anti-protozoa_part 4. folate_inhibitors_flashcards

Question 1

What are the types of inhibitors of folate, and how do they act?

Answer 1

1. Pyrimethamine: Related to trimethoprim.
2. Proguanil: A biguanide derivative.
3. Sulfonamides and Sulfones: Inhibit dihydropteroate synthase.

Question 2

What are the pharmacokinetics (P.K.) of Pyrimethamine?

Answer 2

Slowly but adequately absorbed. Half-life: 3.5 days. Extensively metabolized before excretion.

Question 3

What are the pharmacokinetics (P.K.) of Proguanil?

Answer 3

Slowly but adequately absorbed. Half-life: 16 hours. It is a prodrug; its active form is cycloguanil.

Question 4

What is the mechanism of action (MOA) of Pyrimethamine and Proguanil?

Answer 4

Inhibit plasmodial dihydrofolate reductase, a key enzyme in the folate synthesis pathway.

Question 5

What are the antimalarial effects of Pyrimethamine and Proguanil?

Answer 5

Act slowly against erythrocytic forms of all four malaria species. Proguanil: Has some activity against hepatic forms. No effect on gametocytes or persistent liver stages.

Question 6

What are the clinical uses of Pyrimethamine and Proguanil?

Answer 6

Usually given in combination:
Fansidar (Sulfadoxine + Pyrimethamine), Maloprim (Dapsone + Proguanil).

Treatment of chloroquine-resistant falciparum malaria (combined with quinine in severe cases).

Presumptive treatment of falciparum malaria.

Toxoplasmosis: Leucovorin calcium is given to prevent hematological complications.

Pneumocystis infections.

Question 7

What are the adverse effects of Pyrimethamine and Proguanil?

Answer 7

Usually well tolerated. Rarely: GIT symptoms and skin rash.

Proguanil: May cause mouth ulcers and alopecia.

Proguanil is no longer recommended for prophylaxis.