Antimalarial Drugs

Question 1

What is the most dangerous type of malaria?

Answer 1

P. falciparum

Question 2

What does pre-treatment involve?

Answer 2

72 hours prior to admission, culture parasites to determine sensitivity, measure drug levels and identify markers associated with resistance

Question 3

ATAVOQUONE
What is it effective against?
How does it work?
What does it do?
Where is it not effective?

Answer 3

effective against sporozoites (hepatic stage). Resistant to quinolones.
Transfers electrons to complex 3- bc1 affects electron transport chain blocking ATP synthesis and mitochondrial function.
Competitive antagonist - competes for oxidation pocket of cyto bc1
Less susceptible in erythrocytic stages as these don’t use mitochondria for energy

Question 4

PROGUANIL
What is it effective against?
How does antifolate help?
What is the mechanism of action
what is it selective for

Answer 4

effective against sporozoites
may impair respiration of parasite
converted to cycloguanil, which inhibits DHFR which catalyses formation of DHF to THF required for purine synthesis.
Inhibits cell proliferation and growth

Question 5

Where does quinine work?

Answer 5

red blood cells (erythrotic stage)

Question 6

What is base-trapping?

Answer 6

weak bases accumulate where its acidic impairing action of food vacuole and interacts with haem disposal

Question 7

What do genes for resistance do?

Answer 7

cause decreased drug accumulation and accelerated efflux. ATP dependant p-glycoprotein in FV membrane up regulates the proteins that expel the drug.
pfCRT

Question 8

When is mefloquine used?

Answer 8

used when high risk of chloroquine-resistant falciparum. serious neuropsychiatric side effects

Question 9

How does chloroquine work?

Answer 9

non-falciparum as little resistance. High volume of distribution and lipid soluble, may accumulate in acidic vacioules

Question 10

How does doxycycline work?

Answer 10

tetracycline antibiotic

prophylaxis but not treatment, can be used with quinine.