Lecture Course 4: Anthelmitics

Question 0

Saclicyclides

Answer 0

Target flukes
Proton ionophores are lipophilic molecules which cross membranes and uncouple mitochondria - less selective, more side effects
Also lower tegument pH, decreasing motility (explains selectivity)

Question 1

Benzimidazole
Eg. Thiabendazole
Triclabendazole

Answer 1

Inhibit tubulin polymerisation
-> less vesicle traffic -> slow starvation
Prolonged treatment necessary - bolus administration

Question 2

Diamphenithide

Answer 2

Inhibits glycolysis in flukes by increasing malate concentration

Question 3

Clorsulon

Answer 3

Inhibits phosphoglycerate kinase and mutase
Most active against flukes (which ingest blood)
Combined with ivermectin

Question 4

Praziquantel

Answer 4

Increases calcium permeability and damages tegument
Causes spastic paralysis and allows host access to helminth
Action against cestodes in crypts up as prazi is absorbed and resecreted by gut

Question 5

Cysteine Proteases

Answer 5

Oldest known antihelmintics- found in papaya!
Not actually developed commercially yet
Resistant to acid digestion - oral dose
Attack helminth tegument by breaking down helminth collagen

Question 6

Imidazothiazoles (levamisol)

Answer 6

Nicotinic agonist.

Causes spastic paralysis esp. in lungworms and GI helminths

Question 7

Tetrahydropyrimadines eg. Pyrantel

Answer 7

Nicotinic agonist
More potent than levamisol
Causes spastic paralysis especially in GI helminths and lungworms

Question 8

Pyrimidines

Answer 8

Nicotinic agonist

Spastic paralysis esp. in lungworms and GI helminths

Question 9

Quaternary ammonium salts

Answer 9

Nicotinic agonist

Spastic paralysis especially in GI helminths and lungworms

Question 10

Paraherquamide

Answer 10

Nicotine antagonist

Flaccid paralysis of parasites

Question 11

Piperazine

Answer 11

Helminth GABA agonist
Chloride channels open and cell hyper-polarises
Succinate production is also inhibited
Flaccid paralysis accompanied by ATP depletion

Question 12

Avermectins eg. Ivermectin

Answer 12

Macrocyclic Lactone
Opens glutamine gated chloride channels ~> Hyperpol -> flaccid paralysis
Not for turtles or collies

Question 13

Milbemycin

Answer 13

Macrocyclic Lactone
Activates glutamate gated chloride channels -> Hyperpol -> flaccid
Not for turtles or collies

Question 14

Amino-acetylnitrile derivatives (AADs)

Answer 14

Nicotinic agonists
Target nematode specific AChR subunit
Spastic paralysis

Question 15

Cyclo-octadepsipeptides eg. Emodepside

Answer 15

Broad spec
Possible MODA:
At the pharynx, binds to latrophillin like receptor - activates PLC - DAG - synaptobrevin - neuropeptide release - flaccid paralysis

Neurones - forms pore - calcium entry - Calcium gated potassium channels - hyperpol - flaccid paralysis