Anti-Malaria Drugs Flashcards
Name the artemisinins
Artemether, ACT with Lumefantrine
Drugs effective in blood stage (asexual, gametocyte stage)
Artemisinins, quinolines, atovaquone-proguanil
Basics of artemisinins
Potent and fast-acting. Not good as a monotherapy, hence why combined with other drugs. Resistance building b/c of counterfeit drugs. Believed to form toxic adducts (i.e. free radicals) that kill the protozoa.
Artemisinin-based combination therapy (ACT)
Combined w/ another drug to increase half-life. Artemether-Lumefantrine (Coartem): artemether creates free radicals and lumefantrine forms a complex with heme. Schizonticidal.
Adverse effects of ACT
Category C, substantial interaction w/ anti-retrovirals/protease inhibitors (may need to increase ACT dose)
Mechanism of action of quinine
Interferes w/ heme digestion so protozoa can’t effectively use the amino acids
Mechanism of resistance in quinine
Increased efflux from amplification of pmfdr1 expression
Contraindications for quinine
Cardiac dysrhythmias. Can increase warfarin and digoxin plasma levels. Category C.
Doxycycline, tetracycline, and clindamycin in malaria tx
Ineffective monotherapy, but are schizonticidal and good when combined with quinine in inhibiting protein translation (death of progeny)
Mechanism of action of chloroquine
Interferes with heme digestion, causing heme to build up within protozoa which becomes toxic.
*should be given orally b/c pharmacokinetics varies and can lead to toxic Cp.
Chloroquine resistance
Mutations of pfcrt that cause drug efflux.
Contraindications for chloroquine
Renal, GI, neuro, or blood disorders.
**IS safe with pregnancy, just monitor glucose
Name the quinolines
Quinine, chloroquine, primaquine
Indications and contraindications of primaquine
I: effective against primary and latent stages of plasmodium
C: G6PD deficiency (SCREEN FIRST)- lack of glutathione means RBC can’t get rid of free radicals generated by primaquine and will lead to hemolysis. Don’t give to pregnant/breastfeeding women because G6PD is absent in babies.
Mechanism of action of atovaquone
Active against falciparum asexual blood stages and liver stages (not vivax) but must be combined with proguanil (plasmodium resistant to monotherapy). Inhibits e- transfer to Cyt b (e- transport chain disruption)
