Chloroquine and Other Aminoquinolines
Chloroquine and other aminoquinolines are used in the prophylaxis of or therapy for malaria and other parasitic diseases. Chloroquine and hydroxychloroquine also are used in the treatment of rheumatoid arthritis. Drugs in this class include chloroquine phosphate (Aralen), amodiaquine hydrochloride (Camoquin), hydroxychloroquine sulfate (Plaquenil), mefloquine (Lariam), primaquine phosphate, and quinacrine hydrochloride (Atabrine). Chloroquine overdose is common, especially in countries where malaria is prevalent, and the mortality rate is 10–30%. Quinine toxicity is described in Quinine.
Mechanism of toxicity
Chloroquine blocks the synthesis of DNA and RNA and also has some quinidine-like cardiotoxicity. Hydroxychloroquine has similar actions but is considerably less potent.
Primaquine and quinacrine are oxidizing agents and can cause methemoglobinemia or hemolytic anemia (especially in patients with glucose-6-phosphate dehydrogenase [G6PD] deficiency).
Pharmacokinetics. Chloroquine and related drugs are highly tissue-bound (volume of distribution [Vd] = 150–250 L/kg) and are eliminated very slowly from the body. The terminal half-life of chloroquine is 2 months, and that of hydroxychloroquine is 40 days. Primaquine, with a half-life of 3–8 hours, is extensively metabolized to an active metabolite that is eliminated much more slowly (half-life of 22–30 hours) and can accumulate with chronic dosing (see also Table II–61).
Toxic dose. The therapeutic dose of chloroquine phosphate is 500 mg once a week for malaria prophylaxis or 2.5 g over 2 days for treatment of malaria. Deaths have been reported in children after ingesting one or two tablets—doses as low as 300 mg; the lethal dose of chloroquine for an adult is estimated at 30–50 mg/kg.
Clinical presentation
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