Chloroquine: mechanism of drug action and resistance in plasmodium falciparum

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  1. Keras Moderator

    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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    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. Recent highlights include the discovery of a key gene associated with resistance, pfcrt Plasmodium falciparum chloroquine resistance transporter; PfCRT, encoding a novel transporter, and the characterization of global selective sweeps of haplotypes containing a K76T amino acid change within this protein. Little is known about the cellular mechanism by which resistant parasites escape the effects of chloroquine CQ, one of the most promising drugs ever deployed, due in part to an. In the pharmacological features of the chloroquine resistance in P. falciparun, namely the proposed efflux mechanism and the reversal of resistance by verapamil, desipramine and related compounds led to the proposal that a similar mechanism for drug resistance was operating in P. falciparum.

    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

    On the Mechanism of Chloroquine Resistance in Plasmodium., Pfcrt is more than the Plasmodium falciparum chloroquine.

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  6. Drug transport is believed to be of crucial importance for understanding the mechanisms of chloroquine resistance, as it is clear that less chloroquine accumulates in chloroquine-resistant parasites than in chloroquine-sensitive parasites. It was originally thought that this lack of accumulation was the result of an efflux mechanism, and a P-glycoprotein was implicated as the pump responsible for the efflux.

    • Malaria Dissecting chloroquine resistance - ScienceDirect.
    • MECHANISMS OF DRUG RESISTANCE IN PLASMODIUM FALCIPARUM.io=.
    • Malaria Mode of action of chloroquine and mechanism of..

    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. 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. During the past year, confirmed chloroquine-resistant infections have been described from specific areas in Zambia 3 and Sudan 4; previously, Kenya, Tanzania, Uganda, Madagascar, and the Comoros Islands were acknowledged to have transmission of chloroquine-resistant P. falciparum.

     
  7. testar New Member

    Hydroxychloroquine is a quinoline medicine used to treat or prevent malaria, a disease caused by parasites that enter the body through the bite of a mosquito. Hydroxychloroquine 200 mg Tablets Generic Plaquenil Hydroxychloroquine - an overview ScienceDirect Topics Hydroxychloroquine Uses, Dosage & Side Effects -
     
  8. www.serva4ok.net New Member

    Drug Resistance in the Malaria-Endemic World - CDC Drug-resistant P. falciparum. Chloroquine-resistant P. falciparum first developed independently in three to four areas in Southeast Asia, Oceania, and South America in the late 1950s and early 1960s. Since then, chloroquine resistance has spread to nearly all areas of the world where falciparum malaria is transmitted.

    Malaria Prophylaxis – Malaria Site