Chloroquine is a synthetic 4-aminoquinoline (Figure 52–2) formulated as the phosphate salt for oral use. It is rapidly and almost completely absorbed from the gastrointestinal tract, reaches maximum plasma concentrations in about 3 hours, and is rapidly distributed to the tissues. It has a very large apparent volume of distribution of 100–1000 L/kg and is slowly released from tissues and metabolized. Chloroquine is principally excreted in the urine with an initial half-life of 3–5 days but a much longer terminal elimination half-life of 1–2 months.
When not limited by resistance, chloroquine is a highly effective blood schizonticide. Chloroquine is not reliably active against liver stage parasites or gametocytes. The drug probably acts by concentrating in parasite food vacuoles, preventing the biocrystallization * Malarone is a proprietary formulation of atovaquone plus proguanil.
†Coartem is a proprietary formulation of artemether and lumefantrine.
FIGURE 52–2 Structural formulas of some antimalarial drugs.
of the hemoglobin breakdown product, heme, into hemozoin, and thus eliciting parasite toxicity due to the buildup of free heme.
Resistance to chloroquine is now very common among strains of P falciparum and uncommon but increasing for P vivax. In P falciparum, mutations in a putative transporter, PfCRT, are the primary mediators of resistance. Chloroquine resistance can be reversed by certain agents, including verapamil, desipramine, and chlorpheniramine, but the clinical value of resistance-reversing drugs is not established.
1. Treatment—Chloroquine is the drug of choice in the treatment of uncomplicated nonfalciparum and sensitive falciparum malaria. It rapidly terminates fever (usually in 24–48 hours) and clears parasitemia (in 48–72 hours) caused by sensitive parasites. Chloroquine has been replaced by other drugs, principally artemisinin-based combination therapies, as the standard therapy to treat falciparum malaria in most endemic countries. Chloroquine does not eliminate dormant liver forms of P vivax and P ovale, and for that reason primaquine must be added for the radical cure of these species.
2. Chemoprophylaxis—Chloroquine is the preferred chemoprophylactic agent in malarious regions without resistant falciparum malaria. Eradication of P vivax and P ovale requires a course of primaquine to clear hepatic stages.
TABLE 52–1 Major antimalarial drugs.
1Not available in the USA. 2Available in the USA only as the fixed combination Coartem.
3. Amebic liver abscess—Chloroquine reaches high liver concentrations and may be used for amebic abscesses that fail initial therapy with metronidazole (see below).
Chloroquine is usually very well tolerated, even with prolonged use. Pruritus is common, primarily in Africans. Nausea, vomiting, abdominal pain, headache, anorexia, malaise, blurring of vision, and urticaria are uncommon. Dosing after meals may reduce some adverse effects. Rare reactions include hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient persons, impaired hearing, confusion, psychosis, seizures, agranulocytosis, exfoliative dermatitis, alopecia, bleaching of hair, hypotension, and electrocardiographic changes. The long-term administration of high doses of chloroquine for rheumatologic diseases (see Chapter 36) can result in irreversible ototoxicity, retinopathy, myopathy, and peripheral neuropathy, but these are rarely seen with standard-dose weekly