Download Anti-Malarials - GMERS Medical College Sola

Anti-malarial Drugs
Dr Chetna Desai
Professor and Head
Department of Pharmacology
G.M.E.R.S. Medical College,
Ahmedabad
Antimalarial drugs
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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
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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.
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Choice of antimalarial drug
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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:
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Amebic liver abscess (as chloroquine is concentrated
in the liver).
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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).
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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
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Antifolates (sulfonamides & sulfones):
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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, agranulocytosis
Disadvantages: 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.
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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.
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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
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Use:
 Drug resistant P Falciparum along with quinine
 Prophylaxis
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Adverse Effects:
GIAE
 Oesophageal ulceration
 Take sufficient water
 X Pregnancy and lactation, Children upto 8
years
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Clindamycin
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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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