4-aminoquinoline
Chloroquine is effective against the asexual erythrocytic stages of Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale. It is not active against mature gametocytes of Plasmodium falciparum nor does it does not affect sporozoites or hypnozoites of Plasmodium vivax
The interaction between chloroquine and haem prevents the incorporation of FPIX into haemozoin in vivo, leading to a build-up of toxic FPIX that eventually overwhelms the parasite.
The chloroquine-resistance mechanism regulates the access of chloroquine to haematin. It is believed principally to involve pfcrt1. The protein produced by the pfcrt gene is located in this digestive vacuole and may act as its “gatekeeper”.
In chloroquine-resistant malaria, mutations in pfcrt may encourage chloroquine to "leak" out of the vacuole.
Oral bioavailability about 90%.
Chloroquine has a large apparent volume of distribution due to extensive tissue binding, is eliminated slowly from the body and is detectable in the urine for up to a year after drug administration. The terminal elimination half-life is 45-55 days for chloroquine and 59-67 days for its major plasma metabolite desethylchloroquine.
In uncomplicated malaria, the standard treatment regimen for chloroquine against sensitive parasites is a total dose of 25 mg base/kg, usually given as an initial dose of 10 mg/kg followed by 5 mg/kg at 12-hourly intervals.
When given parentally, an initial dose of 10 mg base/kg should be given over a period of 8 hours by slow intravenous infusion.
Subsequent infusions of 5 mg base /kg should be given every 8 hours up to a total dose of 25 mg base/kg.
Chloroquine can be administered by intramuscular or subcutaneous injection at a dose of 3.5 mg base/kg 6-hourly up to a total dose of 25 mg base/kg.
Nausea, vomiting, weakness, dyspnea, dysphagia, tremors, convulsions and coma.
In curative doses, chloroquine prolongs the QTc interval. In overdose, the main effects are on the cardiovascular system, with cardiac conduction disturbances and shock.
Itching is common in blacks.
Long-term chloroquine administration may produce retinal toxicity leading to blindness.