Pharm - Antiprotozoal Drugs Flashcards
true or false
malaria is linked to bacteria
FALSE - linked to parasites
what parasite accounts for the majority of malaria cases in africa
plasmodium falciparum
explain the life cycle of malaria
when do symptoms start?
infected FEMALE mosquito bites the human and the parasite infects cells within organs, such as the liver (gets into hepatocytes via cell surface receptors)
For around a week, they asexually reproduce in the liver (called exoerythrocyte stage) – called SCHOZONTS
the hepatocytes will rupture eventually (may take a long time - even like a month - but will rupture eventually) and the merozoites will go into systemic circulation. The parasite within the RBCs asexually reproduce (THIS IS WHERE SYMPTOMS START) and can cause the RBC to rupture, and more and more RBC can be infected
if another mosquito bites this infected human, it can ingest a gametocyte and cause infection within that mosquito, and when that mosquito bites ANOTHER human, that human will be infected too
what is the “erythrocytic” parasite
when the parasite is in the blood and causing RBC rupture
what is the hepatic parasite
when hepatocytes are being infected
in pharmacotherapy for malaria, what TWO PARASITE STAGES need to be eradicated?
BOTH the erythrocytic and hepatic parasite
in which 3 continents is prophylactic therapy for malaria given
if traveling to asia, south america, or africa
name 4 categories of antimalarial drugs
(based on the STAGES that they target)
tissue schizonticides - kill the liver forms
blood schizonticides - kill the erythrocyte forms
gametocide - affects the sexual stage and prevents transmission to mosquito
prophylactic drugs
5 CLASSES of antimalarials
artemisinins
quinolones/quinine/quinidines
folate synthesis inhibitors
antibiotics (tetracycline)
lumefantrine
name 2 folate synthesis inhibitors for malaria
proguanil
pyrimethamine
which 2 anti malaria drugs target BOTH erythrocytic and hepatocyte schizonts?
atovaquone and proguanil
which anti malaria drugs targets the primary and latent liver stage, as well as gametocytes?
primaquine
MOST antimalarial drugs affect which stage of the life cycle?
erythrocyte schizonts
name 8 drugs that are erythrocyte schizonts
artemisinins
chloroquine
mefloquine
quinine
quinidine
pyrimethamine
sulfadoxine
tetracycline
for which anti malaria drug is resistance VERY COMMON
for which 2 strains?
chloroquine
mainly falciparum, but also vivax
true or false
artemisinin is a good drug for malaria prophylaxis
FALSE
what is the only area that seems to have no chloroquine resistance
central america
structurally, what is the key structural component of artemisinins
the endoperoxide bridge
active form of artemisinin
dihydroartemisinin
STRUCTURALLY, what is artemisinins
a sesquiterpene lactone ENDOPEROXIDE
what is the MOA of artemisinins
are healthy human cells affected
generates ROS (free radicals) – alters the cell redox cycle
these ROS’s kill both the parasite AND the RBC
HOWEVER, healthy RBC’s are not affected. this is because RBCS that are infected have their heme portion compromised and iron is exposed. this iron portion DIRECTLY REACTS with the peroxide part of the drug which generates ROS. HEALTHY RBCs DO NOT HAVE THEIR IRON FROM THE HEME EXPOSED!!! SO THEY’RE NOT AFFECTED BY THE DRUG!!!!
which stage(s) does artemisinins affect? how can you remember this?
ONLY THE ERYTHROCYTIC STAGE
does NOT affect the hepatic stage because hepatocytes do not have heme/iron to react with the endoperoxide bridge
are artemisinins good for prevention of malaria??
why or why not
NO
has a very short half life of 1-3 hours
any DDI concern with artemisinins?
yes – inducer of CYP2BD and 3A4
