Anti-malarial Drugs

Dr Chetna DesaiProfessor and Head

Department of PharmacologyG.M.E.R.S. Medical College,

Ahmedabad

Antimalarial drugs Malaria is caused by four species of

protozoa:Plasmodium malariae.P. falciparum.P. vivax.P. ovale (rare)

The plasmodium transmitted to human by the

bite of an infected female anopheles mosquito.

Malaria transmission life cycle:

Sporozoites tissue schizonts (in liver) merozoites infect RBC (blood schizonts) rupture of RBC (clinical attack) new crops of merozoites

Sexual form: some merozoites differentiate into male & female gametocytes ingested by a mosquito where they form Sporozoites human

P. malariae & p. falciparum have one cycle of liver invasion and end by the 4th week i.e. no relapse occurs.

P.ovale & p. vivax have dormant stages (hypnozoites) in the liver. These hypnozoites may rupture months or years later causing relapse of the attacks.

Choice of antimalarial drug Efficacy and half-life • Acceptability and adherence to treatment

formulations) • Effectiveness • Adverse effects • Drug interactions and contraindications • Use in special groups, e.g. pregnant women,

infants • Capacity of health system to implement policy • Cost-effectiveness, affordability of various

regimens • Reported resistance and/or cross-resistance

Blood Schizonticides

Chloroquine (4- aminoquinoline derivative)

Mechanism of action: Inhibits synthesis of DNA and RNA in the

plasmodium. Increases pH of the vacuoles in the

parasite, so prevent its utilization of erythrocyte hemoglobin.

Uses: Acute attack

Other uses:

Amebic liver abscess (as chloroquine is concentrated in the liver).

Anti-inflammatory in autoimmune diseases e.g. rheumatoid arthritis

A/E: GIAE rash, headache,

peripheral neuritis, cardiac depressant, retinal damage (X use > 5 years without regular ophthalmic examination),

toxic psychosis.

Quinine:

Mechanism of action: Inhibits DNA strand separation,

transcription and protein synthesis.Uses: CQ resistant P. falciparum (orally). Cerebral malaria (i.v infusion until patient

can take the drug orally).A/E: Cinchonism i.e. headache, dizziness, &

tinnitus. Inhibits cardiac conductivity hemolysis in G-6-P D and black water fever

(intravascular hemolysis).

Qinghaosu (Artemisinin)

Chinese herbal medicine used as antipyretic. Blood schizonticide against all types of

malaria including CQR PF Unknown mechanism of action.Uses: P. falciparum cerebral malaria (oral &

parenteral). Not used for prophylaxis Used in pregnancy – only in 2nd & 3rd

trimesters

Antifolates (sulfonamides & sulfones):

Synergistic blockade of folic acid synthesis Sulfonamide inhibits dihydropteroate

synthetase, inhibits folic acid synthesis.

Pyrimethamine and proguanil inhibit dihydrofolate reductase, so inhibit tetrahydrofolate (folinic acid synthesis).

Fansidar

Combination of sulfadoxine and pyrimethamine.

It is used in CQ R PF.A.E: Sulfonamide: rashes, renal damage, hemolysis

& GIAE, SJ syndrome. Pyrimethamine: FA deficiency, agranulocytosisDisadvantages: slow blood schizonticide

activity, drug resistance & numerous serious adverse effects.

C/I: pregnant & nursing women, G-6-PD, renal impairment & children under 2 months of age.

Primaquine

Tissue schizonticide. It has a cellular oxidant activity and possibly

interferes with mitochondrial function. Gametocide, so inhibits transmission of

infection by mosquito.Uses: Eradication of liver stages (hypnozoites) of

P.vivax & P.ovale, after standard chloroquine therapy to prevent relapse.

A/E: GIT upset, pruritus, headache, methemoglobinemia, hemolysis especially

in G-6-PD.

Doxycycline Tetracycline derivative Longer half life Reliable absorption Better safety profile in renal insufficiency

Use: Drug resistant P Falciparum along with

quinine Prophylaxis

Adverse Effects: GIAE Oesophageal ulceration Take sufficient water X Pregnancy and lactation, Children

upto 8 years

Clindamycin Lincosamide antibiotic Inhibits protein synthesis 90% is absorbed by GIT Use: CQ RPF Safe in pregnancy and children Lesser risk of resistance A/E: ANVD Pseudomembranous colitis Hypersensitivity reactions BM depression Hepatic damage

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