Anti-helminthics

Question 1

Mechanism of action of benzimidazoles

Answer 1

Kills eggs & larvae (and possibly adults); inhibits microtubule polymerization by binding to B-tubulin; also inhibit energy production in the parasites by inhibiting glucose uptake, mitochondrial fumarate reductase, and uncoupling of oxidative phosphorylation

Question 2

Clinical use for benzimidazoles

Answer 2

Used for nematodes - GI lumen and systemic (ascariasis, lymphatic filariasis, etc). Kills eggs and larvae, possibly adults.

Question 3

ADME of mebendazole

Answer 3

Poorly absorbed so little systemic activity, rapid 1st pass metabolism to inactive metabolite and excreted in the urine

Question 4

Contraindications of benzimidazoles

Answer 4

Caution with CYP inhibitors as it will increase concentration of mebendazole/albendazole. Not for children

Question 5

Side effects of benzimidazoles

Answer 5

Very mild if any. Either in high doses can cause alopecia, bone marrow suppression, transient liver abnormalities. Albendazole can cause epigastric distress (n/v/d)

Question 6

Name the avermectins

Answer 6

Ivermectin, praziquantel, diethylcarbamazine, pyrantel pamoate

Question 7

When should you be careful about how you give avermectins?

Answer 7

For high worm burden. Tx with albendazole first THEN come in with one of these to avoid toxic inflammatory response; if there is an inflammatory response with any of these, add corticosteroids

Question 8

Mechanism of action of ivermectin

Answer 8

Activates invertebrate-specific glutamate-gated Cl- channel (100-fold higher affinity for parasite channel than human channel) resulting in flaccid paralysis so worm can no longer move (can’t feed)
*Uses CYP3A4 for absorption/metabolism

Question 9

Mechanism of resistance of ivermectin

Answer 9

upregulate ATP-dependent P-glycoprotein transporter (mediates drug efflux)

Question 10

Indication for ivermectin

Answer 10

Drug of choice for onchocerciasis; not effective for trematodes, flukes, cestodes, or tapeworms because Cl- gated channels lack high affinity for ivermectin

Question 11

Mechanism of action of praziquantel

Answer 11

Increases influx of Ca++ across tegument eliciting a host immune response & spastic paralysis
*metabolized by CYP3A4

Question 12

Contraindications for praziquantel

Answer 12

Pregnancy, intraocular cysticercosis (inflammatory response can cause permanent retinal damage)

Question 13

Indication for praziquantel

Answer 13

Drug of choice for schistosomiasis. Effective against trematodes (schisto) and cestodes (NOT nematodes).

Question 14

Mechanism of action of diethylcarbamazine

Answer 14

Not perfectly understood, but alters the worm’s surface membrane for enhanced killing by host’s immune system

Question 15

Indications for diethylcarbamazine

Answer 15

Loiasis, lymphatic filariasis (in combo w/ albendazole)

Question 16

Contraindications for diethylcarbamazine

Answer 16

Onchocerciasis b/c of severe inflammatory response that will worsen ocular lesions; should give ivermectin + steroids

Question 17

Important details with diethylcarbamazine

Answer 17

Only available through CDC. Rapidly absorbed, renal excretion (dosage adjusted for renal impaired patients)

Question 18

Toxicity with diethylcarbamazine

Answer 18

Rare, but can have severe immune-mediated response to dying worms (Mazzotti-like rxn, leukocytosis, proteinuria, eosinophilia)
*use steroids in this case

Question 19

Uses of pyrantel pamoate

Answer 19

Luminal parasites (e.g. ascaris, pinworm)
*not effective against eggs

Question 20

Mechanism of action of pyrantel pamoate

Answer 20

Depolarizing neuromuscular blocker causing spastic paralysis from excessive release of Ach and inhibition of acetylcholinesterase; worm then expelled from GI tract
*in high doses, can act as neuromuscular blockade in the host

Question 21

ADME of pyrantel pamoate

Answer 21

Poorly absorbed so good for luminal infection only. Excreted via feces.

Question 22

Name the benzimidazoles

Answer 22

Mebendazole, albendazole