Antiprotozoal Drugs

Overview:
Protozoal diseases, such as
1. Amebiasis.
2. Malaria.
3. Leishmaniasis.
4. Trypanosomiasis.
5. Toxoplasmosis.
6. Giardiasis.
Amebiasis:
Amebiasis (also called amebic dysentery) is an infection of the intestinal
tract caused by Entamoeba histolytica. The disease showing varying
degrees of illness, from no symptoms to mild diarrhea to fulminating
dysentery.
Classification of amebicidal drugs:
Therapeutic agents are classified according to the site where the drug is
effective as:
a. Luminal amebicides (act on the parasite in the lumen of the bowel).
b. Systemic amebicides (effective against amebas in the intestinal wall
and liver).
c. Mixed (luminal and systemic) amebicides are effective against both
the luminal and systemic forms of the disease.
Luminal amebicides drugs:
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Iodoquinol: is amebicidal against E. histolytica, and is effective against

the luminal trophozoite and cyst forms.
Mechanism of action involves an inactivation of essential
parasite enzymes.
Side effects from iodoquinol include rash, diarrhea.
Systemic amebicides drugs:
Emetine and dehydroemetine: Emetine and dehydroemetine are
alternative agents for the treatment of amebiasis.
Mechanism of action: inhibit protein synthesis by blocking chain
elongation.
Intramuscular injection is the preferred route.
Side effects:
1. Pain at the site of injection.
2. Transient nausea.
3. Cardiotoxicity (for example, arrhythmias or congestive heart
failure).
4. Neuromuscular weakness, dizziness, and rashes.
Mixed amebicides (metronidazole):
Metronidazole: Metronidazole is the mixed amebicide of choice for
treating amebic infections; it kills the E. histolytica trophozoites.

Note:
Metronidazole also use in the treatment of infections caused by Giardia
lamblia, Trichomonas vaginalis, anaerobic cocci, and anaerobic gramnegative bacilli (for example, Bacteroides species).
Mechanism of action:
Metronidazole Inhibits DNA replication Affects synthesis or structure of
nucleic acids.
Adverse effects: The most common adverse effects are:
1. Gastrointestinal tract: including nausea, vomiting, epigastric
distress, and abdominal cramps.
2. An unpleasant, metallic taste.
3. Other effects include yeast infection of the mouth.
Chemotherapy for Malaria:
Malaria is an acute infectious disease caused by four species of the
protozoal genus Plasmodium.
The parasite is transmitted through the bite of a female Anopheles
mosquito.
Chloroquine: Chloroquine the mainstay of antimalarial therapy, and it
is the drug of choice in the treatment of erythrocytic P. falciparum
malaria.
Side effects:

Primaquine:
Primaquine eradicates primary exoerythrocytic forms of P. falciparum
and P. vivax and the secondary exoerythrocytic forms of malarias (P.
vivax and P. ovale).
Side effects:
1. Primaquine induced hemolytic anemia in patients with genetically
low levels of glucose-6-phosphate dehydrogenase.
2. Other toxic manifestations observed after large doses of the drug
include abdominal discomfort, especially when administered in
combination with chloroquine. Primaquine is contraindicated

during pregnancy. All Plasmodium species may develop resistance

to primaquine.

Chemotherapy for Leishmaniasis

There are three types of leishmaniasis:
1. Cutaneous.
2. Mucocutaneous.
3. Visceral.
Leishmaniasis is transmitted from animals to humans (and between
humans) by the bite of infected sandflies.
Sodium stibogluconate
Mechanism of action:
Inhibition of glycolysis in the parasite.
Because it is not absorbed on oral administration, sodium stibogluconate
must be administered parenterally.
Adverse effects: include pain at the injection site, gastrointestinal
upsets, and cardiac arrhythmias.

Chemotherapy for Trypanosomiasis:

Trypanosomiasis diseases caused by species of Trypanosoma: African
sleeping sickness, and American sleeping sickness. In African sleeping
sickness, initially live and grow in the blood.

The parasite invades the CNS, causing an inflammation of the brain and
spinal cord that produces the characteristic lethargy and, eventually,
continuous sleep. Chagas' disease (American sleeping sickness) is
caused by Trypanosoma cruzi and occurs in South America.

Melarsoprol
Melarsoprol is a derivative of mersalyl oxide, a trivalent arsenical. Its
use is limited to the treatment of trypanosomal infections usually in the
late stage with CNS involvement and it is lethal to these parasites.
Adverse effects:
CNS toxicities are the most serious side effects of melarsoprol
treatment.
1. Encephalopathy
2. Hypersensitivity reactions and fever may follow injection.
3. Gastrointestinal disturbances, such as severe vomiting and
abdominal pain.
4. Hemolytic anemia has been seen in patients with glucose 6phosphate dehydrogenase deficiency.

Suramin:
Suramin is used primarily in the early treatment and, especially, the
prophylaxis of African Trypanosomiasis. It is inhibits many enzymes;
the drug must be injected intravenously. It binds to plasma proteins and

remains in the plasma for a long time, accumulating in the liver and in
the proximal tubular cells of the kidney.
Adverse

reactions

include

nausea,

vomiting,

shock,

loss

of

consciousness and acute urticaria.

Chemotherapy for Toxoplasmosis:

One of the most common infections is caused by Toxoplasma gondii,
which is transmitted to humans when they consume uncooked food and
infected meat. The treatment of choice for this condition is the drug

pyrimethamine, Trimethoprim and sulfamethoxazole.

Inhibit the parasites ability to synthesize folic acid.
Chemotherapy for Giardiasis:
Giardiasis is an infection of the small intestine that is caused by the
parasite, Giardia intestinalis, also known as Giardia lamblia. It is the
most common cause of parasitic gastrointestinal disease; it is estimated
that up to 2.5 million cases of giardiasis occur each year in the U.S., and
up to 20% of the world's population is chronically infected.
Giardia lamblia exists in two forms, an active form called a trophozoite,
and an inactive form called a cyst. The infection is spread from person to
person by contamination of food with feces.
Typical clinical symptoms of giardiasis usually begin 1 to 3 weeks after
ingestion of cysts and are marked by diarrhea, malaise, greasy stools,
and abdominal cramps. Other symptoms commonly include bloating,
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weight loss and anorexia. Vomiting and fever are less common, and
blood- or mucus-tinged feces are rare
Nitroimidazoles:
The nitroimidazoles class of agents used to treat G. lamblia infection
includes metronidazole, tinidazole and ornidazole.
Metronidazole utilizes the anaerobic metabolic pathways present in
Giardia. The drug enters the trophozoite then parasite is death.