Chloroquine: mechanism of drug action and resistance in plasmodium falciparum

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  1. yandyusha Well-Known Member

    Chloroquine: mechanism of drug action and resistance in plasmodium falciparum


    Previously referred to as “Resochin”, Chloroquine was first discovered in 1924 at Bayer laboratories. Its first use was initially ignored as it was found to be toxic to people.

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    Development of Chloroquine Resistance in Plasmodium falciparum. Drug resistance is the ability of a parasite to survive despite the presence of a drug that is meant to kill it in toxic levels. Resistance developed by most parasites that were initially sensitive to drugs mostly result from mutations in the genes responsive to the drug. Krogstad DJ, Gluzman IY, Kyle DE, Oduola AM, Martin SK, Milhous WK, Schlesinger PH. Efflux of chloroquine from Plasmodium falciparum mechanism of chloroquine resistance. Science. 1987 Nov 27; 238 48311283–1285. Krogstad DJ, Schlesinger PH. A perspective on antimalarial action effects of weak bases on Plasmodium falciparum. Biochem Pharmacol. Mar 27, 2003 The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality among inhabitants of some endemic regions. The rationale for chemoprophylaxis is weakening as multiple‐drug resistance develops against well‐tolerated drugs. Plasmodium falciparum drug‐resistant malaria originates from chromosome mutations.

    These trials showed that chloroquine eliminated malaria and was appropriate to be used as an antimalarial drug. Thus, it was not until World War II that the government of the United States sponsored the clinical trials of chloroquine as an antimalarial drug.

    Chloroquine: mechanism of drug action and resistance in plasmodium falciparum

    Drug resistance in Plasmodium Nature Reviews Microbiology, Antimalarial agents mechanism of chloroquine resistance.

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  7. Sanchez, C. P. Stein, W. & Lanzer, M. Trans stimulation provides evidence for a drug efflux carrier as the mechanism of chloroquine resistance in Plasmodium falciparum.

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    Extrusion of chloroquine CQ from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter PfCRT is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. Resistance to chloroquine, in the case of P. falciparum, is linked to mutations in the P. falciparum chloroquine resistance transporter pfcrt gene, which alters the transport and accumulation of the drug in the digestive vacuole DV of the parasite 7, 8. Chloroquine mechanism of drug action and resistance in Plasmodium falciparum. Slater AF1. Author information 1Picower Institute for Medical Research, Manhasset, NY 11030. Quinoline-containing drugs such as chloroquine and quinine have had a long and successful history in antimalarial chemotherapy.

     
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  10. soiskatelb Moderator

    Plaquenil Hydroxychloroquine Uses, Dosage, Side Effects. Hydroxychloroquine sulfate is a colorless crystalline solid, soluble in water to at least 20 percent; chemically the drug is 2-4-7-Chloro-4-quinolylaminopentylethylamino ethanol sulfate 11. PLAQUENIL hydroxychloroquine sulfate tablets contain 200 mg hydroxychloroquine sulfate, equivalent to 155 mg base, and are for oral administration.

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