Chloroquine antimalarial actions

Ginsburg H, Golenser J. Glutathione is involved in the antimalarial action of chloroquine and its modulation affects drug sensitivity of human and murine species of Plasmodium. Redox Rep. 2003 8 276-279. 

Hydroxychloroquine (and also chloroquine, see Ch. 14) in addition to their antimalarial actions exert anti-inflammatory and immunomodulating effects that are useful in rheumatoid disease. Hydroxychloroquine accumulates within lymphocytes, macrophages, polymorphs and fibroblasts, and inhibits phagocyte function but its exact mode of action is unknown. Its action is terminated both by metabolism and renal elimination (t/ 18 days). 

Fitch, C. D., and Russell, N. V. (2006). Accelerated denaturation of hemoglobin and the antimalarial action of chloroquine. Antimicrob. Agents Chemother. 50, 2415-2419. 

MECHANISMS OF ANTIMALARIAL ACTION AND RESISTANCE TO CHLOROQUINE AND OTHER ANTIMALARIAL QUINOLINES... 

Soon after the Second World War (1943), a large number of compounds were synthesized and tested for antimalarial actions, and these eventually gave birth to a host of potent drugs like, chloroquine, proguanil, comoquine and amodiaquine, etc. 

Its antimalarial action is very much similar to that of chloroquine and hence may be used alternatively for the same purpose. 

Sullivan DJ Jr, Gluzman lY, Russell DG, et al. On the molecular mechanism of chloroquine s antimalarial action. Proc Natl Acad Sci USA 1996 93 11865-11869. 

Straub KD, Carver P (1975) Sanguinarine, inhibitor ofNa-K dependent ATP ase. Biochem Biophys Res Commiin 62 913 922 Sudo H, Yamakawa T, Yamazaki M, Aimi N, Saito K (2002) Bioreactor production of camptothecin by hairy root cultures of Ophiorrhiza pumila. Biotechnol Lett 24 359 363 Sullivan DJ Jr, Gluzman lY, Russell D G, Goldberg DE (1996) On the molecular mechanism of chloroquine s antimalarial action. Proc Natl Acad Sci USA 93 11865 11870 Sun XF, Sun RC, Fowler P, Baird MS (2005) Extraction and characterization of original lignin and hemicelluloses Ifom wheat straw. J Agric Food Chem 53 860-870... 

Artemisinin ( qinghaosu ) (18), a sesquiterpene lactone antimalarial compound with an endoperoxide group, discovered in the Peoples Republic of China as a constituent of Artemisia annua L., has created great interest in the biomedical community, owing to its unique mechanism of action on the heme complex. Artemisinin serves as an option for the treatment of chloroquine (4l)-resistant malaria and is used in some Asian countries as an antimalarial. However, the use of artemisinin as a single agent anti-malarial is a potential risk since the malaria parasite may become resistant to this compound class. 

Chloroquine is the drug of choice for preventing and treating acute forms of malaria caused by P. vivax, P. malariae, P ovale, as well as sensitive forms of P. falciparum. The mechanism of its action is not completely clear, although there are several hypotheses explaining its antimalarial activity. Chloroquine and its analogs inhibit synthesis of nucleic acids of the parasite by affecting the matrix function of DNA. This happens by preliminary... 

Thus the main quality of chloroquine that exceeds all other antimalarial drug is its effect on erythrocytic schizonts (hematoschizotropic action). However, chloroquine also possesses amebicidal action. It has also been observed to have immunodepressive and antiarrhythmic properties. 

In terms of its type of action, quinine is an antimalarial drug similar to chloroquine, although it is inferior in its activity. 

Quinine is the principal alkaloid derived from the bark of the cinchona tree. It has been used for malaria suppression for over 300 years. By 1959 it was superseded by other drugs, especially chloroquine. After widespread resistance to chloroquine became manifest quinine again became an important antimalarial. Its main uses are for the oral treatment of chloroquine-resistant falciparum malaria and for parenteral treatment of severe attacks of falciparum malaria. Quinine is a blood schizonticide with some gametocytocidal activity. It has no exoerythrocytic activity. Its mechanism of action is not well understood. It can interact with DNA, inhibiting strand separation and ultimately protein synthesis. Resistance of quinine has been increasing in South-East Asia. 

Hydroxychloroquine Plaquenil) and chloroquine Ara-len) are 4-aminoquinoline antimalarial drugs that possess modest DMARD activity. They are indicated for the treatment of rheumatoid arthritis and systemic lupus erythematosus their use as antimalarials is detailed in Chapter 53. The onset of action of these drugs is longer than that of other DMARDs, and their side effects are relatively mild. Because of this, these agents show promise as ingredients of combination therapies for rheumatoid arthritis. 

Chloroquine and related antimalarials are effective in rheumatoid arthritis and lupus erythematosus, but their mode of action is not known. The anthelmintic drug levamisole (186) is also effective but adverse effects limit its use. 

Mechanism of Action. Although the drug s exact mechanism of action is unknown, mefloquine may exert antimalarial effects similar to chloroquine that is, these drugs inhibit hemoglobin digestion in malarial parasites, thus causing heme by-products to accumulate within the protozoa and cause toxicity and death of this parasite.65... 

Mechanism of Action. The exact mechanism of quinine is not known. This drug probably exerts antimalarial effects similar to those of chloroquine—that is, inhibition of hemoglobin digestion and subsequent accumulation of toxic heme by-products that lead to death in susceptible protozoa.22... 

A special problem arose with respect to the antiplasmodial drugs chloroquine (Resochin) and quinacrine (Atebrin). Plasmodia can not be propagated in cell-free lifeless media and the limited availability of erythrocytic plasmodial cultures severely limits biochemical or molecular pharmacological studies on the action of antimalarials. The actions of chloroquine and quinacrine were, therefore, studied in Bacillus megaterium or E. coli, respectively 22 ... 

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