Quinine is an alkaloid used to treat uncomplicated Plasmodium falciparum malaria. It is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. The plasmodium falciparum invades the erythrocytes in blood. Quinine accumulates in the parasite’s food vacuole and inhibits the enzyme heme ligase. Heme ligase is involved in hemoglobin breakdown. Hemoglobin from the erythrocyte is broken down in the digestive vacuole of the parasite. Hemoglobin is first broken down into heme and globin. Globin is further broken down to amino acids which are used by the parasite for nutrition and protein synthesis. Therefore, hemoglobin breakdown is essential for the parasite survival. The heme from hemoglobin is toxic to the parasite and is further broken down by heme ligase to detoxify heme. By quinine inhibiting heme ligase, there is a build up of heme in the parasite vacuole which becomes toxic to the parasite, thereby killing it. Quinine has a bitter taste, and oral compliance is often poor. It is irritant to the gastric mucosa and can cause nausea and vomiting. Cinchonism can occur with exceeded plasma concentration in which symptoms like nausea, dizziness, tinnitus, headache and blurring of vision are experienced. Excessive plasma levels may also cause hypotension, cardiac dysrhythmias and severe central nervous system (CNS) disturbances such as delirium and coma.

Quinine Pathway References