Pharmacological Effects

Antimalarial Actions Quinine acts primarily against asexual erythrocytic forms and has little effect on hepatic forms of malarial parasites. The alkaloid also is gametocidal for P. vivax and P. malar-iae but not for P. falciparum. Quinine is more toxic and less effective than chloroquine against malarial parasites susceptible to both drugs. However, quinine, along with its stereoisomer quinidine, is especially valuable for the parenteral treatment of severe illness owing to drug-resistant strains of P. falciparum, even though these strains have become more resistant to both agents in certain parts of Southeast Asia and South America. Because of its toxicity and short t1/2, quinine generally is not used for prophylaxis.

Quinine resistance in P. falciparum more closely resembles resistance to mefloquine and halofantrine than to chloroquine. A number of different transporter genes may confer resistance to quinine.

Action on Skeletal Muscle Quinine increases the tension response to a single maximal stimulus delivered to muscle, but it also increases the refractory period of muscle so that the response to tetanic stimulation is diminished. The excitability of the motor end-plate region decreases so that responses to repetitive stimulation and to acetylcholine are reduced. Thus, quinine can antagonize the actions of physostigmine on skeletal muscle. Quinine also may produce respiratory distress and dysphagia in patients with myasthenia gravis.


Quinine is readily absorbed when given orally or intramuscularly. Oral absorption occurs mainly from the upper small intestine and exceeds 80%, even in patients with marked diarrhea. After an oral dose, plasma levels of quinine reach a maximum in 3-8 hours and, after distributing into an apparent volume of ~1.5 L/kg, decline with a t122 of ~11 hours after termination of therapy. Quinine pharmacokinetics may change according to the severity of malarial infection. Values for both the apparent volume of distribution and the systemic clearance of quinine decrease, the latter more than the former, so that the average elimination t122 increases from 11 to 18 hours. After standard therapeutic doses, peak plasma levels of quinine may reach 15-20 mg/L in severely ill patients without causing major toxicity (see below); in contrast, levels >10 mg/L produce severe drug reactions in self-poisoning. The high levels of plasma a ¡-acid glycoprotein in severe malaria may prevent toxicity by binding the drug and reducing its free fraction. Concentrations of quinine are lower in erythrocytes (33-40%) and CSF (2—5%) than in plasma, and the drug readily reaches fetal tissues.

The cinchona alkaloids are metabolized extensively, especially by hepatic CYP3A4, so only ~20% of a dose is excreted unaltered in the urine. The major metabolite of quinine, 3-hydroxyquinine, retains some antimalarial activity and can accumulate and possibly cause toxicity in patients with renal failure. Renal excretion of quinine itself is more rapid when the urine is acidic.

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