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Many drugs
have been tested for their potential anti malarial effects. Research into newer anti
malarials being scanty, such attempts might throw up one or two candidates for use in
malaria, however, these drugs are yet to find a place in standard anti malarial regimen.
Clindamycin, fluoroquinolones like ciprofloxacin and Norfloxacin, azithromycin etc. have
been found to be effective against malarial parasites. Atovaquone; Desferrioxamine;
Pyronaridine; Piperaquine; WR-288, 605; and 566C80 are drugs undergoing trials.
Clindamycin: It acts by inhibiting the
protein synthesis by binding to the 50s subunit of ribosomes. It can be used for drug
resistant malaria along with quinine at a dose of 10 mg/kg 8 hourly for 5 days. Adverse
effects include pseudomembrane colitis and skin rashes. In one study, a cure rate of only
50% was observed. (Hall et al, P. falciparum malaria semiresistant to clindamycin. Br.
Med. J., 1975, 2:12-14; Seaberg et al, Clindamycin activity against chloroquine
resistant P. falciparum. Antimicrob. agents Chemothera., 1984, 150:904-911)
Fluoroquinolones: Both
ciprofloxacin and norfloxacin have been found to have anti malarial activity both in vitro
and in vivo. However, results are not consistent.
Azithromycin: Azithromycin is
found to have anti malarial activity and has been found to be useful as a causal
prophylactic agent. It was found to be effective at the dose of 300 mg stat, followed by
250 mg daily for 7 days as a prophylactic agent against chloroquine resistant P.
falciparum infection.
Atovaquone: A synthetic
hydroxynaphthoquinone developed in the early 1980s, atovaquone has been found to be useful
against the Plasmodia (as well as Toxoplasma and Pneumocystis
carinii). It has a highly lipophilic molecule that supposedly interferes with the
mitochondrial electron transport and thereby ATP and pyrimidine biosynthesis and in Plasmodia,
it is found to target cytochrome bc1 complex and disrupt the membrane
potential. Its bio-availability after oral administration is poor and may be increased by
a fatty meal. It has a long half-life of 2-3 days and it undergoes entero-hepatic
circulation. It is available as 750 mg tablets. It may cause rash, fever, vomiting,
diarrhoea and head ache. Safety in pregnancy, lactation, children, and elderly is yet to
be established.
Atovaquone
plus Proguanil: A fixed dose combination of atovaquone and proguanil hydrochloride
(Malarone™) is now approved for both treatment and prophylaxis of malaria. It is
available as 250 mg atovaquone + 100 mg proguanil per tablet for adults and 62.5 mg
atovaquone + 25 mg proguanil per tablet for children.
It has been shown to be highly
efficacious in the treatment of uncomplicated malaria caused by Plasmodium falciparum,
including malaria that has been acquired in areas with chloroquine-resistant or
multidrug-resistant strains. The daily dose should be taken at the same time each day with
food or milk.
For details: http://www.cdc.gov/travel/diseases/malaria/malarone.htm
Pyronaridine: Structurally, it
resembles amodiaquine and has been found to be highly effective against chloroquine
resistant strains in China.
Piperaquine: Its activity is
similar to that of chloroquine. A combination with artimisinin is undergoing studies.
WR-288, 605: It is 7.4 times more
active than primaquine as a tissue schizonticidal drug. It has lesser toxicity, good oral
bio-availability and longer half-life.
Lumefantrine is an aryl
alcohol related to quinine, mefloquine and halofantrine that is devoid of cardiac toxicity
of halofantrine. It is being tried in combination with artemether.
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