GI Parasites Pharm

Question 1

Metronidazole, Tinidazole - Class and Mechanism

Answer 1

C: Tissue-Dwelling Amebicides
MOA: Reacts with ferredoxin (produced by PFOR gene), making the drug a free-radical carrier, which goes on to cause ssDNA breaks

Question 2

Metronidazole, Tinidazole - Pharmacokinetics, Contraindications, Interactions

Answer 2

Well absorbed, widely distributed.
M: Hepatic (P450s)
E: Renal

Contraindications: Pregnancy + Alcohol
Interactions: Warfarin (increases bleeding risk)

Question 3

Metronidazole, Tinidazole - Uses, ADRs,

Answer 3

Uses: Covers Entamoeba histolytica, Giardia, trichomonas vaginalis, and anaerobic bacteria (B. fragilis, H. pylori, C. difficile). Topical use for Rosacea.

ADRs: GI discomfort, dysgeusia, disulfiram reaction, peripheral neuropathy, mutagenic in 1st trimester pregnancies.

Question 4

Nitazoxanide - Class, Mechanism, Pharmacokinetics, Use, ADRs

Answer 4

C: Lumen-Dwelling Antiprotozoal
MOA: Non-competitive inhibitor of PFOR, interfering with anaerobic metabolism
Kinetics: Metabolized by glucuronidation, eliminated in bile and urine.
Use: Cryptosporidium, Giardia
ADRs: GI Side effects

Question 5

Iodoquinol, Parmomycin - Classes, Mechanisms, Kinetics, Use

Answer 5

C: Lumen-Dwelling Antiprotozoal (parmomycin = aminoglycoside antibiotic)
MOA: Iodoquinol - Unknown. Parmomycin - inhibits 30S ribosomal subunit.
Kinetics: No systemic absorption
Use: Luminal amebiasis (also kills normal gut flora)

Question 6

What are the four species of plasmodium and what are some unique features about them?

Answer 6

P. falciparum - Common, most severe with high fever that persists between cycles.
P. vivax - common, persistent exoerythrocytic liver phase (requires Primaquine)
P. ovale - persistent exoerythrocytic liver phase (requires Primaquine)
P. malariae - least common

Question 7

Quinine, Chloroquine, Mefloquine - MOA, ADRs

Answer 7

MOA: Concentrate in infected RBCs, inhibiting nucleic acid synthesis and use of hemoglobin during erythrocytic schizogony. (anti-malarial)

ADRs
Q: Cinchoism (tinnitius, sweating, auditory and visual impairment)
C: Resistant strains, retinal damage, fetal damage, QT prolongation
M: Neuropsychiatric Symptoms

Question 8

Primaquine - MOA, Use, Contraindicated Population

Answer 8

MOA: Unclear, involves oxidation of schizont membrane in liver. (anti-malarial)
Use: Vivax and Ovale for exoerythrocytic liver phase. Need to be used in combination with other drugs to treat erythrocytic phase.
Contra: G6PD deficiency - oxidative stress causes intravascular hemolysis.

Question 9

Malarone (Atovaquone/Proguanil) - MOA, ADRs

Answer 9

MOA (anti-malarial):
A - Inhibits plasmodial ETC, inhibiting nucleic acid and ATP synthesis (resistance when used alone)
P - inhibits DHF reductase, preventing dTMP synthesis.
ADRs: Fever, headache, GI upset, insomnia, elevated LFTs

Question 10

Primethamine/Sulfadoxine - MOA, ADRs, Supplementation

Answer 10

MOA (analogous to Bactrim (anti-malarial)):
P - Inhibits DHF reductase
S - Competes with pABA for folate synthesis (dihydropterate reductase)

ADRs: GI upset, macrocytic anemia, leukopenia, thrombocytopenia, hemolytic anemia, Stevens-Johnson Syndrome

Supplement: Leucovorin if used long term.

Question 11

Aremether/Lumefantrine - MOA, Use

Answer 11

MOA (developed from Chinese Trad Med) (anti-malarial):
A - metabolized to dihydroartemisin (DHA), which has an internal peroxide (carbon free radical) that inhibits erythrocytic schizogeny by damaging malarial proteins and heme.
L: Unknown, inhibits beta-hematin formation

Use: DOC against severe P. vivax infections (most rapid activity). Only drug NOT used for prophylaxis.

Question 12

4 main options for malarial prophylaxis

Answer 12

1) Doxycycline: Cheap, can be used last minute, but not in kids and pregnant women.
2) Chloroquine/Mefloquine
3) Primaquine
4) Malarone (Atovaquone/Proguanil)

Question 13

Albendazole (Mebendazole - no longer available in US) - Class, MOA

Answer 13

C: Anti-nematode agent (ovicidal)
MOA: Binds beta-tubulin, preventing microtubule formation in the parasite (no polymerization), leading to rapid ATP depletion -> parasite paralysis -> fecal elimination

Question 14

Albendazole - kinetics, uses, contraindications, side effects

Answer 14

K: poorly absorbed, high first pass metabolism
Contra: Pregnancy (inhibits fetal mitosis)
Uses: Intestinal Nematode infection
ADRs: GI upset

Question 15

Pyrantel- Class, MOA, Kinetics, ADRs

Answer 15

C: Anti-nematode agent (non-ovicidal)
MOA:Stimulate nicotinic receptors and inhibits acetylcholinesterase -> muscle contraction in parasites -> paralysis + fecal elimination
Kinetics: Poorly absorbed
ADRs: Well tolerated

Question 16

Ivermectin - Class, MOA, Kinetics

Answer 16

C: Anti-nematode agent
MOA: Activates glutamate-gated Cl- channels, causing hyperpolarization and paralysis of nematode pharyngeal muscles.
Kinetics: Incorporates into lipid bilayer, giving it a huge half-life

Question 17

Ivermectin - Uses, ADRs

Answer 17

Uses: Extra-intesetinal nematodes, e.g. Filariasis (Wuchereria Bancrofti, Brugia malayi) and River Blindness (Onchocera volvulus)

ADRs: Mazotti Reaction

Question 18

Diethylcarbamazine - Class, MOA, Use, ADRs

Answer 18

C: Anti-nematode agent
MOA: Inhibits microfilaria arachadonic acid metabolism, lowers PGI2 and PGE2, causing vasoconstriction to augment immune response to worms.
Use: Filariasis (Wuchereria Bancrofti, Brugia malayi)
ADRs: Mazotti Reaction

Question 19

Praziquantel - Class, MOA, Use, ADRs

Answer 19

C: Anti-trematode, anti-cestode
MOA: Increases calcium permeability, causing paralyzing muscle contractions that lead to detachment of suckers from the vessel wall.
Use: DOC for trematodes and cestodes (esp. flukes, neurocysticerosis)
ADRs: Mazotti Rxns, abdominal discomfort, drowsiness, dizziness, headache

Question 20

What are Mazotti Reactions? Which drugs cause them?

Answer 20

Immune Type Reaction against a dying worm.

Symptoms Include: fever, diarrhea, arthralgia, pruritis, lymphadenopathy, edema

Drugs: Ivermectin and Diethylcarbamazine (anti-nematodes), Praziquantel (anti-trematode/cestode)