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Chloroquine is the prototype anti malarial drug, most widely used
to treat all types of malarial infections. It is also the cheapest, time tested and safe
anti malarial agent.
Mechanism
of action: The mechanism of action of chloroquine is unclear. Being alkaline, the drug
reaches high concentration within the food vacuoles of the parasite and raises its pH. It
is found to induce rapid clumping of the pigment. Chloroquine inhibits the parasitic
enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby
resulting in the accumulation of toxic heme within the parasite. It may also interfere
with the biosynthesis of nucleic acids. Other mechanisms suggested include formation of
drug-heme complex, intercalation of the drug with the parasitic DNA etc.
Absorption, fate and excretion:
90% of the drug is absorbed from G.I.T and rapidly absorbed from intra muscular and
subcutaneous sites. It has a large distribution volume due to extensive sequestration in
tissues of liver, spleen, kidney, lung etc. Hence the need for a larger loading dose.
Therapeutic blood levels persist for 6-10 days and elimination half-life is 1-2 months.
Half of the drug is excreted unchanged by the kidneys, remaining is converted to active
metabolites in the liver.
Anti malarial activity: It is
highly effective against erythrocytic forms of P. vivax, P. ovale and
P. malariae, sensitive
strains of P. falciparum and gametocytes of P. vivax. It rapidly controls acute attack of
malaria with most patients becoming afebrile within 24-48 hours. It is more effective and
safer than quinine for sensitive cases.
Adverse effects: Chloroquine is a
relatively safer anti malarial. At therapeutic doses, it can cause dizziness, headache,
diplopia, disturbed visual accomodation, dysphagia, nausea, malaise, and pruritus of
palms, soles and scalp. It can also cause visual hallucinations, confusion, and
occasionally frank psychosis. These side effects do not warrant stoppage of treatment. It
can exacerbate epilepsy. When used as prophylactic at 300 mg of the base/ week, it can
cause retinal toxicity after 3-6 years (i.e. after 50-100 g of chloroquine). Intra
muscular injections of chloroquine can cause hypotension and cardiac arrest, particularly
in children.
Contra indications: Chloroquine
should be used with caution in patients with hepatic disease, (even though it is not
hepatotoxic per se, it is distributed widely in the liver and is converted to active
metabolites there; hence the caution), severe gastro intestinal, neurological or blood
disorders. The drug should be discontinued in the event of such problems during therapy.
It should not be co-administered with
gold salts and phenyl butazone, because all the three can cause dermatitis.
Chloroquine may interfere with the
antibody response to human diploid cell rabies vaccine.
Availability: Chloroquine is
available as Chloroquine phosphate tablets; each 250-mg tablet contains 150 mg of the
base. Chloroquine hydrochloride injection contains 40 mg of the base per ml.
Dose: Oral- 10mg/kg stat., then
three doses of 5 mg/kg, over 36-48 hours.
Age in years |
Dose of chloroquine (as base) |
(Each 250 mg tablet contains 150 mg base and each
5 ml of suspension contains 50 mg base) |
1st dose |
2nd dose |
3rd dose |
4th dose |
0-1 |
75 mg |
37.5 mg |
37.5 mg |
37.5 mg |
1-5 |
150 mg |
75 mg |
75 mg |
75 mg |
5-9 |
300 mg |
150 mg |
150 mg |
150 mg |
9-14 |
450 mg |
225 mg |
225 mg |
225 mg |
>14 |
600 mg |
300 mg |
300 mg |
300 mg |
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Dose of parenteral chloroquine:
Intra venous infusion |
10
mg / kg (max.600mg) in isotonic fluid, over 8 hours; followed by 15 mg / kg (max.900mg)
over 24 hours. |
Intra muscular or sub cutaneous injections |
3.5
mg of base/ kg (max.200 mg) every 6 hours or 2.5 mg of base/ kg (max.150mg) every 4 hours.
(Intramuscular injection can cause fatal hypotension, especially in children). |
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