Course: S5: Pharmacology

Topic outline

General
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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S5: Pharmacology

Topic outline

General

UNIT 2: ANTHELMINTIC (ANTIHELMINTHIC) DRUGS

UNIT 1: ANTIBIOTICS

UNIT 3: ANTIPROTOZOAL DRUGS

UNIT 4 : ANTIFUNGAL DRUGS

UNIT 5: ANTIVIRAL DRUGS

Table of contents