Antimalarials Flashcards
Quinine
Cinchona alkaloid (quinoline derivative)
Accumulation of medication in food vacuole causes inhibition of heme polymerization and generation of free radicals, while increasing the vacuole pH and blocking hemoglobin proteolysis
Effective against erythrocytic forms. Treatment for drug-resistant P. falciparum and gametocidal for P. vivax and P. malariae.
Cinchonism (tinnitus, high-tone deafness, visual disturbances, headache, nausea, vomiting, abdominal pain, and diarrhea)
Hypoglycemia
Cardiac dysrhythmias and fibrillation
Quinidine
Cinchona alkaloid (quinoline derivative)
Accumulation of medication in food vacuole causes inhibition of heme polymerization and generation of free radicals, while increasing the vacuole pH and blocking hemoglobin proteolysis
Effective against erythrocytic forms. Treatment for drug-resistant P. falciparum and gametocidal for P. vivax and P. malariae.
Cinchonism (tinnitus, high-tone deafness, visual disturbances, headache, nausea, vomiting, abdominal pain, and diarrhea)
Hypoglycemia
Cardiac dysrhythmias and fibrillation
Chloroquine
Quinoline
Accumulation of medication in food vacuole causes inhibition of heme polymerization and generation of free radicals, while increasing the vacuole pH and blocking hemoglobin proteolysis
Effective against erythrocytic forms of P. vivax, P. ovale, P. malariae, and sensitive strains of P. falciparum. Activity on gametocytes of P. vivax, P. ovale, and P malariae.
Hypotension
Vasodilation
Cardiac arrhythmias
Mefloquine
Quinoline
Accumulation of medication in food vacuole causes inhibition of heme polymerization and generation of free radicals, while increasing the vacuole pH and blocking hemoglobin proteolysis
Effective on the erythrocytic form. Used against drug-resistant forms.
Neuropsychiatric effects
Severe but reversible CNS toxicity (seizures, confusion, psychosis, dysphoria, insomnia, vertigo) in 0.5%
Aberrant atrioventricular conduction
Primaquine
Quinoline
May generate reactive oxygen species and interfere with electron transport
Effective against the hepatic stages, latent tissue forms, and gametocytes.
Acute hemolysis (in people with G6PD deficiency, ie. low glutathione)
Artemisin
Effective against the asexual blood stage
In combination therapies, often with mefloquine or lumefantrine
Endoperoxide bridge crucial for anti-malarial activity
Transported to the food vacuole of parasites and interacts with Fe2+ and converts to a free radical. Irreversibly inhibits calcium-dependent ATPase
Transient heart block
Decrease in blood neutrophils
Sulfadoxine
Sulfonamide
Inhibits dihydropteroate synthase in the folic acid pathway, interrupting DNA synthesis
Promotes gametocyte formation, increasing risk of transmission to vector mosquitos
Pyrimethamine
Inhibits the folic acid pathway, interrupting DNA synthesis
Promotes gametocyte formation, increasing risk of transmission to vector mosquitos
Proguanil
Chemically related to pyrimethamine
Inhibits DHFR (folic acid synthesis)
May have an effect on the initial hepatic stage
Atovaquone
Aka hydroxynaphthoquinone
Highly selective for the active asexual blood phase
Acts on mitochondrial cytochrome bc1 complex, inhibiting the ETC and decreasing the membrane potential
Tetracycline
Inhibit protein translation in the parasite plasmid
Given in combination with quinine, quinidine, or artesunate
Slow-acting on blood stage
Doxycycline
Tetracycline
Inhibit protein translation in the parasite plasmid
Given in combination with quinine, quinidine, or artesunate
Slow-acting on blood stage
