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(01) Antibiotics = Historical background, Nomenclature, Stereochemistry, Structure activity relationship, Chemical degradation classification and important products of the following classes-
(02) Macrolide: Erythromycin Clarithromycin, Azithromycin.
Miscellaneous: Chloramphenicol*, Clindamycin.
(03) Prodrugs: Basic concepts and application of prodrugs design.
Antimalarials: Etiology of malaria.
(04) Quinolines: SAR, Amodiaquine,Primaquine hydrochloride, Mefloquine.
Quinine phosphate, sulphate, Pamaquine*, Chloroquine*, Quinacrine
(05) Biguanides and dihydro triazines: Cycloguanil pamoate, Proguanil.
(06) Miscellaneous: Pyrimethamine, Artesunete, Artemether, Atovoquone.
CHLOROQUINE
It has activity against the blood stages of plasmodium ovale, susceptible strains of P. Vivax and P. Falciparum. Widespread resistance in most malaria-endemic countries has led use for the treatment of p. Falciparum, although it remains effective P. Ovale, P. Malariae and, in most regions, P. Vivax.
Mechanism of action :
Hemoglobin is composed of a protein unit (digested by the parasite) and a heme unit (not used by the parasite). During this process, the parasite releases the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a nontoxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.[citation needed]
Chloroquine enters the red blood cell by simple diffusion, inhibiting the parasite cell and digestive vacuole. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form the FP-chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. Parasites that do not form hemozoin are therefore resistant to chloroquine.
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Негізгі бет Topic (23) Antimalarial Drugs | Chloroquine Mechanism of Action | Chloroquine MOA | Antimalarial
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