Diseases caused by protozoans constitute a worldwide health problem. This chapter concerns the drugs used to combat malaria, amebiasis, toxoplasmosis, pneumocystosis, trypanosomiasis, and leishmaniasis.
Malaria is one of the most common diseases worldwide and a leading cause of death. Plasmodium species that infect humans (P falciparum, P malariae, P ovale, P vivax) undergo a primary developmental stage in the liver and then parasitize erythrocytes. 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. Primary tissue schizonticides (eg, primaquine) kill schizonts in the liver, whereas blood schizonticides (eg, chloroquine, artemisinins, quinine) kill these forms only in the erythrocyte. 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. |Favorite Table|Download (.pdf) 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 |
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.
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 antimalarial drugs. Resistance in P falciparum can also result from decreased intravacuolar accumulation of chloroquine via a transporter encoded by the pfcrt (P ...