Antiprotozoals

Question 1

Metronidazole

Answer 1

• mechanism: Bioactivation of Metronidazole’s nitro group by electron transport proteins in anaerobic bacteria and protozoa produces cytotoxic intermediates (free radicals)
• kinetics: Oral; hepatic metabolism. Penetrates breast tissue and CSF
• clinical: Protozoa (Giardia, Trichomonas, Entamoeba), anaerobic bacteria (bacteroides and clostridium). For clostridium, remember that this is drug of choice in pseudomembranous colitis (caused by c.diff)
• toxicity/interactions: Metallic Taste (high-yield association); nausea, diarrhea, disulfram-like effect
• misc: Leaves a metallic taste in your mouth

Question 2

Primaquine

Answer 2

• mechanism: Unknown mechanism, is an antimalarial. Is metabolized in the liver, and metabolites may be directly toxic to malarial parasites
• kinetics: Oral; widely distributed to tissues and rapidly metabolized to urine
• clinical: Malarial Treatment. Used in conjunction with chloroquine.
• toxicity/interactions: Rare side effects. Contraindicated in patients with G6PD deficiency (due to hemolysis); don’t use in pregnant patients

Question 3

Mefloquine

Answer 3

• mechanism: Unknown mechanism, is an antimalarial.
• kinetics: Oral (irritation if used parenterally). Distributes well to tissues and eliminated slowly, so only needs single dose
• clinical: Malarial Treatment, often used in prophylaxis. Not appropriate for severe malaria
• toxicity/interactions: Nausea with weekly dosing, neuropsychiatric symptoms with higher dose

Question 4

Chloroquine

Answer 4

• mechanism: Inhibits malarial heme polymerase (parasite catabolizes hemoglobin, and heme polymerase detoxifies breakdown products. THUS, toxic free heme molecules build-up once polymerase is inhibited)
• kinetics: Oral, rapidly absorbed with good distribution
• clinical: Drug of choice for malaria (now has resistance). Also used as prophylaxis. Used in combination with Primaquine to treat P.vivax and P. ovale
• toxicity/interactions: Resistance common in P. Falciparum strain and some P.vivax due to mutation in transporter. Toxicity: may cause hemolysis in patients with G6PD deficiency

Question 5

Halofantrine

Answer 5

• mechanism: Unknown mechanism, not even available in USA…
• kinetics: Oral, taken with food due to toxicity.
• clinical: Effective against erythrocytic stage of malarial species only
• toxicity/interactions: Cardiotoxicity. Also, GI disturbance
• misc: not a high-yield drug.

Question 6

Quinine

Answer 6

• mechanism: Unknown mechanism
• kinetics: Oral; widely distributed.
• clinical: Works for all 4 malarial species (plasmodium falciparum, vivax, malariae, ovale). Drug of choice for severe falciparum malaria
• toxicity/interactions: Cause cinchonism (constellation of symptoms including tinnitus, headache, nausea, dizziness, visual disturbances, flushing). May have hemolysis

Question 7

Pyrimethamine

Answer 7

• mechanism: Inhibits Folic Acid synthesis (needed for production of purines & pyrimidines). Inhibits plasmodial dihydrofolate reductase. Similar to trimethoprim
• kinetics: Oral, slowly absorbed, given only once/week
• clinical: Used in treatment of malaria usually in combination with other drugs. Also used in toxoplasmosis and pneumocystosis
• toxicity/interactions: Resistance in some areas for p.falciparum strains due to mutations in dihydrofolate reductase

Question 8

Doxycycline

Answer 8

-also seen in tetracyclines but is an antiprotozoal drug that is used to treat p. falcifarum

Question 9

Artemisinin

Answer 9

• mechanism: Unclear mechanism, may result from production of free radicals.
• kinetics: rapidly absorbed
• clinical: Taken from a Chinese herbal medicine, now used in combination therapy for uncomplicated malaria via p.falciparum
• toxicity/interactions: well tolerated

Question 10

Proguanil

Answer 10

• mechanism: Same as pyrimethamine except it’s a prodrug and needs to be taken daily for prophylaxis! So it inhibits Folic Acid synthesis (needed for production of purines & pyrimidines). Inhibits plasmodial dihydrofolate reductase. Similar to trimethoprim
• kinetics: Oral, absorbed faster than pyrimethamine
• clinical: Used in treatment of malaria usually in combination with other drugs
• toxicity/interactions: Resistance in some areas for p.falciparum strains due to mutations in dihydrofolate reductase

Question 11

Dapsone

Answer 11

-also an antimycobacterial drug used to treat leprosy but can also be used to treat malaria

Question 12

Sulfadoxine

Answer 12

-also a sulfonamine; can be used to treat Pneumocystis pneumonia, Nocardia, Toxoplasma, and malaria