Anti-Helminths

Question 1

Clinical Use of Praziquantel

Answer 1

Effective against adults and immature stages

Drug of choice for trematode and cestode infections but not nematodes

Question 2

Is Praziquantel contraindicated in pregnancy?

Answer 2

Yes

Question 3

The mechanism of action of Praziquantel…

Answer 3

Increases influx of calcium across tegument, leading to disruption of tegument and antigen exposure

Increase Ca influx in muscles cells –> increased muscle contraction –> spastic paralysis

Question 4

The other contraindication of Praziquantel

Answer 4

Intraocular Cysticerosis: parasite killing can lead to irreversible damage to the retina due to the inflammatory response

Question 5

What can happen with high doses of pyrantel pamoate?

Answer 5

Neuromuscular blockade

Question 6

Mechanism of Actions of Pyrantel Pamoate…

Answer 6

Depolarizing neuromuscular blockade

Stimulated nicotinic acetylcholine receptor at the neuromuscular junction –> release of acetylcholine –> inhibits acetylcholinesterase

All this causes spastic paralysis

Question 7

Anti-Helminthic actions of pyrantel pamoate

Answer 7

Not effective against migratory stages in tissues

Kills larvae and adults in intestines; not effective against eggs

Question 8

What causes the adverse reaction from DEC use?

Answer 8

The antigens released from dying microfilariae and/or adult worms

Steroids can decrease this reaction

Question 9

Clinical Uses of DEC

Answer 9

Loiasis caused by Loa Loa

Controls and treats lymphatic filariasis in combination with albendazole

Question 10

MOA of DEC??

Answer 10

Alters worm surface membrane resulting in enhanced killing by the host immune system

Stimulates platelet aggregation around membrane-damaged parasites

Question 11

Alkalinized urine does what to DEC?

Answer 11

DEC gets reabsorbed across the proximal tubules, leading to elevated plasma levels and prolonged half-life

Question 12

Ivermectin Resistance

Answer 12

Increased ATP-dependent PGP transporter activity on the surface of worm to mediate drug efflux

Mutations in ligand-gated Cl- channel leading to decreased drug binding

Question 13

What is a Mazzotti-like reaction?

Answer 13

Caused by Ivermectin

Itching, swollen tender lymph nodes
Headache, dizziness, somnolence, fever, tachy, hypotension, myalgia, arthralgia, diarrhea, facial/peripheral edema

Question 14

MOA of Ivermectin

Answer 14

Activates invertebrate specific glutamate gated Cl- channel –> hyperpolarization and muscle paralysis

Binds with high affinity to GABA-gated Cl- channels in nematodes

Question 15

Clinical Uses of Ivermectin

Answer 15

Nematode infections leading to…

Onchocerciasis (river blindness)
Lymphatic filariasis (combined with albendazole for adult worms)

Question 16

Benzimidazoles: Three drugs

Answer 16

Mebendazole
Albendazole
Thiabendazole

Question 17

MOA of benzimidazoles

Answer 17

Inhibits microtubule polymerization by binding to B-tubulin

Absence of microtubules causes:

• Inhibition of mitosis
• Cessation of cellular secretion
• Inhibition of mitochondrial fumarate reductase
• Uncoupling of oxidative phosphorylation

Question 18

Resistance to Benzimidazole…

Answer 18

Change in B-tubulin isotype usage

-Point mutation in B-tubulin isotype to tyrosine at position 200

Question 19

Clinical Uses of Benzimidazoles

Answer 19

GI lumen and systemic

• Ascariasis
• Enterobiasis
• Trichuriasis
• Necatoriasis
• Lymphatic filariasis

Question 20

Dosage of Benzimidazole

Answer 20

Either a single dose or a 3-day regimen

Question 21

Mebendazole and Albendazole have very similar toxicities. But which one can cause liver abnormalities with long term use?

Answer 21

Albendazole

Question 22

What drug can increase the systemic drug levels of Mebendazole?

Answer 22

Cimetidine

Question 23

Which drug is the drug of choice for schistosomiasis?

Answer 23

Praziquantel

Question 24

Which drug is not useful for trematodes and cestodes?

Answer 24

Ivermectin