Anti-protozoal Drugs

Question 1

Describe the malaria life cycle

Answer 1

1. bite
2. sporozoites invade liver
3. transform into merozoites
4. released form liver and infect RBCs
5. become trophozoites
6. RBCs (trophozoites containing merozoites) rupture, release merozoites
7. at skin surface, ingested by mosquito

Question 2

This form of malaria, if treated after acute attack, can be cured. It produces severe symptoms and can be fatal

Answer 2

Plasmodium flaciparum

Question 3

This form of malaria, if treated after acute attack, can be suppressed but it will remain dormant in the liver. Relapse can occur. This form produces milder symptoms.

Answer 3

Plasmodium vivax

Question 4

What is the clinical indication for chloroquine?

Answer 4

erythrocytic form of malaria

Question 5

What is the MOA of chloroquine?

Answer 5

gets concentrated in the parasite’s lysosomes; may also block synthesis of nucleic acid and may impair ability of plasmodia to utilize Hb

Question 6

What are the adverse effects of chloroquine?

Answer 6

prophylaxis: mild

larger doses: visual disturbances, GI effects

Question 7

What are the contraindications of chloroquine?

Answer 7

patients with psoriasis or porphyria

Question 8

What is the clinical use of Primaquine?

Answer 8

hepatic forms of malaria (p. vivax)

Question 9

What is the MOA of Primaquine?

Answer 9

converted to oxidizing intermediates in the body - could generate ROS or interfere with ETC in parasites

Question 10

What are the adverse effects of Primaquine?

Answer 10

CNS symptoms, hypertension, dysrhythmias

Question 11

What are the contraindications of Primaquine?

Answer 11

patients with G6PD deficiency - get hemolytic anemia

Question 12

What is the clinical use of Quinine?

Answer 12

chloroquine-resistant strains of both P. vivax and P. falciparum

note: active against erythrocytic forms but not hepatic forms

Question 13

What are the adverse effects of Quinine?

Answer 13

tinnitus, high tone deafness, visual disturbances, headache, vomiting
hypoglycemia
hypotension

Question 14

This is a rare hypersensitivity reaction to Quinine that results in massive hemolysis, hemoglobinemia, and hemoglobinuria

Answer 14

blackwater fever

Question 15

What are the contraindications for Quinine?

Answer 15

pregnancy

Question 16

____ selectively inhibits the parasitic ETC and ____ acts synergistically with it to inhibit ____ function

Answer 16

atovquone; proguanil

Question 17

Artemether and Artensunate are agents very effective against what form of malaria?

Answer 17

chloroquine-resistant P. falciparum

Question 18

What is the clinical use of metronidazole?

Answer 18

active against a wide variety of aerobic protozoal parasites and obligate anaerobic bacteria

Question 19

Metronidazole kills ____ but does not kill ____ of E. histolytica

Answer 19

trophozoites; cysts

Question 20

What is the MOA of metronidazole?

Answer 20

prodrug that is reduced by ferredoxin - product kills organisms through DNA damage

Question 21

What are the adverse effects of metronidazole?

Answer 21

dark urine (not really adverse effect)
nausea, headache, dry mouth, metallic taste
disulfiram-like reaction with alcohol

Question 22

What are the drug interactions of metronidazole?

Answer 22

drugs that induce CYP3A4 may reduce its action
drugs that inhibit CYP3A4 may increase its action
cholestyramine - reduces availability by 20%

Question 23

What is the clinical use of Idoquinol?

Answer 23

asymptomatic intestinal amoebiasis and cysts

note: not absorbed well so not useful for systemic amoebiasis, only the amoeba residing in intestinal tract

Question 24

What is the clinical use of Nitazoxanide?

Answer 24

treatment of three important protozoal infections: giardiasis, amoebiasis, and trichomoniasis

Question 25

What is the MOA of Nitazoxanide?

Answer 25

blocks a specific enzyme involved in ETC resulting in inhibition of aerobic energy metabolism