradication phase): the high-intensity 
  phase is given first, then the continuation phase, the two phases divided by a slash. 
  So, 2HREZ/4HR3 means isoniazid, rifampicin, ethambutol, pyrazinamide daily for 
  two months, followed by four months of isoniazid and rifampicin given three times 
  

  a week. 

  There are six classes of second-line drugs (SLDs) used for the treatment of TB. A 
  drug may be classed as second-line instead of first-line for one of three possible 
  reasons: it may be less effective than the first-line drugs (e.g.: p-aminosalicylic acid); 
  or, it may have toxic side-effects (e.g.: cycloserine); or it may be unavailable in many 
  developing countries (e.g., fluoroquinolones): Aminoglycosides: e.g., amikacin 
  (AMK), kanamycin (KM); Polypeptides: e.g., capreomycin, viomycin, enviomycin; 
  Fluoroquinolones: e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF); 
  Thioamides: e.g. ethionamide, prothionamide; Cycloserine (the only antibiotic in its 
  

  class); and P-aminosalicylic acid (PAS or P).

  In Rwanda, the following are the therapeutic diagrams of tuberculosis treatment:
  Primotreatment: 2HREZ7/4HR7 (for a person who suffers from pulmonary 
  

  tuberculosis for the first time).

  Retreatment: 2S7RHZE7/1RHZE7/5RHE7: A person who received TB treatment 
  for some time in the past, and has a positive sputum smear or needs to take/resume 
  antituberculosis drugs again. In this case, injectable streptomycin is added to the 
  

  therapeutic diagram (protocol) for the first 2 months, administered intramuscularly.

                  Self-assessment 1.5.2

   1) After 5 months of tuberculosis treatment in the learning activity 1.6.2, the 
  

  patient still has positive sputum smear that reveals tuberculosis bacteria.

  The healthcare personnel decide that such patient requires antituberculosis 

  retreatment, and the treatment is immediately started.

  As the relative, you need to give clear details on the drugs to receive, with focus 
  on the additional drugs, their mode of administration, and for how long these 
  

  drugs will be taken.

  Referring to the data above, answer the following questions:

  a) Which drug will be added on the usual tuberculosis primo-treatment 
  drugs?
  b) What is the route of administration for the added drug?
  

  c) For how long will the added drug be given to the patient?

  1.6. End unit assessment

  End of unit assessment

  After going through the unit of antibiotics, attempt the following 

  questions:

  1) Which of the following terms refers to the ability of an antimicrobial drug 
  to harm the target microbe without harming the host?
  a) Mode of action
  b) Therapeutic level
  c) Spectrum of activity
  d) Selective toxicity
  2) Selective toxicity antimicrobials are easier to develop against bacteria 
  because they are ________ cells, whereas human cells are eukaryotic
  3) The spectrum of activity of an anti-infective indicates:
  a) The anti-infective’s effectiveness against different invading organisms.
  b) The acidity of the environment in which they are most effective.
  c) The cell membrane type that the anti-infective affects.
  d) The resistance factor that bacteria have developed to this anti-infective. 
  4) A bacteriostatic substance is one that:
  a) Directly kills any bacteria it comes in contact with.
  b) Directly kills any bacteria that are sensitive to the substance.
  c) Drevents the growth of any bacteria.
  d) Prevents the growth of specific bacteria that are sensitive to the 
  substance.
  5) Ciprofloxacin, a widely used antibiotic, is an example of:
  a) A penicillin
  b) A fluoroquinolone. 
  c) An aminoglycoside.
  d) A macrolide antibiotic
  6) Which of the following is ototoxic and nephrotoxic?
  a) Erythromycin
  b) Doxycycline
  c) Ampicillin
  d) Gentamicin
  7) Which of the following antibiotics is contraindicated in pregnant women 
  and small children due to its tendency to irreversibly stain developing 
  teeth?
  a) Aminoglycosides
  b) Tetracyclines
  c) Penicillins
  d) Fluoroquinolones
  8) Which of the following is an example of an aminoglycoside antibiotic?
  a) Azithromycin
  b) Erythromycin
  c) Streptomycin
  d) Clindamycin
  9) Differentiate a bacteriostatic antibiotic from bactericidal antibiotic.
  10) Classify antibiotics into 5 categories according to their                                                                                                                    mechanism of action.
  

• UNIT 3: ANTIPROTOZOAL DRUGS

                   KEY UNIT COMPETE

  Utilize antiprotozoal drugs to manage 
  different health condition at the primary 
  

   healthcare settings

     Introductory activity 3.0

     

  1) The images above show two 
  different medications used in management 
  of protozoal diseases.
  a) Have you ever seen or used any of the 
  medications above?
  b) Which conditions does the 
  

  above medications are indicated?

   3.1. Definition and Classification
          of antiprotozoal  medications
  
        Learning Activity 3.1
  Read the scenario below carefully and try
   to find answers to the following 
  questions:
  A client X was received at health post complaining
  of fever, chills and arthralgia 
  for 3 days and diarrhea for 2 days.
  
  The laboratory results reveal positive blood 
  smear and Entamoeba histolytica in the stool.
  a) Read the book of pharmacology in the library,
   and define antiprotozoal 
  medication and list the classes
  of antiprotozoal drugs.
  
  

  b) Think about the drugs you can                                                                                                                                                                                            give to the patient X in the scenario.

  CONTENT SUMMARY

  Protozoans are single-celled organisms that are
   the smallest and simplest members 
  of the animal kingdom. This topic will focus on
  the chemotherapy to treat diseases 
  caused by Trypanosoma cruzi (Chagas’ disease),
  Trypanosoma b. gambiense 
  and Trypanosoma b. rhodesiense (sleeping sickness),
   Plasmodium (malaria), 
  Leishmania (leishmaniasis) and amebiasis.
  
  Protozoal diseases are less easily treated
  than bacterial infections because many 
  of antiprotozoal drugs cause serious toxic
   effects and most of them are not safe 
  in pregnancy and unicellular protozoal cells
  have metabolic processes closer to 
  human cells than bacteria. 
  
  Antiprotozoal drug is a drug that destroys protozoans,
   inhibits their growth, ability to 
  reproduce and prevent the development
  of protozoans in humans. The actions of 
  antiprotozoal drugs against the infections
  are complex and are not fully understood. 
  Some of them may interfere with reproduction
  of or damage protozoal DNA to 
  limit the spread of an infection.
  Antiprotozoal drugs are classified into 2 classes: 
  antimalarial drugs and miscellaneous antiprotozoal.
   
  Antimalarial drugs
  Antimalarial drugs include mefloquine,
  chloroquine, proguanil with atovaquone and 
  doxycycline.
  They kill or inhibit the growth of protozoa
  by affecting different stage of 
  the parasitic life cycle.
  They are used both to treat and prevent malaria. 
  
  Miscellaneous antiprotozoal.
  Commonly used miscellaneous antiprotozoal
   include metronidazole, tinidazole 
  and so on. Metronidazole is the most common treatment
   for trichomoniasis and giardiasis. Its action in the treatment
  of protozoal infections remains poorly 
  understood, however, it may work
   by damaging protozoal DNA. Tinidazole works 
  as well as metronidazole and
  has many of the same side effects, but it can be given 
  

  in a single dose. See table 3.1.1 below:

  The table 3.3.1: The classifications of antiprotozoal 
  (Drugs of Choice for 
  

  Protozoal Infection), causative protozoa, and disease

                   

                 Self-assessment 3.1
  

  The medical clinic has received 3 patients this morning. Patient A is being seen 
  for an intestinal disorder that he acquired after swimming in a local lake and be 
  diagnosed for giardiasis. Patient B has acquired immunodeficiency syndrome 
  (AIDS) and is showing early signs of pneumonia. After clinical review he/she 
  was diagnosed for pneumocytosis. Patient C is being treated and evaluated 
  on a regular basis for a sexually transmitted infection and was diagnosed with 
  

  trichomoniasis. 

  3) Select the drugs you feel the physician
      is likely to prescribe for patient A
  a) Chloroquine,
  b) Artemisinin,
  c) Amoxicillin
  d) Metronidazole
  4) Select the drugs you feel the physician
      is likely to prescribe for patient B
  a) Chloroquine,
  b) Artemisinin,
  c) Pentamidine
  d) Nitazoxanide
  5) Select the drugs you feel the physician is likely to
      prescribe for patient C
  a) Artemisinin,
  b) Metronidazole
  c) Chloroquine
  

  d) Suramin

  3.2. Plasmodium’s life cycle
         Learning Activity 3.2
  

  1) Read the scenario below and answer related questions: A 40 years 
  

  old female is brought to you with a history of fever for 2 days, chills, 
  

  headache, and arthralgia. On examination, you find that she weighs 
  

  63 kg, has temperature of 39.20 C. A blood slide reveals plasmodium 
  

  falciparum ring stage ++
  

  a) According to you, what should be the diagnosis for this case?
  

  b) What are two main phases of the disease development?
  

  c) How is the disease transmitted?
  

  d) Is the disease preventable?
  

  2) Which of the following is infective form of plasmodium for human?
  

  a) Schizont
  

  b) Merozoite
  

  c) Sporozoites
  

  d) Oocyst

  Content summary

  Malaria is a disease characterized by a cycle of fever and chills transmitted through 
  a bite of a female Anopheles mosquito. Identified causes include Plasmodium 
  falciparum, vivax, malariae, and ovale. Malaria is endemic in many parts of the 
  

  world.

  Sporozoites travel through bloodstream and become lodged in the liver and other 
  

  tissues.

  In approaching the antimalarial drugs, we begin by reviewing the life cycle of the 
  malaria parasite in order to understand the drugs, specific applications of antimalarial 
  

  drugs and the rationale behind treatment of patients with malaria. 

  Malaria develops via two phases: an exoerythrocytic and an erythrocytic phase. 
  The exoerythrocytic phase involves infection of the hepatic system, or liver, 
  whereas the erythrocytic phase involves infection of the erythrocytes, or red blood 
  cells. When an infected mosquito pierces a person’s skin to take a blood meal, 
  sporozoites in the mosquito’s saliva enter the bloodstream and migrate to the liver. 
  Within minutes of being introduced into the human host, the sporozoites infect 
  hepatocytes, multiplying asexually and asymptomatically for a period of over 5-16 
  

  days depending on the species. Once in the liver, these organisms differentiate to

  yield thousands of merozoites, which, following rupture of their host cells, escape 
  into the blood and infect red blood cells, thus beginning the erythrocytic stage of 
  

  the life cycle. 

   Then, the merozoites infect red blood cells, where they develop into ring forms, 
  trophozoites and schizonts which in turn produce further merozoites over 1-3 days 
  

  depending on the species. 

  This asexual multiplication can result in thousands of parasite-infected cells in the 
  host bloodstream, leading to illness and complications of malaria that can last for 
  months if not treated. Some of the merozoite-infected blood cells leave the cycle of 
  

  asexual multiplication. 

  Instead of replicating, the merozoites in these cells develop into sexual forms of 
  the parasite, called male and female gametocytes, that circulate in the bloodstream 
  which, if taken up by a mosquito, will infect the insect and continue the life cycle. 
  

  When a mosquito bites an infected human, it ingests the gametocytes. 

  In the mosquito gut, the infected human blood cells burst, releasing the gametocytes, 
  which develop further into mature sex cells called gametes. Male and female 
  gametes fuse to form diploid zygotes, which develop into actively moving ookinetes 
  that burrow into the mosquito midgut wall and form oocysts. Growth and division 
  of each oocyst produces thousands of active haploid forms called sporozoites. 
  After 8-15 days, the oocyst bursts, releasing sporozoites into the body cavity of the 
  mosquito, from which they travel to and invade the mosquito salivary glands. The 
  cycle of human infection restarts when the mosquito takes a blood meal, injecting 
  

  the sporozoites from its salivary glands into the human bloodstream.

  Some P. vivax and P. ovale sporozoites do not immediately develop into 
  exoerythrocytic phase (merozoites), but instead produce hypnozoites that remain 
  dormant for periods ranging from several months (6–12 months typically) to as long 
  as three years. After a period of dormancy, they reactivate and produce merozoites. 
  Hypnozoites are responsible for long incubation and late relapses in these two 
  

  species of malaria.

  The fever in malaria occurs at the end of erythrocytic phase. During this phase, 

  the merozoites lyse the RBCs and this hemolysis is accompanied by the release of 

  hemozoin pigment which directly goes and disturbs the hypothalamic functioning 

  and causes the occurrence of fever. 

  The erythrocytic phase occurs every 48 h in cases of P. falciparum, P. vivax and P. 
  ovale and 72 hours in case of P. malariae. Thus, P. falciparum causes the malignant 
  form of tertian fever, P. vivax and P. ovale are responsible for the benign form of 
  Tertian fever (fever occurring at every 3rd day or after 2 days) and P. malariae is 
  responsible for quartan fever (fever occurring at every 4th day or after 3 days). 
  

  Then, the fever is intermittent (fever occurring at regular intervals).

                           

                               Self-assessment 3.2

  1) Fever during malaria disease is associated
  with which of the following 
  phenomena in malaria cycle?
  
  a) The exoerythrocytic phase involves
   infection of the hepatic system, or 
  liver and gives rise fever
  b) When an infected mosquito pierces
  a person’s skin to take a blood 
  meal, sporozoites infect the liver then fever developed.
  
  c) During the phase of erythrocytic, the merozoites lyse the RBCs and this 
  hemolysis is accompanied by the release of hemozoin pigment which 
  directly goes and disturbs the hypothalamic functioning and causes the 
  occurrence of fever.
  d) Instead of replicating, the merozoites develop into sexual forms of the 
  parasite, called male and female gametocytes, that circulate in the 
  bloodstream and disturbs the hypothalamic function that cause fever.
  
  2) Using library book and internet, state the body                                                                                                                                                  areas/parts affected in the 
  following phases of malaria development:
  a) Exoerythrocytic phase
  b) Erythrocytic phase
  3) Which of the following species of
  plasmodium causes quartan fever?
  a) Plasmodium vivax
  b) Plasmodium ovale
  c) Plasmodium malariae
  d) Plasmodium falciparum
  
  4) Which of the following species of plasmodium
  causes malignant form of tertian fever?
  a) Plasmodium vivax
  b) Plasmodium ovale
  c) Plasmodium malariae
  d) Plasmodium falciparum
  5) Which of the following species of                                                                                                                                                              plasmodium causes benign form of tertian fever?
  a) Plasmodium vivax
  b) Plasmodium ovale
  c) Plasmodium malariae
  

  d) a and b

      3.3. Antimalarial medications

            Learning Activity 3.3

  1)The nurse is reviewing the medication history of a patient who is taking 
  Coartem. However, the patient’s chart reveals a history of fever, headache 
  and polyarthralgia. The patient is most likely taking this medication for: 
  a) Plasmodium.
  b) Thyroid disorders.
  c) Roundworms.
  d) Rheumatoid arthritis.
  2) Identify three antimalarial medications used in Rwanda that you know.
  3) What malaria prophylaxis approach will you recommend for travellers 
  

  visiting malaria endemic area?

  CONTENT SUMMARY

  Our goal in this sub-lesson is to describe the Antimalarial medications. One of the 
  

  greatest protozoal problems worldwide is the treatment and prevention of malaria. 

  Antimalarials are agents used to attack Plasmodium at various stages of its life 
  cycle. Through this, it becomes possible to prevent acute malarial reaction in 
  

  individuals who have been infected by the parasite.

  Antimalarial drugs can be classified according to antimalarial activity and according 
  

  to structure.

  1. According to antimalarial activity:

  Tissue schizonticides for causal prophylaxis: These drugs act on the primary 
  tissue forms of the plasmodia which after growth within the liver, initiate the 
  erythrocytic stage. By blocking this stage, further development of the infection 
  can be theoretically prevented. Pyrimethamine and Primaquine have this activity. 
  However, since it is impossible to predict the infections before clinical symptoms 
  

  begin, this mode of therapy is more theoretical than practical.

  Tissue schizonticides for preventing relapse:These drugs act on the hypnozoites 
  of P. vivax and P. ovale in the liver that cause relapse of symptoms on reactivation. 
  

  Primaquine is the prototype drug; pyrimethamine also has such activity.

  Blood schizonticides: These drugs act on the blood forms of the parasite and 
  thereby terminate clinical attacks of malaria. These are the most important drugs 
  in antimalarial chemotherapy. These include chloroquine, quinine, mefloquine, 
  

  halofantrine, pyrimethamine, sulfadoxine, sulfones, Tetracyclines etc.

  Gametocytocides: These drugs destroy the sexual forms of the parasite in the 
  blood and thereby prevent transmission of the infection to the mosquito. Chloroquine 
  and quinine have gametocytocidal activity against P. vivax and P. malariae, but 
  not against P. falciparum. Primaquine has gametocytocidal activity against all 
  

  plasmodia, including P. falciparum.

  Sporontocides: These drugs prevent the development of oocysts in the mosquito 
  

  and thus ablate the transmission. Primaquine and chloroguanide have this action. 

  Thus in effect, treatment of malaria would include a blood schizonticide, a 
  gametocytocide and a tissue schizonticide (in case of P. vivax and P. ovale). A 
  

  combination of chloroquine and primaquine is thus needed in ALL cases of malaria.

  Principles of antimalarial therapy are based on therapeutic objectives. Drug 
  responsiveness of the malaria parasite changes as the parasite goes through 
  its life cycle. The erythrocytic forms are killed with relative ease, whereas the 
  exoerythrocytic (hepatic) forms are much harder to kill and sporozoites do not 
  respond to drugs at all. Because sporozoites are insensitive to available drugs, 
  

  drugs cannot prevent primary infection of the liver.

  Because of these differences, antimalarial therapy has three separate objectives/ 
  Three methods used to eradicate malaria: (1) treatment of an acute attack (clinical 
  cure), (2) prevention of relapse (radical cure), and (3) prophylaxis (suppressive 
  

  therapy). 

  • Treatment of an acute attack 

  Clinical cure is accomplished with drugs that are active against erythrocytic forms of 
  the malaria parasite. By eliminating parasites from red blood cells, the erythrocytic 
  

  cycle is stopped and symptoms cease. 

  For patients with vivax malaria, clinical cure will not prevent relapse, because 
  hypnozoites remain in the liver. However, for patients with falciparum malaria, 
  

  successful treatment of the acute attack prevents further episodes.

  For mild to moderate malaria, oral therapy is employed. Chloroquine is the drug of 
  choice for an acute attack caused by chloroquine-sensitive strains of P. falciparum 
  or P. vivax. As a rule, a 3-day course of treatment produces clinical cure. For strains 
  of P. falciparum or P. vivax that is chloroquine resistant, quinine is a drug of first 
  

  choice, combined with either doxycycline, tetracycline, or clindamycin. 

  Malarone, a fixed-dose combination of atovaquone plus proguanil, is an effective 
  alternative. Mefloquine may also be used but is considered less desirable owing to 
  

  concerns about neuropsychiatric effects. 

  For severe malaria caused by P. falciparum or P. vivax, parenteral therapy is 
  

  required. Quinidine gluconate is approved by the Food and Drug Administration 

  (FDA) for parenteral use in malaria. When used for severe malaria, IV quinidine 
  should be combined with doxycycline, tetracycline, or clindamycin. An alternative to 
  

  quinidine, known as artesunate, is recommended by the World Health Organization.

  The various antimalarial drugs work during different phases of the parasite’s 
  growth inside the human. The antimalarials that exert the greatest effect on all four 
  Plasmodium organisms during the erythrocytic or blood phase are chloroquine, 
  

  hydroxychloroquine, and pyrimethamine. 

  Primary tissue schizonticides (eg, primaquine) kill schizonts in the liver, 
  whereas blood schizonticides (eg, chloroquine, quinine) kill these parasitic forms 
  

  only in the erythrocyte. 

  Sporonticides (proguanil, pyrimethamine) prevent sporogony and multiplication 
  in the mosquito. Other drugs that are known to work during the blood phase are 
  

  quinine, quinidine, and mefloquine. 

  The most effective antimalarial drug for eradicating the parasite during the 
  exoerythrocytic phase is primaquine, which works during both phases. Primaquine 
  

  is indicated specifically for infection with P. vivax. 

  Chloroquine and hydroxychloroquine (4-aminoquinolines) are the drugs of choice 
  for the treatment of susceptible strains of malarial parasites. They are highly toxic 
  to all Plasmodium spp., except resistant strains of P. falciparum. Pyrimethamine is 
  an antimalarial antibiotic that is used in combination with the sulfonamide antibiotic 
  sulfadoxine (Fansidar) for prophylaxis against chloroquine-resistant P. falciparum 
  

  and P. vivax. 

  The drug combination atovaquone and proguanil (Malarone) is also used for 
  

  prevention and treatment of P. falciparum infection.

  Antimalarial drugs administered to humans cannot affect the parasite during its 
  sexual cycle when it resides in the mosquito. Instead, these drugs work against the 
  parasite during its asexual cycle, which takes place within the human body. Often 
  these drugs are given in various combinations to achieve an additive or synergistic 
  antimalarial effect. One example is the combination of the two antiprotozoal drugs 
  atovaquone and proguanil (Malarone). The antibiotic combination of pyrimethamine 
  and sulfadoxine (Fansidar) is also commonly used, especially in cases caused by 
  

  drug-resistant organisms.

  The mechanisms of action of the various antimalarial drugs differ depending on the 
  

  chemical family to which they belong. 

  The drug effects of the antimalarial drugs are mostly limited to their ability to kill 
  parasitic organisms, most of which are Plasmodium species (spp.). However, some 
  

  of these drugs have other effects and therapeutic uses. 

  Hydroxychloroquine also has anti-inflammatory effects and is sometimes used in the 
  treatment of rheumatoid arthritis and systemic lupus erythematosus. Quinine and 
  quinidine can also decrease the excitability of both cardiac and skeletal muscles. 
  

  Quinidine is still used to treat certain types of cardiac dysrhythmias.

  • Prevention of relapse

  People infected with P. vivax harbor dormant parasites in the liver, in order to 
  prevent relapse, a drug that can kill these hepatic forms must be taken. The use 
  of drugs to eradicate hepatic P. vivax is referred to as radical cure. The agent of 
  choice for preventing relapse of vivax malaria is primaquine, a drug that is highly 
  active against the hepatic forms of P. vivax. For falciparum malaria, no treatment is 
  

  needed, since relapse does not occur following clinical cure.

  P falciparum and P malariae have only 1 cycle of liver cell invasion. The other species 
  

  have a dormant hepatic stage responsible for recurrent infections and relapses.

  • Prophylaxis 

  Selection of drugs for prophylaxis is based on the drug sensitivity of the plasmodial 
  

  species found in the region to which travel is intended.

  Malaria can often be avoided by using the ABCD approach which are both drugs 
  and nondrug prevention measures (Awareness of risk, Bite prevention, Check 
  

  whether you need to take malaria prevention tablets and Diagnosis).

  a) Awareness of risk: find out whether the patient is at risk of getting malaria. It’s 
  important to visit a health care provider before the travel for advice, check whether 
  it is necessary or need to take preventative malaria treatment depending on the 
  country you are visiting. Some country it is not necessary to take preventative 
  malaria treatment before travelling. Even if you grew up in a country where malaria 
  is common, you still need to take precautions to protect yourself from infection if 
  

  you’re travelling to a risk area.

  NB: In area where malaria vaccine is not yet introduced, health care provider has 
  to educate people that nobody has complete immunity to malaria, and any level of 
  natural protection you may have had is quickly lost when you move out of a risk 
  

  area.

  There’s vaccine available currently approved by world health organization that 
  offers protection against malaria. A first Malaria Vaccine Approved by W.H.O. RTS, 
  S/ASO1 (RTS. S), trade name Mosquirix, which was endorsed by the World Health 
  Organisation (WHO) on Wednesday (October 6/2021), is the first and, to date only, 
  vaccine shown to have the capability of significantly reducing malaria, and life                                                                                  threatening severe malaria, in tests on young African children and it requires four 
  

  injections.

  b) Bite prevention: avoid mosquito bites by using insect repellent, covering your 
  arms and legs, and using a mosquito net. It’s not possible to avoid mosquito bites 
  completely, but the less you’re bitten, the less likely you are to get malaria.
  
  c) Check whether you need to take malaria prevention tablets: if you do, make 
  sure you take the right antimalarial tablets at the right dose, and finish the course to 
  

  reduce your chances of getting the disease until vaccine become available for all.

  However, antimalarials only reduce your risk of infection by about 90%, so taking 
  

  steps to avoid bites is also important. 

  Depending on the type you’re taking, continue to take your tablets for up to 4 weeks 
  

  after returning from your trip to cover the incubation period of the disease.

  NB: In some cases, you may be prescribed emergency standby treatment for 
  malaria before you travel. This is usually if there’s a risk of you becoming infected 
  

  with malaria while travelling in a remote area with little or no access to medical care. 

  Examples of emergency standby medications include:

  Atovaquone with Proguanil
  Artemether with Lumefantrine
  Quinine plus Doxycycline
  

  Quinine plus Clindamycine

  The list below outlines which medications are safe or unsafe to use while 
  

  pregnant:

  Mefloquine: not usually prescribed during the first trimester of pregnancy, or if 
  pregnancy is a possibility during the first 3 months after preventative antimalarial 
  medication is stopped. This is a precaution, even though there’s no evidence to 
  

  suggest mefloquine is harmful to an unborn baby.

  Doxycycline: never recommended for pregnant or breastfeeding women as it 
  

  could harm the baby.

  Atovaquone plus proguanil: not generally recommended during pregnancy or 
  breastfeeding because research into the effects is limited. However, if the risk of 
  

  malaria is high, they may be recommended if there›s no suitable alternative.

  Chloroquine combined with proguanil is suitable during pregnancy, but it is rarely 
  used as it’s not very effective against the most common and dangerous type of 
  

  malaria parasite.

  d) Diagnosis: Malaria can get worse very quickly, so it’s important that it’s diagnosed 
  

  and treated as soon as possible.

  Treatment for malaria is not initiated until the diagnosis has been confirmed by 
  laboratory tests and it is recommended that the treatment should be completed 
  

  once the treatment has been started. 

  Once confirmed, appropriate antimalarial treatment must be initiated immediately. 
  Treatment is guided by these main factor0s: the infecting Plasmodium species, the 
  clinical status of the patient, the organism’s life cycle and the drug susceptibility of 
  the infecting parasites, as determined by the geographic area where the infection 
  was acquired. Because the resistance patterns are constantly changing depending 
  

  on geographic locations.

  2. According to the structure:

  a) Aryl-amino-alcohols: Quinine, quinidine (cinchona alkaloids), mefloquine, 
        halofantrine.
  b) 4-aminoquinolines: Chloroquine, amodiaquine.
  c) Folate synthesis inhibitors: Type 1 – competitive inhibitors of 
  dihydropteroate synthase – sulphones, sulphonamides; Type 2 – inhibit 
  dihydrofolate reductase – biguanides like proguanil and chloroproguanil; 
  diaminopyrimidine like pyrimethamine
  d) 8-aminoquinolines: Primaquine
  e) Antimicrobials: Tetracycline, doxycycline, clindamycin, azithromycin, 
  fluoroquinolones
  f) Peroxides: Artemisinin (Qinghaosu) derivatives and analogues – 
  artemether, arteether, artesunate, artelinic acid
  g) Naphthoquinones: Atovaquone
  

  h) Iron chelating agents: Desferrioxamine

                        

           Figure 2: plasmodium’s Life cycle and antimalarial medication

                Self-assessment 3.3

  1) On which criteria is the selection of drugs for malaria prophylaxis based? 
  2) When treatment for malaria must be initiated? 
  3) Antimalarial therapy has three separate objectives, enumerate them. 
  4) The sporozoites do not respond to antimalarial drugs at all. True or False
  5) Why is antimalarial treatment guided by the infecting plasmodium species, 
  the clinical status of the patient, the organism’s life cycle and the drug 
  

  susceptibility of the infecting parasites, considering geographic area?

  3.4. Antimalarial drugs prototypes
  

         Learning Activity 3.4

  1) During your clinical practice in health center, a senior nurse diagnosed 
  malaria for a patient complaining of fever and arthralgia. As an associate 
  nurse student, list antimalarial drugs you know.
  2) A 40 years old female is brought to you with a history of fever for 2 days, 
  chills and anorexia of 1 day. On examination you find that she looks 
  stable, weighs 62 kg, temperature is 39.20 C. Other systems are normal. 
  A blood slide reveals plasmodium falciparum ring stage ++
  a) What is the treatment? 
  

  b) If the malaria slide were negative, would you give antimalarial drugs?

  CONTENT SUMMARY

  Malaria is the most prevalent parasitic endemic disease which is preventable, 
  treatable, and curable. Antimalarial medication is usually given as tablets or capsules. 
  If someone is very ill, it will be given through a drip into a vein (intravenously) in 
  hospital. Many of the same antimalarial medicines used to prevent malaria can also 
  

  be used to treat the disease. 

  QUININE

  Quinine is the chief alkaloid of cinchona bark (known as ‘Fever Bark’), a tree found 
  in South America. Even today, quinine is obtained entirely from the natural sources 
  

  due the difficulties in synthesizing the complex molecule.

  Mechanism of action: Quinine acts as a blood schizonticides although it also has 
  gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, 
  it is concentrated in the food vacuoles of P. falciparum. It is said to act by inhibiting 
  

  heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme.

  As a schizonticidal drug, it is less effective and more toxic than chloroquine. 
  However, it has a special place in the management of severe falciparum malaria in 
  

  areas with known resistance to chloroquine.

  Absorption, fate and excretion: Quinine is readily absorbed when given orally or 
  intramuscularly. Peak plasma concentrations are achieved within 1 – 3 hours after 
  oral dose and plasma half-life is about 11 hours. In acute malaria, the volume of 
  distribution of quinine contracts and clearance is reduced, and the elimination half                                                                             life increases in proportion to the severity of the illness. Therefore, maintenance 
  dose of the drug may have to be reduced if the treatment is continued for more than 
  48 hours. The drug is extensively metabolized in the liver and only 10% is excreted 
  

  unchanged in the urine. There is no cumulative toxicity on continued administration.

  Adverse effects: Quinine is a potentially toxic drug. The typical syndrome of 
  quinine side effects is called as cinchonism and it can be mild in usual therapeutic 
  dosage or could be severe in larger doses. Mild cinchonism consists of ringing in 
  the ears (tinnitus), headache, nausea and disturbed vision. Functional impairment 
  of the eighth nerve results in tinnitus decreased auditory acuity and vertigo. Visual 
  symptoms consist of blurred vision, disturbed colour perception, photophobia, 
  diplopia, night blindness, and rarely, even blindness. These changes are due to 
  

  direct neurotoxicity, although vascular changes may contribute to the problem.

  Gastrointestinal symptoms like nausea, vomiting, abdominal pain and diarrhea 
  may be seen. Rashes, sweating, angioedema can occur. Excitement, confusion, 
  delirium are also seen in some patients. Coma, respiratory arrest, hypotension, and 
  death can occur with over dosage. Quinine can also cause renal failure. Massive 
  hemolysis and hemoglobinuria can occur, especially in pregnancy or on repeated 
  

  use. Hypoprothrombinemia, agranulocytosis are also reported.

  Quinine has little effect on the heart in therapeutic doses and hence regular 
  cardiac monitoring is not needed. However it can cause hypotension in the event 
  of overdose. Quinine reduces the excitability of the motor end plate and thus 
  antagonises the actions of physostigmine. It can cause respiratory distress and 
  

  dysphagia in patients of myasthenia gravis.

  Quinine stimulates insulin secretion and in therapeutic doses it can cause 
  hypoglycemia. This can be more severe in patients with severe infection and in 
  pregnancy. Hypoglycemia in malaria may go unnoticed and could even cause 
  death. Therefore, it is advisable to monitor blood glucose levels at least once in 4-6 
  hours while quinine is administered, especially in severe infection and in pregnancy. 
  Quinine induced hypoglycemia can recur even after administration of 25% or 50% 
  dextrose. In such situations, maintenance with a 10% dextrose infusion is advisable. 
  Resistant hypoglycemia due to quinine can be managed with Injection Octreotide, 
  

  50 microgram subcutaneously, every 6 to 8 hours.

  Contraindications: Hypersensitivity in the form of rashes, angioedema, visual and 
  auditory symptoms are indications for stopping the treatment. It is contraindicated 
  in patients with tinnitus and optic neuritis. It should be used with caution in patients 
  with atrial fibrillation. Hemolysis is indication for immediately stopping the drug. It is 
  

  also contraindicated in patients suffering from myasthenia gravis.

  Availability: It is available as tablets and capsules containing 300 or 600 mg of the 
                            base. It is also available as injections, containing 300mg /ml.
  Quinidine: The anti-arrhythmic drug related to quinine can also be used in the 
  treatment of severe P. falciparum malaria. Dose is 10 mg of base / kg by infusion 
  

  over 1-2 hours, followed by 0.02 mg/kg/min with ECG monitoring.

  Chloroquine

  Chloroquine is the prototype antimalarial drug, most widely used to treat all types 
  

  of malarial infections. 

  Mechanism of action: The mechanism of action of chloroquine is unclear. Being 
  alkaline, the drug reaches high concentration within the food vacuoles of the 
  parasite and raises its pH. It is found to induce rapid clumping of the pigment. 
  Chloroquine inhibits the parasitic enzyme heme polymerase that converts the toxic 
  heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme 
  within the parasite. It may also interfere with the biosynthesis of nucleic acids. Other 
  mechanisms suggested include formation of drug-heme complex, intercalation of 
  

  the drug with the parasitic DNA etc.

  Absorption, fate and excretion: 90% of the drug is absorbed from G.I.T and rapidly 
  absorbed from intra muscular and subcutaneous sites. It has a large distribution 
  volume due to extensive sequestration in tissues of liver, spleen, kidney, lung etc. 
  Hence the need for a larger loading dose. Therapeutic blood levels persist for 6-10 
  days and elimination half-life is 1-2 months. Half of the drug is excreted unchanged 
  

  by the kidneys, remaining is converted to active metabolites in the liver.

  Antimalarial activity: It is highly effective against erythrocytic forms of P. vivax, P. 
  ovale and P. malariae, sensitive strains of P. falciparum and gametocytes of P. 
  vivax. It rapidly controls acute attack of malaria with most patients becoming afebrile 
  

  within 24-48 hours. It is more effective and safer than quinine for sensitive cases.

  Adverse effects: Chloroquine is a relatively safer antimalarial. At therapeutic 
  doses, it can cause dizziness, headache, diplopia, disturbed visual accommodation, 
  dysphagia, nausea, malaise, and pruritus of palms, soles and scalp. It can also 
  cause visual hallucinations, confusion, and occasionally frank psychosis. These 
  

  side effects do not warrant stoppage of treatment. It can exacerbate epilepsy. 

  When used as prophylactic at 300 mg of the base/ week, it can cause retinal toxicity 
  after 3-6 years (i.e. after 50-100 g of chloroquine). Intra muscular injections of 
  

  chloroquine can cause hypotension and cardiac arrest, particularly in children.

  Contra indications: Chloroquine should be used with caution in patients with 
  hepatic disease, (even though it is not hepatotoxic per se, it is distributed widely in 
  the liver and is converted to active metabolites there; hence the caution), severe 
  gastro intestinal, neurological or blood disorders. The drug should be discontinued 
  

  in the event of such problems during therapy.

  It should not be co-administered with gold salts and phenyl-butazone, because 
  all the three can cause dermatitis. Chloroquine may interfere with the antibody 
  

  response to human diploid cell rabies vaccine.

  Availability: Chloroquine is available as Chloroquine phosphate tablets; each 
  250-mg tablet contains 150 mg of the base. Chloroquine hydrochloride injection 
  

  contains 40 mg of the base per ml.

  Sulfadoxine+Pyrimethamine

  Pyrimethamine and sulphadoxine are very useful adjuncts in the treatment of 
  uncomplicated, chloroquine resistant, P. falciparum malaria. It is now used in 
  combination with artesunate for the treatment of P. falciparum malaria. It is also 
  

  used in intermittent treatment in pregnancy (IPTp).

  Antimalarial activity: Pyrimethamine inhibits the dihydrofolate reductase of 
  plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which 
  are so essential for DNA synthesis and cell multiplication. This leads to failure 
  of nuclear division at the time of schizont formation in erythrocytes and liver. 
  Sulfadoxine inhibits the utilisation of para-aminobenzoic acid in the synthesis of 
  dihydropteroic acid. The combination of pyrimethamine and sulfa thus offers two 
  

  step synergistic blockade of plasmodial division.

  Absorption, fate and excretion: Pyrimethamine is slowly but completely absorbed 
  after oral administration and is eliminated slowly with a plasma half-life of about 80-
  95 hours. Suppressive drug levels may be found in the plasma for up to 2 weeks. 
  

  The drug is excreted in breast milk.

  Sulfonamides are rapidly absorbed from the gut and are bound to plasma proteins. 
  They are metabolised in the liver and are excreted in the urine. They pass through 
  the placenta freely. Sulfadoxine is a long acting sulfonamide with a half-life of 7-9 
  

  days.

  Toxicity and contraindications: Pyrimethamine can cause occasional skin rashes 
  and depression of hematopoiesis. Excessive doses can produce megaloblastic 
  

  anemia.

  Sulfonamides can cause numerous adverse effects. 

  Agranulocytosis; aplastic anemia; hypersensitivity reactions like rashes, fixed drug 
  eruptions, erythema multiform of the Steven Johnson type, exfoliative dermatitis, 
  serum sickness; liver dysfunction; anorexia, vomiting and acute hemolytic anemia 
  

  can also occur. 

  At the doses employed for malaria, pyrimethamine produces few adverse effects. 
  However, at high doses, such as those used to treat toxoplasmosis, pyrimethamine 
  

  can produce symptoms of folic acid deficiency

  Effects on the bone marrow manifest as leukopenia, thrombocytopenia, and anemia. 
  Effects on the GI mucosa manifest as ulcerative stomatitis, atrophic glossitis, 
  pharyngitis, and diarrhea. These responses reverse upon discontinuing treatment, 
  

  and can be prevented by giving folic acid or folinic acid. 

  To minimize risk, sulfadoxine should not be given to patients with a history of 
  hypersensitivity to sulfonamides or chemically related drugs, including thiazide 
  

  diuretics, loop diuretics, and sulfonylurea-type oral hypoglycemics (eg, tolbutamide).

  The drug is contraindicated in patients with known hypersensitivity to sulfa, infants 
  below 2 months of age, patients with advanced renal disease and first and last 
  

  trimesters of pregnancy.

  Availability: Pyrimethamine and sulphadoxine is no longer used as a single drug, 
  but only in combination with artesunate.
  The Artemisinin Derivatives
  Antimalarial activity: Most clinically important artemisinins are metabolised to 
  dihydroartemisinin (elimination half-life of about 45 min), in which form they have 
  comparable antimalarial activity. However, their use in monotherapy is associated 
  with high incidences of recrudescent infection, suggesting that combination with 
  

  other antimalarials might be necessary for maximum efficacy.

  It is the fastest acting antimalarial available. It inhibits the development of the 
  trophozoites and thus prevents progression of the disease. Young circulating 
  parasites are killed before they sequester in the deep microvasculature. These 
  drugs start acting within 12 hours. These properties of the drug are very useful 
  in managing complicated P. falciparum malaria. These drugs are also effective 
  

  against the chloroquine resistant strains of P. falciparum.

  Artesunate and artemether have been shown to clear parasitaemias more effectively 
  than chloroquine and sulfadoxine/pyrimethamine. Meta-analysis of mortality in 
  trials indicated that a patient treated with artemether had at least an equal chance 
  

  of survival as a patient treated with quinine. 

  It has also been reported that artemisinin drugs cleared parasites faster than 
  quinine in patients with severe malaria but fever clearance was similar. Also, 
  parenteral artemether and artesunate are easier to use than quinine and do not 
  

  induce hypoglycaemia.

  Gametocytocidal action: Artemisinin compounds have been reported to reduce 
  gametocytogenesis, thus reducing transmission of malaria, this fact being especially 
  

  significant in preventing the spread of resistant strains.

  These drugs prevent the gametocyte development by their action on the ring stages 
  and on the early (stage I-III) gametocytes. In studies including over 5000 patients 
  in Thailand, it was shown that gametocyte carriage was significantly less frequent 
  

  after treatment with artemisinin derivatives than after treatment with mefloquine.

  Absorption, fate and excretion: Artemisinin derivatives are absorbed well after 
  

  intra muscular or oral administration. The drug is fully metabolised and the major 
  

  metabolite is dihydroartemisinin, which also has Antiparasitic effects. It is rapidly 
  

  cleared, predominantly through the bile.

  Toxicity: Toxic effects have been reported less frequently with the artemisinins 
  than with other antimalarial agents. The most common toxic effects that have been 
  identified are nausea, vomiting, anorexia, and dizziness; these are probably due, in 
  many patients, to acute malaria rather than to the drugs. More serious toxic effects, 
  including neutropenia, anemia, hemolysis, and elevated levels of liver enzymes, 
  

  have been noted rarely. 

  Extensive studies in many species showed that intramuscular dosing was more 
  toxic than oral dosing and that, by any route; fat-soluble artemisinins were more 
  

  toxic than artesunate. 

  Another concern about artemisinins is embryotoxic effects, which have been 
  demonstrated in animals. Studies from Asia and Africa, including treatment during 
  the first trimester, showed similar levels of congenital abnormalities, stillbirths, and 
  abortions in patients who received and those who did not receive artesunate during 
  pregnancy. Limited data are available on the use of intravenous artesunate for 
  

  severe malaria during pregnancy.

  Availability: Artemisinin is available as its derivatives, artemether and artesunate. 
  The ether derivatives are more soluble in oil and are available as injections for intra 
  muscular use. Artemether is available as injections of 80 mg in 1 ml. Artemether 
  

  capsules containing 40 mg of the drug are also now available. 

  Artesunate is an ester derivative that is more soluble in water. The drug is available 
  as a powder. It should be first dissolved in 1 ml of 5% sodium bicarbonate (usually 
  

  provided with the vial) and shaken for 2-3 minutes. 

  After it dissolves completely, it is diluted with 5% dextrose or saline (for intravenous 
  use, dilute with 5 ml and for intramuscular use, dilute with 2 ml). Intravenous dose 
  should be injected slowly at a rate of 3-4 ml/minute. It is also available as tablets, 
  

  each containing 50 mg of the drug.

  Rectal artemisinins rapidly eliminate malarial parasites 

  Resistance: The short half-lives of artemisinins limit the possibility of selection 
  for resistance. However, at present, the likelihood of true artemisinin resistance in 
  malaria parasites is low, and this concern should not prevent the use of intravenous 
  

  artesunate to treat severe malaria.

  ARTEMETHER AND ARTESUNATE 

  Artemether [Artenam] and artesunate are the most effective drugs available for 
  multidrug resistant falciparum malaria. Both agents are derivatives of artemisinin, 
  a compound isolated from the sweet wormwood plant, Artemisia annua. To 
  be effective, artemether and artesunate must undergo conversion to an active 
  metabolite dihydroartemisinin which kills plasmodia by releasing free radicals that 
  attack the cell membrane. Kill also requires high concentrations of iron, as are 
  

  found in red blood cells. 

  Artemether and artesunate are remarkably safe. These drugs can produce transient 
  first-degree heart block, as well as a dose-related decrease in red blood cells and 
  neutrophils. They can also prolong coma and promote fever. However, serious or 
  

  persistent side effects have not been reported. 

  Indications

  Treatment of severe malaria and initial treatment of uncomplicated malaria, when 
  

  persistent vomiting precludes oral therapy.

  Artesunate is an artemisinin derivative with antimalarial actions much like those 
  of artemether. At this time, artesunate, administered IV, is considered the drug of 
  choice for severe malaria. Artesunate appears to be more effective than IV quinine 
  

  and safer than IV quinidine. 

  ARTEMETHER/LUMEFANTRINE 

  Indications and Efficacy

  The combination of artemether (20 mg) and lumefantrine (120 mg), sold as Coartem, 
  

  is indicated for oral therapy of uncomplicated falciparum malaria.

  The combination is not approved for prophylaxis of falciparum malaria, for treatment 
  

  of severe falciparum malaria, or for prophylaxis or treatment of vivax malaria. 

  Both artemether and lumefantrine can kill erythrocytic forms of the malarial parasite, 
  

  but these drugs cannot kill primary or latent hepatic forms. 

  In clinical trials, artemether/lumefantrine has been highly effective against 
  falciparum malaria: 28 days after a short course of treatment, the cure rate is more 
  than 95%, even against multidrug-resistant P. falciparum. Efficacy against P. vivax 
  

  is less dramatic.

  Mechanism of Action

  To be effective, artemether must undergo conversion to an active metabolite—
  dihydroartemisinin— which appears to kill plasmodia by releasing free radicals 
  that attack the cell membrane. Lumefantrine probably works like chloroquine, 
  causing death by preventing malaria parasites from converting heme to nontoxic 
  

  metabolites. 

  Pharmacokinetics

  The kinetics of artemether and lumefantrine differ in three important ways. First, 
  lumefantrine is highly lipophilic, so oral absorption is enhanced by dosing with fatty 
  food. Second, absorption of artemether is relatively rapid (plasma levels peak about 
  2 hours after dosing), whereas absorption of lumefantrine is delayed (plasma levels 
  peak 6 to 8 hours after dosing). Third, the half-life of artemether is short (1.5 hours), 
  

  whereas the half-life of lumefantrine is prolonged (100 hours). 

  Adverse Effects 

  Artemether/lumefantrine is generally well tolerated. Approximately one-third or 
  more of adults taking this drug experience adverse effects such as headache, 
  anorexia, dizziness, weakness, joint pain, and muscle pain. Among children, the 
  

  most common adverse effects are fever, cough, vomiting, anorexia, and headache. 

  Lumefantrine may prolong the QT interval, posing a risk of serious dysrhythmias. 
  Accordingly, artemether/lumefantrine should not be used by patients with electrolyte 
  disturbances (e.g., hypokalemia, hypomagnesemia) or congenital prolonged QT 
  syndrome, or by patients using other drugs that prolong the QT interval (e.g., 
  

  quinine, erythromycin, and ketoconazole).

  Why Do We Combine Artemether With Lumefantrine? 

  Compared with lumefantrine, artemether is much more effective. As a result, when 
  the drugs are administered together, most of the benefit comes from artemether. 
  

  Why, then, do we combine these drugs? 

  There are two reasons:

  First, adding lumefantrine enhances efficacy. (Because lumefantrine has a much 
  longer half-life than artemether, lumefantrine remains in the body long enough to kill 
  

  the few parasites not killed by artemether). 

  Second, adding lumefantrine helps prevent development of resistance to 
  artemether. Why? Because the odds of developing resistance to the two drugs 
  simultaneously are much lower than the odds of developing resistance to artemether 
  

  alone. Accordingly, 

  In 2006 the World Health Organization requested that all drug companies stop 
  selling artemisinin-only products and replace them with artemisinin combination 
  therapies (ACTs). Four ACTs are recommended: 
  • Artemether/lumefantrine [Coartem] 
  • Artesunate/mefloquine 
  • Artesunate/amodiaquine 
  • Artesunate/pyrimethamine/sulfadoxine 
  Pharmacology | Associate Nursing Program | Senior 5 87
  N.B: These combinations are indicated only for the treatment of malaria not for 
  

             prophylaxis. 

  The other medications used to treat malaria are: Chloroguanide (Proguanil), 
  Halofantrine, Mefloquine, Atovaquone, Pyronaridine, Piperaquine, 
  Clindamycin, ciprofloxacin, Norfloxacin, azithromycin, Tetracyclines, Doxycycline
  

  and Clindamycin. 

      SUMMARY OF COMMON DRUGS USED TO TREAT MALARIA

                      

                      Self-assessment 3.4

  3) A 32-year-old female student developed fever for last 3 days. She consulted 
  a nearby health center and the health care provider suspect malaria 
  and he asked for blood film for malaria. Results showed plasmodium 
  falciparum and he decided to give quinine. What are the adverse effects 
  that can be associated with quinine at usual therapeutic doses?
  4) A patient with a history of malaria presently being treated with chloroquine 
  is admitted to the hospital. What are the side effects should the nurse 
  anticipate at therapeutic doses? 
  5) True and false questions 
  a) The erythrocytic forms are not killed with relative ease whereas the 
  exoerythrocytic (hepatic) forms are very easy to kill. True or false
  b) Tissue schizonticides for causal prophylaxis: These drugs act on the 
  primary tissue forms of the plasmodia which after growth within the liver, 
  initiate the erythrocytic stage. True or false 
  c) Tissue schizonticides for preventing relapse: These drugs that do not 
  act on the hypnozoites of P. vivax and P. ovale in the liver that cause 
  relapse of symptoms on reactivation. True or false
  d) Blood schizonticides: These drugs act on the blood forms of the parasite 
  and thereby terminate clinical attacks of malaria. True or false
  e) Gametocytocides: These drugs destroy the sexual forms of the parasite 
  in the blood and thereby prevent transmission of the infection to the 
  mosquito. True or false
  f) Sporontocides: These drugs prevent the development of oocysts in the 
  mosquito and thus ablate the transmission. True or false  
  
        3.5. Antimalarial drug dosage.
                Learning Activity 3.5
  

  1) Two different patients were received at the medical clinic. Patient A was 
  diagnosed for simple malaria and patient B diagnosed for simple malaria 
  on first term pregnancy. Physician recommends quinine tablets as 
  treatment for patient B and Coartem for patient A.
  a) The patient B who received quinine weighs 60 kilograms. Using 
  pharmacology book and internet, and discuss the dosage the healthcare 
  provider will follow while prescribing quinine injection for patient B.
  b) The patient A who received coartem weighs 30 kilograms. Using 
  pharmacology book and internet, and discuss the dosage the healthcare 
  

  provider will follow while prescribing coartem for patient A.

  CONTENT SUMMARY

  Our goal in this lesson is to describe the antimalarial drug dosage calculation. 
  
  CHLOROQUINE
  Chloroquine phosphate [Aralen] is available in tablets (250 and 500 mg) for oral 
  administration.
   
  Adult: Malaria
  Prophylaxis
  Indicated for prophylaxis of malaria in geographic areas where resistance to 
  chloroquine is not present; 500 mg (300-mg base) weekly on the same day each 
  week; begin 1-2 weeks before travel, during travel, and for 4 weeks after leaving 
  endemic area.
  
  Treatment
  Indicated for acute attacks of malaria due to P. vivax, P. malariae, P. ovale, and 
  susceptible strains of P. falciparum.
  
  Acute attack
  • 1 g (600-mg base) PO, THEN
  • 500 mg (300 mg-base) PO after 6-8 hr THEN
  • 500 mg (300 mg-base) PO at 24 hr and 48 hr after initial dose
  Total dose of 2500 mg (1500 mg-base) in 3 days
  
  Pediatric: Malaria
  
  Prophylaxis
  Indicated for prophylaxis of malaria in geographic areas where resistance to 
  chloroquine is not present; 5 mg/kg PO q1Week, not to exceed 500 mg (300-mg 
  base), on the same day each week; begin 1-2 weeks before travel, during travel, 
  and for 4 weeks after leaving endemic area.
  
  Treatment
  Indicated for acute attacks of malaria due to P. vivax, P. malariae, P. ovale, and 
  susceptible strains of P. falciparum for adults, infants, and children
  
  • Acute attack
  Note: Dosing is based chloroquine base; chloroquine phosphate 16.6 mg is 
  equivalent to 10 mg chloroquine base
  
  • First dose: 10 mg base/kg (not to exceed 600-mg base/dose)
  • Second dose: (6 hr after first dose) 5 mg base/kg (not to exceed 300 mg 
  base/dose)
  90 Pharmacology | Associate Nursing Program | Senior 5
  
  • Third dose: (24 hr after first dose): 5 mg base/kg (not to exceed 300 mg 
  base/dose)
  • Fourth dose36 hr after first dose): 5 mg base/kg (not to exceed 300 mg 
  base/dose)
  Total dose of 25mg base/kg
  
  QUININE
  
  Dose:
  Oral: 10 mg/kg 8 hourly for 7 days.
  
  Intra venous: 20 mg of salt/kg in 10 ml/kg isotonic saline or 5% dextrose over 4 
  hours, then 10 mg of salt/kg in saline or dextrose over 4 hours, every 8 hours until 
  patient is able to take orally or for 5-7 days.
  
  Intra muscular: 20 mg/kg stat, followed by 10 mg/kg 8 hourly by deep intra muscular 
  injections for 5-7 days.
  
  Quinine dihydrochloride IR (intra-rectal) for children: 15 mg per kg body weight 
  diluted in 4 ml of distilled water or physiological solution and administered rectally 
  with a 5-ml syringe every eight hours. Note: If the drug is ejected during the first 10 
  minutes following its administration, administer other half dose.
  
  Quinine dihydrochloride IV administration (Children and adults): 
  In infusion, it is administered as 10 mg per kg body weight per dose, diluted in 5 to 
  10 ml of 5% or 10% glucose per kg body weight, every eight hours. If the patient’s 
  condition does not improve within 24 hours of treatment, refer patient to the nearest 
  district hospital.
                          
                      
   DOXYCYCLINE (Monodox/Vibramycin)
  

  100mg orally daily, 1-2 days before travel and for 4 weeks after return from endemic 

  area.

  PYRIMETHAMINE/SULFADOXINE 

  Pyrimethamine and sulfadoxine are available in a fixed-dose combination sold as 
  Fansidar. Tablets contain 25 mg of pyrimethamine and 500 mg of sulfadoxine. 
  
  To treat an acute attack of chloroquine-resistant malaria, Fansidar, used in 
  

  conjunction with quinine, is given as a single dose on the last day of quinine dosing. 

  Fansidar dosages are as follows: 

  • Adults, 2 to 3 tablets; 
  • Children 9 to 14 years, 2 tablets; 
  • Children 4 to 8 years, 1 tablet;
  • Children under 4 years, one-half tablet. 
  Prevention: 1 tablet orally weekly
  
  ARTEMETHER/LUMEFANTRINE (Coartem)
  These combinations are indicated only for treatment of malaria not for prophylaxis. 
  The ACT used most widely is a fixed-dose combination of artemether (20 mg) 
  and lumefantrine (120 mg), sold as Coartem. Patients take a 3 days course, with 
  

  dosage based on body weight. The cure rate is about 95%, even against multidrug                                                                       resistant P. falciparum. To date, there have been no reports of resistance to either                                                                      component.

  Adult/Child >35 kg: PO: 4 tabs of artemether 80 mg/ lumefantrine 480 mg upon 
  diagnosis, then 4 tabs in 8 h, then 4 tabs b.i.d. for 2 days 
  Adult/Child 25-35 kg: PO: 3 tabs artemether 60 mg with lumefantrine 360 mg in 
  

  same regimen 

  Child 15-25 kg: PO: 2 tabs artemether 40 mg with lumefantrine 240 mg in same 
  regimen 
  Child 5-15 kg: PO: 1 tab artemether 20 mg with lumefantrine 120 mg in same 
  regimen
  
  Artemether by IM: administered as dose of:
  • For children:3.2 mg per kg body weight immediately after a positive blood 
  smear or positive rapid diagnostic test, followed by 1.6 mg/kg after 12 hours
  • For adults: 160 mg IM of artemether immediately after a positive blood smear 
  

  or a positive rapid diagnostic test and 80 mg after 12 hours. 

  If the patient’s condition does not improve within 24h of treatment, refer the patient 
  to the nearest district hospital. If the patient’s condition improves, change to oral 
  Artemether-lumefantrine twice a day for three consecutive days. 
  

              

             ARTESUNATE 

  Artesunate is antimalarial drug indicated for initial treatment of severe malaria; 
  should always be followed by a complete treatment course of an appropriate PO 
  

  antimalarial regimen (Coartem)

  Dosage and duration:

  • Child under 20 kg: 3 mg/kg/dose
  

  • Child 20 kg and over and adult: 2.4 mg/kg/dose

  One dose given on admission (time = 0), the following dose will be administered 
  at 12h then at 24h, then once a day. Administer parenterally at least 24 hours (3 
  doses), then, if the patient can tolerate the oral route, change to a complete 3-day 
  course of an artemisinin-based combination. If not, continue parenteral treatment 
  once daily until the patient can change to oral route (without exceeding 7 days of 
  

  parenteral treatment).

                  

                  

                  Use a 1 ml syringe graduated in 0.01 ml when the dose required is less than 1 ml.
                 For patients over 25 kg, a second vial must be prepared to obtain the volume 
  

                 needed, a third vial for patients over 50 kg and a fourth vial for patients over 76 kg.

  Self-assessment 3.5
  1) In urban district of a country highly endemic for malaria, a boy aged 6 
  years weighing 23 kilograms wakes up in the morning and refuses to 
  eat. He is rather quiet but does not have fever. The mother gives three 
  tablets of artemether-lumefantrine (AL). That day when he returned from 
  school he was apparently well. The AL was stopped. Two days later in the 
  evening, he develops fever and vomiting. The mother then gives another 
  3 tablets of AL. The following morning, he again refused food, and he had 
  a low-grade fever to touch. The mother decides to take the child to the 
  clinic. 
  
  a) Was the mother right to give the AL? Explain your answer.
  b) If the child had malaria, would the mother have stopped the treatment 
  after the initial first dose of AL when the child was apparently well? 
  Please explain
  c) How would the health care provider manage this patient?
  2) Explain how to calculate artesunate dosage to be administered via IV
  3) Explain dosage calculation for quinine injection for an adult patient with 
  

  severe malaria

  3.6. Treatment of simple malaria

            Learning Activity 3.6

  1) You are a S5 nurse student in the clinical placement at a district hospital, 
  and there is a patient taking coartem. During the nursing round, your 
  colleague from S4 asks a senior nurse why the patient is on Coartem. 
  The senior nurse responds to the student that it is because the patient 
  has been diagnosed with simple malaria and tasks you to deeply give 
  explanation of how to manage simple malaria at the health facility level 
  in Rwanda.
  a) What deep explanation will you provide to your colleague regarding the 
  reason of taking coartem?
  b) Who are in-charge of simple malaria management at the community 
  level?
  c) What drug may be used at the health facility level when coartem is 
  

  contraindicated?

  CONTENT SUMMARY

  According to clinical manifestations, malaria is classified into three forms: Simple 
  malaria, Simple malaria with minor digestive symptoms and severe malaria.
  I. Treatment of simple malaria
   Information Education and Communication (IEC)at family level:
  Strengthening information, education and communication (IEC): 
  • Knowledge of the mode of transmission of malaria in Rwanda
  • Utilization of long-lasting insecticide treated nets (LLINs) as the principal 
  means of prevention and utilization of other preventive measures 
  • Membership to the community health insurance scheme as means of ensuring 
  early access to health care. 
  • Recognition by the family members of the signs of simple malaria, simple 
  malaria with minor digestive symptoms and severe malaria
  • Seeking care in a timely manner from a community health worker or the 
  nearest health facility, after reducing fever, if present by using sponging.
  
   At community level (Community health workers)
   The role of the community health worker is to: 
  • Sensitize the population on the mode of transmission of malaria in Rwanda
  • Sensitize the population on the recognition of the signs of the simple malaria, 
  malaria with minor digestive symptoms and severe malaria 
  • Sensitize the population on seeking care in a timely manner from a community 
  health worker or the nearest health facility, after reducing fever, if present by 
  using tepid sponging.
  • Manage cases of children under five with malaria in accordance with the 
  national guidelines after confirmation using a rapid diagnostic test (RDT), 
  under the framework of CCM (community case management ), and when 
  necessary refer to a health facility
  • Orient the population to the health facility for appropriate management
  • Sensitize the population to the use of the long lasting insecticide treated nets 
  as principal means of prevention, environment hygiene and sanitation as well 
  as other preventive measures
  • Participate in other malaria control activities at the community level such as 
  indoor residual spraying campaigns, application of larvicides, etc.
   At the level of the health facility
  It is indicated to prescribe the first line of treatment only after obtaining a positive 
  96 Pharmacology | Associate Nursing Program | Senior 5
  blood smear or positive rapid diagnostic test. A negative blood smear or rapid 
  diagnostic test excludes the diagnosis of malaria and the administration of an 
  antimalarial. Another cause of the fever should be sought systematically and treated 
  accordingly. 
  The first line treatment recommended is an artemisinin combination therapy (ACT) 
  of 2 molecules in one tablet. That is: Artemether 20 mg and Lumefantrine 120 mg 
  to be taken preferably during meals. 
  The combination of artemether – lumefantrine (COARTEMR) is administered orally, 
  twice a day for 3 days.
  Important instructions to follow: 
  • Respect the dose prescribed by the health provider 
  • Directly observe the administration of the first dose 
  

  • Do not exceed the prescribed dose 

   Table 3.6.1: Posology of artemether-lumefantrine (COARTEMR) in function of 
  

     body weight or age

                         

  • Artemether-lumefantrine is contraindicated 
  – In children weighing less than 5 kg; 
  – During first trimester of pregnancy, 
  – In case of allergy to one of the two drugs in the combination and
  – In cases of severe liver or renal disease. 
  In such cases, oral quinine sulphate is indicated as 10 mg per kg body weight per 
  

  dose, taken three times a day over seven consecutive days.

           Table 3.6.2: Posology of oral quinine in function of weight or age
  

                          

  N.B: If there is no improvement after 48 hours of treatment, verify if the patient 
  swallowed the drugs correctly, re-examine the patient carefully and do another 
  peripheral blood smear. If the test is positive, change the treatment to oral quinine 
  sulphate as 10 mg per kg body weight per dose, taken three times a day over seven 
  consecutive days. If the peripheral blood smear is negative, exclude and treat other 
  causes of illness and/or refer the patient to the nearest district hospital.
  
  If there is no improvement after 48 hours of treatment with quinine, refer the patient 
  to the nearest District hospital because there is suspicion of other associated 
  pathologies rather than malaria. 
  
  II. The management of simple malaria with minor digestive symptoms
  The minimum required criteria for treating simple malaria with minor digestive 
  symptoms at a health facility are the following: 
  • Qualified and trained staff 
  • The existence of a continuous system of clinical and paraclinical monitoring 
  of patients, 24 out of 24 hours;
  • A laboratory with the capacity to do a peripheral blood smear, rapid diagnostic 
  tests and measure haemoglobin.
  The management of simple malaria with minor digestive symptoms is done at the 
  health centre, or when not possible in the district hospital. 
  
  The patient must be admitted in the health centre where he/she will receive 
  treatment for 24 hours maximum.
   
  After this period, a clinical and paraclinical re-evaluation is done to assess if 
  the patient can be discharged to go home (if there has been improvement and 
  transition towards simple malaria), or be transferred to the district hospital (in cases 
  

  where there has been no improvement).

  The recommended drugs are artemether IM or quinine IR or quinine in IV infusion 
  if diarrhoea is present.
   Modes of administration of the antimalarials
  Depending on the general status and level of hydration of the patient, drugs may be 
  administered as follows:
  1) Artemether by IM: administered as dose of:
  – For children:3.2 mg per kg body weight immediately after a positive blood 
  smear or positive rapid diagnostic test, followed by 1.6 mg/kg after 12 
  hours
  – For adults: 160 mg IM of artemether immediately after a positive blood 
  smear or a positive rapid diagnostic test and 80 mg after 12 hours. 
  
  If the patient’s condition does not improve within 24h of treatment, refer the patient 
  to the nearest district hospital. If the patient’s condition improves, change to oral 
  Artemether-lumefantrine twice a day for three consecutive days. 
  
  2) Quinine dihydrochloride IR (intra-rectal) for children: 15 mg par kg 
  body weight diluted in 4 ml of distilled water or physiological solution and 
  administered rectally with a 5-ml syringe every eight hours. This dose is 
  justified by the slow absorption of quinine by the rectal mucosa. The drug is 
  administered slowly through the anus, and the buttocks are held together for 
  5 minutes to prevent a premature reflex ejection of the drug. If the patient’s 
  condition does not improve after 24 hours of treatment, refer the patient 
  to the nearest hospital. If the patient’s condition improves, change to oral 
  Artemether-Lumefantrine, twice a day for three consecutive days, or in the 
  case of contraindications to Artemether-Lumefantrine, give oral quinine. 
  
  Note:
  – If the drug is ejected during the first 10 minutes following its administration, 
     administer other half dose.
  – Diarrhoea and anal lesions limit the use of this route of administration. 
  3) Quinine dihydrochloride IV administration (Children and adults): 
  In infusion, it is administered as 10 mg per kg body weight per dose, diluted in 5 to 
  10 ml of 5% or 10% glucose per kg body weight, every eight hours. If the patient’s 
  condition does not improve within 24 hours of treatment, refer patient to the nearest 
  district hospital. 
  If the patient’s condition improves, change to oral Artemether-Lumefantrine, twice 
  a day for three consecutive days, or to oral quinine in case of contraindications to 
  Artemether-Lumefantrine.
  NB: Whatever the medicine and the mode of administration used, (IM artemether, 
  IR/IV quinine), if the state of health of the patient doesn’t improve in 24 hours, do 
  Pharmacology | Associate Nursing Program | Senior 5 99
  a rapid diagnostic test and refer the patient with the referral note or treatment file, 
  giving detailed information on the treatment provided so far, to the nearest hospital. 
  Symptomatic treatment
  In case of diarrhoea and/or vomiting: 
  • Evaluate and monitor the hydration status of the patient;
  • Rehydrate the child with ORS or other available liquids, encourage breast 
  feeding and other modes of feeding and if necessary use a naso-gastric tube; 
  • Antiemetic should be avoided. 
  In case of fever, give oral Paracetamol 15 mg/ kg, or any other antipyretic drug as 
  it may be indicated. 
  N.B. In case of pregnant woman with this type of malaria, the treatment is as follows:
  
  1st trimester of pregnancy: give Quinine dihydrochloride in infusion until she is 
  able to take oral quinine and continue oral quinine to complete the totality of 7 days
  
  2nd and 3rd trimester of pregnancy: give Artemether IM or quinine IV infusion until 
  she is able to take oral treatment and pass to oral COARTEM 4 tablets twice a day 
  

  in 3 days.

             Self-assessment 3.6

  1) A 38-year-old male with no significant past medical history has returned 
  to Rwanda from traveling to malaria endemic region. He forgot to take 
  chemoprophylaxis for malaria and now presents with fever, chills, rigors, 
  and blood smear test reveals plasmodium. Which therapy should be 
  initiated to this patient? 
  a) Coartem 
  b) Quinine 648 mg 
  c) Mefloquine 250 mg 
  d) Quinidine 300 mg 
  2) A pregnant mother in the first trimester was diagnosed with simple 
  malaria. The fellow student in the clinical placement asks you the reason 
  why quinine was given, and not coartem. What would be your answer to 
  this student?
  3) A 10-year-old male patient weighing 28 kilograms is admitted at the 
  health facility. He complains of fever, headache, vomiting, and mild 
  diarrhea. The laboratory exam reveals malaria. The nurse decides to 
  give artesunate, and she tasks to calculate the dose to administer to this 
  

  patient immediately. How would you calculate this dosage?

          3.7. Treatment of severe malaria

                  Learning Activity 3.7

   As an associate nurse student, you are carrying out clinical practice at the health 
  center, and you receive a patient with history of fever, inability to stand still, and 
  chills. On the assessment, the patient is weak with pale palpebral conjunctivae, 
  and you decide to order the laboratory investigations.
  The blood smear reveals the plasmodium. In addition, you take the glycaemia 
  which reveals 40mg/dL. You take a decision to refer the patient to the district 
  hospital.
  1) What are the antimalarial medications you may use in pretransfer 
  treatment?
  2) What are the minimum tests should the laboratory be able to perform in 
      order to confirm severe malaria?
  

  3) List 2 antibiotic medications used to manage cerebral malaria in Rwanda

      CONTENT SUMMARY

  The management of severe malaria must be done in either district hospital or the 
  national referral hospital (private or public) as ordered by the ministry of health. 
  The management of severe malaria should be done in either a district hospital 
  or a national referral hospital (private or public) that meets the corresponding 
  

  requirements of the Ministry of Health.

  The minimum required criteria are:
  1) Qualified staff, trained in the clinical management of malaria-by-Malaria Unit; 
  2) The existence of a continuous system of 24 hours clinical and paraclinical 
  follow-up of patients; 
  3) A laboratory with the capacity to at least do: 
  – Peripheral blood smear, 
  – Haemoglobin and haematocrit,
  – Blood sugar and 
  – Proteinuria
  4) Capacity to do a lumbar puncture (recommended in cerebral   malaria form); 
  5) Possibility to transfuse in case of severe anaemia; 
  6) Possibility to provide oxygen; 
  7) Availability of the drugs and consumables required for the treatment of 
  severe malaria (IV quinine, 50% and 5% glucose, Phenobarbital, diazepam, 
  

  antipyretics and furosemide).

  Pre-transfer treatment at the health centre
  While preparing for the transfer of the patient, urgently administer IM artemether 
  or quinine IR or IV (IV infusion). Depending on the general condition of the patient 
  (weak pulse or not, dehydration or none), the health centre staff will administer, 
  either:
  • Quinine, preferably by intravenous infusion as a loading dose of 20 mg per 
  kg body weight to run in 4 hours (not exceeding a total dose of 1200 mg for 
  the loading dose); or
  • Quinine by intrarectal route in children, as 20 mg per kg body weight diluted 
  in 4 ml of distilled water or physiological solution, administered with a 5-ml 
  syringe. The drug is gently guided through the anus and the buttocks are held 
  together for 5 minutes to prevent the premature reflex expulsion of the drug. 
  
  If the drug is expelled within the first 10 minutes following its administration, 
  administration is repeated using half the original dose. Diarrhoea and anal 
  lesion limit the use of this route for the administration of drugs
  • Arthemether IM 3.2 mg per kg body weight administered as a single dose 
  before transferring the patient. 
  Note: 
  • Regardless of the pre-transfer treatment that is given (loading dose of Quinine 
  or Arthemether), treatment with Quinine in intravenous infusion continues at 
  a dose of 10 mg of quinine per kg body weight diluted in 10ml of 5% or 10% 
  Glucose per kg body weight every 8 hours. 
  
  • For cerebral malaria, administer the first dose of antibiotics: 
  For children: Ampicillin 50 mg/kg body weight per dose, four times a day to which is 
  added chloramphenicol 25 mg/ kg body weight per dose, four times a day. 
  For adults: Ampicillin 1.5 g four times a day and chloramphenicol 1 g four times a 
  day; 
  Note: The intramuscular use of Quinine is prohibited in all health facilities in 
  Rwanda!!
  • In case of hypovolaemia (severe anemia, rapid breathing, coma or systolic 
  BP < 80 mm Hg), start with normal saline or Ringer’s lactate infusion in a 
  dose of 20 ml/kg to run for 30 minutes to move the patient out of shock. 
  • For malnourished children (kwashiorkor or marasmus), give the loading dose 
  of quinine in IV perfusion without fluid replacement (as it is difficult to assess 
  hypovolaemia and dehydration, fluid replacement can increase the risk of 
  circulatory overload).
  • The administration of quinine in intravenous infusion is preferable in cases of 
  signs of vital distress (repeated convulsions, coma, respiratory distress, and 
  cardio-vascular shock).
  In the case where it has been impossible to establish 
  an intravenous line to administer quinine intravenously, use intramuscular 
  artemether or intra-rectal quinine.
  
   Symptomatic treatment
  If the temperature is higher or equal to 38°C: 
  • Do sponging; 
  • Give Paracetamol 15 mg /kg body weight by oral route or suppository form, 
  or any other antipyretic that may be indicated. 
  To prevent hypoglycaemia (characterized by lack of consciousness, severe 
  weakness):
  • Give 20-50 ml of 50% hypertonic serum of glucose by intravenous injection 
  administered over 5-10 minutes in adults; and for children 3 ml/kg body weight 
  of 10% glucose or if not available 1 ml/kg of 50% glucose; 
  • Or administration of water with 10% sugar per mouth or with nasogastric 
  tube, at a rate of 5 ml/kg for children and 50 -100 ml for the adults. 
  
  Water with 10% sugar is readily prepared in the following way: take 100 ml of boiled 
  clean water and add 10 g of sugar or 2 coffee spoons. 
  
  In case of convulsions: 
  • Administer Diazepam 0.5 mg/kg body weight intrarectally for children and 10 
  mg slow IV for adults; 
  • If convulsions persist, give Phenobarbital 10-15 mg/kg IM; 
  • Treat or prevent hypoglycaemia; 
  • Treat fever if necessary. 
  Refer the patient to the nearest district hospital or national reference hospital.
  
   Treatment of the severe malaria in the hospital
  In children and adults
  Administer a loading dose of 20 mg/kg body weight of quinine dihydrochloride (do 
  not exceed 1200 mg) diluted in an isotonic solution or 5 or 10% glucose on the 
  basis of 5 to 10 ml/kg body weight to run for 4 hours in IV perfusion. Then run IV 
  glucose 5 or 10% for 4 hours as maintenance drip. 
  
  Thereafter, i.e. 8 hours after the beginning of the administration of the loading dose 
  or 4 hours after the beginning of the maintenance drip, administer a maintenance 
  dose of 10 mg/kg body weight of quinine dihydrochloride in infusion, to run for 4 
  hours. This maintenance dose of quinine will be repeated every 8 hours until the 
  

  patient can swallow, normally within 48 hours at the most. 

   If after 48 hours the patient’s state doesn’t permit the patient to take quinine orally, 
  one may continue the drip of quinine by reducing the doses to 7 mg/kg every 8 
  

  hours to run for 4 hours. 

  Change to oral quinine 10 mg/kg of quinine sulphate every 8 hours as soon as the 
  patient can swallow, to complete the 7 days of treatment or oral Artemether 20 mg 
  

  and Lumefantrine 120 mg, as recommended for the treatment of simple malaria.

  NB: For the patient whose body weight is over 60 kg, give the loading dose and 
  decrease the dose from 1200 mg to 800 mg after, divided into two doses for not 
  

  exceeding 2000 mg per day,

  • The loading dose of quinine is not administered if the patient received quinine 
  in the past 12 hours 
  • Never exceed 2 gm of daily dose of quinine. 
  • For the cerebral form of severe malaria (cerebral malaria or neurological 
  malaria), the association of IV antibiotherapy is recommended namely: 
  – Children: (Ampicillin 50 mg/kg /dose 4 times a day, plus Chloramphenicol 
  25 mg/kg/dose 4 times a day)
  – Adults: (Ampicillin 1.5 g 4 times a day, plus Chloramphenicol 1g 4 times 
      day)
  • For the anaemic form of severe malaria antibiotherapy is not indicated.
  • The recommended dose for oral quinine is 10 mg Quinine salt per kg body 
     weight every 8 hours for 7 days;
  

  • Quinine Syrup is not nowadays recommended

       Self-assessment 3.7

  An adult pregnant woman is a worker in a sugar cane company. A week ago she 
  got tired by the end of the day. At home, she developed fever with sweating and 
  she vomited twice. She diagnosed herself as having malaria and she asked her 
  son to bring anti-malarial medication from a nearby pharmacy. She took the drug 
  for 2 days. Five days later she again developed fever, severe headache, nausea 
  and severe weakness. This time, she decided to go to the hospital. On physical 
  exam, the physician noticed conjunctiva pallor and laboratory results showed 
  haemoglobin of 5g/dL with positive blood smear. The physician diagnosed the 
  patient as having severe malaria, anaemic form.
  1) Discuss how to manage this patient at the hospital.
  

  2) Is it advisable to give the antibiotic to this patient?

        3.8. Treatment of malaria for pregnant women
  

                 Learning Activity 3.8

  A health care provider working in the health centre received a call to see a 
  25-year-old pregnant woman presenting with fever. On examination, the provider 
  couldn’t detect any abnormality apart from the axillary temperature of 38.5°C. 
  The health care provider highly suspected malaria, although he thought of other 
  possible diseases. He then requested for the blood smear which showed malaria 
  parasite seen with + and he decided to institute the treatment.
  1) What antimalarial medicine (s) would you give a pregnant woman with 
  uncomplicated simple malaria 
  2) A pregnant woman may never be treated with coartem because it can 
  

  harm the baby. True or False

  CONTENT SUMMARY

  The malaria causes many problems to the pregnant women, prevention, early 
  detection and treatment are very important to reduce the mortality and morbidity 
  caused by malaria in pregnant women. This lesson is going to discuss the 
  management of malaria in pregnant women at family level, community level and 
  Health facility.
  
  At the family level
  Strengthen IEC on: 
  • Knowledge of the mode of transmission of malaria in Rwanda
  • Utilisation of long-lasting insecticide treated mosquito nets as principle means 
  of prevention and other preventive measures
  • Membership to the community health insurance schemes as a way of ensuring 
  better access to care
  • Recognition of the signs of simple malaria, simple malaria with minor digestive 
  symptoms and severe malaria by the family members; 
  • Seeking timely care from the community health care worker or the nearest 
  health facility after lowering fever, if any, using tepid sponging. 
  
  At the Community level (Health Animator)
  The role of the community health worker is to educate the pregnant woman on: 
  • The mode of transmission of malaria (mosquito bite);
  

  • The effects of malaria on pregnancy (on the mother and the baby)

  • Recognition of the signs of the simple malaria, malaria with minor digestive 
  symptoms and severe malaria, and the ill effects of fever during pregnancy; 
  • The benefits of sleeping under long lasting insecticide treated nets 
  • Destruction of breeding sites (stagnant water)
  • Seeking health care from the health facility as soon as they feel signs of 
  malaria
  • The importance of taking all the drugs as prescribed by the health worker;
  • The benefits of 4 ANC visits 
  
  At the level of the Health facility
  To educate the pregnant woman on the preventive measures of malaria in pregnancy 
  during the antenatal consultations: 
  • What causes malaria and its transmission; 
  • The effects of malaria on the mother and the baby; 
  • The advantages of sleeping under long lasting insecticide treated mosquito 
  nets; 
  • The danger signs of severe malaria; 
  • The importance of seeking medical care when the symptoms of malaria 
  present; 
  • The importance of taking a complete dose of antimalarials, 
  • The benefits of 4 ANC visits. 
  
  Antenatal care
  During antenatal care, the health facility staff must do the following to the pregnant 
  woman: 
  • Give her a long lasting insecticide treated mosquito net;
  • Give other components of antenatal care: vaccination, iron, vitamin A and 
  Mebendazole;
  • Discuss with her the program of the ANC visits;
  • Record on the ANC card, her ANC appointment card, role of LLINs
  • Register all illness relate to the pregnancy in the ANC register. 
  
  The management of malaria in pregnant women
   Simple malaria 
  Because Malaria during pregnancy can aggravate latent anaemia, it is recommended 
  to do a complete clinical exam. 
  • The first line treatment of malaria in pregnancy is quinine sulphate per os 10 
  mg/kg/dose, 3 times a day for 7 days during the first trimester of pregnancy. 
  COARTEM is indicated during the 2nd and 3rd trimesters of pregnancy only. 
  Note:
  • In case of fever, administer paracetamol tablets, 500 mg three times per day; 
  • Directly observe the woman as she swallows the first dose of antimalarials; 
  • Respect the dose prescribed by the health provider; 
  • Record all the information on the ANC card, ANC register and the hospitalization 
  file; 
  • Give advice on the prevention of the malaria and the necessity to consult in 
  time in case of illness; 
  • Recommend to the pregnant woman to come back any time if the symptoms 
  persist and/or she develops signs of severe malaria.
  
   Simple malaria with minor digestive symptoms
  The symptomatology of this type of malaria is similar to the one described earlier in 
  children and adults. The alteration of the general status can be accentuated by the 
  vomiting and other symptoms related to the pregnancy. 
  
  • Curative treatment 
  First trimester: 
  Administer Quinine dihydrochloride in intravenous infusion: 10 mg/kg/dose diluted 
  in 10 ml of 5% or 10% glucose per kg, every eight hours until patient is able to take 
  drugs orally making sure the treatment does not exceed 24 hours. Once the patient 
  can take orally, complete the remaining quinine 3 X10 mg/kg/day to make 7 days 
  by oral route of drug administration.
  
  Second and third trimester: 
  Depending on the general status and level of hydration of the patient, drugs may be 
  administered as follows:
  
  Artemether by intramuscular injection: 
  Administered as dose of 160 mg immediately after the diagnosis followed by 80 mg 
  twelve (12) hours after.
  If the patient’s condition does not improve within 24 of treatment, refer the patient 
  to the nearest district hospital. If the patient’s condition improves, change to oral 
  Artemether-lumefantrine twice a day for three consecutive days. 
  
  Quinine dihydrochloride by intravenous administration: 
  Administered as 10 mg per kg body weight per dose, diluted in 5 to 10 ml of 5% or 
  10% glucose per kg, every eight hours. If the patient’s condition does not improve 
  within 24 hours of treatment, refer the patient to the nearest district hospital. 
  
  If the patient’s condition improves, change to oral Artemether-Lumefantrine, twice 
  a day for three consecutive days, or to oral quinine in case of contraindications to 
  Artemether-Lumefantrine. 
  
  NB: Whatever the medicine and the mode of administration used, (IM artemether, 
  IR/IV quinine infusion), if the state of health of the patient doesn’t improve in 24 
  hours, do a rapid diagnostic test or blood smear and refer the patient with the 
  referral note or treatment file, giving detailed information on the treatment provided 
  so far, to the nearest hospital. 
  
  In this case of transfer, the loading dose won’t be administered at hospital. 
  • Symptomatic treatment
  In case of diarrhoea or vomiting: 
  • Evaluate and monitor the state of hydration; 
  • Rehydrate with ORS or other available liquids and even introduce nasogastric 
  tube if necessary; 
  • Anti-emetics are not recommended. 
  In case of fever, administer paracetamol 15 mg/kg orally or any other antipyretic 
  that may be indicated. 
  
   Severe malaria in the pregnant woman
  At the health centre
  Severe malaria in the pregnant woman is characterized by the same signs as those 
  described earlier for adults and children. 
  While organizing an emergency transfer, administer loading dose by intravenous 
  infusion of quinine 20 mg/kg body weight in 10 ml of 5% or 10 % dextrose per kg to 
  run for 4 hours (without exceeding 1200 mg); 
  Artemether, 3.2 mg/ kg can be administered by intramuscular route during the 2nd
  and 3rd trimester as pre- transfer treatment. It is important to do a complete clinical 
  examination of the woman and to regularly check the vitality of the fœtus.
  
  • Symptomatic treatment
  If the axillary temperature is ≥ 38°C, give paracetamol 500 mg 3 times per day if the 
  client is able to swallow, or any other antipyretic as it may be indicated.
  For the prevention of hypoglycaemia that may be manifested by loss of 
  consciousness, severe asthenia:
  • Give 20-50 ml of 50 % of dextrose by intravenous injection to run for 5-10 
  minutes; or administer water with 10 % sugar orally or by NGT (50 -100 ml). 
  
  

  Preparation of water with 10% sugar 

  To make 100 ml of water with 10% sugar: take 100 ml of clean water and add to it 
  10 g (also equivalent to 2 teaspoons) of sugar. 
  • In case of convulsions:
  – Administer diazepam, 10 mg IV slow; and if convulsions persist, administer 
       diazepam, 10 mg in 500 ml of 5 % glucose to run slowly. 
  – Treat or prevent hypoglycaemia; 
  – Treat the fever if necessary; 
  – Fill in the transfer card correctly and clearly, 
  – Record all the necessary information in the register and the ANC card;
  – Refer the patient immediately to the nearest district or national reference 
  

      hospital.

  At the hospital 

  The treatment of severe malaria in pregnant women at the hospital level is the same 
  as in others adults. Some complications are more frequent in pregnant women and 
  require a particularly close monitoring. These include hypoglycaemia, respiratory 
  

  distress (APO) and severe anaemia. 

  NB: It is important to do close obstetrical follow-up in general and monitoring of the 
  fetal vitality in particular. 
  Choice of antimalarial drugs for the treatment of simple malaria with minor digestive 
  

  symptoms.

              

                   Self-assessment 3.8

  1) An adult pregnant woman patient was admitted to the hospital because 
  of malaise, myalgia, abdominal pain, and high fever. The recent history 
  of the patient was significant for two paroxysmal attacks of chills, fever, 
  and vomiting. Physical examination revealed an acutely ill patient and 
  examination of a stained blood specimen revealed ring like and crescent                                                                                                        like forms within the RBCs reflecting malaria disease.
  
  a) Discuss curative treatment for pregnant woman suffering from malaria 
        with minor digestive symptoms in the first trimester
  b) Discuss curative treatment for pregnant woman suffering from malaria 
        with minor digestive symptoms in the second and third trimesters. 
  c) Discuss treatment for pregnant woman suffering from malaria with minor 
  

       digestive symptoms in symptomatic treatment.

       3.9. Non-malarial antiprotozoal medications 
  

             (miscellaneous antiprotozoals)

               Learning Activity 3.9

  A 35-year-old woman presents with a history of diarrhea and abdominal pain 
  for the past 3 days. You learnt that she recently had a trip in areas with poor 
  sanitation, and swallowed considerable amounts of river water. Her relative 30 
  years old man also presents with a history of diarrhea and abdominal pain for past 
  2 days after eating unfamiliar food during the trip. The first patient is diagnosed 
  with giardiasis after laboratory exams. The second patient is diagnosed with 
  amebiasis, and treatment should begin after obtaining appropriate specimens.
  
  a) List at least three examples of drugs that can be used in the management 
       of the condition for the first patient with giardiasis.
  b) List at least three examples of drugs that can be used in the management 
  

        of the condition for the second patient with amebiasis.

  CONTENT SUMMARY

  Several drugs used to treat malaria are also used to treat nonmalarial protozoal 
  infections, including chloroquine, primaquine, pyrimethamine, and atovaquone. 
  Other antiprotozoal drugs normally used against nonmalarial parasites include 
  iodoquinol, metronidazole, paromomycin, and pentamidine.
  
  Use of other antiprotozoal agents may result to these adverse effects:
  • CNS: headache, dizziness, ataxia, loss of coordination, peripheral neuropathy
  • GI: nausea, vomiting, diarrhea, unpleasant taste, cramps, changes in liver 
      function
  • Superinfections
  The following are drug-drug interactions involved in the use of other antiprotozoal 
  agents:
  • Alcohol: severe adverse effects with tinidazole and metronidazole. Avoid 
  alcohol for at least 3 days after treatment.
  • Oral anticoagulants: increased bleeding with metronidazole and tinidazole
  • Disulfiram: increased psychotic reactions with metronidazole and tinidazole. 
  Two weeks should elapse between tinidazole therapy and start of disulfiram.
  
  AMEBIASIS 
  It is an intestinal infection caused by Entamoeba histolytica. It is often known as 
  amoebic dysentery. The disease is transmitted through fecal-oral route. Amebiasis is 
  characterized by mild to fulminant diarrhea. In worst cases, it is able to invade 
  extra intestinal tissue. Drugs of choice for amebiasis are iodoquinol, paromomycin, 
  metronidazole, and tinidazole.
  
  Metronidazole 
  Metronidazole [Flagyl, Protostat, Metric 21], a drug in the nitroimidazole family, is 
  active against several protozoal species, including E. histolytica, G. lamblia, and 
  Trichomonas vaginalis. The drug is also active against anaerobic bacteria.
  
  Therapeutic Uses 
  Metronidazole is a drug of choice for symptomatic intestinal amebiasis and 
  systemic amebiasis. Because most of each dose is absorbed in the small intestine, 
  metronidazole concentrations in the colon remain low, allowing amebas there to 
  survive. 
  To kill these survivors, metronidazole is followed by iodoquinol, an amebicidal drug 
  that achieves high concentrations in the colon. 
  Metronidazole is a drug of choice for giardiasis, and for trichomoniasis in males as 
  well as females. Many anaerobic bacteria are sensitive to metronidazole.
   
  Metronidazole interacts with alcohol. Alcohol should be avoided 24 hours before 
  therapy and at least 48 hours after the last dose due a disulfiram type reaction. 
  Metronidazole decreased absorption of vitamin K from the intestines due to 
  elimination of the bacteria needed to absorb vitamin K, increased plasma 
  acetaldehyde concentration after ingestion of alcohol. Resultat: Alcohol causes a 
  disulfiram-like reaction; action of warfarin may be increased (increased bleeding 
  risk).
  Adverse Effects. 
  Metronidazole produces a variety of untoward effects, but these rarely lead to 
  termination of treatment. The most common side effects are nausea, headache, dry 
  mouth, and an unpleasant metallic taste. Other common effects include stomatitis, 
  vomiting, diarrhea, insomnia, vertigo, and weakness. Harmless darkening of the 
  urine may occur, and patients should be forewarned. Certain neurologic effects 
  (numbness in the extremities, ataxia, and convulsions) occur rarely.
  
  If these develop, metronidazole should be withdrawn. Metronidazole should not be 
  used by patients with active disease of the CNS. Carcinogenic effects have been 
  observed in rodents, but there is no evidence of cancer in humans. 
  
  Use in Pregnancy and Lactation. 
  Metronidazole readily crosses the placenta and is mutagenic in bacteria. 
  However, experience to date has not shown fetal harm in humans. Nonetheless, 
  it is recommended that metronidazole be avoided during the first trimester, and 
  employed with caution throughout the rest of pregnancy. 
  Metronidazole can be detected in breast milk up to 72 hours after administration. 
  Mothers should interrupt breast-feeding until 3 days after the last dose. 
  
  Preparations, Dosage, and Administration
  Metronidazole [Flagyl, Protostat, Metric 21] is available in capsules (375 mg), 
  standard tablets (250 and 500 mg), and extended-release tablets (750 mg); in 
  solution for injection (5 mg/mL); and as a powder to be reconstituted for injection.
   
  For protozoal infections, the oral formulations are used. Antibacterial therapy 
  usually requires IV treatment. 
  Dosages: 
  • adults, 500 to 750 mg 3 times a day for 7 to 10 days; 
  • children 35 to 50 mg/ kg/day in three divided doses for 7 to 10 days. 
  • Following treatment with metronidazole, iodoquinol is given for 20 days.
  
   Tinidazole 
  Tinidazole [Tindamax] is an antiprotozoal drug similar to metronidazole. Both 
  agents are nitroimidazoles, and both have similar actions, indications, interactions, 
  and adverse effects.
  Tinidazole has a longer half-life than metronidazole, and hence dosing is more 
  convenient (it’s done less often and on fewer days). However, metronidazole is 
  much less expensive. 
  
  Therapeutic Uses
  Tinidazole is indicated for trichomoniasis in adults, and for giardiasis, intestinal 
  amebiasis, and amebic liver abscesses in adults and children over 3 years of 
  age. Like metronidazole, tinidazole is considered a drug of choice for all of these 
  infections.
  Tinidazole has a half-life of 12 to 14 hours, nearly twice that of metronidazole. 
  
  Adverse Effects
  Adverse effects are like those of metronidazole, although tinidazole is better 
  tolerated. Gastrointestinal effects metallic taste, stomatitis, anorexia, dyspepsia, 
  nausea, vomiting are most common. Like metronidazole, tinidazole carries a small 
  risk of seizures and peripheral neuropathy. If abnormal neurologic signs develop, 
  tinidazole should be immediately withdrawn. In patients with existing CNS disease, 
  tinidazole should be used with caution. 
  
  Use in Pregnancy and Lactation 
  Tinidazole is in FDA Pregnancy Risk Category C: Animal studies show a risk of fetal 
  harm, but no controlled studies have been done in women. Like metronidazole, 
  tinidazole should not be used during the first trimester of pregnancy.
  
  Tinidazole can be detected in breast milk up to 72 hours after administration. 
  Mothers should not breast-feed while taking the drug and for 3 days after.
  Drug Interactions 
  Like metronidazole, tinidazole has disulfiram-like actions, and hence patients should 
  not consume disulfiram itself, alcoholic beverages, or any product that contains 
  alcohol. 
  
  Preparations, Dosage, and Administration
  Tinidazole [Tindamax] is available in 250- and 500-mg tablets. For patients unable 
  to swallow tablets whole, the tablets may be crushed and mixed with cherry syrup. 
  To minimize GI distress, tinidazole should be taken with food. 
  
  Dosages are as follows: 
  Intestinal amebiasis:
  • adults, 2 gm once daily for 3 days; 
  • children, 50 mg/kg (maximum 2 gm) once daily for 3 days 
  Amebic liver abscess:
  • adults, 2 gm once daily for 5 days; 
  • children, 50 mg/kg (maximum 2 gm) once daily for 5 days 
  
  TRICHOMONIASIS 
  It is caused by Trichomonas vaginalis, a flagellated protozoan.
  A common cause of vaginitis (reddened, inflamed vaginal mucosa, itching, burning, 
  and yellowish-green discharge).
  It is usually transmitted through sexual intercourse and Asymptomatic in men
  Metronidazole is the traditional drug of choice.
  
  Dosage:
  • Adults, either 2 gm just once or 500 mg twice a day for 7 days; 
  • Children, 5 mg/kg 3 times a day for 7 days. 
  However, tinidazole is just as effective and somewhat better tolerated but much 
  more expensive.
  
  Tinidazole
  Dosage:
  • adults, 2 gm once; 
  • children, 50 mg/kg (maximum 2 gm) once 
  TRYPANOSOMIASIS 
  There are two major forms of trypanosomiasis: American trypanosomiasis and 
  African trypanosomiasis. Both forms are caused by protozoal species in the genus 
  Trypanosoma. 
  American Trypanosomiasis (Chagas’ Disease) 
  Chagas’ disease is caused by T.cruzi, a flagellated protozoan. It is passed to 
  humans by common housefly. It is characterized by severe cardiomyopathy.
  In its early phase, Chagas’ disease can be treated with nifurtimox or benznidazole. 
  Unfortunately, these drugs are less effective against chronic infection.
  
  African Trypanosomiasis (Sleeping Sickness)
  African trypanosomiasis, transmitted by the bite of the tsetse fly, is caused by 
  two subspecies of Trypanosoma brucei: T. brucei gambiense, which causes West 
  African sleeping sickness, and T. brucei rhodesiense, which causes East African 
  sleeping sickness.
   
  During the early (hemolymphatic) phase of African trypanosomiasis, pentamidine 
  and suramin are the drugs of choice. (Pentamidine is preferred for disease caused 
  by T. brucei gambiense, and suramin is preferred for disease caused by T. brucei 
  rhodesiense.) During the late (CNS) stage, melarsoprol and eflornithine are drugs of 
  choice. (Either drug can be used against T. brucei gambiense, but only melarsoprol 
  is preferred for T. brucei rhodesiense). 
  All four drugs pentamidine, suramin, eflornithine, and melarsoprol can produce 
  serious side effects. Treatment is difficult and frequently unsuccessful.
  
  Benznidazole 
  Benznidazole [Rochagan, in Brazil], a relative of metronidazole and tinidazole, is a 
  drug of choice for American trypanosomiasis (Chagas’ disease). The adult dosage 
  is 2.5 to 3.5 mg/kg twice daily, and the pediatric dosage is 5 mg/kg twice daily. For 
  adults and children, the duration of treatment is 30 to 90 days.
  
  Pentamidine 
  Target Diseases and Actions. 
  Pentamidine [Pentam 300, Pentacarinat, NebuPent] is highly effective against 
  West African sleeping sickness, a disease is caused by T. brucei gambiense, and 
  against pneumocystis pneumonia (PCP), a disease caused by a fungus named 
  Pneumocystis jiroveci (formerly thought to be Pneumocystis carinii). The drug has 
  multiple actions, including disrupting the synthesis of DNA, RNA, phospholipids, 
  and proteins. However, we don’t know which of these actions is responsible for 
  antiprotozoal effects.
  
  • West African Sleeping Sickness 
  Pentamidine is given by IM injection to treat sleeping sickness.
  Pharmacokinetics
  For treatment of active PCP, Pentamidine is administered IM or IV. Equivalent blood 
  levels are achieved with both routes. The drug is extensively bound in tissues. 
  Penetration to the brain and cerebrospinal fluid is poor. Between 50% and 65% of 
  each dose is excreted rapidly in the urine. The remaining drug is excreted slowly, 
  over a month or more. 
  
  Adverse Effects Associated with Parenteral Pentamidine
  Pentamidine can produce serious side effects when given IM or IV. Caution is 
  needed.
  Sudden and severe hypotension occurs in about 1% of patients. The fall in blood 
  pressure may cause tachycardia, dizziness, and fainting. To minimize hypotensive 
  responses, patients should receive the drug while lying down. Blood pressure 
  should be monitored closely. 
  
  Hypoglycemia and hyperglycemia have occurred. Hypoglycemia has been 
  associated with necrosis of pancreatic islet cells and excessive insulin levels. The 
  cause of hyperglycemia is unknown. Because of possible fluctuations in glucose 
  levels, blood glucose should be monitored daily. 
  
  Intramuscular administration is painful. Necrosis at the injection site followed by 
  formation of a sterile abscess is common. 
  Some adverse effects can be life threatening when severe. These reactions and 
  their incidences are leukopenia (2.8%), thrombocytopenia (1.7%), acute renal 
  failure (0.5%), hypocalcemia (0.2%), and dysrhythmias (0.2%).
  
  Adverse Effects Associated with Aerosolized Pentamidine
   Inhaled pentamidine does not cause the severe effects associated with parenteral 
  pentamidine. The most common reactions are cough (38%) and bronchospasm 
  (15%). Both reactions are more pronounced in patients with asthma or a history 
  of smoking. Fortunately, these reactions can be controlled with an inhaled 
  

  bronchodilator. They rarely necessitate pentamidine withdrawal.

  Preparations, Dosage, and Administration of Pentamidine
  West African Sleeping Sickness
  Administration of pentamidine is by IM injection. The dosage for adults and children 
  is 4 mg/kg/day for 7 days. 
  
  Suramin
   Actions and Uses 
  Suramin sodium [Germanin] is a drug of choice for the early phase of East African 
  trypanosomiasis (sleeping sickness); for the late phase of the disease (ie, the stage 
  of CNS involvement), melarsoprol and eflornithine are preferred. Suramin is known 
  to inhibit many trypanosomal enzymes; however, its primary mechanism of action 
  has not been established. 
  
  Pharmacokinetics
  The drug is poorly absorbed from the GI tract, and hence must be given parenterally 
  (IV). Suramin binds tightly to plasma proteins and remains in the bloodstream for 
  months. Penetration into cells is low. Excretion is renal.
  
  Adverse Effects
  Side effects can be severe, and hence treatment should take place in a hospital. 
  Frequent reactions include vomiting, itching, rash, paresthesias, photophobia, and 
  hyperesthesia of the palms and soles. Suramin concentrates in the kidneys and 
  can cause local damage, resulting in the appearance of protein, blood cells, and 
  casts in the urine. If urinary casts are observed, treatment should cease. 
  
  Rarely, a shock-like syndrome develops after IV administration. To minimize the risk 
  of this reaction, a small test dose (100 to 200 mg) is administered; in the absence 
  of a severe reaction, full doses may follow.
   
  Preparations, Dosage, and Administration
  Suramin sodium [Germanin] is available from the CDC Drug Service. The drug 
  is supplied in 1-gm ampules. Administration is by slow IV infusion. Suramin is 
  unstable, and hence fresh solutions must be made daily. The adult dosage is 1 gm 
  IV on days 1, 3, 7, 14, and 21. The paediatric dosage is 20 mg/kg IV on days 1, 
  3, 7, 14, and 21. Possible revisions in these dosage recommendations should be 
  obtained from the CDC. 
  Melarsoprol 
  
  Therapeutic Use 
  

  Melarsoprol [Arsobal, Mel-B] is a drug of choice for both East African and West 
  African trypanosomiasis (sleeping sickness). The drug is employed during the late 
  stage of the disease (ie, after CNS involvement has developed). For earlier stages, 
  

  suramin and pentamidine are preferred.

  Mechanism of Action 

  Melarsoprol is an organic arsenical compound that reacts with sulfhydryl groups of 
  proteins. Antiparasitic effects result from inactivation of enzymes. This same action 
  appears to underlie the serious toxicity of the drug. 
  Melarsoprol is more toxic to parasites than to humans because it penetrates 
  

  parasitic membranes more easily than human cells. 

  Adverse Effects

  Melarsoprol is quite toxic, and hence adverse reactions are common. Frequent 
  effects include hypertension, albuminuria, peripheral neuropathy, myocardial 
  damage, and Herxheimer-type reactions. Reactive encephalopathy develops in 
  

  10% of patients, and carries a 15% to 40% risk of death. 

  Preparations, Dosage, and Administration

  Melarsoprol [Arsobal, Mel-B] is administered by slow IV injection. The drug is highly 
  irritating to tissues, and hence avoiding extravasation is important. Because of its 
  toxicity, melarsoprol should be administered in a hospital setting. Melarsoprol can 
  

  be obtained through the CDC Drug Service. The drug is not available commercially. 

  East African Trypanosomiasis 

  Treatment for adults and children consists of an initial course (2 to 3.6 mg/kg IV 
  daily for 3 days) followed in 7 days by a second course (3.6 mg/kg IV daily for 3 
  

  days), followed in 7 days by a third course (3.6 mg/kg IV daily for 3 days). 

  West African Trypanosomiasis 

  The dosage for adults and children is 2.2 mg/kg/day for 10 days. 

   Eflornithine 

  Actions and uses

  Eflornithine [Ornidyl] is indicated for patients with late-stage African trypanosomiasis 
  (sleeping sickness). The drug is highly effective against T. gambiense (West African 
  sleeping sickness), but only variably active against T. rhodesiense (East African 
  sleeping sickness). In both cases, benefits derive from irreversible inhibition of 
  ornithine decarboxylase, an enzyme needed for biosynthesis of polyamines, which 
  are required by all cells for division and differentiation. Parasites weakened by 
  eflornithine become highly vulnerable to lethal attack by host defenses. Because 
  cells of the host can readily synthesize more ornithine decarboxylase to replace 
  inhibited enzyme, cells of the host are spared. Eflornithine is also available in a 
  topical formulation, marketed as Vaniqa, for use by women to remove unwanted 
  

  facial hair.

  Pharmacokinetics 

  Eflornithine is given IV. Once in the blood, the drug is well distributed to body fluids 
  and tissues, including the CNS. Eflornithine has a half-life of 100 minutes and is 
  

  eliminated largely unchanged in the urine. 

  Adverse Effects

  The most common adverse effects are anemia (48%), diarrhea (39%), and leukopenia 
  (27%). Seizures may occur early in therapy but then subside, despite continued 
  treatment. Because IV administration of eflornithine requires large volumes of fluid, 
  fluid overload may develop over the course of treatment. Eflornithine can also cause 
  

  hair loss. In fact, the drug is now available for topical use to remove facial hair. 

  Preparations, Dosage, and Administration

  Eflornithine is supplied as a concentrated solution (200 mg/mL in 100-mL vials) and 
  must be diluted for IV infusion. To treat West African sleeping sickness in adults and 
  

  children, the dosage is 100 mg/kg IV 4 times a day for 14 days.

  Nifurtimox 

  Therapeutic Use 

  Nifurtimox [Lampit] is a drug of choice for American trypanosomiasis (Chagas’ 
  disease). The drug is most effective in the acute stage of the disease, curing about 
  80% of patients. Chronic disease is less responsive. 
  Pharmacokinetics
  Nifurtimox is well absorbed from the GI tract and undergoes rapid and extensive 
  

  metabolism. Metabolites are excreted in the urine.

  Adverse Effects

  Therapy is prolonged, and significant untoward effects occur often. Gastrointestinal 
  effects (anorexia, nausea, vomiting, abdominal pain) and peripheral neuropathy are 
  especially common. Weight loss resulting from GI disturbance may require treatment 
  to stop. Additional common reactions include rash and CNS effects (memory loss, 
  insomnia, vertigo, headache). In people with a deficiency of glucose-6-phosphate 
  

  dehydrogenase, nifurtimox can cause hemolysis. 

  Preparations, Dosage, and Administration

  Nifurtimox [Lampit] is supplied in 100-mg tablets. In the United States, the drug is 
  available only from the CDC Drug Service. The adult dosage is 8 to 10 mg/kg/day
  (in three or four doses) for 90 to 120 days. For young children (ages 1 through 10 
  years), the dosage is 15 to 20 mg/kg/day (in four doses) for 90 to 120 days. For 
  older children (ages 11 to 16 years), the dosage is 12.5 to 15 mg/kg/day (in four 
  

  doses) for 90 to 120 days.

  PNEUMOCYSTOSIS

  It is caused by Pneumocystis jirovecii (formerly Pneumocystis carinii), used to be 
  classified as a protozoal infection; however, it is now classified as fungal infection. It 
  is a common infection that complicates HIV and AIDS. It is discussed in this chapter, 
  as opposed to the antifungal, because antifungal drugs are not effective to treat it.
  
  For therapy of PCP, pentamidine is given parenterally and by inhalation. Parenteral 
  therapy is used to treat active PCP. In contrast, inhalational therapy is used to 
  prevent PCP in high-risk HIV positive patients, defined as patients with (1) a history 
  of one or more episodes of PCP or (2) peripheral CD4 lymphocyte counts below 
  200 cells/mm3. Bronchospasm or cough is more likely to occur when inhaled 
  treatments of pentamidine are given.
  
  Pentamidine isethionate for injection [Pentam 300, Pentacarinat] is supplied in                                                                                     300-mg, single-dose vials. 
  For treatment of active PCP, the dosage for adults and children is 3 to 4 mg/kg IV 
  daily for 2 to 3 weeks. Administration must be done slowly (over 60 minutes). 
  
  Pentamidine isethionate aerosol [NebuPent] is used for prophylaxis of PCP in 
  patients with AIDS. The dosage is 300 mg once every 4 weeks. Administration is 
  performed with a Respirgard II nebulizer by Marquest. Solutions should be freshly 
  prepared. 
  
  TOXOPLASMOSIS 
  Toxoplasmosis is caused by infection with Toxoplasma gondii, a protozoan of the 
  class Sporozoa. The treatment of choice is pyrimethamine plus sulfadiazine.
  
   Pyrimethamine
  Pyrimethamine [Daraprim], combined with sulfadiazine, is the treatment of choice 
  for toxoplasmosis. Pyrimethamine (combined with sulfadoxine) is also used to treat 
  malaria. For toxoplasmosis, the adult dosage is 25 to 100 mg PO daily for 3 to 4 
  weeks. The pediatric dosage is 2 mg/kg PO daily for 2 days, followed by 1 mg/kg 
  PO daily for 4 weeks.
  
  For adults and children, each dose of pyrimethamine should be accompanied by 
  10 mg of folinic acid (to reduce side effects). In addition, the regimen must include 
  sulfadiazine: for adults, 1 to 1.5 gm 4 times a day for 3 to 4 weeks; for children, 100 
  

  to 200 mg/kg/day for 3 to 4 weeks.

  GIARDIASIS 

  Giardiasis is an infection with Giardia lamblia, also known as G. duodenalis. 
  Transmission is through contaminated water or food, and trophozoites.
  Characterized by diarrhea, rotten egg-smelling stool, and pale and mucus-filled 
  stool. Some patients experience epigastric pain, weight loss, and malnutrition.
  Drugs of choice are metronidazole, Tinidazole, and nitazoxanide.
  
  Metronidazole: •adults, 250 mg 3 times a day for 5 days; children, 5 mg/kg 3 times 
  a day for 5 days. (more information on Metronidazole check on amebiasis drugs).
  Tinidazole: adults, 2 gm once; children, 50 mg/kg (maximum 2 gm) once 
   Nitazoxanide 
  Nitazoxanide [Alinia] is the treatment of choice. The drug is very effective in 
  immunocompetent patients, and may also work in some who are immunosuppressed.
  
  Therapeutic Uses
  Nitazoxanide [Alinia] is approved for diarrhea caused by G. lamblia in children and 
  adults. Although we have other effective drugs for giardiasis (eg, metronidazole, 
  tinidazole), nitazoxanide is our first effective drug for cryptosporidiosis. Unfortunately, 
  when used for C. parvum infections, nitazoxanide is only effective in children who 
  are immunocompetent; among children who are immunosuppressed, the drug is no 
  more effective than placebo. 
  Results in immunocompromised adults may be more favorable: When given to 
  adults with cryptosporidiosis and AIDS, a dosage of 1000 mg twice a day for 14 
  days cured 67% of patients, compared with 25% of those receiving placebo. 
  
  Actions 
  Nitazoxanide appears to work by disrupting protozoal energy metabolism. 
  Specifically, the drug blocks electron transfer mediated by pyruvate: ferredoxin 
  oxidoreductase, and thereby inhibits anaerobic energy metabolism. 
  In addition to its activity against C. parvum and G. lamblia, nitazoxanide is active 
  against other enteric protozoa (Isospora belli and Entamoeba histolytica) as well as 
  some helminths, including Ascaris lumbricoides, Ancylostoma duodenale, Trichuris 
  trichiura, Taenia saginata, and Fasciola hepatica. 
  
  Pharmacokinetics 
  Nitazoxanide is well absorbed following oral administration. In the blood, the 
  drug undergoes rapid conversion to its active metabolite, tizoxanide, which 
  then undergoes nearly complete (more than 99.9%) binding to plasma proteins. 
  Tizoxanide levels peak between 1 and 4 hours after nitazoxanide administration, 
  

  and then decline owing to excretion in the urine, bile, and feces. 

  Adverse Effects

  Nitazoxanide is generally well tolerated. In clinical trials, the most common adverse 
  effects were abdominal pain, diarrhea, vomiting, and headache. However, these 
  

  effects were just as common in subjects taking placebo. 

  In some patients, the drug caused yellow discoloration of the sclerae (whites of the 
  eyes), which resolved following drug withdrawal. Nitazoxanide is in FDA Pregnancy 
  

  Risk Category B: Animal studies show no evidence of impaired fertility or fetal harm.

  Drug Interactions

  Because nitazoxanide is highly protein bound, it might interact with other agents 
  that are highly bound. Specifically, nitazoxanide might displace other drugs from 
  their binding sites, thereby increasing their effects and, conversely, other highly 
  bound agents could displace nitazoxanide, thereby increasing its effects. 
  

  Preparations, Dosage, and Administration

  Oral Suspension

  Nitazoxanide oral suspension [Alinia] is indicated for diarrhea caused by G. lamblia 
  or C. parvum in children ages 1 through 11 years, and for diarrhea caused by G. 
  lamblia (but not C. parvum) in adults. Nitazoxanide is supplied as a pink powder 
  that, when mixed with 48 mL of water, forms a strawberry-flavored, 20-mg/mL 
  suspension. Administration is done with food. The suspension may be stored at 
  room temperature for 7 days, after which it should be discarded. Dosage depends 
  on age as follows: 
  • For children ages 12 to 48 months, give 100 mg (5 mL) every 12 hours for 3 
  days. 
  • For children ages 4 to 11 years, give 200 mg (10 mL) every 12 hours for 3 
  days. 
  • For patients 12 years and older, give 500 mg (25 mL) every 12 hours for 3 
  days. 
  Nitazoxanide tablets [Alinia] are indicated only for diarrhea caused by G. lamblia, 
  and only for patients at least 12 years old. The dosage is 1 tablet (500 mg) every 12 
  

  hours for 3 days. Administration is done with food. 

  LEISHMANIASIS 

  The term leishmaniasis refers to infestation by certain protozoal species belonging 
  to the genus Leishmania.
  It is a disease caused by a protozoan that is passed from sand flies to humans. It 
  is characterized by serious lesions in the skin, viscera, and mucous membranes of 
  

  host.

  For all forms of leishmaniasis, sodium stibogluconate (given IM or IV) is the 
  traditional treatment of choice. Amphotericin B (given IV) is an effective alternative. 
  Miltefosine, an oral agent, is highly curative against visceral leishmaniasis, and 
  probably against cutaneous disease. The drug appears reasonably safe and, owing 
  to oral administration, is more convenient than stibogluconate or amphotericin B, 
  

  both of which are given parenterally.

   Sodium Stibogluconate

   Sodium stibogluconate [Pentostam] is a drug of choice for leishmaniasis. The 
  mechanism of action is unknown. The drug is poorly absorbed from the GI tract, 
  and hence must be given parenterally (IM or IV). Sodium stibogluconate undergoes 
  little metabolism and is excreted rapidly in the urine. Although severe side effects 
  can occur, the drug is generally well tolerated. The most frequent adverse reactions 
  

  are muscle pain, joint stiffness, and bradycardia. 

  Changes in the electrocardiogram are common and occasionally precede serious 
  dysrhythmias. Liver and renal dysfunction, shock, and sudden death occur rarely. 
  Sodium stibogluconate is supplied in aqueous solution for IM and IV injection. For 
  leishmaniasis, the usual adult and paediatric dosage is 20 mg/kg/day (IM or IV) for 
  

  20 to 28 days. 

   Miltefosine 

  Miltefosine [Impavido] is the first oral agent for leishmaniasis. The drug was originally 
  developed to treat cancer. Antiprotozoal activity wasn’t revealed until miltefosine was 
  tested in cancer patients who also had leishmaniasis. The mechanism underlying 
  

  benefits in leishmaniasis is unclear. 

  Studies conducted in India indicate that oral miltefosine is both safe and effective 
  for treating visceral leishmaniasis. Preliminary studies indicate the drug is also 
  

  highly effective against cutaneous disease. 

  Because miltefosine is taken by mouth, rather than by injection, the drug is much 
  more convenient than the alternatives, namely, sodium stibogluconate (administered 
  

  IM or IV) and amphotericin B (administered IV).

  Miltefosine is better tolerated than either sodium stibogluconate or amphotericin B. 
  

  The most common reactions are vomiting (38%) and diarrhea (20%). 

  Mild hepatotoxicity is seen in some patients, but it resolves during the second week 
  of treatment. Reversible renal damage may also occur. Miltefosine causes fetal 
  abnormalities in laboratory animals, and hence must not be used during pregnancy. 
  Effective contraception is required while taking the drug and for 2 months after.
  

   The recommended dosage for adults and children is 2.5 mg/kg/day for 28 days.

  CRYPTOSPORIDIOSIS 

  Cryptosporidiosis is caused by Cryptosporidium parvum, a protozoan of the 
  subclass Coccidia. Nitazoxanide [Alinia] is the treatment of choice. The drug is 
  very effective in immunocompetent patients, and may also work in some who are 
  

  immunosuppressed.

   Nitazoxanide [Alinia] is approved for diarrhea caused by C. parvum in children only. 
  Unfortunately, when used for C. parvum infections, nitazoxanide is only effective in 
  children who are immunocompetent; among children who are immunosuppressed, 
  

  the drug is no more effective than placebo. 

  Results in immunocompromised adults may be more favorable: When given to 
  adults with cryptosporidiosis and AIDS, a dosage of 1000 mg twice a day for 14 
  days cured 67% of patients, compared with 25% of those receiving placebo. More 
  

  information on Nitazoxanide please read on G. lamblia.

  Self-assessment 3.9

  1) Which drug is used mainly for the management of Pneumocystis jirovecii 
  (formerly Pneumocystis carinii) pneumonia? 
  a) Metronidazole (Flagyl)
  b) Pentamidine (NebuPent) 
  c) Iodoquinol (Yodoxin)
  d) Chloroquine 
  2) An adult woman complains of itching and burning around her vagina and 
  foul-smelling vaginal discharge. A nurse suspects trichomoniasis. Which 
  of the following drugs would be appropriate for this patient? 
  a) Iodoquinol 
  b) Suramin 
  c) Sulfadoxine 
  d) Metronidazole 
  3) In which of the following conditions may suramin be indicated?
  a) Trypanosomiasis
  b) Trichomoniasis
  c) Giardiasis
  d) Amebiasis
  4) All of the following are the uses of metronidazole, EXCEPT:
  a) Amebiasis
  b) Giardiasis
  c) Trichomonas vaginitis
  

  d) Malaria

  3.10. Health Education about Malaria and Amebiasis Treatment

   Learning Activity 3.10

  1) Why is it important to take a person with symptoms of malaria to the 
  nearest health centre or hospital immediately?
  2) Why is it important to finish all medications even if patient starts feeling 
  better? 
  3) The nurse teaches a patient who is prescribed metronidazole (Flagyl) that 
  it is very important to report which possible adverse effect of the drug to 
  the prescriber? 
  a) Darkening of the urine 
  b) Metallic taste 
  c) Mouth ulcers 
  d) Both A and B
  4) The following precaution should be advised to the patient who is taking 
  metronidazole
  a) To avoid driving
  b) To get leucocyte count checked every second day
  c) To avoid alcoholic beverages
  

  d) To avoid fatty/ fried food

  CONTENT SUMMARY

  A health education interventional is important to take appropriate prevention 
  measures to promote success of treatment and prevention of protozoal diseases. 
  Health education messages can provide information and address a variety 
  of misconceptions regarding the use of antiprotozoal drugs to prevent drug 
  administration’s errors.
  
  Patient education is also a basic right of the patients and healthcare members. 
  People should receive instruction in clear language or information on treatment 
  and prevention measures from health care providers by using posters, video clips, 
  radio, and other forms of mass media. Other methods include peer education, 
  

  mobilization at all levels of public sectors, and school-based programs. 

  Health education about malaria treatment is guided by many main factors 
  include: the infecting species/parasites, the clinical status of the patient, and the 
  drug susceptibility of the infecting parasites. People should receive instruction or 
  information on treatment and prevention when traveling to known malaria-endemic 
  regions of the world.
  
  When health care provider is preparing health education about malaria treatment 
  he/she must emphasize on why it is important to take a person with symptoms of 
  malaria to the nearest health care facility immediately.
  
  – Because to be tested for malaria or other illness. The only way to know for 
  sure if you have malaria is to be tested. If you test positively, then you can 
  receive the proper treatment for malaria.
  – because to get proper diagnosis and appropriate treatment help health 
  care providers to avoid complications that might lead to serious condition 
  or even death of patient.
  
  Emphasize also on why it is important to finish all medications even if patient start 
  feeling better? Patients should receive instruction to take medication as prescribed 
  and adhere to the full prescription regimen in order to promote success of treatment 
  (kills the parasite in the sick person & saving the life of an infected person), to 
  prevent treatment failure, stops transmission to healthy people, ensure complete 
  cure, on-going protection and will prevent the drug from becoming less effective to 
  malaria infection (development of drug resistance).
  
  Advice the patient to read carefully and follow carefully drugs manufacturer’s 
  instructions because every drug differs to another.
  Explain to the patient and family members what they should do if they missed a 
  dose.
  In the instance that you miss a dose, take it as soon as possible that day. For daily 
  regimes, if you miss the dose completely for that day, skip the missed dose entirely 
  and continue with your next dose. Never take a double dose to make up for a 
  missed dose.
  It’s important to take your antimalarial medication consistently and for the full course 
  of your prescription. If your medication regime requires you to take it daily, take it 
  at the same time each day (follow dosing orders and instructions as prescribed, 
  with specific attention to the loading doses, subsequent doses, and prophylactic 
  dosing). For weekly regimes, take it on the same day each week.
  
  It’s always advisable to purchase all necessary medication prior to your departure. 
  However, in the event that you need antimalarial medication at your destination, 
  

  you should only purchase medication from a reputable pharmacy. 

  With antimalarials, encourage adequate dietary and fluid intake while the patient is 
  fighting the infection and taking the medications. Oral doses need to be taken with 
  water or other fluid. Increase fluids unless contraindicated, because antimalarials 
  

  concentrate in the liver first. 

  Never take more than the prescribed dose. Taking too much quinine can cause 
  serious problems. Also, quinine is dangerous if it is taken by a child, so keep the 
  tablets away from children. If you suspect that someone has taken an overdose of 
  

  quinine or has swallowed some by accident, you must contact a doctor straightaway. 

  Alternatively, go to the accident and emergency department of a local hospital. Do 
  not delay. Take the container with you, even if it is empty. This helps the doctor to 
  know what patient has been taken. If you are being treated for diabetes, quinine 
  can lower the level of sugar in your blood. Your doctor will be able to advise you 
  

  about this.

  Keep all medicines out of the reach and sight of children. Store in a cool and dry 
  

  place away from direct heat and light.

  Photosensitivity may occur with quinine; provide adequate teaching about the 
  use of sunscreen and sun safety. Sun protection must include coverage against 
  

  ultraviolet rays.

  Educations session on malaria prevention must emphasize on both drug and 
  nondrug (controlling Anopheles Mosquitoes) prevention measures by using the 
  using the ABCD approach (Awareness of risk, Bite prevention, Check whether you 
  

  need to take malaria prevention tablets and Diagnosis). 

  For awareness of risk: find out whether the patient is at risk of getting malaria. It’s 
  important to visit a health care provider before the travel for advice, check whether 
  it is necessary or need to take preventative malaria treatment depending on the 
  country you are visiting. Some country it is not necessary to take preventative 
  malaria treatment before travelling. Even if you grew up in a country where malaria 
  is common, you still need to take precautions to protect yourself from infection if 
  

  you’re travelling to a risk area.

  NB: In area where malaria vaccine is not yet introduced, health care provider has 
  to educate people that nobody has complete immunity to malaria, and any level of 
  natural protection you may have had is quickly lost when you move out of a risk 
  

  area.

  For bite prevention: An Integrated Mosquito Management (IMM) program helps 
  to prevent mosquito bites and transmission of serious vector diseases. To target 
  all phases of the mosquito’s life cycle, four approaches are useful in controlling 
  

  Anopheles Mosquitoes.

  1) Public Education: we rely on a well-educated public in order to have a 
  successful mosquito control program. Educating the public empowers 
  people to take control of the mosquitoes.
  2) Surveillance: allows us to detect mosquito species in a given area as well 
  as any changes in populations. With this surveillance, we are able to have 
  more effectively time larvicides applications and more accurately target 
  adulticide activities.
  3) Larval Mosquito Control: sources of standing water and any newly 
  discovered sites for the presence of mosquito larvae. Eliminating mosquitoes 
  prior to their becoming adults is an important element of controlling malaria 
  and other mosquito-borne diseases because it stops mosquitoes before 
  they acquire the virus and have the opportunity to transmit it to people.
  4) Adult Mosquito Control: when necessary, adulticide applications are 
  conducted to prevent them from developing resistance; thereby, minimizing 
  the number of applications needed to control the population.
  
  For prevent mosquito bites and transmission of serious vector diseases:
  avoid mosquito bites by using insect repellent, covering your arms and legs, and 
  using a mosquito net. It’s not possible to avoid mosquito bites completely, but the 
  less you’re bitten, the less likely you are to get malaria.
  To avoid being bitten:
  • Stay somewhere that has effective air conditioning and screening on doors 
     and windows. If this isn’t possible, make sure doors and windows close 
     properly.
  • If you’re not sleeping in an air-conditioned room, sleep under an intact 
     mosquito net that’s been treated with insecticide.
  • Wear light, loose-fitting trousers rather than shorts, and wear shirts with long 
     sleeves particularly during early evening and at night, when mosquitoes 
     prefer to feed.
  • Use insect repellent on your skin and in sleeping environments. Remember 
  to reapply it frequently. The most effective repellents contain diethyltoluamide 
  (DEET) and are available in sprays, roll-ons, sticks and creams.
   The chemical DEET is not recommended for babies who are less than 2 months 
  old.
  DEET is safe for older children, adults and pregnant women if you follow the 
  manufacturer’s instructions: use on exposed skin, don’t spray directly on to your 
  face, spray into your hands and pat on to your face, avoid contact with lips and 
  eyes, wash your hands after applying, don’t apply to broken or irritated skin and 
  

  make sure you apply DEET after applying sunscreen, not before.

  For check whether you need to take malaria prevention tablets: if you do, make 
  sure you take the right antimalarial tablets at the right dose, and finish the course to 
  

  reduce your chances of getting the disease until vaccine become available for all.

  However, antimalarials only reduce your risk of infection by about 90%, so taking 
  steps to avoid bites is also important. Depending on the type you’re taking, continue 
  to take your tablets for up to 4 weeks after returning from your trip to cover the 
  

  incubation period of the disease.

  Check with your health care provider to make sure you’re prescribed a medication 
  you can tolerate. You may be more at risk from side effects if you: have HIV or AIDS, 
  have epilepsy or any type of seizure condition, are depressed or have another 
  mental health condition, have heart, liver or kidney problems, take medicine, such 
  as warfarin, to prevent blood clots and use combined hormonal contraception, such 
  

  as the contraceptive pill or contraceptive patches.

  If you’ve taken antimalarial medication in the past, don’t assume it’s suitable for 
  future trips. The antimalarial you need to take depends on which strain of malaria 
  is carried by the mosquitoes and whether they’re resistant to certain types of 
  

  antimalarial medication.

  NB: In some cases, you may be prescribed emergency standby treatment for 
  malaria before you travel. This is usually if there’s a risk of you becoming infected 
  

  with malaria while travelling in a remote area with little or no access to medical care.

  Pregnant women: If you’re pregnant, it’s advisable to avoid travelling to areas 
  where there’s a risk of malaria because a pregnant women have an increased risk 
  of developing severe malaria, and both the baby and mother could experience 
  serious complications. It’s very important to take the right prophylactic measures 
  of malaria prevention (both drug and nondrug) if you’re pregnant and unable to 
  postpone or cancel your trip to an area where there’s a malaria risk. Some of the 
  antimalarials used to prevent and treat malaria are unsuitable for pregnant women 
  

  because they can cause side effects for both mother and baby.

  Malaria is also particularly life-threatening and dangerous to pregnant women 
  and their babies. Malaria is harmful to pregnant women and their babies as the 
  malaria parasite destroys the blood cells and makes women anaemic. Anaemia in 
  the mother and malaria parasites in the placenta can lead to women giving birth to 
  babies early (pre mature) or born very small or die while still in the womb. Babies 
  who are born too early or are very small at birth as less likely to survive and be 
  

  healthy.

  For diagnosis: seek immediate medical advice if you have malaria symptoms, 
  including up to a year after you return from travelling. You must seek medical help 
  straight away if you become ill while travelling in an area where malaria is found, or 
  

  after returning from travelling, even if you’ve been taking antimalarial tablets.

  Malaria can get worse very quickly, so it’s important that it’s diagnosed and treated 
  

  as soon as possible.

  If you develop symptoms of malaria while still taking antimalarial tablets, either 
  while you’re travelling or in the days and weeks after you return, remember to 
  tell the health care provider which type you have been taking. The same type of 
  

  antimalarial shouldn’t be used to treat you as well.

  Health education about amebiasis treatment

  When health care provider is preparing health education about malaria treatment 
  he/she must emphasize on appropriate information on treatment and preventive 
  

  measures.

  When an Antiparasitic is prescribed on an outpatient basis; give the patient or 
  family member complete instructions about taking the drug, as well as household 
  

  precautions that should be followed until the parasite is eliminated from the body. 

  When developing a patient education plan, be sure to include the following:
  • Follow the dosage schedule exactly as prescribed to eradicate the parasite. 
  It is important to explain to the patient how amebiasis treated, once your 
  health care provider has told you that you have amebiasis, you have to take 
  medication. Treatment must be prescribed by a health care provider and 
  specific treatment will vary from person to person.
  • Advice the patient to read carefully and follow carefully drugs manufacturer’s 
  instructions because every drug differs to another.
  • Follow-up stool/urine specimens will be necessary after taking Antiparasitic 
  drugs because this is the only way to determine the success of drug therapy. 
  • When an infection is diagnosed, multiple members of the family may be 
  

  infected, and all household members may need to be treated.

  It is important to explain to the patient how is amebiasis spread. Amebiasis is 
  transmitted from person to person by the fecal-oral route. The spread of amebiasis 
  can occur if an infected person does not wash their hands properly after going to 
  the bathroom. When people touch objects or eat contaminated food they can get 
  the parasite on their hands and into their mouths. People are infectious as long 
  as the parasite is shed in the stool. The spread of amebiasis can be prevented by 
  public education about the importance of hand hygiene (perform wash hand with 
  

  soap and water) after defecation and before preparing or eating food.

  It is important to ask patient inform if is pregnancy or breast feeding because some 
  antiprotozoal drugs should not be taken by women who are pregnant or breast 
  

  feeding.

  • It is important to wash all bedding and bed clothes once treatment has started. 
  

  • Daily bathing (showering is best) is recommended. 

  Disinfect toilet facilities daily, and disinfect the bathtub or shower stall immediately 
  after bathing. Use the disinfectant recommended by the primary health care provider 
  

  or use chlorine bleach. 

  Scrub the surfaces thoroughly and allow the disinfectant to remain in contact with 
  

  the surfaces for several minutes. 

  During treatment for a ringworm infection, keep towels and facecloths for bathing 
  separate from those of other family members to avoid the spread of the infection. It 
  

  is important to keep the affected area clean and dry. 

  • Wash the hands thoroughly after urinating or defecating and before preparing 
  and eating food. Clean under the fingernails daily and avoid putting fingers in 
  the mouth or biting the nails. 
  • Food handlers should not resume work until a full course of treatment is 
  completed and stools do not contain the parasite.
  • Child care workers should be especially careful of diaper disposal and proper 
  hand washing to prevent the spread of infections. 
  • Inform the patient taking metronidazole/Tinidazole for a sexually transmitted 
  disease like trichomoniasis to avoid sexual intercourse (as they may become 
  reinfected) until a full course of treatment is completed and samples (urine 
  or/and stool) do not contain the parasite , and advise the client that sexual 
  

  partners must be treated also. 

  If you are having giardiasis, you should wash your hands regularly and avoid 
  sharing utensils or towels to prevent the spread of infection among your household 
  

  members.

  Before taking metronidazole, it is important that your health care provider knows: 
  If you are pregnant or breastfeeding.
  • If you feel you will be unable to stop drinking alcohol for the duration of your 
  treatment.
  • If you have any problems of liver function.
  • If you are taking any other medicines
  

  • If you have ever had an allergic reaction to a medicine.

  Advise the patient to take the tablets or liquid medicine exactly as prescribed. 
  Space your doses evenly throughout the day, and keep taking the medicine until 
  

  the course is finished, unless he/she is told to stop by his/her doctor. 

  • Take each of your doses with a snack or just after eating a meal. Swallow the 
  tablets whole (that is, without chewing or crushing them) with a full glass of 
  water.
  • If patient forget to take a dose, advise him/her to take it as soon as he/she 
  remember and try to space the remaining doses evenly throughout the rest 
  

  of the day. Do not take two doses together to make up for a forgotten dose.

  • Advise the patients to avoid drink alcohol while they are on metronidazole and 
  for 48 hours after finishing the course of treatment. This is because drinking 
  alcohol with metronidazole is likely to make you feel very sick (nauseated) and 
  cause other unpleasant effects, such as the sensation of having a ‘thumping 
  heart’ (palpitations), hot flushes and headache.
  • Tell the patients that while they are taking metronidazole their urine may look 
  a darker colour than normal. On its own this is nothing to worry about. 
  • When the patient is taking metronidazole for amebiasis instruct the patient 
  how to collect stool samples correctly and safely and how to dispose of 
  

  samples properly.

  Self-assessment 3.10

  1) What should a patient do when he/she misses a dose of antiprotozoals?
  2) What should patient do if she/he runs out or loses an antimalarial 
  medication?
  3) What should patient do if he/she thinks that he/she has malaria?
  4) A patient tells a nurse that he/she has been infected with malaria in the 
  past and asks a nurse whether he/she still needs to take antimalarial 
  

  medication?

  3.11. End unit assessment

           End of unit assessment
  

  1) Which of the following are the factors which determine antimalarial agent 
  efficacy?
  a) Species of the plasmodium
  b) Life-cycle stage-dependencies
  c) Both A and B are correct
  d) Neither of the above 
  2) Which of the following drugs can cause cinchonism?
  a) Chloroquine
  b) Quinine 
  c) Artenisinin 
  

  d) Primaquine

  3) A patient is infested by plasmodium ovale and is suffering from repeated 
  relapses. Which ONE of the following drugs can be used to prevent 
  relapses?
  a) Chloroquine
  b) Quinine
  c) Artenisinin 
  d) Primaquine
  4) Neuropsychiatric reactions are most likely to occur in persons treated 
  with:
  e) Halofantrine
  f) Quinine
  g) Mefloquine
  h) Artemisinin derivatives
  5) All of the following are uses of metronidazole EXCEPT
  a) Amebiasis
  b) Giardiasis
  c) Trichomoniasis
  d) Malaria
  6) For which of the following diseases is pentamidine the first line drug?
  a) Toxoplasmosis
  b) Pneumocystis carinii pneumonia
  c) Actinomycosis
  d) Leishmaniasis
  7) Which of the following diseases is treated with metronidazole?
  a) Roundworm infestation
  b) Hookworm infestation
  c) Kala-azar
  

  d) Giardiasis

  8) Tick the drug used for toxoplasmosis treatment:
  a) Chloroquine
  b) Tetracycline
  c) Suramin
  d) Pyrimethamine
  9) Tick the drug used for amebiasis treatment:
  a) Nitrofurantoin
  b) Tinidazole
  c) Pyrazinamide
  d) Mefloquine
  10) Choose correct answer Treatment of malaria is guided by;
  a) The infecting plasmodium species
  b) The clinical status of the patient
  c) All the responses are correct
  

  d) The stage of the organism’s life cycle 

• UNIT 4 : ANTIFUNGAL DRUGS

               Key Unit Competence:

  Utilize appropriately antifungal medications to manage different                                                                                                                        health condition at the primary healthcare settings
  
  Introductory activity 4.0
   The images below show different patients with fungal infections                                                                                                                  and they are being treated with different medications. 
                  
      
  1) Have you ever seen some of the medical conditions above?
  2) Which types of medications have you seen being used for these medical 
  conditions above?
  

  3) Have you ever seen these medications in the images above?

  4.1 Definition and classification of antifungal drugs

         Learning Activity 4.1
  

        Read the scenario below:

  A 35-year-old male patient is on drugs that she applies as a cream between her 
  toes. The only explanations she got from the prescribers is to apply the cream 
  as prescribed and dry the area before application of the drug. She has limited 
  information regarding the intent of the drug, and what she only knows is that the 
  drug was prescribed for an infectious disease. She then doubts whether she is 
  taking an antibiotic or antifungal or any other drug. She wants you to provide 
  detailed information. Answer the following questions to provide explanations to 
  him: 
  a) Explain what an antifungal drug is.
  b) What are different classes of antifungal drugs according to where they 
  

  exert their effects?

  CONTENT SUMMARY

  Fungal infections in humans range from conditions such as the annoying “athlete’s 
  foot” to potentially fatal systemic infections. An infection caused by a fungus is 
  called a mycosis. Fungi differ from bacteria in that the fungus has a rigid cell wall 
  that is made up of chitin and various polysaccharides and a cell membrane that 
  contains ergosterol. The composition of the protective layers of the fungal cell 
  makes the organism resistant to antibiotics. Conversely, because of their cellular 
  makeup, bacteria are resistant to antifungal drugs. 
  
  The incidence of fungal infections has increased with the rising number of 
  immunocompromised individuals-patients with acquired immune deficiency 
  syndrome (AIDS) and AIDS-related complex, those taking immunosuppressant 
  drugs, those who have undergone transplantation surgery or cancer treatment, and 
  members of the increasingly large elderly population, whose body is no longer able 
  to protect itself from the many fungi that are found throughout the environment. 
  For example, Candida, a fungus that is normally found on mucous membranes, 
  can cause yeast infections or “thrush” in the gastrointestinal (GI) tract and yeast 
  infections or “vaginitis” in the vagina.
  
  Continued advancement of medical science offers life-saving treatment 
  options for a variety of hematologic, oncologic, and rheumatologic conditions. 
  Immunosuppression, a common therapeutic side-effect, predisposes patients to 
  invasive fungal infections, which are escalating in prevalence. The development of 
  

  effective, well tolerated antifungals has lagged behind the advances of antibacterial 

  therapy. Amphotericin B deoxycholate, an antifungal developed in the 1950s, 
  marked a major therapeutic advance. Although very effective for the treatment of 
  numerous invasive fungal infections, it is not without cost, and its side-effects often 
  limit its use.
  
  Antifungal drug can simply be defined as a drug used to treat fungal infections. 
  An antifungal agent is a drug that selectively eliminates fungal pathogens from a 
  host with minimal toxicity to the host.
  
  Antifungal agents are classified according to either their mechanism of action/
  structure or where they exert their effect.
  According to where they exert their effects, the antifungal drugs may be classified 
  as systemic antifungals or topical antifungals
  Most antifungal drugs interfere with biosynthesis or integrity of ergosterol, the major 
  sterol in the fungal cell membrane. Others cause disruption of the fungal cell wall. 
  
  According to their mechanism of action or structure, antifungals are categorized 
  in 4 main classes. These are azole antifungal drugs, polyene antifungal drugs, 
  allylamine and morpholine antifungal drugs, and echinocandin antifungal drugs.
  
  The azoles are a large group of antifungals used to treat systemic and topical fungal 
  infections. The azoles include fluconazole, itraconazole, ketoconazole (Nizoral), 
  posaconazole, and voriconazole. Although azoles are considered less toxic than 
  some other antifungals, such as amphotericin B, they may also be less effective in 
  very severe and progressive infections.
  
  The polyene antifungal drugs include amphotericin, nystatin, and pimaricin. They 
  interact with sterols in the cell membrane (ergosterol in fungi, cholesterol in humans) 
  to form channels through which small molecules leak from the inside of the fungal 
  cell to the outside.
  
  Allylamines (naftifine, terbinafine) inhibit ergosterol biosynthesis at the level of 
  squalene epoxidase. The morpholine drug, amorolfine, inhibits the same pathway 
  at a later step.
  The echinocandin antifungals are another group of antifungals. Drugs in this class 
  

  include anidulafungin, caspofungin, and micafungin.

  Self-assessment 4.1

  3) You have a colleague of class in the associate nursing program who tells 
  you that she has an onychomycosis (fungal infection of the nails). She 
  has been prescribed an antifungal drug, and the prescribing person told 
  her that there are 4 main classes of antifungal drugs according to their 
  structure/mechanism of action, with specifications that the drug prescribed 
  belongs to one of the classes. However, she does not remember these 
  classes of antifungal drugs, and needs your assistance to remind her. 
  Which classes of antifungal drugs will you tell your colleague?
  
  4) A patient with a fungal infection asks the nurse why she cannot take 
  antibiotics. The nurse explains that the reason for this is that a fungus is 
  resistant to antibiotics because: 
  
  a) A fungal cell wall has fewer but more selective protective layers.
  b) The composition of the fungal cell wall is highly rigid and protective. 
  c) A fungus does not reproduce by the usual methods of cell division. 
  

  d) Antibiotics are developed to affect only bacterial cell walls.

  4.2 Antifungal drugs available at the primary health care settings
  

  4.2.1 Systemic antifungals: azole and echinocandin antifungals
  

  5) Read carefully the scenario below:
  A 50-year-old female patient is admitted at the healthcare facility with features 
  of a fungal infection. The thorough assessment reveals that the patient has an 
  infection that can be treated by antifungals for systemic use. You decide to avoid 
  using an antifungal for topical use because you think it cannot work appropriately 
  for this specific patient. Read the pharmacology book on systemic antifungals, 
  with focus on focus on azoles and echinocandin antifungals and come up with at 
  least 5 examples of antifungals for systemic use, belonging to these categories.
  
  Guidance: Read the book of pharmacology brought by the teacher in class, on 
  

  topic of antifungal drugs (focus on azoles and echinocandin antifungals)

  CONTENT SUMMARY

  The drugs used to treat systemic fungal infections can be toxic to the host and are 
  not to be used indiscriminately. It is important to get a culture of the fungus causing 
  the infection to ensure that the right drug is being used so that the patient is not put 
  

  at additional risk from the toxic adverse effects associated with these drugs.

  I. AZOLE ANTIFUNGALS 

  The azoles are a large group of antifungals used to treat systemic and topical 
  fungal infections. The azoles include fluconazole, itraconazole, ketoconazole, 
  posaconazole, and voriconazole (Vfend). Although azoles are considered less 
  toxic than some other antifungals, such as amphotericin B, they may also be less 
  

  effective in very severe and progressive infections. 

  1) Therapeutic Actions and Indications 

  These drugs bind to sterols and can cause cell death (a fungicidal effect) or 
  interfere with cell replication (a fungistatic effect), depending on the type of fungus 
  being affected and the concentration of the drug. Ketoconazole, fluconazole, and 
  itraconazole work by blocking the activity of a sterol in the fungal wall. In addition, 
  

  they may block the activity of human steroids, including testosterone and cortisol. 

  Posaconazole is one of the newest antifungals. This drug and voriconazole inhibit 
  the synthesis of ergosterol, which leads to the inability of the fungus to form a cell 
  

  wall, which results in cell death. 

  Fluconazole is indicated in the treatment of candidiasis, cryptococcal meningitis, 
  other systemic fungal infections; prophylaxis for reducing the incidence of 
  

  candidiasis in bone marrow transplant recipients.

  Its usual dosage is: 
  • Adults: 200–400 mg PO on day 1, followed by 100 mg/d PO; IV route can be 
  used, but do not exceed 200 mg/h, 
  

  • Paediatric population: 3–6 mg/kg PO; do not exceed 12 mg/kg.

  Ketoconazole (Nizoral) is indicated in the treatment of aspergillosis, leishmaniasis, 
  cryptococcosis, blastomycosis, moniliasis, coccidioidomycosis, histoplasmosis, and 
  mucormycosis; topical treatment of mycoses (cream), and to reduce the scaling of 
  

  dandruff (shampoo).

  Its usual dosage is: 
  • Adult: 200 mg/d PO, up to 400 mg/d PO in severe cases 
  • Paediatric population (≥2 y): 3.3–6.6 mg/kg/d PO 
  • Paediatric (<2 y): Safety has not been established.
  

   • Topical: as a shampoo and topical agents

  Other indications of the azoles for systemic use include treatment of blastomycosis, 
  histoplasmosis, and aspergillosis; prophylaxis of invasive Aspergillus and Candida 
  infections in adults and children >13 y who are immunosuppressed secondary 
  to antineoplastic, chemotherapy, graft-vs.-host disease following transplants, or 
  

  hematological malignancies.

  2) Pharmacokinetics 

  Ketoconazole, itraconazole and posaconazole are administered orally. Ketoconazole 
  is also available as a shampoo and a cream. Fluconazole and voriconazole are 
  available in oral and intravenous (IV) preparations, making it possible to start the 
  drug intravenously for a serious infection and then switch to an oral form when 
  the patient’s condition improves and he or she is able to take oral medications. 
  Ketoconazole is absorbed rapidly from the GI tract, with peak levels occurring 
  within 1 to 3 hours. It is extensively metabolized in the liver and excreted through 
  the feces. 
  
  Fluconazole reaches peak levels within 1 to 2 hours after administration. Most of 
  the drug is excreted unchanged in the urine, so extreme caution should be used in 
  the presence of renal dysfunction. Itraconazole is slowly absorbed from the GI tract 
  and is metabolized in the liver by the CYP450 system. It is excreted in the urine and 
  feces. Posaconazole is given orally, has a rapid onset of action, and peaks within 
  3 to 5 hours. It is metabolized in the liver and excreted in the feces. Voriconazole 
  reaches peak levels in 1 to 2 hours if given orally, and at the onset of the infusion 
  if given IV. It is metabolized in the liver with a half-life of 24 hours and is excreted 
  in the urine.
  3) Contraindications and Cautions
  Ketoconazole has been associated with severe hepatic toxicity and should be 
  avoided in patients with hepatic dysfunction to prevent serious hepatic toxicity. 
  In addition, ketoconazole is not the drug of choice for patients with endocrine or 
  fertility problems because of its effects on these processes. Although fluconazole 
  should be used with caution in the presence of liver or renal impairment, because it 
  could cause liver or renal toxicity, fluconazole is not associated with the endocrine 
  problems seen with ketoconazole. 
  Because itraconazole has been associated with hepatic failure, should not be used 
  in patients with hepatic failure, and should be used with caution in those with hepatic 
  impairment. It is not known whether posaconazole crosses the placenta or enters 
  breast milk, so it should not be used during pregnancy or lactation unless the benefi 
  

  ts clearly outweigh the potential risks. Caution should be used if posaconazole is 

  used in the presence of liver impairment because it can cause liver toxicity. Carefully 
  monitor patients for bone marrow suppression and GI and liver toxicity if using this 
  

  drug.

  Voriconazole should not be used with any other drugs that prolong the QTc interval 
  because that could be worsened and can cause ergotism if taken with ergot alkaloid; 
  

  so it should not be combined with ergots.

  4) Adverse Effects 

  Many of the azoles are associated with liver toxicity and can cause severe effects 
  on a fetus or a nursing baby.
  5) Clinically Important Drug–Drug Interactions 
  Ketoconazole and fluconazole strongly inhibit the CYP450 enzyme system in the 
  liver and are associated with many drug–drug interactions, such as increased 
  serum levels of the following agents: cyclosporine, digoxin, oral hypoglycemics, 
  warfarin, oral anticoagulants, and phenytoin. If these combinations cannot be 
  avoided, closely monitor patients and anticipate the need for dose adjustments. 
  A drug guide should be consulted any time one of these drugs is added to or 
  removed from a drug regimen. Itraconazole has a black box warning regarding the 
  potential for serious cardiovascular effects if it is given with lovastatin, simvastatin, 
  triazolam, midazolam, pimozide, or dofetilide. These combinations should be 
  avoided. Voriconazole and posaconazole should not be used with any other drugs 
  that prolong the QTc interval and can cause ergotism if taken with ergot alkaloids. 
  
  II. ECHINOCANDIN ANTIFUNGALS 
  The echinocandin antifungals are another group of antifungals. Drugs in this class 
  include anidulafungin, caspofungin, and micafungin.
  
  1) Therapeutic Actions and Indications 
  The echinocandins work by inhibiting glucan synthesis. Glucan is an enzyme that is 
  present in the fungal cell well but not in human cell walls. If this enzyme is inhibited, 
  the fungal cell wall cannot form, leading to death of the cell wall.
   
  The echinocandins are mainly used in the treatment of candidemia (infection of the 
  blood stream) and other forms of Candida infection, intraabdominal infections, and 
  esophageal candidiasis.
  They are also used in the treatment of invasive aspergillosis in patients who do not 
  respond or are intolerant to other therapies.
  Finally, they can be used in the treatment of patients with esophageal candidiasis; 
  

  prophylaxis of Candida infections in patients with hematopoietic stem cell transplant.

  The usual dosage of anidulafungin is 100–200 mg IV on day 1, then 50–100 mg/d 
  

  IV for 14 d; with the dose varying with infection being treated.

  2) Pharmacokinetics 

  Anidulafungin is given as a daily IV infusion for at least 14 days. It has a rapid 
  onset of action, is metabolized by degradation, and has half-life of 40 to 50 hours. 
  This drug is excreted in the feces. Caspofungin is available for IV use. This drug is 
  slowly metabolized in the liver, with half-lives of 9 to 11 hours, then 6 to 48 hours, 
  and then 40 to 50 hours. It is bound to protein and widely distributed throughout the 
  body. It is excreted through the urine. Micafungin is an IV drug. It has a rapid onset, 
  a half-life of 14 to 17 hours, and is excreted in the urine.
  3) Contraindications and Cautions 
  Anidulafungin may cross the placenta and enter breast milk and should not be 
  used by pregnant or lactating women. Caution must be used in the presence of 
  hepatic impairment because it can be toxic to the liver. Caspofungin can be toxic 
  to the liver; therefore, reduced doses must be used if a patient has known hepatic 
  impairment. Caspofungin is embryotoxic in animal studies and is known to enter 
  breast milk; therefore, it should be used with great caution during pregnancy and 
  lactation. Because of the potential for adverse reactions in the fetus or the neonate, 
  micafungin should be used during pregnancy and lactation only if the benefits 
  clearly outweigh the risks.
  4) Adverse Effects 
  Anidulafungin and caspofungin are associated with hepatic toxicity, and liver 
  function should be monitored closely when using these drugs. Potentially serious 
  hypersensitivity reactions have occurred with micafungin. In addition, bone marrow 
  suppression can occur; monitor patients closely
  5) Clinically Important Drug-Drug Interactions 
  Concurrent use of cyclosporine with caspofungin is contraindicated unless the 
  

  benefit clearly outweighs the risk of hepatic injury.

  Self-assessment 4.2.1

  6) The antifungal drugs for systemic use are more likely to be less toxic 
  compared to the antifungal drugs for topical use. TRUE or FALSE
  7) Ketoconazole is an echinocandin antifungal for systemic use. TRUE or 
  FALSE
  8) Anidulafungin and caspofungin are associated with hepatic toxicity, and 
  

  liver function should be monitored closely when using these drugs.

  4.2.2 Systemic antifungals: other antifungal agents
  

           Learning Activity 4.2.2
  

        Read carefully the scenario below:

  A 5-year-old male patient consults the healthcare facility where you are carrying 
  out the clinical practice. He has mouth and tongue ulcerations following longterm use of cephalosporins of third generation. You decide that the patient has a 
  fungal condition that requires to be treated with an antifungal known as “nystatin”. 
  You then decide to prescribe that antifungal agent.
  i) What are the main indications of nystatin?
  j) What is the usual dosage of nystatin?
  Guidance: Read the book of pharmacology brought by the teacher in class, on 
  

  topic of antifungal drugs.

  CONTENT SUMMARY

  Other antifungal drugs that are available do not fit into either of these classes. 
  These include amphotericin B, flucytosine, griseofulvin, and nystatin.
  1) Therapeutic Actions and Indications
  Other antifungal agents work to cause fungal cell death or to prevent fungal cell 
  reproduction. Amphotericin B is a very potent drug with many unpleasant adverse 
  effects. The drug binds to the sterols in the fungus cell wall, changing cell wall 
  permeability. This change can lead to cell death (fungicidal effect) or prevent the 
  fungal cells from reproducing (fungistatic effect). Because of the many adverse 
  effects associated with this agent, its use is reserved for progressive, potentially 
  fatal infections. 
  Amphotericin B is mainly used in the treatment of aspergillosis, leishmaniasis, 
  cryptococcosis, blastomycosis, moniliasis, coccidioidomycosis, histoplasmosis and 
  mucormycosis; use is reserved for progressive, potential fatal infections due to 
  many associated adverse effects.
  The usual dosage for amphotericin B is 0.25–1.5 mg/kg/d IV based on the infection 
  being treated.
  Flucytosine is a less toxic drug that alters the cell membrane of susceptible fungi, 
  causing cell death. The uses of flucytosine are limited to the treatment of systemic 
  infections caused by Candida or Cryptococcus. Its usual dosage is 50–150 mg/kg/d 
  

  PO in divided doses at 6-h intervals.

  Griseofulvin is an older antifungal that acts in much the same way, changing cell 
  membrane permeability and causing cell death. Griseofulvin is usually indicated 
  in the treatment of variety of ringworm or tinea infections caused by susceptible 
  Trichophyton species, including tinea corporis, tinea pedis, tinea cruris, tinea 
  barbae, tinea capitis, and tinea unguium.
  The dosage of griseofulvin is as follows:
  Tinea corporis, tinea cruris, and tinea capitis: 
  Adult: 500 mg (microsize) or 330–375 mg/d (ultramicrosize) PO 
  Tinea pedis and tinea unguium: 
  Adult: 0.75–1 g (microsize) or 660–750 mg (ultramicrosize) PO daily 
  Paediatric population: (>2 y): 11 mg/kg/d (microsize) or 7.3 mg (ultramicrosize) 
  PO daily (not recommended for children ≤2 y)
  Nystatin binds to sterols in the cell wall, changing membrane permeability and 
  allowing leaking of the cellular components, which will result in cell death. Nystatin 
  is usually indicated in the treatment of candidiasis (oral form); treatment of local 
  candidiasis, vaginal candidiasis, and cutaneous and mucocutaneous infections 
  caused by Candida species.
  Its usual dosage is 500,000–1,000,000 units t.i.d. PO; continue for 48 h after 
  resolution to prevent relapse; also used topically.
  1) Pharmacokinetics 
  Amphotericin B and flucytosine are available in IV form. They are excreted in the 
  urine, with an initial half-life of 24 hours and then a 15-day half-life. Their metabolism 
  is not fully understood. Flucytosine is well absorbed from the GI tract, with peak 
  levels occurring in 2 hours. Most of the drug is excreted unchanged in the urine 
  and a small amount in the feces, with a half-life of 2.4 to 4.8 hours. Griseofulvin is 
  administered orally and reaches peak levels in around 4 hours. It is metabolized 
  in the liver and excreted in the urine with a half-life of 24 hours. Nystatin is not 
  absorbed from the GI tract and passes unchanged in the stool.
  2) Contraindications and Cautions
  Amphotericin B has been used successfully during pregnancy, but it should be 
  used cautiously. It crosses into breast milk and should not be used during lactation 
  because of the potential risk to the neonate. Because flucytosine is excreted primarily 
  in the urine, extreme caution is needed in the presence of renal impairment because 
  drug accumulation and toxicity can occur. Toxicity is associated with serum levels 
  higher than 100 mcg/mL. Because of the potential for adverse reactions in the 
  

  fetus or neonate, flucytosine should be used during pregnancy and lactation only

  if the benefits clearly outweigh the risks. It is not known whether nystatin crosses 
  the placenta or enters breast milk, so it should not be used during pregnancy or 
  

  lactation unless the benefits clearly outweigh the potential risks.

  3) Adverse Effects 

  Adverse effects of these drugs are related to their toxic effects on the liver and 
  kidneys. Patients should be monitored closely for any changes in liver or kidney 
  functions. Bone marrow suppression has also been reported with the use of 
  these drugs. Rash and dermatological changes have been reported with these 
  antifungals. Amphotericin B is associated with severe renal impairment, bone 
  marrow suppression, GI irritation with nausea, vomiting, and potentially severe 
  diarrhea, anorexia and weight loss, and pain at the injection site with the possibility of 
  phlebitis or thrombophlebitis. Adverse effects of griseofulvin are relatively mild, with 
  

  headache and central nervous system (CNS) changes occurring most frequently.

  4) Clinically Important Drug-Drug Interactions 

  Patients who receive amphotericin B should not take other nephrotoxic drugs such 
  as nephrotoxic antibiotics or antineoplastics, cyclosporine, or corticosteroids unless 
  

  absolutely necessary because of the increased risk of severe renal toxicity.

  Self-assessment 4.2.2

  A 55-year-old male patient is being treated for cryptococcal meningitis following 
  his immunosuppression with AIDS. The treating team decides to prescribe 
  amphotericin B because they judge it may be beneficial for this patient.
  a) What are other indications of amphotericin B?
  

  b) What are the adverse effects of amphotericin B?

  4.2.3 Topical antifungal agents
  

            Learning Activity 4.2.3
  

  A 20-year-old female patient consults the healthcare facility where you are 
  carrying out your clinical practice as an associate nurse student. The patient 
  complains of ulcerations between toes, itching and pain. He reports that she 
  does not usually taker care of her toes properly, and most of the time she does 
  not dry her feet adequately after bath, as she rushes for work early morning.
  On your physical examination, you realize that the patient has athlete’s foot, and 
  you decide to prescribe a topical antifungal agent.
  c) Give any three examples of topical azole-type antifungals
  d) What are the nursing considerations would you take into account while 
  prescribing topical antifungals?
  Guidance: Use the book of pharmacology brought by the teacher in class, and 
  

  read on topic of antifungals, subtopic of topical antifungals

  CONTENT SUMMARY

  Some antifungal drugs are available only in topical forms for treating a variety of 
  mycoses of the skin and mucous membranes. Some of the systemic antifungals 
  are also available in topical forms. Fungi that cause these mycoses are called 
  dermatophytes. These diseases include a variety of tinea infections, which are often 
  referred to as ringworm, although the causal organism is a fungus, not a worm. 
  
  These mycoses include tinea infections such as athlete’s foot (tinea pedis), jock 
  itch (tinea cruris), and yeast infections of the mouth and vagina often caused by 
  Candida. Because the antifungal drugs reserved for use as topical agents are often 
  too toxic for systemic administration, care is necessary when using them near open 
  or draining wounds that might permit systemic absorption. 
  
  Topical antifungals include the azole-type antifungals such as butoconazole, 
  clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sertaconazole 
  nitrate, sulconazole, terconazole, and tioconazole. Topical antifungals also include 
  other antifungals such as butenafine, ciclopirox, gentian violet, naftifine, tolnaftate, 
  and undecylenic acid.
  1) Therapeutic Actions and Indications 
  The topical antifungal drugs work to alter the cell permeability of the fungus, 
  causing prevention of replication and fungal death. They are indicated only for local 
  treatment of mycoses, including tinea infections. 
  Butoconazole is available as vaginal cream; applied only once a day for 4 wk. It is 
  available over the counter (OTC) for treatment of vaginal Candida infections.
  Clotrimazole is available OTC as a cream, lotion, or solution; applied as a thin 
  layer twice a day for 2–4 wk. It is used in the treatment of oral and vaginal Candida 
  infections; tinea infections.
  Ketoconazole is available in cream, gel, foam, and shampoo form; applied once 
  to twice daily for 2–4 wk. It is used in the treatment of seborrheic dermatitis, tinea 
  corporis, tinea cruris, tinea pedis.
  Miconazole is available as an OTC product in several topical forms (vaginal 
  suppository, cream, powder, solution, ointment, gel and spray); applied twice daily 
  for 2–4 wk. It is used in the treatment of local, topical mycoses, including bladder 
  and vaginal infections and athlete’s foot.
  Terbinafine is available as a cream or gel; used for 1–4 wk; applied twice daily. It 
  is used in the short-term (1–4 wk) treatment of topical mycosis; treatment of tinea 
  

  infections.

  Gentian violet is available as a topical solution; applied twice a day to affected 
  area. It is used in the treatment of topical mycosis.
  Naftifine is available as a cream or gel; applied twice a day for up to 4 wk.                                                                                               hortterm treatment of severe topical mycosis (up to 4 wk). It is used in the short-term 
  treatment of severe topical mycosis (up to 4 wk).
  2) Pharmacokinetics 
  These drugs are not absorbed systemically and do not undergo metabolism or 
  excretion in the body.
  3) Contraindications and Cautions 
  Because these drugs are not absorbed systemically, contraindications are limited 
  to a known allergy to any of these drugs and open lesions. Econazole can cause 
  intense, local burning and irritation and should be discontinued if these conditions 
  become severe. Gentian violet stains skin and clothing bright purple; in addition, 
  it is very toxic when absorbed, so it cannot be used near active lesions. Naftifine, 
  oxiconazole, and sertaconazole nitrate should not be used for longer than 4 weeks 
  due to the risk of adverse effects and possible emergence of resistant strains of 
  fungi. Sulconazole should not be used for longer than 6 weeks due to the risk of 
  adverse effects and possible emergence of resistant strains of fungi. Terbinafine 
  should not be used for longer than 4 weeks. This drug should be stopped when the 
  fungal condition appears to be improved or if local irritation and pain become too 
  great to avoid toxic effects.
  4) Adverse Effects 
  When these drugs are applied locally as a cream, lotion, or spray, local effects 
  include irritation, burning, rash, and swelling. When they are taken as a suppository 
  or troche, adverse effects include nausea, vomiting, and hepatic dysfunction (related 
  to absorption of some of the drug by the GI tract) or urinary frequency, burning, and 
  

  change in sexual activity (related to local absorption in the vagina).

  Self-assessment 4.2.3

  After going through the session of topical antifungals, answer the following 
  questions:
  1) What are the adverse effects of topical antifungals used as suppositories?
  

  2) Give the indications of topical clotrimazole.

  4.3 End unit assessment
  

  End of unit assessment
  

  1) The order reads, “Give nystatin (Mycostatin) suspension, 500,000 units 
  by mouth (swish and swallow) 4 times a day for 1 week.” The medication 
  is available in a suspension of 100,000 units per mL. How many milliliters 
  will the nurse give per dose?
  2) The nurse notes in a patient’s medication history that the patient is taking 
  terbinafine (Lamisil). Based on this finding, the nurse interprets that the 
  patient has which disorder? 
  a) Vaginal candidiasis 
  b) Cryptococcal meningitis 
  c) Invasive aspergillosis 
  d) Fungal infection of toenails or fingernails
  3) What are the adverse effects of topical antifungal agents?
  4) Terbinafine cream should be used in the long-term (at least 10 weeks) 
  treatment of topical mycosis in order to get the result. TRUE or FALSE
  5) Antifungals in topical forms are used to treat a variety of systemic mycoses 
  

  of the internal body organs. TRUE or FALSE

  
  

• UNIT 5: ANTIVIRAL DRUGS

            Key Unit Competence:

  Utilize antiretroviral medications to limit HIV/AIDS transmission 
  

  Introductory activity 5.0
  

                    
  

  Observe the images (A, B, C) above and describe briefly what they indicate for 
  

  you.

  5.1. Introduction to antiretroviral drugs
  

          Learning Activity 5.1

         During your clinical practice ,you receive a client in consultation. In data collection, 

  the client reports that he is taking antiretroviral drug.

  1) What is an antiretroviral drug?

  2) What is a protease inhibitor?

  Guidance: Use internet and library textboks. 

  CONTENT SUMMARY

  Antiviral: An agent that kills a virus or that suppresses its ability to replicate and, 
  hence, inhibits its capability to multiply and reproduce.
  For example, amantadine (Symmetrel) is a synthetic antiviral. It acts by inhibiting the 
  multiplication of the influenzaA virus. It was used to lessen the severity of the disease, 
  particularly in individuals at high-risk such as those who are immunosuppressed or 
  in a nursing home. 
  The antivirals that have been developed are generally less effective than one 
  would like. Viruses can replicate rapidly and, in many cases sloppily, giving rise to 
  mutations that make them resistant to drugs. And for fast-moving viral infections 
  like flu or a cold, a drug must be very powerful to make a difference before the 
  disease runs its natural course.
  Antivirals and Antiretrovirals are a class of medication specifically used to treat 
  viral and retroviral infections caused by viruses like HIV, herpes viruses, hepatitis 
  B and C. Antivirals are a class of drugs which are used to treat viral infections. 
  The antiviral drugs target diverse group of viruses such as herpes, hepatitis, and 
  influenza viruses. Whereas antiretroviral drugs are the drugs that are used to fight 
  retrovirus infections which mainly include HIV. Different classes of antiretroviral 
  drugs act on different stages of the HIV life cycle.
  Retrovirus is a group of viruses that belong to the family Retroviridae and that 
  characteristically carry their genetic blueprint in the form of ribonucleic acid (RNA). 
  Retroviruses are named for an enzyme known as reverse transcriptase, which was 
  discovered independently in 1971 by American virologists Howard Temin and David 
  Baltimore. Reverse transcriptase transcribes RNA into deoxyribonucleic 
  acid (DNA), a process that constitutes a reversal of the usual direction of 
  cellular transcription (DNA into RNA). The action of reverse transcriptase makes it 
  possible for genetic material from a retrovirus to become permanently incorporated 
  into the DNA genome of an infected cell; the enzyme is widely used in the biological 
  sciences to synthesize genes.
  Integrase inhibitor: a drug that inhibits the activity of the virus-specific enzyme 
  integrase, an encoded enzyme needed for viral replication; blocking this enzyme 
  prevents the formation of the HIV-1 provirus.
  Interferon: tissue hormone that is released in response to viral invasion; blocks 
  viral replication nonnucleoside reverse transcriptase inhibitors: drugs that bind to 
  sites on the reverse transcriptase within the cell cytoplasm, preventing RNA- and 
  DNA-dependent DNA polymerase activities needed to carry out viral DNA synthesis; 
  prevents the transfer of information that allows the virus to replicate and survive.
  Nucleoside reverse transcriptase inhibitors: drugs that prevent the growth of the 
  viral DNA chain, preventing it from inserting into the host DNA, so viral replication 
  

  cannot occur.

  Protease inhibitors: drugs that block the activity of the enzyme protease in HIV; 

  protease is essential for the maturation of infectious virus, and its absence leads to 

  the formation of an immature and noninfective HIV particle.

  CCR5 coreceptor antagonist: a drug that blocks the receptor site on the T cell 

  membrane that the HIV virus needs to interact with in order to enter the cell.

  Fusion inhibitor: a drug that prevents the fusion of the HIV-1 virus with the human 

  cellular membrane, preventing it from entering the cell. 

  Self-assessment 5.1

  1) which of the following is a definition of antiviral drugs?
  a) Antivirals are a class of drugs which are used to treat viral infections
  b) Antivirals are a class of drugs which are used to treat viral and bacterial 
  infections
  c) Antivirals are a class of drugs which are used to treat retroviral infections
  d) Antivirals are a class of drugs which are used to treat viral and retroviral 
  infections
  2) You receive a client with signs and symptoms of helps simplex. Among 
  the two following groups of drugs, which one will you choose as effective 
  to the disease?
  a) Antiretroviral drugs
  b) Antiviral drugs
  3) With an example of the virus infections. Differentiate antiviral and retroviral 
  

  drugs.

  5.2. Classification of antiretroviral drugs

           Learning Activity 5.2
  

  You are an asociate nurse carrying out the clinical placement. You receive a 
  patient at the health facility who has been diagnosed with HIV/AIDS. What does 
  an associate nurse will tell the patient?
  1) Which classes of antiretroviral drugs can be used in HIV/AIDS 
       management?
  

  2) What are the five basic goals of ART?

  CONTENT SUMMARY

  In this lesson we discuss on classification of antiretroviral drugs. HIV infection has 
  been transformed from a near-certain death sentence to a manageable chronic 
  disease. Because of viruses are contained inside human cells while they are in 
  the body, researchers have difficulty developing effective drugs that destroy a virus 
  without harming the human host. Since the introduction of ART, the incidence of 
  new opportunistic infections has declined dramatically. For example, the incidences 
  of cytomegalovirus retinitis and disseminated mycobacterial infection have fallen 
  by as much as 75% to 80%. In many patients with low CD4 T-cell counts, ART 
  has caused CD4 counts to rise, restoring some immunocompetence and permitting 
  withdrawal of prophylactic drugs. 
  
  Patients with HIV infection should receive ART regardless of the CD4 count or 
  phase of HIV disease. Treatment has five basic goals: Maximal and long-lasting 
  suppression of viral load, restoration and preservation of immune function, improved 
  quality of life, reduction of HIV-related morbidity and mortality and prevention of 
  HIV transmission. Most patients take several antiretroviral drugs typically two 
  nucleoside reverse transcriptase inhibitors (NRTIs) combined with either a PI or 
  non-nucleoside reverse transcriptase inhibitors (NNRTIs).
   
  These highly effective regimens can reduce plasma HIV to undetectable levels, 
  causing CD4 T-cell counts to return toward normal, thereby restoring some immune 
  function. However, despite these advances, treatment cannot cure HIV. The HIV 
  mutates over time, presenting a slightly different configuration with each new 
  generation. Treatment of AIDS and ARC has been difficult for two reasons: (1) 
  the length of time the virus can remain dormant within the T cells (i.e., months to 
  years), and (2) the adverse effects of many potent drugs, which may include further 
  depression of the immune system. A combination of several different antiviral drugs 
  is used to attack the virus at various points in its life cycle to achieve maximum 
  effectiveness with the least amount of toxicity.
  
  Antiretroviral drugs are classified into six classes of antiretroviral drugs. Four 
  classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non                                                                                      nucleoside reverse transcriptase inhibitors (NNRTIs), integrase strand transfer 
  inhibitors (INSTIs), and protease inhibitors (PIs) inhibit HIV enzymes. 
  The other two classes: HIV fusion inhibitors and CCR5 antagonists, work outside 
  CD4 cells to block HIV entry. 
  
  NRTIs suppress HIV replication in two ways: (1) they become incorporated into 
  the growing strand of viral DNA (through the actions of reverse transcriptase) and 
  thereby prevent further strand growth, and (2) they compete with natural nucleoside 
  triphosphates for binding to the active center of reverse transcriptase and thereby 
  competitively inhibit the enzyme. To interact with reverse transcriptase, NRTIs must 
  

  first undergo intracellular conversion to their active (triphosphate) forms.

  The NNRTIs differ from the NRTIs in structure and mechanism of action. As 
  their name suggests, the NNRTIs have no structural relationship with naturally 
  occurring nucleosides. Also unlike NRTIs, the NNRTIs are active only against HIV1. In practice, they are usually combined with an NRTI. The NNRTIs bind to the 
  active center of reverse transcriptase enzyme. At this location, the NNRTI causes 
  stereochemical changes (i.e., changes in the spatial arrangement of atoms forming 
  the structure of molecules). This hampers the ability of nucleosides to bind, which 
  inhibits DNA replication and promotes premature termination of the growing DNA 
  strand.
  NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)
  The NRTIs were the first drugs used against HIV infection. As their name suggests, 
  the NRTIs are chemical relatives of naturally occurring nucleosides or nucleotides, 
  the building blocks of DNA. At this time, seven NRTIs are available: Abacavir, 
  didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine. The 
  NRTIs are effective against both HIV-1 and HIV-2; however, their activity is greater 
  for HIV-1. The NRTIs are ineffective as monotherapy because resistance develops 
  rapidly. First-line antiretroviral regimens include two NRTIs and one other drug. The 
  availability of combination antiretroviral products has simplified treatment. 
  Mechanism of Action 
  All NRTIs are prodrugs that inhibit HIV replication by suppressing synthesis 
  of viral DNA. To do this, they must first undergo intracellular conversion to their 
  active (phosphate) form. In their active form, they act as substrates for reverse 
  transcriptase. However, after they become incorporated into the growing DNA 
  strand, they prevent reverse transcriptase from adding more bases. As a result, all 
  further growth of the DNA strand is blocked. In addition to causing premature strand 
  termination, the activated NRTI competes with natural nucleoside triphosphates for 
  binding to the active site of reverse transcriptase. 
  Adverse Effects 
  The NRTIs share a core of adverse effects associated with mitochondrial toxicity. 
  Recall that mitochondria are cellular organelles that take in nutrients and convert 
  them into ATP for energy. NRTIs can disrupt synthesis of mitochondrial DNA and 
  can thereby impair mitochondrial function. 
  The main adverse effects of NRTIs are: Lactic acidosis, hepatic steatosis. Other 
  adverse effects include: pancreatitis and myopathies, which are likely tied to lactic 
  acidosis. Adverse effects of individual NRTIs are discussed separately. 
  Drug Interactions 
  NRTIs have fewer drug interactions than most antiretroviral drugs, in part because 
  most are not metabolized by the P450 enzymes. Interactions of individual drugs are 
  

  discussed separately.

  Table 5.1.1: NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)

                             

                          

         NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

  The NNRTIs differ from the NRTIs in structure and mechanism of action. As their 
  name suggests, the NNRTIs have no structural relationship with naturally occurring 
  nucleosides. Also unlike NRTIs, the NNRTIs are active only against HIV-1. In 
  practice, they are usually combined with an NRTI. At this time, five NNRTIs are 
  available: efavirenz (Sustiva), nevirapine (Viramune), Delavirdine (Rescriptor), 
  

  etravirine (Intelence), and rilpivirine (Edurant). 

  Mechanism of Action
  In contrast to the NRTIs, the NNRTIs bind to the active center of reverse transcriptase 
  enzyme. At this location, the NNRTI causes stereochemical changes (i.e., changes 
  in the spatial arrangement of atoms forming the structure of molecules). This 
  hampers the ability of nucleosides to bind, which inhibits DNA replication and 
  promotes premature termination of the growing DNA strand. 
  Adverse Effects 
  Unlike NRTIs, there are no adverse effects shared by all NNRTIs. However, two of 
  the NNRTIs, efavirenz and rilpivirine, can both cause CNS effects. 
  Drug Interactions 
  The NNRTIs have multiple drug interactions with commonly used drugs across 
  many drug classes. These vary according to the individual NNRTI in question.
  
  

  Table 5.1.2: NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

                            

       PROTEASE INHIBITORS 

  PIs are active against both HIV-1 and HIV-2. They are among the most effective 
  antiretroviral drugs available. When used in combination with NRTIs, they can 
  reduce viral load to a level that is undetectable with current assays.
  As with other antiretroviral drugs, HIV resistance can be a significant problem. 
  Mutant strains of HIV that are resistant to one PI are likely to be cross-resistant 
  to other PIs. In contrast, since PIs do not share the same mechanism as other 
  antiretroviral drugs, cross-resistance between PIs and these drugs does not occur. 
  To reduce the risk for resistance, PIs should never be used alone; rather, they 
  should always be combined with at least one reverse transcriptase inhibitor, and 
  preferably two. 
  Nine PIs are available: atazanavir, darunavir, fosamprenavir, indinavir, lopinavir 
  (with ritonavir), nelfinavir, ritonavir, saquinavir, and tipranavir.
  Mechanism of Action 
  Maturation is necessary for HIV to infect CD4 cells; immature forms are noninfectious. 
  Protease inhibitors prevent HIV maturation by blocking the HIV enzyme protease. It 
  may help to look at the process of HIV maturation. 
  When the various enzymes and structural proteins of HIV are synthesized, they 
  are not produced as separate entities; rather, they are strung together in large 
  polyproteins. Protease catalyzes the cleavage of bonds in the polyproteins, thereby 
  freeing the individual enzymes and structural proteins. Once these components 
  have been freed, HIV uses them to complete its maturation. Protease inhibitors 
  bind to the active site of HIV protease and prevent the enzyme from cleaving HIV 
  polyproteins. As a result, the structural proteins and enzymes of HIV are unable to 
  function, and hence the virus remains immature and non-infectious.
  Adverse Effects 
  There are several adverse effects that all protease inhibitors have in common. 
  These include hyperglycemia and the development of diabetes, lipodystrophy 
  (fat redistribution), elevation of serum transaminases, and decreased cardiac 
  conduction velocity. They can also increase bleeding in patients with hemophilia. 
  Drug Interactions 
  All PIs are metabolized by cytochrome P450 enzymes, and all PIs can inhibit 
  selected cytochrome P450 enzymes. Typically, they will also induce other enzymes. 
  As a result, PIs can interact with drugs that inhibit or induce P450 enzymes and 
  with drugs that are substrates for P450 enzymes. Not all interactions are harmful, of 
  course. By inhibiting selected P450 enzymes one PI can increase the level of another 
  

  PI and can thus intensify therapeutic effects. One PI—ritonavir [Norvir]—is routinely     

  combined with other PIs with the specific purpose of increasing the therapeutic 
  effects of the other PI. In this technique, known as ritonavir boosting, the dose of 
  ritonavir is low: 100 to 400 mg/day. This dosage is too low to contribute significant 
  antiviral effects, but still high enough to inhibit P450 metabolism. Unfortunately, 
  most interactions with PIs are not beneficial. We will highlight interactions commonly 
  

  experienced by patients with HIV in our discussion of individual PIs.

  Table 5.1.3: PROTEASE INHIBITORS

                     

                      

          INTEGRASE STRAND TRANSFER INHIBITORS 

  HIV integrase strand transfer inhibitors (INSTIs), or simply integrase inhibitors, 

  target HIV by terminating the integration of HIV into DNA. Integrase is one of three 

  viral enzymes needed for HIV replication. As its name implies, integrase inserts 

  HIV genetic material into the DNA of CD4 cells. By inhibiting integrase, these drugs 

  prevent insertion of HIV DNA and thereby stop HIV replication. They are effective 

  against both HIV-1 and HIV-2. 

  We currently have three approved INSTIs: raltegravir, dolutegravir, and elvitegravir. 

  All are indicated for combined use with other antiretroviral agents to treat adults 

  infected with HIV-1. 

  
  

  Actions and Use 

  Raltegravir [Isentress] was the first HIV integrase strand transfer inhibitor to be 

  developed. Raltegravir stops HIV replication by preventing insertion of HIV DNA. 

  Raltegravir is active against HIV strains resistant to some of the other drugs. 

  Raltegravir was originally approved only for treatmentexperienced patients but is 

  now approved for treatment-naïve patients as well. In current guidelines, raltegravir 

  (in combination with tenofovir plus either emtricitabine or lamivudine) is considered 

  a first-choice drug for HIV treatment. In clinical trials, raltegravir demonstrated 

  increased viral suppression when compared to protease inhibitors and the NNRTI 

  efavirenz. Unfortunately, HIV resistance was also more likely to develop. 

  Adverse Effects 

  Raltegravir is generally well tolerated by most. The most common adverse effect 

  is an elevation in liver enzymes that occurs in about 10% of those taking the 

  drug. Approximately 4% to 5% will have elevations in serum amylase and lipase. 

  Symptomatic adverse effects occur infrequently. In fact, the most common adverse 

  effects, insomnia and headache, occur in only 2% to 4% of those taking this drug. 

  In clinical trials, a few patients experienced myopathy and rhabdomyolysis, but 

  a causal relationship has not been established. Rarely, patients have developed 

  severe hypersensitivity reactions. Skin reactions include Stevens-Johnson 

  syndrome and toxic epidermal necrolysis, which can be fatal. Organ dysfunction, 

  including liver failure, may also develop. 

  Patients who develop signs of a hypersensitivity reaction (e.g., severe rash, or rash 

  associated with blisters, fever, malaise, fatigue, oral lesions, facial edema, hepatitis, 

  angioedema, muscle or joint aches) should discontinue raltegravir immediately. 

  Contraindications 

  There are no contraindications to taking raltegravir. Those with pre-existing hepatic 

  impairment may be at risk for worsening of this condition. Caution should be 

  maintained when taken by patients with a history of rhabdomyolysis or by those 

  taking other drugs that have this adverse effect. 

  Drug Interactions 

  Because raltegravir is metabolized by glucuronidation, it does not have as many 

  drug interactions as those with roles in P450 enzyme systems. Atazanavir and other 

  inhibitors of UGT can increase levels of raltegravir. Conversely, inducers of UGT 

  (e.g., efavirenz, fosamprenavir, rifabutin, tipranavir) can lower raltegravir levels. 

  HIV FUSION INHIBITORS 

  Unlike most other drugs for HIV, which inhibit essential viral enzymes (i.e., reverse 

  transcriptase, integrase, protease), HIV fusion inhibitors block entry of HIV into 

  CD4 T cells. Earlier in the chapter, we discussed the replication cycle of HIV. Recall 

  that in step 2, the lipid bilayer envelope of HIV fuses with the lipid bilayer of the host 

  cell membrane. HIV fusion inhibitors block this fusion process. 

  Enfuvirtide 

  Enfuvirtide [Fuzeon], widely known as T-20, is the first and only HIV fusion inhibitor 

  currently approved by the FDA. Unfortunately, although enfuvirtide is effective, 

  it is also inconvenient (treatment requires twice-daily subQ injections) and very 

  expensive (treatment costs about $52,000 a year). Furthermore, injection-site 

  reactions occur in nearly all patients. 

  Mechanism of Action 

  Enfuvirtide prevents the HIV envelope from fusing with the cell membrane of CD4 

  cells, and thereby blocks viral entry and replication. Fusion inhibition results from 

  binding of enfuvirtide to gp41, a subunit of the glycoproteins embedded in the 

  HIV envelope (see Fig. 94.1). As a result of enfuvirtide binding, the glycoprotein 

  becomes rigid, and hence cannot undergo the configurational change needed to 

  permit fusion of HIV with the cell membrane. 

  Resistance 

  Resistance to enfuvirtide has developed in cultured cells and in patients. The cause 

  is a structural change in gp41. In clinical trials, reductions in drug susceptibility have 

  ranged from 4- to 422-fold. Fortunately, the HIV mutations that confer resistance to 

  enfuvirtide do not confer cross-resistance to NRTIs, NNRTIs, PIs, INSTIs, or CCR5 

  antagonists. Conversely, resistance to NRTIs, NNRTIs, PIs, INSTIs, or CCR5 

  antagonists does not confer cross-resistance to enfuvirtide. The rate at which 

  resistance develops depends on the efficacy of the drugs used concurrently. When 

  the patient’s other antiretroviral drugs are still effective, resistance to enfuvirtide 

  develops relatively slowly. However, when there is significant resistance to the 

  other drugs, resistance to enfuvirtide develops rapidly.

  Therapeutic use

  Use Enfuvirtide is reserved for treating HIV-1 infection that has become resistant 

  to other antiretroviral agents. Specifically, the drug is indicated for HIV-1 infection 

  in patients who are treatment experienced and have evidence of HIV replication 

  despite ongoing ART. To delay emergence of resistance, enfuvirtide should always 

  be combined with other antiretroviral drugs.

  Adverse Effects 

  They include injection-site reactions, pneumonia, and hypersensitivity 

  reactions.

  Drug Interactions 

  Enfuvirtide appears devoid of significant drug interactions. There are no interactions 

  with other antiretroviral drugs that would require a dosage adjustment for either 

  enfuvirtide or the other agent. 

  Table 5.1.4: INTEGRASE INHIBITORS 

                

                 CCR5 ANTAGONISTS 

  CCR5 antagonists, like the fusion inhibitors, block entry of HIV into CD4 T cells. 
  However, the mechanism by which they accomplish this is different. 
  Maraviroc 
  Maraviroc [Selzentry, Celsentri ] is the first, and currently only, representative of 
  the CCR5 antagonists. Maraviroc isn’t usually used for initial treatment of HIV. It 
  appears most effective in treating patients with drug-resistant HIV. 
  Mechanism of Action 
  CCR5 is a co-receptor that some strains of HIV must bind with to enter CD4 cells. 
  Maraviroc binds with CCR5 and thereby blocks viral entry. HIV strains that require 
  CCR5 for entry are referred to as being CCR5 tropic. Between 50% and 60% 
  of patients are infected with this type of HIV. Maraviroc and enfuvirtide (a fusion 
  inhibitor) are the only antiretroviral drugs that block HIV entry.
  Therapeutic Use 
  Maraviroc is indicated for combined use with other antiretroviral agents to treat 
  patients age 16 years and older who are infected with CCR5-tropic HIV-1 strains. 
  The drug was originally approved only for treatment-experienced patients but is 
  now approved for treatment-naïve patients as well. Before maraviroc is used, a test 
  must be performed to confirm that the infecting HIV strain is CCR5 tropic. 
  Adverse Effects 
  The most common side effects are cough, dizziness, pyrexia, rash, abdominal 
  pain, musculoskeletal symptoms, and upper respiratory tract infections. Intensity is 
  generally mild to moderate. Liver injury has been seen in some patients and may be 
  preceded by signs of an allergic reaction (e.g., eosinophilia, pruritic rash, elevated 
  immunoglobulin E). 
  Patients should be informed about signs of an evolving reaction (itchy rash, jaundice, 
  vomiting, and/or abdominal pain) and instructed to stop maraviroc and seek medical 
  attention. During clinical trials, a few patients experienced cardiovascular events, 
  including myocardial ischemia and MI. Maraviroc should be used with caution in 
  patients with cardiovascular risk factors. 
  Drug Interactions 
  Because maraviroc is metabolized by CYP3A4, drugs that inhibit or induce this 
  enzyme will affect maraviroc levels. Levels will be raised by strong CYP3A4 
  inhibitors, including protease inhibitors (except tipranavir/ritonavir) and delavirdine. 
  Conversely, maraviroc levels will be lowered by strong CYP3A4 inducers, including 
  etravirine and efavirenz. As always, it is important to check for interactions via a 
  

  comprehensive database before administering drugs such as this one.

  Table 5.1.5: FUSIOIN INHIBITORS

                 
  

                   

                         Self-assessment 5.2

  1) Why is combination therapy necessary in HIV treatment?
  2) Which of the following antiretroviral drugs is classified in the protease 
  inhibitors?
  a) Enfuvirtide
  b) Raltegravir
  c) Atazanavir
  d) Nevirapine
  

  3) What is the mechanism of action of enfuvirtide?      

  5.3. Antiretroviral treatment in adolescents and adults
  

          Learning Activity 5.3

   A 33-year-old newly diagnosed HIV patient was advised to start antiretroviral 
  treatment at ART sevice where you are appointed as an associate nurse. During 
  pre-treatment counselling, you focus on the number of combined medications 
  to use.
  1) What is the number of medications combinations is required to use in 
  HIV/AIDS management?
  2) What should the nurse include in the teaching as the ideal time to initiate 
  

  ARVs after HIV diagnosis?

  CONTENT SUMMARY

  People with HIV should take medicine to treat HIV as soon as possible. HIV 
  medicine reduces the amount of HIV in the body (viral load) to a very low level, 
  which keeps the immune system working and prevents illness. It can even make 
  the viral load so low that a test can’t detect it. This is called an undetectable viral 
  load. Getting and keeping an undetectable viral load* is the best thing people with 
  HIV can do to stay healthy.
  
  Initiating Antiretroviral Therapy: ART regimens typically contain at least three 
  drugs. Regimens that contain only two drugs are not generally recommended, 
  and monotherapy should always be avoided, except possibly during pregnancy. 
  Additionally, all ART regimens contain drugs from at least two different classes. 
  By using drugs from different classes, we can attack HIV in two different ways 
  (e.g., inhibition of reverse transcriptase and inhibition of protease) and can thereby 
  enhance antiviral effects. 
  
  Criteria for Eligibility to ART in Adults and adolescent: Antiretroviral therapy 
  (ART) is recommended for all persons with HIV to reduce morbidity and mortality 
  and to prevent the transmission of HIV to others. The Panel on Antiretroviral 
  Guidelines for Adults and Adolescents recommends initiating ART immediately (or 
  as soon as possible) after HIV diagnosis in order to increase the uptake of ART and 
  linkage to care, decrease the time to viral suppression for individual patients, and 
  improve the rate of virologic suppression among persons with HIV.
  
  In addition to enhancing antiviral effects, the use of multiple drugs reduces the risk 
  for resistance. Resistance reduction occurs because the probability that HIV will 
  undergo a mutation that confers simultaneous resistance to three or four drugs is 
  much smaller than the probability of undergoing a mutation that confers resistance 
  to just one drug. 
  
  Below are key considerations in clinical management of adolescents and adults 
  living with HIV:
  • Clinical and laboratory evaluations are the cornerstones of care and treatment 
     of HIV positive adolescents and adults. 
  • Renal creatinine clearance is mandatory for adolescents and adults since 
     they initiate with TDF based regimen. 
  • Viral load monitoring should be conducted at 6 months and at 12 months 
     after ART initiation, and annually thereafter. DTG-based regimen remains the 
     preferred first-line option. 
  

  • TDF/3TC/EFV600mg is the alternative first-line regimen for adults and 
     adolescents who cannot take TLD 
  • DTG-based regimen is the preferred 2nd line option for patients failing                                                                                                              a non DTG 1st line regimen. 
  • For patients failing DTG-based regimen, specialist consultation and 
     genotyping should be considered. 
  • PLHIV with advanced HIV disease should be offered a package of interventions 
  including screening, treatment and/or prophylaxis for major OIs, rapid ART 
  initiation and intensified adherence support.
  • TB screening should be done at enrolment and at each clinical visit 
  • Cotrimoxazole should be given to patients with advanced diseases.
  Clinical evaluation
  • Present and past medical history
  • Comprehensive physical examination 
  • WHO staging 
  • Drug history 
  • Sexual history 
  • Nutrition status assessment 
  • OI screening (e.g. TB) 
  • NCDs screening mainly (Refer annex V).
  • Cardiovascular disease: blood pressure, cardiomyopathies 
  • Malignancies: cervical cancer, breast cancer 
  • Metabolic diseases: diabetes, hyperlipidemia, hypocholesteremia 
  • Mental health illness
  Laboratory evaluation Baseline: 
  • CD4 cell count, 
  • Cryptococcus antigen (if CD4 count < 200 cells/mm3) 
  • Renal function (creatinine and calculation of creatinine clearance)
  • Hepatitis B surface antigen (Ag HBs)
  • Hepatitis C antibody (HCV Ab) 
  • LFTs
  • GeneXpert if TB screening is positive 
  • Additional investigations as clinically indicate
  
  ART Regimen in adolescents and Adult
                  
  

   First line ART regimen options
  There are two options recommended in first line regimen
  DTG-based
  NNRTI-based 
               
   Dosage and administration of first-line regimen

  Dosage and administration of first-line regimen

                

  Prescription of ART first line regimen
  1) TDF/3TC/DTG (300/300/50 mg) (OD)
  2) ABC/3TC (600/300 mg) + DTG (50 mg) (OD)
  3) TDF/3TC/EFV (300/300/400mg) 
  4) ABC/3TC (600/300mg) + EFV 600mg
  
  Notes:
  • Encourage taking EFV based regimens in the evening before 8:00 pm to 
  minimize dizziness 
  • Patients with EFV associated side effects should be advised to take it either 
  1-2 hours before or after meals to minimize side effects
  Management of treatment failure among adolescents and adults
  The monitoring of ART response and identification of treatment failure are the same 
  as for children 
  • For early management of treatment failure as well as second line treatment 
  failure refer to the treatment failure algorithm in children section.
  
  Recommended regimens for second-line ART
  
  Recommended regimens for 2nd line ART in adults after failure of specific first line 
  

  regimens.

                

  If TDF is contraindicated, replace with ABC
  In case of hepatitis B co-infection, maintain TDF: TDF+AZT/3TC+ATC/r or LPV/r
  Recommended regimens for third-line
  • DTG 50mg BID + Darunavir/ritonavir + Optimized NRTI or Etravirine can be 
    used based on genotyping results
  • The 3rd line regimen must only be given upon expert consultation and usually 
     with the assistance of genotyping results.
  

  • Before prescribing third-line therapy, the patient must undergo extensive 

  additional adherence counselling and should have a treatment partner 
  involved in adherence assistance. Adherence counselling is critical to the 
  success of this regimen. 
  • NRTI backbone may be necessary based on genotyping test or in case of 
  Hepatitis B co-infection
  Monitoring of adolescents and adults on ART
  Clinical evaluation and laboratory tests play a key role in assessing adolescents 
  and adults before ART initiation, and then monitoring their treatment response as 
  well as possible toxicity of antiretrovirals. Note that once started, ART is a treatment 
  for life but should be changed in the following cases:
  • Drug toxicity 
  • Drug-drug interactions
  • Co-infection
  • Treatment failure confirmed by viral load
  Notes: 
  • The follow up of CD4 count should be done whenever clinically indicated. 
  • For STIs management, refer to national guidelines for STIs and hepatitis.
  1) TREATMENT FAILURE
  Treatment failure is arguably the most compelling reason for changing the regimen. 
  Failure is indicated if: 
  • Plasma HIV RNA remains above 200 copies/mL after 24 weeks 
  • Plasma HIV RNA remains above 50 copies/mL after 48 weeks 
  • Plasma HIV RNA rebounds after falling to an undetectable level 
  • CD4 T-cell counts continue to drop despite antiretroviral treatment 
  • Clinical disease progresses despite antiretroviral treatment
  2) DRUG TOXICITY
  If a patient experiences toxicity typical of a particular drug in the regimen, that drug 
  should be withdrawn and replaced with a drug that is (1) from the same class and 
  (2) of equal efficacy. For example, if a patient taking zidovudine were to develop 
  anemia and neutropenia, zidovudine should be discontinued and replaced with 
  another NRTI (e.g., stavudine). Note that when toxicity is the reason for altering the 
  regimen, changing just one drug is proper, whereas when resistance or suboptimal 
  treatment is the reason, at least two of the drugs should be changed.
  3) Promoting Patient Adherence 
  To achieve treatment goals and delay emergence of resistance, strict adherence 
  to the prescribed regimen is critical. Unfortunately, several factors: duration of  
  

  treatment, complex medication regimens, multiple adverse drug effects, drug-drug 

  interactions, and drug-food interactions make adherence to ART challenging for 
  patients. 
  The factors that predict poor adherence (e.g., poor clinician-patient relationship, 
  active use of alcohol or street drugs, depression and other mental illnesses), as well 
  as factors that predict good adherence (e.g., availability of emotional and practical 
  support, ability to fit dosing into the daily routine, appreciation that poor adherence 
  

  will cause treatment failure).

  Self-assessment 5.3

  1) What is the preferred 1st line regimen for adolescents and adults?
  2) What is the alternative first-line regimen for adults and adolescents who 
  cannot take TLD?
  3) What can be done if a patient experiences toxicity typical of a particular 
  

  drug in the regimen?

  5.4. Antiretroviral treatment in Children

          Learning Activity 5.4
  

  You are an associate nurse and you receive a mother bringing her 2-year-old baby 
  who was born with HIV. She wants the baby to be started on antiretroviral drugs, 
  and there is a student in the clinical placement who doubts on the antiretroviral 
  drugs to administer to the baby.
  1) Which regimen should the baby start with?
  2) The symptoms of HIV infection generally start later compared to the time 
  it takes for adults to develop symptoms. TRUE or FALSE
  3) The preferred 1st line ART option for children of 30kgs and above is 
  

  ABC/3TC+LPV/r. TRUE or FALSE

  CONTENT SUMMARY 

  In young children, the course of HIV infection is accelerated. Whereas adults 
  generally remain symptom free for a decade or more, many children develop 
  symptoms by their first birthday. Death often ensues by age 5 even with ART. Why 
  do young children succumb so quickly? 
  Primarily because their immune systems are immature, and hence less able to fend 
  off the virus. Because immune function is limited, levels of HIV RNA climb higher in 
  toddlers than in adults, and then decline at a much slower rate. 
  

  In very young patients, diagnosis and monitoring of HIV infection employs different 

  methods than those used in adolescents and adults. In particular, for infants under 
  18 months of age, diagnosis should be based on viral load assays, not on antibody 
  tests. For children under 5 years of age, monitoring of immune status should be 
  based on the percentage of CD4 cells, not on absolute CD4 counts. 
  
  Like older patients, young patients should be treated with a combination of 
  antiretroviral drugs, with the goals of (1) reducing plasma viral HIV to an undetectable 
  level and (2) stabilizing or improving immune status. 
  Clinical and laboratory evaluations are the cornerstones of care and treatment of 
  HIV positive children of ≤10 years old. DTG is used for children with weight ≥ 20kgs. 
  The preferred 1st line option for children less than 20kg is ABC/3TC+LPV/r. The 
  preferred 1st line option for children of ≥ 20kg ABC/3TC+DTG. The preferred 1st 
  line option for children of 30kgs and above without renal failure is TDF/3TC/DTG. 
  For children on LPV/r, the preferred formulation is pellet (40mg/10mg, oral pellet) 
  due to its storage and palatability reasons. 
  
  For children with more than 15kg, ATV/r can be used to replace LPV/r. For children 
  on ABC/3TC, 120/60mg is the preferred strength. ABC is contra-indicated for 
  children less than 3 months. If HIV is confirmed before 3 months, the recommended 
  1st line ART regimen is AZT+3TC+LPV/r. Switch to AZT-based regimen in case 
  of intolerance to ABC. LPV/r is contra-indicated for new-born less than 15 days. 
  If switching from AZT-based regimen, consider VL (viral load) suppression. If 
  treatment failure, consider second line regimen. 
  
  TB screening is mandatory for all children at enrolment and at each clinical visit. 
  TPT (Tuberculosis preventive therapy) should be integrated in HIV management. 
  IPT (Isoniazid preventive therapy: Isoniazid 10mg/Kg) is used for 6 Months to all 
  HIV children of ≤5 years old without active TB but with a history of TB contact.                                                                                            Anti TB should be initiated immediately and ART within 2 to 8 weeks. The treatment 
  failure (TF) is defined by the virological failure (plasma viral load >1000 copies/ml) 
  based on two consecutive viral load measurements after 3 months with intensive 
  adherence support. The management of 1st line TF is done after identifying its 
  probable cause and then act as shown by figure 7. The recognition of 2nd line TF 
  is similar to the 1st line TF and the shift to 3rd line is guided by genotyping and 
  expert consultation. The monitoring of children on ART encompasses clinical and 
  laboratory monitoring in order to assess treatment response and potential drug 
  

  toxicity.

  ART Regimen for children younger than 10 years of age 
  

  Table 5.4.1 First line options for ART regimen in children:

                

                 Table 5.1.2: Initiation of ART in children

                   

                     Table 5.1.3:Children who are already on ART

                      Second-line ART in Children

                       

                           Self-assessment 5.4

  1) When the HIV positive children should be screened for TB infection?
  2) Which ART regimen should a 9-year-old child be started with?
  3) Which of the following options is true with regard to treatment of patients 
  with HIV and TB coinfection?
  a) ART should be initiated immediately and anti-TB within 2 to 8 weeks
  b) Anti-TB should be initiated immediately and ART within 2 to 8 weeks
  c) ART should be initiated immediately and anti-TB within 6 weeks
  

  d) Anti-TB should be initiated immediately and ART within 12 weeks

          5.5. ARV Treatment in Pregnant Women
  

                  Learning Activity 5.5

   A woman of 25 years of age was diagnosed for HIV positive during antenatal 
  care at the health center. According to WHO/CDC, it is recommended that all 
  HIV positive women should take ARTs.
  Read the pharmacology book and respond the following questions
  1) When a pregnant woman newly diagnosed HIV positive should start the 
       treatment?
  

  2) What is the ART regimen for an HIV positive pregnant woman?

       CONTENT SUMMARY

  In general, the management of HIV infection in pregnant women should follow the 
  same guidelines for managing HIV infection in nonpregnant adults. Accordingly, 
  current guidelines recommend ART for all pregnant HIV-infected women. ART is 
  needed not only for maternal health, but also to reduce the risk for perinatal HIV 
  transmission. 
  Drug selection is challenging in that information on pharmacokinetics and safety 
  during pregnancy is limited.
  
  When treating HIV infection in pregnant women, the goal is to balance the benefits 
  of treatment, reducing viral load, thereby promoting the health of the mother and 
  decreasing the risk for vertical HIV transmission (i.e., transmission to the foetus) 
  against the risks of drug-induced fetal harm (e.g., teratogenesis, lactic acidosis, 
  death). As a rule, the benefits of treatment outweigh the risks.
   
  The primary determinants of therapy are the clinical, virologic, and immunologic 
  status of the mother; pregnancy is a secondary consideration. Nonetheless, 
  pregnancy should not be ignored. 
  Routine HIV testing for all pregnant women attending ANC for first time during 
  current pregnancy together with their male partners (unless already known HIV 
  positive status). It is preferable that these services are offered during the first 
  trimester of pregnancy but they should be ongoing until delivery.
  
  Every HIV-positive woman will be provided with specific counselling on family 
  planning and get an access to a family planning method of her choice.
  HIV positive pregnant and breastfeeding women should be offered index testing, 
  

  partner notification and family testing services.

  Every pregnant woman whose HIV status is unknown during ANC should be tested 
  for HIV at the time of delivery.
  Every pregnant woman who tested HIV negative during ANC should be retested at 
  the time of delivery. Thereafter, retesting during postnatal period will be based on 
  HIV risk assessment outcomes.
  Women tested HIV positive during ANC or at the time of labor, should start anti                                                                                  retroviral therapy immediately. In case of delay, ART initiation should not go beyond 
  7days.
  Every pregnant or breastfeeding woman newly tested positive for HIV should start 
  with ART regimen Tenofovir + Lamivudine + Dolutegravir.
  
  Every pregnant or breastfeeding woman newly tested HIV-positive and on ART, 
  should receive the first viral load test three months after ART initiation and then 
  after every six months until the end of PMTCT follow up.
  
  All infants born to a known HIV positive mother should receive ART prophylaxis 
  with zidovudine and Nevirapine immediately. If not done immediately, it should be 
  in first 72 hours post-partum or as soon as possible during the first six weeks of life.
  
  All HIV exposed or infected children should have regular growth monitoring to enable 
  early detection of growth retardation and undertake appropriate management.
  
  Pre exposure prophylaxis is offered in the context of PMTCT to HIV negative 
  pregnant and/or breastfeeding women in the following circumstances:
  • Women in discordant relationship whose partners are either not on ART or 
     are on ART but not virally suppressed
  • Women practicing sex work
  
  The regimen recommended for PrEP is a once daily TRUVADA or Tenofovir and 
  Lamivudine for the entire pregnancy and breastfeeding period.
  The use of ART for HIV positive pregnant women will depend on whether she was 
  already on ART or not. The following situations are possible during pregnancy:
  
  c) If the HIV-Positive pregnant woman is already initiated on ART, 
  consider the following aspects:
  • Adherence to the current ART regimen
  • Viral load suppression as per the most recent viral load test results
  • Consider viral load result as ‘recent’ if it was performed less than six months 
  prior to the first ANC visit.
  • It is mandatory to repeat the viral load test for all pregnant women not tested 
  at the first ANC, before the third term of pregnancy (preferably at 6 months of 
  pregnancy)
  • If the woman is virally suppressed, she will be kept on her current ART 
  

  regimen

  • If the woman is not virally suppressed (>200 copies/ml), she will be switched 
      to a Dolutegravir based regimen plus two NRTIs.
  • The switch to Dolutegravir- based regimen will be conducted concurrently with 
  the adherence counselling for patients with documented poor adherence.
  d) If a woman is newly diagnosed HIV positive during pregnancy:
  • The woman is immediately enrolled in care and initiated on ART
  • The preferred ART regimen is Tenofovir + Lamivudine + Dolutegravir 
  (TDF+3TC+DTG)
  • Any woman with impaired renal function or any contraindication to TDF will 
     receive ABC + 3TC+DTG
  NOTE: Doses are the same as in non-pregnant adults’ HIV treatment. 
  

  Monitoring of renal function is important.

  NOTE: Doses are the same as in non-pregnant adults’ HIV treatment. 
  

  Monitoring of renal function is important.

          Self-assessment 5.5

  1) Any pregnant woman whose HIV status is unknown during ANC doesn’t 
  need to be tested for HIV at the time of delivery. TRUE or FALSE
  2) Given their fragile status, the pregnant women with HIV positive status 
  should benefit from lower doses of ARTs compared to the non-pregnant 
  adults. TRUE or FALSE
  3) Which of the following treatment regimens is used as ART initiation among 
  pregnant women in Rwanda?
  a) Abacavir + Lamivudine + Dolutegravir.
  b) Tenofovir + Lamivudine + Dolutegravir.
  c) Efavirenz + Lamivudine + Dolutegravir.
  

  d) Nevirapine + Lamivudine + Dolutegravir.

  5.6. Prophylaxis in new-borns with Perinatal HIV Exposure 
  

  or HIV Infection

       Learning Activity 5.6
  

  Visit library and read pharmacology books /use internet and respond to following 
  question:
  When should the newborn exposed perinatally to HIV start taking newborn ARV 
  

  regimens?

  CONTENT SUMMARY

  A child is considered as ‘exposed to HIV’, if he/she is born to an HIV positive mother. 
  The initiation of infant prophylaxis depends on the time the mother was diagnosed 
  HIV positive. Children born to HIV negative mothers in discordant couple will not 
  receive any prophylaxis as long as their mothers remain HIV negative.
  
  Infant born to a known HIV-positive mother: 
  All children born to a known HIV positive mother (before or during labour) will receive 
  zidovudine and Nevirapine (AZT+ NVP) as soon as possible within 72 hours after 
  birth up to six weeks of life. The baby will also start cotrimoxazole prophylaxis at 
  the age of 6 weeks until the final confirmation of HIV negative status at the age of 
  24 months.
  
  Infant born to a mother diagnosed for HIV after delivery
  If the mother is identified to be HIV-positive at the time of breastfeeding, she should 
  be put on ART. The child will start a combined AZT and NVP as soon as possible 
  for six weeks. At the end of 6 weeks ART prophylaxis; the child will also start 
  cotrimoxazole prophylaxis until the final confirmation of HIV negative status at 24 
  months of life.
  
  All Breastfed infants who are at high risk of acquiring HIV, including those first 
  identified as exposed to HIV during the postpartum period, should continue infant 
  prophylaxis for an additional 6 weeks (total of 12 weeks of infant prophylaxis) using 
  NVP and AZT.
  High-risk infants are defined as:
  Infant born to women with established HIV infection who have received less than 
  four weeks of ART at the time of delivery; or born to women with established HIV 
  infection with viral load >1000 copies/mL in the four weeks before delivery, if viral 
  load measurement available; OR identified for the first time during the postpartum 
  

  period, with or without a negative HIV test prenatally.

        Self-assessment 5.6

  1) During clinical practice in maternity ward, you receive a woman with 
  baby at the second day of home delivery. You take blood sample for HIV 
  testing. After 3 hours you receive a laboratory technician’ s call informing 
  you that the mother is HIV positive. Explain the management of mother 
  

  and her baby to prevent mother to child transmission.

  5.7. HIV Prevention among Discordant Couples
  

           Learning Activity 5.7  

  1) A couple consults the healthcare facility where you are carrying out the 
  clinical placement, and they report they are discordant. The senior nurse 
  tasks you to explain to the couple the overall interventions package for 
  that discordant couple. What is that package?
  

  2) What are the objectives of these interventions?

  CONTENT SUMMARY

  Evidence-based interventions package for HIV sero-discordant couples can 
  be provided through facility based and/or community interventions. Although 
  these interventions are delivered in a package, providers must ensure that they 
  contextualize the specific, particular needs of the couple since different couples 
  may have different needs.
  The objectives of these interventions are:
  • To protect the negative partners from acquiring HIV infection
  • To provide care and treatment to HIV positive partners, allowing them access 
     to early treatment that improves clinical outcomes
  • To protect future children from HIV infections
  • To offer the appropriate HIV prevention package for children and other family 
     members of the HIV positive individuals
  • To support the prevention of unwanted pregnancies in discordant couples
  The overall intervention package for discordant couples consists of the 
   following:
  • Risk reduction counselling and condom provision
  • Initiation of pre-exposure prophylaxis for those whose HIV positive partner is 
  not yet on ARV or are not virally suppressed
  • Family planning counselling and service provision
  • Repeat HIV testing for the uninfected partner every 12 months
  • Care and treatment for the HIV-positive partner
  • STI screening and treatment
  In case of a pregnant HIV-negative partner:
  • The HIV testing shall be done every three months
  • A pre-exposure prophylaxis should be offered in case of non-viral suppression 
     for the positive partner.
  • At labor a single dose of TDF+3TC+DTG will be offered for all women who 
  

     are not taking the pre-exposure prophylaxis.

  The health care provider should encourage the discordant couple to follow up in 
  the same health facility and synchronize with pharmacy refills and appointment 
  schedule. Ongoing psychosocial support and counselling shall be offered to the 
  

  discordant couple.

          Self-assessment 5.7

  1) The health care provider should encourage the discordant couple to 
  follow up in the same health facility and synchronize with pharmacy refills 
  and appointment schedule. TRUE or FALSE
  2) Pregnant HIV-negative partner in discordant couples should receive a 
  

  single dose of TDF+3TC+DTG at labor if they are not taking the pre exposure prophylaxis.                                                                           TRUE or FALSE

  5.8. ART for Post-Exposure Prophylaxis (PEP)
  

          Learning Activity 5.8
  

  3) While he was giving IM injection to a known HIV positive patient, an 

  associate nurse injured himself with a needle after injecting the drug. The 

  senior nurse sends him to the ART service for post exposure prophylaxis. 

  Which drugs may preferably be administered to this patient?

  4) An HIV serology test should be performed for the exposed caregiver as 

  soon as possible (ideally within 72 hours). TRUE or FALSE

  CONTENT SUMMARY

  Every person who has experienced exposure to blood/body fluids, victim of sexual 
  

  assault, or accidental sexual exposure 
  

  (i.e., condomless, sex with a known HIV positive person; condom breakage)                                                                                                  must have access to an early evaluation of the risk of HIV infection and antiretroviral                                                                     prophylaxis if indicated. It is therefore necessary to have PEP services.
  

  Evidence shows that initiating ART prophylaxis 
  

  soon after exposure to HIV reduces the risk of HIV infection by about 80%. 
  

  Postexposure prophylaxis (PEP) is short-term ART to reduce the likelihood of 
  

  acquiring HIV infection after potential exposure.
  
  

  Post-exposure prophylaxis should be provided immediately or preferably within 
  

  72 hours of exposure. An HIV serology test should be performed on the exposed 
  

  individual as soon as possible (ideally within 48 hours).
  

  Case of Accidental Exposure to Blood (AEB) or Other Biological Fluids
  

  In case of accidental exposure to blood, always clean the exposed area immediately. 
  

  In case of exposure through needle stick or skin injury, clean the wound immediately

   with clean water and soap. In case of splash on the mucous membranes (particularly 
  the conjunctiva), rinse at least for 5 minutes with copious amounts of water or 
  preferably physiological saline or any available saline and do not apply disinfectant 
  on the mucous membranes. One of the health care providers from the health facility 
  

  must evaluate the actual risk for a given patient. 

  This evaluation includes:

  • The severity of the exposure, which is directly linked to the depth of the wound 
  and the type of needle that was responsible for the injury (venipuncture 
  needle, needle for injection, non sharp instrument). 
  • For external contact of secretions with the skin or mucosa (splash), the risk is 
  higher with blood than with any other body secretions (amniotic fluid, serous 
  fluid). The person assumed to be the source should be assessed on his 
  or her HIV status, clinical and immunological status and history of ART. If 
  the HIV status is not known, it is important to establish it with his/her free 
  consent. If the HIV status of the source person cannot be obtained within 
  4 hours, prophylaxis for the exposed person should be started immediately 
  after a negative HIV test. If eventually the person assumed to be the source is 
  proven to be HIV-negative, then ARV prophylactic treatment may be stopped
  
  Case of Sexual Assault or Rape
  In case of rape, the provider must first follow the HIV counselling and testing.PEP 
  should be offered to the sexual assault victim once the clinician has assessed all 
  the factors involved in the likelihood of HIV transmission (suspicion of HIV positivity 
  in the assailant, probability of HIV transmission). PEP might help the victim gain 
  a sense of control and decrease their anxiety about acquiring HIV. Consider HIV 
  post-exposure prophylaxis for survivors of sexual assault presenting within 72 
  hours of the assault. In addition to HIV post-exposure prophylaxis, women should 
  be offered emergency contraception to prevent unintended pregnancy immediately 
  or preferably within 72 hours after sexual exposure.
  
  ART Prophylaxis in PEP
  The current recommended duration of post-exposure prophylaxis for HIV infection 
  is 28 days. Treatment should start as early as possible, within the first 4 hours 
  following the exposure, without waiting for results of HIV serology of the source 
  person. A limit of 72 hours is reasonable in seeking maximum efficacy, however the 
  sooner the better.
  The recommended post-exposure prophylaxis drugs are based on the current 
  second and first line regimen:
  1.TDF+ 3TC / FTC +ATV/r
  2. AZT + 3TC/ FTC + ATV/r(If noTDFor a contraindication)
  NB: The recommended ART Prophylaxis is the same in rape/sexual assault and 
  

  exposure to biological fluids.

  Self-assessment 5.8

  1) When HIV post-exposure prophylaxis for survivors of sexual assault is 
  taken into consideration?
  2) What are the actual risks the health care providers from the health facility 
  

  must evaluate in case of exposure through needle stick or skin injury?

  5.9. End unit assessment
  

          End of unit assessment

   I. Complete the empty spaces with the appropriate terms.

  a) Antiretroviral drugs
  b) Antiviral
  c) Retrovirus
  1) ………………………An agent that kills a virus or that suppresses its ability 
  to replicate and, hence, inhibits its capability to multiply and reproduce.
  2) ………………………is a group of viruses that belong to the family 
  Retroviridae and that characteristically carry their genetic blueprint in the 
  form of ribonucleic acid (RNA). 
  3) ………………………….. are the drugs that are used to fight retrovirus 
  infections which mainly include HIV. Different classes of antiretroviral 
  drugs act on different stages of the HIV life cycle.
  II. Respond by true or false 
  1) Abacavir (Ziagen), lamivudine (Epivir) and stavudine (Zerit XR), tenofovir 
  (Viread). 
  2) Efavirenz (Sustiva), nevirapine (Viramune) are drugs in the class of 
  protease inhibitors 
  3) Abacavir (Ziagen) lamivudine (Epivir), stavudine (Zerit XR), tenofovir 
  (Viread), and zidovudine (Retrovir) drugs in the class of Nonnucleoside 
  reverse transcriptase inhibitors . 
  4) Atazanavir, indinavir and lopinavirare drugs in protease inhibitors.
  5) Like older patients, HIV positive young patients should be treated with a 
  combination of antiretroviral drugs. 
  6) Antiretroviral therapy (ART) is recommended for all persons with HIV to 
  

  cure the patient by killing the virus.

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  Electronic links:

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  • https://www.cdc.gov/malaria/travelers/drugs.html

  • https://www.ncbi.nlm.nih.gov/books/NBK8263/

  • https://patient.info/medicine/metronidazole-for-infection-flagyl

  • https://patient.info/medicine/quinine-for-malaria

  • https://medlineplus.gov/druginfo/meds/a609024.html

  • https://www.ncbi.nlm.nih.gov/books/NBK8263/

  • HIV Drugs and the HIV Lifecycle | The Well Project

  • https://www.medicinenet.com/antiviral/definition.htm

  • https://www.britannica.com/science/retrovirus

  • https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/initiation ;                                                                           antiretroviral-therapy?view=full

  • https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/when-initiate-therapy ;                                                                                     antiretroviral-naive-children

  • https://clinicalinfo.hiv.gov/en/guidelines/perinatal/antiretroviral-management ;                                                                                    newborns-perinatal-hiv-exposure-or-hiv-infection

  • https://courses.lumenlearning.com/microbiology/chapter/introduction-to ;                                                                                                     antimicrobial-drugs/

  • https://courses.lumenlearning.com/microbiology/chapter/drug-resistance/

  • https://www.rxlist.com/mefoxin-drug.htm#description, https://www.rxlist.com/

  mefoxin-drug.htm#indicationshttps://www.webmd.com/drugs/2/drug-18352/

  cefoxitin-intravenous/details/list-contraindications

  • https://www.webmd.com/drugs/2/drug-3779-8011/cefuroxime-axetil-oral/

  cefuroxime-oral/details/list-contraindications

  • https://www.drugs.com/dosage/cefadroxil.html

  • https://www.rxlist.com/duricef-side-effects-drug-center.htm

  • https://www.sciencedirect.com/topics/medicine-and-dentistry/ ;                                                                                                                          cephalosporin derivative

  • https://www.rxlist.com/cefazolin-drug.htm#description

  • https://medlineplus.gov/druginfo/meds/a682731.html

  • https://www.drugs.com/dosage/cefazolin.html

  • https://www.medicines.org.uk/emc/product/7072/smpc#gref

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  • https://reference.medscape.com/drug/cipro-xr-ciprofloxacin-342530

  • https://www.rxlist.com/levaquin-drug.htm

  • https://reference.medscape.com/drug/levaquin-levofloxacin-systemic ;                                                                                                        levofloxacin-342532

  • https://www.ncbi.nlm.nih.gov/books/NBK8263/