Anthelmintics Flashcards
What is an anthelmintic agent?
Expel parasitic worms from the body by stunning or killing the parasites
What do helminths require?
A feeding site
A working GI tract
Neuromuscular coordination
Homeostasis
What are the different preparations of anthelmintic agents?
Oral preparations
Slow release bolus
Pro drug
Injections
What are the 3 mechanisms of action of anthelmintic agents?
Affect microtubular function
Cause helminth paralysis
Affect energy-generating systems
What are the 5 classification groups of anthelmintic agents?
Benzimidazoles Levamisole Macrocyclic lactone Amino-acetonitrile derivatives Spiroindoles
What are the properties of an ideal anthelmintic?
Selective toxicity - wide therapeutic index Broad spectrum of activity Cost effective Drug resistance not likely Efficacy and potency
What is benzimidazoles mechanism of action?
Compromises beta-tubulin cytoskeleton
Glucose uptake is microtubule dependent - causes starvation
What spectrum of activity are benzimidazoles?
Wide
Mostly nematodes
What is a pro-drug?
Inactive compound that is metabolised in the body to make it biologically active
What is an example of a pro-drug?
Febantel
What factors affect benzimidazoles efficacy?
Diet - fibre
GI flow rate
Parasite infection
Ruminant oesophageal groove closure
What neurotransmitters do helminths use?
Cholinergic (ACh) - excitation
GABAergic - inhibition
What is levamisole’s mechanism of action?
Prolonged activation of excitatory nicotinic ACh receptors - Nicotinic receptor agonists
Spastic muscle paralysis
What are the two groups of levamisoles?
Imidazothiazoles and tetrahydropyrimidines
What are the two semisynthetic derivatives of macrocyclic lactones?
Avermectins
Milbemycins
What is the mechanism of action of avermectins?
Activate the glutamate-gated chloride channels - targets neuromuscular junction
Causes flaccid paralysis/starvation
What toxicity can be caused by avermectin?
MDR1 gene in collies
What is the difference between milbemycin and avermectin?
Milbemycin has a longer half life
Also effects ticks and fleas
Given in combination with praziquantel
What is the mechanism of action of amino-acetonitrile derivatives?
Activate the nematode specific ACh receptor
Causes irreversible paralysis
What are amino-acetonitrile derivatives active against?
Adults and maturing larvae
Triple resistant nematodes
What is the mechanism of action of spiroindoles?
Block cholinergic neuromuscular transmission
Flaccid paralysis
What are spiroindoles used to treat?
Broad range of adult/immature nematodes in sheep
What anthelmintic is used to treat tapeworms?
Praziquantel
What is the mechanism of action of praziquantel?
Increases the permeability of cell membranes to Ca2+
Sustained muscle contraction and tegmental disruption
What are the main trematodal agents?
Triclabendazole - fasciola hepatica
What is anthelmintic resistance?
The ability of parasites to survive treatments at the reccomended dose rate
What is the clinical definition of resistance?
95% or less reduction in a faecal egg count test
What is triple resistance?
Resistance to the 3 different anthelmintic agents
1 - BZ
2 - LV
3 - ML
What human factors contribute to resistance?
Under dosing
Unnecessary dosing
Misdiagnosis - inappropriate drugs
What helminth factors contribute to resistance?
Molecular changes
Modified activity of parasitic enzymatic systems
Changes to receptors
Amplification of target genes
What causes benzimidazole resistance?
Cross resistance due to altered beta-tubulin
What causes Levamisole resistance?
Modified nicotinic ACh receptors - altered drug binding
What causes Macrocyclic lactone resistance?
Alterations in multiple genes
How to minimise resistance?
Cycle through classes
Combination products
Correct dosing and product
What is an example of a combination product?
Abamectin and derquantel
What is an example of a parasite that has a vaccination?
Dictyocaulus viviparus
What are some alternative options to anthelmintics?
Use genetically resistant host species
Nematophagous fungi
Vaccination
