Anthelmintics

Question 1

Fenbendazole

Answer 1

Benzimidazole
Targeted against nematode and adult flukes
Inhibit tublin polymerisation - binds to b-tublin and prevents elongation, therefore cellular transport and energy production
Require repeated oral administration
100 fold greater affinity for helminth than veterbrate
Febantil prodrug

Question 2

Thiabendazole

Answer 2

Benzimidazole
Targeted against nematodes and flukes 
Inhibits tublin polymerisation - bind to b-tublin and prevents elongation 
Requires repeat oral administration 
100 fold greater affinity for helminth

Question 3

Triclabendazole

Answer 3

Benzimidazole
Selective for FLUKES
Inhibits tublin production - binds to B-tublin
Requires repeat oral administration

Question 4

Diamphenithide

Answer 4

Aromatic amine
Selective against flukes
Inhibits glucose metabolism but increase malate concentration

Question 5

Clorsulon

Answer 5

Sulphonamide
Inhibits glycolysis by inhibiting phosphoglycerate kinase and mutase essential in glucose production
Binds to plasma proteins therefore most effective for helminths within the blood like liver fluke

Question 6

Closantel

Answer 6

Salicylanilide
Uncouples oxidative phosphorylation by release of H+ moity, dissipating the proton gradient across mitochondria = protonaphore, lipophilic so can cross cell membrane
Reduce tegmentum pH = decrease mobility and ATP production
Not selective for helminths - ADR’s

Question 7

Nitroxynil

Answer 7

Subsitute phenol
Uncouples oxidative phosphorylation by release of H+ moiety, disrupts mitochondrial proton gradient, lipohillic so can cross cell membrane
Also reduce tegmentum pH = decreased mobility and ATP production
Protonaphore

Question 8

Praziquantel

Answer 8

Pyrazinoisoquinolone
Selective against chested - schistosoma species
Acts to increase Ca permeability causes rapid contraction and activation of Ca induced Ca channels eventually leading to spastic paralysis - loss of suckers
Also causes damage to tegmentum + cuticle = vacuolisation and influx of host immune cells

Question 9

Cystine proteinases

Answer 9

Act on helminth cuticle to hydrolyse (via cystine thiol and hystidine residues) the peptide bonds in collagen, destroying collagen in the cuticle and inhibiting egg production

Question 10

Dichlorvos

Answer 10

Organophosphorus
Cholinesterase inhibitor, leads to spastic paralysis
Covalently bind to esteratic site - phosphorylates serine
Autonomic and somatic side effects

Question 11

Aldicarb

Answer 11

Carbomate
Cholinesterase inhibitor, leads to spastic paralysis
Covalently bind to esteratic site - carbomylates serine
Autonomic and somatic side effects

Question 12

Levamisole

Answer 12

Imidazothiazole
Nicotinic agonist (synaptic and extrasynaptic receptors)
Cause spastic paralysis, self antagonism can occur however where they block the Na+ or K+ channel causes depolarisation therefore leading to flaccid paralysis (less)
Selective against nematodes

Question 13

Pyrantel

Answer 13

Tetrahydropyridine
Nicotinic agonist (synaptic and extrasynaptic receptors) 
cause spastic paralysis, self antagonism can occur however where they block the Na+ or K+ channel causes depolarisation therefore leading to flaccid paralysis 
selective against nematodes 
Insoluble - restricted to helminths in GI tract

Question 14

Paraherquamide

Answer 14

Oxindale Alkaloid

Nictotinic Antagonist - results in flaccid paralysis and eventual expulsion

Question 15

Piperazine

Answer 15

GABA agonist, activates Cl- channels leading to hyperpolaristation and flaccid paralysis
Selective against nematodes
Requires high CO2 concentration to function
And inhibits succinate production depleting ATP

Question 16

Diethylcarbamzine

Answer 16

Derivative of piperazine, agonist for GABA channel leading to flaccid paralysis
Used against canine heart worm

Question 17

Ivermectin

Answer 17

Macrocyclic lactone
Only effective against Nematodes
Glutamate gated Cl- channel Agonist - increases Cl- permeability causing hyperpolarisation and flaccid paralysis
Locks channel in open confirmation
Also opens non-GABA gated Cl channels in the muscle

Question 18

Milbemycin

Answer 18

Glutamate gated Cl- channel agonist - increases Cl- permeability leading to flaccid paralysis
Locks channel in open confirmation
Only effective against nematodes

Question 19

Collie Dogs sensitive to…

Answer 19

Avermectins - ataxia, hypersalivation, Coma, death, blindness
Deletion mutation in MDR-1a gene encoding for the P-glycoprotein - causes toxic drugs to accumulate in brain

Question 20

Emodepside

Answer 20

Broad spectrum against nematodes and filaria
Ultimately cause hyperpolarisation + flaccid paralysis, mechanism unsure:
Pore forming, activate Ca+ sensitive K+ channels, Stimulate SLO-1 K+ channels, acts as inophore, interacts with LAT 1+@

Question 21

Monepantel

Answer 21

Nicotinic agonist,
amino-actenitrile derivative
selective against nematodes
currently licensed for sheep