Review of Pharmacology - 9E (2015)

Review of Pharmacology
Chloroquine
It is the drug possessing largest volume of distribution (>1300 L). It accumulates in the food
vacuole of the plasmodium. Thus, it is selectively concentrated in the parasitized erythrocytes.
It prevents polymerization of heme to hemozoin resulting in accumulation of heme that is toxic
for the parasite. It is the drug of choice for treatment and prophylaxis of non-falciparum malaria and
chloroquine sensitive P. falciparum malaria. It is an erythrocytic schizonticide and has no effect
on exo-erythrocytic stages. It is also used for other indications that are
DOC for radical cure of P. vivax
malaria is primaquine
• Rheumatoid arthritis
• Extraintestinal amoebiasis
• Discoid lupus erythematosis
• Lepra reaction
• Infectious mononucleosis
• Photogenic reactions
• Malaria
• Giardiasis
Chemotherapy B: Antimicrobials for Specific Conditions
Prolonged use of high doses
of chloroquine can result in
blindness due to retinal damage
(Bull’s eye maculopathy).
Primaquine is contra-indicated in
G-6-PD deficiency
Mefloquine is effective as a
single dose treatment of malaria.
Note: This can be remembered from the mnemonic: RED LIP Mahatma Gandhi
Adverse effects of chloroquine include skin rashes (lichenoid eruptions), peripheral
neuropathy, hypotension, myocardial depression (T wave changes in ECG), auditory
impairment and toxic psychosis. Prolonged use of high doses can result in blindness due
to retinal damage (Bull’s eye maculopathy). It can also precipitate porphyria and cause
discolouration of nails and mucous membranes. Chloroquine is the drug of choice for
treatment of malaria in pregnant women.
Quinine
Its mechanism of action is not clear and may be similar to chloroquine. Its major use is
treatment of P. falciparum infections resistant to chloroquine (drug of choice). It is often used
with doxycycline or clindamycin to decrease the duration of therapy and limit toxicity. To
delay emergence of resistance, it is not advocated for chemoprophylaxis. It is 70% bound
to plasma proteins especially α1 acid glycoprotein, such binding increases in acute attacks
of malaria, so that patients of malaria can tolerate much higher doses of quinine than other
subjects. Its d-isomer, quinidine can be used i.v. for severe P. falciparum infections. It can
cause hypoglycemia manifested by palpitations, sweating and tachycardia. To prevent
hypoglycemia, i.v. infusion of quinine should always be given in 5% dextrose solution
(instead of normal saline). At toxic doses, cinchonism can occur which manifests as symptoms
of gastrointestinal distress, vertigo, blurred vision, headache and tinnitus. It can also cause
cardiac conduction abnormalities and hemolysis in G-6-PD deficient patients. According to
WHO guidelines, quinine is safe in pregnancy and can be used for severe or chloroquine
resistant malaria.
Mefloquine
It can be used for chloroquine resistant P. falciparum infections, both for treatment as
well as prophylaxis. It can cause cardiac conduction disturbances, psychosis and seizures.
Administration with halofantrine or quinine is contraindicated because it can cause prolongation
of QT interval. It is effective as a single dose treatment of malaria.
Proguanil potentiates the action
of atovaquone
Primaquine
It acts by forming redox compounds that act as cellular antioxidants. It is a tissue (pre as
well as exo-erythrocytic) schizonticide and gametocide. It is always used along with blood
schizonticides for radical cure of malaria. It can cause methemoglobinemia and hemolysis in G-6-
PD deficient patients. It is contra-indicated in pregnancy. It has no role (for radical cure) in P.
falciparum malaria because this organism has no exo-erythrocytic stage.
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