Concise Information on Amimalarials

NAME	MECH. OF ACTION	Elimination half life	ACTION	ADVANTAGE	DISADVANTAGE
Chloroquine	? Inhibits plasmodial heme polymerase Toxic drug-heme complex form n Dg. Intercalation of Pl. DNA Intravacuolar pH alteration	10 days	Schizonticidal for all species Gametocidal for Pv. PO.PM. No action on hypnozoites	Highly potent against sensitive strains Long half life Effective at once a week dose as prophylactic agent	Rapid development of resistance
Quinine	(Same as Chloroquine)	11 hrs.	Primary blood schizonticide Little effect on sporozoite Gametocidal to PV and PM	Rapid development of resistance not yet seen	Higher toxicity
Artesunate /   Artemether /   Arteether	Activated by heme/ molecular iron to produce carbon centered free radicals Membrane damage by free radical	< 1 hr.   3-11 hrs   > 20 hrs.	Blood schizonticide Gametocidal action recently described	Broader window period of effectiveness Little/ no cross resistance Resistance not yet recorded	High recrudescence rate when used as monotherapy (10-50%) when used for <5 days="" o:p="">

 

NAME	MECH. OF ACTION	T ½	ACTION	ADVANTAGE	DISADVANTAGE
Mefloquine	Formation of toxic subs. with heme Damages membrane and other comp. Causes swelling of food vacuole	20 days	Strong schnizonticidal action against all species. Gametocidal l against PV, PM, PO Sporonticidal act	Useful as prophylactic agent for non-immune travellers Single dose sufficient Good alt. To quinine in MDR Pf.	Only oral prep. available.  So cannot be used in sev. Pf malaria High chances of cross-resistance, might lead to quinine resistance as well
Halofantrine	Concentrates and combines with ferri protop orphyrin IX, leading to memb. Damage1	10-90 hrs.	Schizonticidal to all species No action on latent tissue form of PV and gametocytes	Good alternative to mefloquine/ quinine in chloroquine/ MDR Pf.	Oral absorption erratic High chances of cross resistance with mefloquine Cardiotoxicity
Atovaquone	Inhibits parasite mitochondrial electron transport chain (complex III )(	70 hrs.	Blood schizonticide (used primarily for MDR Pf.)_		Erratic absorption High recrudescence rate when used alone
Pyronaridine	Inhibits vacuolar degradation, leading tot impaired Hb degradation	60 hrs.	Schizonticide for PF,PV, MDR, PF	Good oral absorption Cross resistance not yet documented Well tolerated

 

NAME	MECH. OF ACTION	T ½	ACTION	ADVANTAGE	DISADVANTAGE
Sulfadoxine - Pyrimethamine	Acts against the parasite dihydrofolate reductase enzyme	Sulfadoxine – 180 hrs. Pyrimethamine – 95 hrs	Active against blood schizonts of P.falciparum.  Less active against other species	Can be used against chloroquine resistant P.falciparum. No cross resistance with the 4 aminoquinolines, mefloquine, quinine, artemisinin derivatives	Risk of severe skin reactions
Primaquine	May get converted to electrophiles that act as redox mediators	6 hrs.	Destroys late hepatic stage and latent forms of PV and PO Gametocidal to all sp., mainly Pf. No action on erythrocyte stage of Pf., though active against the hepatic stage	Useful for the terminal prophylaxis and radical cure of PV and PO	Cannot be used in patient with G-6PD deficiency.
Proguanil	Selective inhibition of the bi-functional dihydrofolate reductase-thymidylate synthetase of Pl.	16 hrs.	Weak schizonticidal action against all species.	Good prophylactic agent for Pf or mixed infection, when used with chloroquine	Can not be used alone in treatment of malaria