1) The document classifies and describes various antimalarial drugs including chloroquine, quinine, artemisinin derivatives, halofantrine, and lumefantrine.
2) It provides details on the mechanism of action, administration, metabolism, and side effects of chloroquine which accumulates in parasitized erythrocytes and inhibits parasite enzymes.
3) Quinine is described as an alkaloid derived from cinchona that is administered orally or intravenously for severe malaria cases. Its mechanism of action is unclear.
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Anti malarial drugs
1. Anti Malarial Drugs
Dr Nishant Kumar
Assistant Professor
Department of Community Medicine
Madhubani Medical College , Madhubani ,
Bihar
2. Classification of Antimalarial drugs
Classification Name
Chinoca Alkaloids Quinine
4 Aminoquionoline Chloroquine,Hydroxychloroquine
8 Aminoquionoline Primaquine
Biguanides Proguanil
Diaminopyridines Pyrimethamine
Quinoline methanol Mefloquine
Phenantherene
i. Artemisinin derivative
ii. Acridine
Halofantherine
i. Arthesunate, Artemeter, Arteether,
ii. Mepacrine Quinacarine
Misellaneous Sulfonamides, tetracycling,atavaquone
3. CHLOROQUINE
• Route of administration- oral , or by IM injection or by slow I.V infusion
• Almost completely absorbed from GIT
• Distributed widely and extensively bound to liver and other body tissue
including cornea and RBCs.
• Undergoes metabolism in the liver
• Mainly excreted in urine (70%)as unchanged , 30% as metabolites
• Initial half life is 3-4 days but as it is slowly released from the tissue the
terminal half life may be extended to 1-2 months
4. CHLOROQUINE (contd.)
• Preferential accumulation in parasitized erythrocytes
• Diffuse freely into the parasite lysosome
• Inside , at acidic pH of the lysosome , it get ionized (impermeable) and gets
trapped inside the parasite
• Its accumulation in parasite food vacuoles , inhibit peptide formation and
reduces the supply necessary for parasite viability .
• Inhibits the parasite enzyme polymerase and thus protect the host’s haem from
being converted into haemozoin
• At high concentration , it inhibits RNA and DNA synthesis by intercalating
with parasite DNA but these effects at that high concentration are less likely to
be involved in its anti – malarial activity.
5. CHLOROQUINE (contd.)
• Antimalarial action and clinical use
– Asexual erythrocytic state (+); gametocidal (+) only in P.vivax and P.Ovale, not for
P.Falciparum ; pre and exoerythrocytic state(-).
• Resistance to chloroquine among the stains of P. falciparum is most common
and result due to mutations in putative chloroquine transporter (PfCRT).
6. CHLOROQUINE (contd.)
• Contraindication and Drug interaction
– Avoid in patients with retinal and visual field abnormalities
– Aggravates psoriasis or porphyria
– In G6PD deficient persons its use may result in hemolytic anemia
– Ca2+ and Mg 2+ containing antacids decrease its absorption
– Contaminant use of metoclopramide with chloroquine sometimes precipitates paradoxical
extrapyramidal side effects.
– Chloroquine is considered safe in pregnancy and in younger children above 2 year of age
7. Quinine
• An alkaloid derived used in the treatment and prevention of malaria
• Usually given orally but can be given by slow I.V infusion for severe P.
falciparum malaria and in patients who are vomiting
• Well absorbed from GIT following oral ingestion
• Widely distributed in body tissue
• Primarily metabolized in liver excreted in the urine
• Plasma half life is 10-11 hrs.
• Mechanism of action is not clear
8. Quinine (contd.)
• Asexual erythrocytic state (+) ; gametocidal activity (+) ; only in P.vivax and
P.ovale but not for P. Falciparum ; pre and exoerythrocytic state (-) .
• Adverse Effects
– Bitter taste , poor compliance
– G.I irritant and can cause nausea and vomiting
– Higher plasma level in cinchonism
– Potentially neurotoxic in higher doses
– Stimulates insulin release and may cause hypoglycemia
9. ARTMISININ DERIVATIVES
• It is a pro drug and is rapidly metabolized to an active metabolite dihydroartemisinin
.
• Mode of Action
– The intraparasitic ferrous protoporphyrin –IV ( present in parasitc food vaculole) catalyses
breakdown of endoperoxide (-0-0-) bridge of the artemisinin molecule.
– This is followed by the generation of highly reactive free radcials that damage the parasite
membrane by covalently binding to membrane protein .Intact endoperoxide linkage in
artemisisinin structute is essential for antimalarial activity of these compounds
10. HALOFANTEINE AND
LUMEFANTRINE
• A antimalarial drug with potent blood schizonticidal properties against all four
human malarial species.
• Unknown mechanism of action may involve possible inhibition of plasmodial
proton pump.
• Erratic bioavalabilty and manifest potential lethal cardiotoxicity.
