Antimalarials

1. Chloroquine
-large volume of distribution-->need large dose so that drug can be in blood
-sequestered in tissues
-erythrocytic stage
-prevents conversion of heme to hemozoin-->oxidative stress
-K76T PfCRT mutation causes drug to accumulate in parasite's food vacuole
-G6PD deficiency and porphyria->toxic

2. Mefloquine
-widely distributed, including CNS
-neurologic side effects such as vivid dreams, anxiety, sleep disturbance
-disrupt hemozoin polymerization
-associated with amplification of pfmdr1

3. Quinine and Quinidine
-disrupt hemozoin polymerization/DNA intercalation
-short half-life
-cardiotoxic
-cinchonism, hypoglycemia, hypotension, blackwater fever, thrombocytopenia, QTc interval prolongation
-used with doxycycline-->in pregnant women and children, use clindamycin

4. Primaquine
-generation of oxidation-reduction mediators
-prophylaxis to prevent primary and latent hepatic stages
-erythrocytic, primary hepatic, latent hepatic, gametocytes
-pneumonia
-G6PD deficiency and methemoglobinemia-->toxic
-pregnancy contradicted

5. Atovaquone-Proguanil
-inhibit ETC-->collapse mitochondrial membrane
-erythrocytic and primary hepatic

6. Sulfadoxine-Pyrimethamine
-(S) inhibit dihydropteroate reductase
-(P) inhibit dihydrofolate reductase
-high resistance and slow acting

7. Artemisinin
-cleavage of artemisinin endoperoxide bridge-->free radical-->damage to macromolecules
-short half-life
-erythrocytic and gametocytes
-first line
-anemia, hemolysis, hypersensitivity
-combination with Lumefantrine (forms heme complex/decrease synthesis?, risk of QTc prolongation)

8. Doxycycline and Clindamycin
-delayed death mechanism-->impaired apicoplast gene-->death of progeny
-GI problems and photosensitivity