Lecture 37: Antimalarial & Antiparasitic Flashcards
What are the two parasites that are the most common to cause Malaria?
- Plasmodium Falciparum [most malaria deaths; in tropics]
- Plasmodium Vivax [causes relapse & hypnozoites in liver; 50% of infections in asia & 80% in americas]
What is the Life Cycle of Plamodium Falciparum?
- Mosquito injects sporozoites
- then moves to liver to make merozolites
- released to invade RBC
- trophozolite divides making merozolites
- merozolites into gametocytes
- female mosquito sucks up gametocytes to remake the sporozoites
When should you do Prophylaxis for Malaria and what are some of the options for it?
- Should be taken before, during and after traveling
- Atovaquone-Proguanil is most common; Cholorquine [sensitive parasites]; Mefloquine [longer trips]; Primaquine [high P. Vivax in area]
What are the Drug Classifications of Antimalarial Drugs?
- Tissue Schizonticides [kills liver parasites]
- Blood Schizonticides [Kills erythrocytics]
- Gametocytocides [no pathogen]
What is the MOA for Artemisinin?
- Activated by Heme-Iron to form free radicals [breaks the lactone endoperoxide bridge]
- Maybe inhibits [PfPI3K]??
What is important to know about Artemisinin?
- For Blood Schizonticide
- NOT Active for Liver Stage
- Short half life [1-2h] = needs longer half life drugs to help kills rest of parasites
What is the Resistance towards Artemisinin?
- Mutations in Kelch 13; causes drug to eliminate and parasite to regrow
What is important to know about Hemoglobin Metabolism in Parasites?
- Malaria Parasites eat up the Hemoglobin from host; which makes it to Free Heme =Toxic
What is the MOA of Chloroquine?
Resistance?
- Builds up in Food Vacuole and inhibits heme polymerization
RESISTANCE: Mutations in PfCRT1
What is the MOA of Quinine?
- Builds up in Food Vacuole and inhibits heme polymerization
What are some of the Adverse Effects for Quinines?
- Tinnities, Headache, Nausea, Dizziness, Flushing, Visual Problems
- Hemolysis [G6PD Deficiency]
What is Primaquine good for when it becomes Active?
- DOC for liver stages [actively growing and hypnozoites] of P. Vivax and Ovale
What is the MOA for Primaquine?
- Hydoxylated by 2D6 = [OH-PQm]
- Then oxidation of OH-PQm to make H2O2
- Then CPR reduces H2O2 back to OH-PQm to then make H2O2 again by oxidation
- REPEAT
What is important to know about Primaquine?
- HIGH RISK for Hemolysis in G6PD Deficiency
- NOT used in Pregnancy
What are the Two Drugs that make up Malarone and what is it good against??
- Atovaquone + Proguanil
- Kills Liver and Blood stages
Atovaguone helps with Toxo and PJP [duh]