Mefloquine Chloroquine

Quinine, mefloquine, chloroquine, artesunate, artemether and primaquine (gametocytocides) act on sexual forms and prevent transmission of the infection because the patient becomes noninfective and the parasite fails to develop in the mosquito (site 4). 

Mefloquine, chloroquine, proguanil, and pyrimethamine plus dapsone (Maloprim), alone or in combination are most commonly advised for prophylaxis regimens and doxycycline for special cases (drug resistance or intolerance) primaquine is being re-evaluated. 

Photodegradation in the solid state takes place only at the sample surface. The degradation rate is therefore dependent on factors that will influence the depth of light penetration, i.e., change the absorption and reflection at the surface (e.g., particle size, crystal modification, color, thickness of powder bed, and coating of the individual particles or the dosage form). Mefloquine, chloroquine, carbamazepine, and furosemide are examples of drug substances that show different decomposition rates dependent on their polymorphous modiflcation.P ... 

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

Quinacrine (49) is an acridine that was used extensively from the mid-1920s to the end of World War 11. It acts much like chloroquine and is reasonably effective. Because it causes the skin to turn yellow and, in high doses, causes yellow vision, the dmg is no longer in use as an antimalarial. Pyronaridine (77), a 1-azaacridine developed in China, appears to be effective against mefloquine-resistant, but not entirely against chloroquine-resistant, strains of P falciparum. 

Malaria, a tropical disease caused by protozoan parasites of the genus Plasmodium, has been a major concern for centuries and has now extended to a great deal of the world s population, killing every year 1-2 million people. Different medicines are in use to cure or to prevent malaria. The classical natural medicine quinine was soon replenished with synthetic compounds such as primaquine, chloroquine and mefloquine. However, a major problem is still an increasing resistance towards these compounds. 

Antimalarial drugs are designed to prevent or treat malaria. Antimalarial drugs currently used for treatment for prophylaxis are mefloquine, primaquine, chloroquine, pyrimethamine, amodiaquin, quinine/quinidine, chloroguanide. 

VI.a.2.1. AminoquinoUnes. The aminoquinolines currently used as antimalarials include the 4-amino-quinolines chloroquine and mefloquine and the 8-aminoquinoline primaquine. 

VLa.2,6. Other antimalarials. Doxycydine (see Section ILb) is a useful and effective short-term prophylactic agent for travellers to chloroquine-resistant areas and can be used as an alternative when mefloquine or proguanil is unavailable or mefloquine is contraindicated. In combination with quinine also tetracycline is used as an antimalarial. 

Knowledge of local resistance patterns is important to determine the treatment regimen. There is increasing chloroquine and pyrimethamine-sulfado-xine (Fansidar) resistance in Africa and in some areas at the border of Thailand there is resistance for almost all antimalarial drugs including halofantrine, mefloquine and quinine. In these areas only the artemisinin derivatives (artemether, arteether, arte-sunate, dihydroartemisinin) are effective. 

Non-falciparum malaria (like P. vivax) can still be treated with chloroquine although chloroquine resistant P. vivax has been reported from Irian Jaya and Papua New Guinea. In those areas treatment with mefloquine is recommended. To treat the liverstages an additional 2-3 weeks treatment with primaquine is given. It appears that tafenoquine (dosed once a week), a new 8-aminoquinoline, would be a better replacement for primaquine in preventing relapses in P. vivax malaria. 

Chloroquine phosphate, administered orally, is again the drug of choice unless one suspects the presence of a chloroquine-resistant organism. Oral mefloquine or... 

Antimalarials Mefloquine is a major drug for malaria, in particular, for chloroquine-resistant malaria." However, some cases of neuropsychiatric adverse events and the apparition of resistance tend to limit its use. Metabolism into inactive and phototoxic 1 -7/-2-oxoquinoline is blocked by the presence of the CF3 group." Instead of performing the resolution of enantiomers at the end of the synthesis," the asymmetric reduction of the carbonyl group in the presence of ruthenium catalyst and a chiral diphosphine provided mefloquine with an excellent enantiomeric excess (Figure 8.25). °... 

Quinoline derivatives chloroquine phosphate hydroxychloroquine sulfate mefloquine hydrochloride primaquine phosphate... 

It is derivative of artemisinin. These agents produce a more rapid clearance of parasites than quinine, chloroquine and mefloquine in treatment of severe... 

Travelers to areas endemic for chloroquine-resistant disease Mefloquine, doxycycline, or atovaquone/proguanil Excellent... 

Mefloquine Areas with chloroquine-resistant P falciparum 250 mg weekly... 

Areas without known chloroquine-resistant P falciparum are Central America west of the Panama Canal, Haiti, Dominican Republic, Egypt, and most malarious countries of the Middle East. Malarone or mefloquine are currently recommended for other malarious areas except for border areas of Thailand, where doxycycline is recommended. 

Mefloquine is effective therapy for many chloroquine-resistant strains of P falciparum and against other species. Although toxicity is a concern, mefloquine is one of the recommended chemoprophylactic drugs for use in most malaria-endemic regions with chloroquine-resistant strains. 

Sporadic resistance to mefloquine has been reported from many areas. At present, resistance appears to be uncommon except in regions of Southeast Asia with high rates of multidrug resistance (especially border areas of Thailand). Mefloquine resistance appears to be associated with resistance to quinine and halofantrine but not with resistance to chloroquine. 

Mefloquine is effective in prophylaxis against most strains of P falciparum and probably all other human malarial species. Mefloquine is therefore among the drugs recommended by the CDC for chemoprophylaxis in all malarious areas except for those with no chloroquine resistance (where chloroquine is preferred) and some rural areas of Southeast Asia with a high prevalence of mefloquine resistance. As with chloroquine, eradication of P vivax and P ovale requires a course of primaquine. 

Chloroquine-resistant Quinine Artemisinin derivatives Atovaquone-proguanil Mefloquine Pyrimethamine-sulfadoxine Antibacterials (e.g., clindamycin, doxycycline, sulfamethoxazole, or tetracycline] ... 

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