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P A R T 2
Chemotherapeutic agents
Trypanosomiasis
Trypanosomiasis
is caused by infection with
Trypano-
soma.
Two parasitic protozoal species cause very serious
and often fatal diseases in humans:
• African sleeping sickness, which is caused by
Trypanosoma brucei gambiense,
is transmitted
by the tsetse fly. After the pathogenic organism
has lived and grown in human blood, it eventually
invades the CNS, leading to an acute inflammation
that results in lethargy, prolonged sleep and even
death.
• Chagas disease, which is caused by
Trypanosoma
cruzi,
is almost endemic in many South American
countries. It is passed to humans by the common
housefly. This protozoan results in a severe
cardiomyopathy that accounts for numerous deaths
and disabilities in certain regions.
Trichomoniasis
Trichomoniasis
, which is caused by another flagellated
protozoan,
Trichomonas vaginalis
, is a common cause
of vaginitis. This infection is usually spread during
sexual intercourse by men who have no signs and
symptoms of infection. In women, this protozoan causes
reddened, inflamed vaginal mucosa, itching, burning
and a yellowish-green discharge. Trichomoniasis is par-
ticularly prevalent among the Aboriginal and Torres
Strait Islander population in Australia.
Giardiasis
Giardiasis
, which is caused by
Giardia lamblia
, is a very
commonly diagnosed intestinal parasite in Australia.
This protozoan forms cysts, which survive outside the
body and allow transmission through contaminated
water or food, and trophozoites, which break out of
the cysts in the upper small intestine and eventually
cause signs and symptoms of disease. Diarrhoea, rotten
egg–smelling stool, and pale and mucus-filled stool are
commonly seen. Some individuals experience epigastric
distress, weight loss and malnutrition as a result of the
invasion of the mucosa.
Pneumocystis carinii pneumonia
Pneumocystis carinii
is an endemic protozoan that does
not usually cause illness in humans. When an individual’s
immune system becomes suppressed because of acquired
immune deficiency syndrome (AIDS) or AIDS-related
complex (ARC), the use of immunosuppressant drugs or
advanced age, this parasite is able to invade the lungs,
leading to severe inflammation and the condition known
as
Pneumocystis carinii
pneumonia (PCP)
. This disease
is the most common opportunistic infection in people
with AIDS.
OTHER ANTIPROTOZOAL AGENTS
Drugs that are available specifically for the treatment
of these various protozoan infections include many of
the malarial drugs; chloroquine is effective against
extraintestinal amoebiasis, and pyrimethamine is effec-
tive in treating toxoplasmosis. Other drugs, including
some tetracyclines and aminoglycosides, are used for
treating these conditions at various stages of the disease.
Other antiprotozoals include atovaquone (
Wellvone
),
metronidazole (
Flagyl
,
Metronide
), pentamidine (
DBL
Pentamidine Isethionate
), pyrimethamine (
Daraprim
)
and tinidazole (
Fasigyn, Simplotan
). (See Table 12.2.)
Therapeutic actions and indications
These antiprotozoal agents act to inhibit DNA synthe-
sis in susceptible protozoa, interfering with the cell’s
ability to reproduce, subsequently leading to cell death
(see Figure 12.1). These drugs are indicated for the treat-
ment of infections caused by susceptible protozoa. See
Table 12.2 for usual indications for each of these agents.
Pharmacokinetics
Atovaquone is slowly absorbed and is highly protein
bound in circulation. It is excreted slowly through the
faeces, with a half-life of 67 to 76 hours.
Metronidazole is well absorbed orally, reaching
peak levels in 1 to 2 hours. It is metabolised in the liver
with a half-life of 8 to 15 hours. Excretion occurs pri-
marily through the urine.
Pentamidine is readily absorbed through the lungs.
Excretion occurs in the urine, with traces found in the
urine for up to 6 weeks.
Pyrimethamine is readily absorbed from the GI
tract, with peak levels occurring within 2 to 6 hours. It
is metabolised in the liver and has a half-life of 4 days.
It usually maintains suppressive concentrations in the
body for about 2 weeks.
Tinidazole is rapidly absorbed after oral administra-
tion, reaching peak levels within 60 to 90 minutes. It is
excreted in the urine with a half-life of 12 to 14 hours.
Contraindications and cautions
Contraindications include the presence of any known
allergy or hypersensitivity to any of these drugs and
pregnancy
because drug effects on developing fetal
DNA and proteins can cause fetal abnormalities and
even death.
Use caution when administering these
drugs to people with CNS disease
because of possible
disease exacerbation due to drug effects on the CNS
;
hepatic disease
because of possible exacerbation when
hepatic drug effects occur
; candidiasis
because of the
risk of superinfections
; and women who are breast-
feeding
because these drugs may pass into breast milk
