Indication |
For treatment of acute malarial attacks in non-immune subjects. |
Pharmacodynamics |
Amodiaquine, a 4-aminoquinoline similar to chloroquine in
structure and activity, has been used as both an antimalarial and an
anti-inflammatory agent for more than 40 years. Amodiaquine is at least
as effective as chloroquine, and is effective against some
chloroquine-resistant strains, although resistance to amodiaquine has
been reported. The mode of action of amodiaquine has not yet been
determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac
conductivity, and produce vasodilatation with resultant hypotension.
They depress respiration and cause diplopia, dizziness and nausea. |
Mechanism of action |
The mechanism of plasmodicidal action of amodiaquine is not
completely certain. Like other quinoline derivatives, it is thought to
inhibit heme polymerase activity. This results in accumulation of free
heme, which is toxic to the parasites. The drug binds the free heme
preventing the parasite from converting it to a form less toxic. This
drug-heme complex is toxic and disrupts membrane function. |
Absorption |
Rapidly absorbed following oral administration. |
Volume of distribution |
Not Available |
Protein binding |
Not Available |
Metabolism |
Hepatic biotransformation to desethylamodiaquine (the principal
biologically active metabolite) is the predominant route of amodiaquine
clearance with such a considerable first pass effect that very little
orally administered amodiaquine escapes untransformed into the systemic
circulation. |
Route of elimination |
Not Available |
Half life |
5.2 ± 1.7 (range 0.4 to 5.5) minutes |
Clearance |
Not Available |
Toxicity |
LD50 (mouse, intraperitoneal) 225 mg/kg, LD50
(mouse, oral) 550 mg/kg. Symptoms of overdose include headache,
drowsiness, visual disturbances, vomiting, hypokalaemia, cardiovascular
collapse and cardiac and respiratory arrest. Hypotension, if not
treated, may progress rapidly to shock. Electrocardiograms (ECG) may
reveal atrial standstill, nodal rhythm, prolonged intraventricular
conduction time, broadening of the QRS complex, and progressive
bradycardia leading to ventricular fibrillation and/or arrest. |
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