Dr. Roane Antiprotozoals EXAM 3

Question 1

What are common diseases caused by Antiprotozoals?

Answer 1

-Malaria (mosquito)
-Amebiasis (contaminated water)
-Leishmaniasis (bug bite)
-Trypanosomiasis (bug bite)
-Trichomoniasis (sexually transmitted protozoan)
-Giardiasis – Beaver fever (contaminated water)
-Toxoplasmosis (cat feces)

Question 2

Difference between Bacteria and Protozoa

Answer 2

-Protozoa are eukaryotic
-Protozoa contain a nucleus and other cell organelles

Question 3

What is the most common STD in the world?

Answer 3

Trichomonas vaginalis

Question 4

What is the most common drug used for infections of Protozoa?

Answer 4

-Metronidazole
-bc it also effective on bacteria

Question 5

What determines the drug therapy against protozoa?

Answer 5

-the life cycle (dormant, proliferative)
-often long therapy required

Question 6

What is an Amoebic dysentery?

Answer 6

-GI infection of Entamoeba histolytica
-contaminated water

Question 7

What is the active form in the life cycle of E. histolytica?

Answer 7

-Trophozoites
-Ability to penetrate the colon wall -> Sporozoites enter hepatic portal system -> infect liver cells -> Merozoits infect blood cells -> Gametocytes remain in the blood cells and can be picked up by new mosquitos -> convert into Sporozoites in the mosquito

Question 8

What are the 3 groups of drugs that target Amebiasis in different areas of the body?

Answer 8

-Luminal amebicides (works in the lumen of the intestine)
-Systemic amebicides
-Mixed amebicides (luminal and systemic)

Question 9

Amebic dysentery

Answer 9

-ranges from diarrhea to fulminating dysentery (can be fatal)
-acute or chronic
-asymptomatic carriers exist

Question 10

MOA Flagyl (Metronidazole)

Answer 10

-it picks up electrons from bacteria and gets reduced -> donates electrons onto proteins and DNA

Question 11

Spectrum of Metronidazole

Answer 11

-kills Giardia, trichomonas
-Bacteria, especially anaerobes

Question 12

Adverse

Answer 12

-N & V
-Additional GI effects (cramping)
-Unpleasant metallic taste in the mouth
-Tendency for yeast infections in the mouth
-Rare neurological effects (means stop the drug)
-Disulfiram-like effects

Question 13

What are the luminal amebicides?

Answer 13

-Paromomycin (Aminoglycoside) , is not absorbed and stays in the lumen

-Diloxanide furoate (Furamide): PO 90% absorbed, 10% is active + ADMINISTERED with metronidazole

Question 14

Which luminal amebicide is also active against tapeworms?

Answer 14

Paromomycin

Question 15

What causes trichomoniasis (Trich)?

Answer 15

Protozoa -> Trichomonas vaginalis
-STD (1-5% of people in the US with some kind of STD)

Question 16

What are the symptoms of Trichomonas vaginalis

Answer 16

-from a mild irritation to severe inflammation with bad-smelling discharge
-50% asymptomatic

Question 17

How is Trichomonas vaginalis treated?

Answer 17

-metronidazole
OR
-tinidazole (more efficacious better tolerated)

Question 18

What are the four species of plasmodia from anopheles mosquito that causes Malaria?
!!

Answer 18

-P. falciparum is the most common and can be fatal !!!
-P. vivax is milder
-P. malariae is tropical
-P. ovale is rare

resistance occurring to drugs and insecticides, prophylaxis is important

Question 19

What is a significant characteristic of RBC infected with Plasmodium vivax?

Answer 19

visible rings infected RBC

Question 20

Which effect does the saliva to the blood?

Answer 20

-Stops the blood from clotting
-The saliva contains the plasmodia causing Malaria

Question 21

What are the erythrocytic drugs against Malaria?

Answer 21

-work when the organism is in the RBC
-Artemisinin
-Chloroquine
-Quinine
-Mefloquine
-Pyrimethamine

Question 22

Drugs against the exoerythrocyctic and gametocytic form

Answer 22

Primaquine

Question 23

Which factors must be considered in the decision tree by the CDC?

Answer 23

-Combination of treatments to prevent resistence
-treatment depends on where the pt has acquired the infection
-G6PD deficiency

Question 24

Where does Primaquine work?
MOA?
Well absorbed?
Well tolerated?

Answer 24

-Effective against exoerythrocytic and
gametocytic forms (often used in conjunction with erythrocytic active drugs)

-MOA is unknown
-well absorbed orally
-well tolerated except in patients with anemia due to G6P-DH

Question 25

Why is Primaquine less tolerated in pt with G6P-DH deficiency?

Answer 25

G6P-DH is needed to produce NADP(H) NADP(H) reduces glutathione, reduced glutathione provides protection against free radicals (produced by drugs) -Primaquine oxidizes glutathione -> so G6P-DH deficient patients have less GSH available to protect RBC from the damage -> hemolytic anemia

Question 26

How does Chloroquine work for malaria parasites in the RBC (Erythrocytic)

Answer 26

-MOA (same as hydroxychloroquine): Blocks the polymerization of heme to hemozoin -> the parasite can not get rid of the consumed heme -MOA: Alkalinizes the food vacuole to inhibit digestion (changing the pH of an intracellular compartment - was proposed to be effective against SARS-COV-19)

Question 27

What is the mechanism of resistance for Chloroquine?

Answer 27

Drug efflux pump

Question 28

Adverse effects

Answer 28

-Dose-dependent -Arrhythmias (rare) -GI disturbance -Skin rash -Headache

Question 29

What are other uses for Chloroquine and Hydroxychloroquine?

Answer 29

-in arthritic disorders to reduce inflammation -anti-inflammatory in COVID, but not proven

Question 30

How does Quinine work?

Answer 30

Erythrocytic -MOA is unknown, heme accumulation -Reserved use only, due to toxicity -Used in combination therapies

Question 31

What are the adverse effects of Quinine?

Answer 31

-Cinchonism: N/V, tinnitis, vertigo, confusion -Fetotoxic -Interacts with Al++ antacids -Potentiates neuromuscular blockers -Blindness -Cardiotoxicity

Question 32

What is the MOA for Mefloquine?

Answer 32

-Targets the ribosome to inhibit protein synthesis -Works on multidrug resistant falciparum

Question 33

What are the side effects of Mefloquine?

Answer 33

-Concentrates in the liver -Can cause CNS side effects including hallucinations and depression -EKG changes

Question 34

Which drug may be used for prophylaxis or treatment? MOA?

Answer 34

Tetracyclines -Prevents the expression of genes needed to form "apicoplast" - essential for plasmodial growth and development

Question 35

Artesunate is a derivative of which drug?

Answer 35

Artemisinin (Erythrocytic and Gametocyctic)

Question 36

What is the First-line drug for Malaria recommended by the FDA? (combined with other anti-malaria)

Answer 36

-Artemisinin -only when combined with other anti-malaria (to prevent resistance) -for severe cases: IV -MOA: free radical generator disrupting the heme metabolism

Question 37

Of which drugs does Coartem consist of?

Answer 37

-Artemether and lumefantrine -Artemether is an arteminisin derivative -Lumefantrine has a similar MOA (free radical generator)