Anthelmintics Flashcards
Levamisole (imidazothiazole)
nAChR agonist
Causes spastic paralysis
Higher affinity for helminth nAChR
Pyrantel (tetrahydropyrimidine)
nAChR agonist
Causes spastic paralysis
Higher affinity for helminth nAChR
Piperazine
GABA receptor agonist to cause muscle hyperpolarisation
Thiabendazole (benzimidazole)
Inhibits tubulin polymerisation via binding to beta tubulin
Benzimidazoles in general
Target beta tubulin (different in helminths)
Best for nematodes except for TCZ which targets fluke
Low solubility so stay in gut lumen
Slow killing so need multiple doses?
Closantel (salicylanilides)
Disrput mitochondrial H+ gradient to uncouple oxidative phosphorylation
Become concentrated in blood ingesting helminths; flukes
Praziquantel
Trematodes and cestodes
Causes muscle depolarisation by acting as calcium mobiliser via interaction with CaV
Also damages tegument as another MoA (histidine proton shuttle)
Avermectin/Ivermectin (macrocyclic lactones)
Act on glutamate gated Cl- channels to open them causing hyperpolarisation
Also potentiates Glu effects
Removed from BBB by P-glycoprotein
- Inadequate in Collies and chelonians
PZQ (cysteine protease)
Uses histidine proton shuttle to hydrolyse peptide bonds and damage tegument
Carbamates/organophosphorus compounds
Anticholinesterases
Cause spastic paralysis
Low therapeutic index
Need antidotes: atropine (to block mAChR) and pralidoxime to reactivate ACE
Clorsulon and Diamphethide
Act on flukes to inhibit ATP production
Startect
Abamectin and derquantel
Emodepside
Hyperpolarising agent
Causes flaccid paralysis
Adults more sensitive; inhibits egg laying
Inhibits cholinergic NMJ via interaction with latrophilin-like receptor/SLO-1
