Antihelminths Flashcards
Nematodes
Cylindrical, non-segmented worms (roundworms/ nemalthminthes)
Treated with benzimidazoles (BDZ)
Cheimistry of BDZ’s and Pro-BDZ’s
Insoluble or slightly soluble in water
Higher solubility at low pH (stomach)
BZD drugs
Methycarbamates (most used): Al-BZ and Fen-BZ
Halogenated BZD thiols: triclabendazole (TCBZ)
Pro-BZDs: Febantel (FBT), netobin (NTB)
MOA of BDZ’s and Pro-BDZ’s
Bind to parasite B-tubulin (inhibiting tubular functions)
Higher binding affinity and lower rate of dissociation
Blocks glucose uptake by parasite- ↓ energy/ paralysis
Metabolism and elimination of BDZ
Biotransformation in the liver
Extrahepatic metabolism in the lung and SI
PK of BDZ
Binding less than 50% to plasma protein
Blood tissue and Gi distribution
Parent drug short lived and metabolites predominate in plasma, all tissues and excreta
PK for Pro-BDZ
Microflora-mediated reductive metabolism in the GI tract
BDZ has a relatively fast elimination rate in ________
ruminants (sheep and goats)
PK of BDZ in non ruminants
Shorter gut transit time limits rates of dissolution and absorption
Multi-dose regimes (higher dose, given with food)
Host related factors
Dissolution, absorption, and biotransformation
Ruminal esophageal groove closure
Effect of GI transit time
Effect of diet type (concentrate base, ↑ absorption)
Mechanisms of drug transfer into target parasites
Diffusion (predom pathway)
Liphophilicity
Structural differences between external surfaces of nematodes
Acidic environment of nematode surface (ion trapping)
How are BZDs and Pro- BZDs classified?
Broad spectrum anthelmintics expect triclabendazole (TCBZ)
Albendazole
Broad-spectrum for cattle and sheep
Fenbendazole
Broad spectrum in cattle, sheep, goats and horses,
In zoo and wildlife (FDA approved)
Safety and toxicity of BZDs
Milk of treated animals not recommended
Overall safe
Slaughter clearance times required
Levamisole (imidazothiazoles)
Used world wide and oldest
Highly water soluble and formulation flexibility
In cats, dogs, sheep, cattle, goats, swine, poultry
MOA of levamisole
Nicotinic AChR agonist that causes spastic paralysis of muscle
PK of levamisole
Rapidly absorbed (2 hrs)
Distributed in all tissues and metabolized in the liver
Formulations of levamisole
Drinking water for pigs and poultry
Injectable in cattle
IM/SC phosphate salt preferred
NEVER IV
Safety and toxicity of levamisole
Not used in dairy cows
Avoid in horses
2-11 day slaughter clearance time
Pyrantel and morantel (tetrahydro-pyrimididines)
Adult stages of GI nematodes
Sustained release bolus of morantel tartrate for dairy and beef cattle
Equine tapeworms
Pyrantel pamoate
Used against A. perforliata (tapeworm/ cestode) treatment
Piperzaine
Blocks transmission by hyperpolarizing nerve membranes @ NMJ leading to flaccid paralysis
Mainly ascarids in dogs, cats, horses, pigs and poultry
Diethylcarbamazine citrate (DEC)
Heterocyclic compounds
Used for microfilaria in dogs
Adulticide therapy (heartworm)
Doxycycline and ivermectin prior to 3 dose regimen of melarsomine
Used micocycline if doxy not available
Therapeutic failures
Inadequate integration between management strategies and drug therapy
Incorrect use of drugs
Host-related factors
Drug resistance
Parasites resistance mechanisms
Modified activity of parasite enzymatic systems
Amplification of target genes to overcome the effect of the anthelmintic drug
Molecular changes that affect intracellular accumulation of drugs at the site of action
Changes on the #, structure and affinity of cellular drug receptors
Optimize the use of antinematodal therapy
Use drug class that’s effective
Combine drugs with diff MOA
Rotation among chemical groups
Use few drug treatments as possible
Early detection of resistance and provision of information to farmers
