Anti-Helminths Flashcards
Clinical Use of Praziquantel
Effective against adults and immature stages
Drug of choice for trematode and cestode infections but not nematodes
Is Praziquantel contraindicated in pregnancy?
Yes
The mechanism of action of Praziquantel…
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
The other contraindication of Praziquantel
Intraocular Cysticerosis: parasite killing can lead to irreversible damage to the retina due to the inflammatory response
What can happen with high doses of pyrantel pamoate?
Neuromuscular blockade
Mechanism of Actions of Pyrantel Pamoate…
Depolarizing neuromuscular blockade
Stimulated nicotinic acetylcholine receptor at the neuromuscular junction –> release of acetylcholine –> inhibits acetylcholinesterase
All this causes spastic paralysis
Anti-Helminthic actions of pyrantel pamoate
Not effective against migratory stages in tissues
Kills larvae and adults in intestines; not effective against eggs
What causes the adverse reaction from DEC use?
The antigens released from dying microfilariae and/or adult worms
Steroids can decrease this reaction
Clinical Uses of DEC
Loiasis caused by Loa Loa
Controls and treats lymphatic filariasis in combination with albendazole
MOA of DEC??
Alters worm surface membrane resulting in enhanced killing by the host immune system
Stimulates platelet aggregation around membrane-damaged parasites
Alkalinized urine does what to DEC?
DEC gets reabsorbed across the proximal tubules, leading to elevated plasma levels and prolonged half-life
Ivermectin Resistance
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
What is a Mazzotti-like reaction?
Caused by Ivermectin
Itching, swollen tender lymph nodes
Headache, dizziness, somnolence, fever, tachy, hypotension, myalgia, arthralgia, diarrhea, facial/peripheral edema
MOA of Ivermectin
Activates invertebrate specific glutamate gated Cl- channel –> hyperpolarization and muscle paralysis
Binds with high affinity to GABA-gated Cl- channels in nematodes
Clinical Uses of Ivermectin
Nematode infections leading to…
Onchocerciasis (river blindness) Lymphatic filariasis (combined with albendazole for adult worms)
Benzimidazoles: Three drugs
Mebendazole
Albendazole
Thiabendazole
MOA of benzimidazoles
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
Resistance to Benzimidazole…
Change in B-tubulin isotype usage
-Point mutation in B-tubulin isotype to tyrosine at position 200
Clinical Uses of Benzimidazoles
GI lumen and systemic
- Ascariasis
- Enterobiasis
- Trichuriasis
- Necatoriasis
- Lymphatic filariasis
Dosage of Benzimidazole
Either a single dose or a 3-day regimen
Mebendazole and Albendazole have very similar toxicities. But which one can cause liver abnormalities with long term use?
Albendazole
What drug can increase the systemic drug levels of Mebendazole?
Cimetidine
Which drug is the drug of choice for schistosomiasis?
Praziquantel
Which drug is not useful for trematodes and cestodes?
Ivermectin
