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Chapter: Basic & Clinical Pharmacology - Antiprotozoal Drugs

Other Quinolines - Malaria

Amodiaquine is closely related to chloroquine, and it probably shares mechanisms of action and resistance with that drug.

OTHER QUINOLINES

Amodiaquine is closely related to chloroquine, and it probably shares mechanisms of action and resistance with that drug. Amodiaquine has been widely used to treat malaria because of its low cost, limited toxicity, and, in some areas, effectiveness against chloroquine-resistant strains of P falciparum. Reports of toxicities of amodiaquine, including agranulocytosis, aplastic anemia, and hepatotoxicity, have limited use of the drug in recent years. However, recent reevaluation has shown that serious toxicity from amodiaquine is rare, and it may be used as a replacement for chlo-roquine in areas with high rates of resistance but limited resources. The most important current use of amodiaquine is in combination therapy. The World Health Organization (WHO) lists amodiaquine plus artesunate as a recommended therapy for falciparum malaria in areas with resistance to older drugs (Table 52–4). This combina-tion is now available as a single tablet (ASAQ, Arsucam, Coarsucam) and is the first-line therapy for the treatment of uncomplicated falciparum malaria in many countries in Africa. Another combina-tion, amodiaquine plus sulfadoxine-pyrimethamine, remains reasonably effective for the treatment of falciparum malaria in many areas with some resistance to the individual drugs, and it ispreferred alternative treatment if artemisinin-containing thera-pies are unavailable. Chemoprophylaxis with amodiaquine is best avoided because of its apparent increased toxicity with long-term use.


Piperaquine is a bisquinoline that was used widely to treat chloroquine-resistant falciparum malaria in China in the 1970s through the 1980s, but its use waned after resistance became widespread. 

Recently, piperaquine has been combined with dihydroartemisinin in co-formulated tablets (Artekin, Duocotecxin) that have shown excellent efficacy and safety for the treatment of falciparum malaria, without apparent drug resistance. Piperaquine has a longer half-life ( 28 days) than amodiaquine ( 14 days), mefloquine ( 14 days), or lumefan-trine ( 4 days), leading to a longer period of post-treatment prophylaxis with dihydroartemisinin-piperaquine than with the other leading artemisinin-based combinations; this feature should be particularly advantageous in high transmission areas. Dihydroartemisinin-piperaquine is now the first-line therapy for the treatment of uncomplicated malaria in Vietnam.


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