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Chapter 52: Antiprotozoal Drugs

INTRODUCTION

Diseases caused by protozoans constitute a worldwide health problem. This chapter concerns the drugs used to combat malaria, amebiasis, toxoplasmosis, pneumocystosis, trypanosomiasis, and leishmaniasis.

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DRUGS FOR MALARIA

Malaria is one of the most common diseases worldwide and a leading cause of death. Four species of Plasmodium commonly infect humans (P falciparum, P malariae, P ovale, P vivax) and undergo a primary developmental stage in the liver and then parasitize erythrocytes. P falciparum and P malariae have only one cycle of liver cell invasion. The other species have a dormant hepatic stage responsible for recurrent infections and relapses. A fifth species, P knowlesi, has been recognized as a human pathogen but little is known about it. Primary tissue schizonticides (eg, primaquine) kill schizonts in the liver, whereas blood schizonticides (eg, chloroquine, artemisinins, quinine) kill these forms only in erythrocytes. Sporonticides (proguanil, pyrimethamine) prevent sporogony and multiplication in the mosquito.

Drugs used for the treatment of malaria are shown in Table 52–1.

TABLE 52–1Drugs used in the treatment of malaria.
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TABLE 52–1 Drugs used in the treatment of malaria.
Drug Uses Adverse Effects
Chloroquine Prophylaxis and treatment in areas without resistant P falciparum; treatment of P vivax and P ovale malaria GI distress, rash, headache; auditory dysfunction and retinal dysfunction (high dose)
Artemisinins Standard of care for all chloroquine-resistant malaria GI distress, rare neutropenia, anemia, liver enzymes, allergic reactions
Mefloquine Prophylaxis and treatment in areas with resistant P falciparum GI distress, rash, headache; cardiac conduction defects and neurologic symptoms (high dose)
Quininea Treatment of multidrug-resistant malaria Cinchonism, hemolysis in G6PD deficiency, blackwater fever
Primaquine Eradication of liver stages of P vivax and P ovale GI distress, methemoglobinemia, hemolysis in G6PD deficiency
Antifolates Prophylaxis and treatment of multidrug-resistant P falciparum malaria GI distress, renal dysfunction, hemolysis, folate deficiency
Atovaquone-proguanil (Malarone) Prophylaxis and treatment of multidrug-resistant P falciparum malaria GI distress, headache, rash hemolysis, folate deficiency

aIn most cases quinine is used together with doxycycline or clindamycin, or an antifolate. Quinidine gluconate (IV) is used in severe infections or for patients unable to take oral quinine.

A. Chloroquine

1. Classification and pharmacokinetics

Chloroquine is a 4-aminoquinoline derivative. The drug is rapidly absorbed when given orally, is widely distributed to tissues, and has an extremely large volume of distribution. Antacids may decrease oral absorption of the drug. Chloroquine is excreted largely unchanged in the urine.

2. Mechanism of action

Chloroquine accumulates in the food vacuole of plasmodia and prevents polymerization of the hemoglobin breakdown product heme into hemozoin. Intracellular accumulation of heme is toxic to the parasite. Decreased intracellular accumulation via increased activity of membrane transporters is a mechanism of resistance to chloroquine and other ...

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