Chemotherapy of Malaria Flashcards
malaria
infectious disease from protozoa of the genus plasmodium. transmitted by the bite of the female Anopheles mosquito.
most lethal form of malaria?
P. falciparum. most resistance to major drugs too
clinical signs of malaria
periodic episodes of chills and fever. usually enlarged spleen and liver. identified parasites in blood smears
treatment of malaria
prophylaxis, treatment of acute attack, radical cure
4 quinoline derivatives
quinine, chloroquine, mefloquine, primaquine
PfCRT mutations
mutations in this allow the parasite to expel drugs, reducing the effect!! this is bad!!!!!!
mechanism of quinoline drugs
accumulate in parasite’s food vacuoles and disrupt heme polymerization to hemozoin, causing oxidative damage to membranes and digestive proteases
chloroguanide mechanism
inhibits dihydrofolate reductase
atovaquone mechanism
depolarizes parasitic mitochondria and inhibits their electron transport.
name two artemisinin compounds
artemether and artesunate
artemisinin compound mechanism
inhibits Ca2+ ATPase (SERCA) by pretending to be thapsigargin. inhibit the SERCA of P. falciparum.
primaquine mechanism
inhibits exoerythrocitic schyzogony. oxidizes schizont membranes. used for prophylaxis and prevention of relapses
chemoprophylaxis in a chloroquine sensitive zone
chloroquine
chemoprophylaxis in a chloroquine resistant zone
mefloquine, doxycycline, atovaquone/proguanil
chemoprophylaxis in mefloquine resistant zone
doxycycline, atovaquone/proguanil
terminal prophylaxis
primaquine
mechanism for RTS,S/AS02A vaccine
targets pre-erythrocytic stages of P falciparum. strong humoral immune response against surface exposed sporozoite proteins. vacciine should also elicit CD8 and CD4 T cell types to get rid of infected liver cells
treatment of severe malaria
IV quinidine plus antibiotic. IV artesunate followed by atovaquone, mefloquine, or doxycycline. Exhange blood transfusion
treatment of uncomplicated malaria: chloroquine sensitive strains (falciparum, malariae, knowlesi)
cholorquine. alternative: hydroxychloroquine
treatment of chloroquine sensitive strains (vivax, ovale)
chloroquine and primaquine. alternative: hydroxychloroquine and primaquine
treatment of chloroquine resistant falciparum
atovaquone. alternatives: artemether, quinine + doxycycline (or clindomycin on kids under 8), mefloquine.
treatment of chloroquine resistant vivax
quinine + doxycycline or tetracycline + primaquine. alt: atovaquone + primaquine. Mefloquine + primaquine
radical cure!
for eradication of persistant exoerythrocytic parasites, use primaquine phosphate!
new developments
sequencing falciparum genome. sequencing mosquito genome
