| Chloroquine |
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Information AboutChloroquine |
| CATEGORIES ABOUT CHLOROQUINE | |
| antimalarial agents | |
| quinolines | |
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Chloroquine is a commonly used form of Medication against Malaria . As it also mildly suppresses the immune system, it is used in some Autoimmune Disorder s, such as Rheumatoid Arthritis . PHARMACOLOGY It has a very high Volume Of Distribution , as it diffuses into the body's Adipose Tissue . MECHANISM OF ACTION Inside the Red Blood Cell s, the Parasite must degrade the Hemoglobin for the acquisition of essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. This is essential for parasitical growth and division inside the red blood cell. It is carried out in the digestive vacuole of the parasite cell. During this process, the parasite produces the toxic and soluble molecule Heme . The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX. To avoid destruction by this molecule, the parasite polymerises heme to form hemozoin , an non-toxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals. Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. 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 polymerisation of heme. Thus leading to heme build up. Chloroquine binds to heme (or FP) to form what is known as 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 ultimatly parasite cell autodigestion. Basically the parasite cell drowns in its own metabolic products. The effectiveness of chloroquine against the parasite has declined as some resistant forms of the parasite can effectively neutralize the drug by developing a mechanism that drains chloroquine away from the digestive vacuole. CQR cells efflux chloroquine at 40 times the rate of CQS cells, this is related to a number of mutations that trace back to transmembrane proteins of the digestive vacuole, including a essential mutation in the PfCRT gene. This mutated protein may actively pump chloroquine from the cell. Research on the mechanism of chloroquine and how the parasite has aquired chloroquine resistance is still ongoing, and this article is not by any means fact. Against rheumatoid arthritis, it operates by inhibiting Lymphocyte proliferation, Phospholipase A , release of Enzyme s from Lysosome s, release of Reactive Oxygen Species from Macrophage s, and production of IL-1 . |
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