Antihelminths

Question 1

Nematodes

Answer 1

Cylindrical, non-segmented worms (roundworms/ nemalthminthes)
Treated with benzimidazoles (BDZ)

Question 2

Cheimistry of BDZ’s and Pro-BDZ’s

Answer 2

Insoluble or slightly soluble in water
Higher solubility at low pH (stomach)

Question 3

BZD drugs

Answer 3

Methycarbamates (most used): Al-BZ and Fen-BZ
Halogenated BZD thiols: triclabendazole (TCBZ)
Pro-BZDs: Febantel (FBT), netobin (NTB)

Question 4

MOA of BDZ’s and Pro-BDZ’s

Answer 4

Bind to parasite B-tubulin (inhibiting tubular functions)
Higher binding affinity and lower rate of dissociation
Blocks glucose uptake by parasite- ↓ energy/ paralysis

Question 5

Metabolism and elimination of BDZ

Answer 5

Biotransformation in the liver
Extrahepatic metabolism in the lung and SI

Question 6

PK of BDZ

Answer 6

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

Question 7

PK for Pro-BDZ

Answer 7

Microflora-mediated reductive metabolism in the GI tract

Question 8

BDZ has a relatively fast elimination rate in ________

Answer 8

ruminants (sheep and goats)

Question 9

PK of BDZ in non ruminants

Answer 9

Shorter gut transit time limits rates of dissolution and absorption
Multi-dose regimes (higher dose, given with food)

Question 10

Host related factors

Answer 10

Dissolution, absorption, and biotransformation
Ruminal esophageal groove closure
Effect of GI transit time
Effect of diet type (concentrate base, ↑ absorption)

Question 11

Mechanisms of drug transfer into target parasites

Answer 11

Diffusion (predom pathway)
Liphophilicity
Structural differences between external surfaces of nematodes
Acidic environment of nematode surface (ion trapping)

Question 12

How are BZDs and Pro- BZDs classified?

Answer 12

Broad spectrum anthelmintics expect triclabendazole (TCBZ)

Question 13

Albendazole

Answer 13

Broad-spectrum for cattle and sheep

Question 14

Fenbendazole

Answer 14

Broad spectrum in cattle, sheep, goats and horses,
In zoo and wildlife (FDA approved)

Question 15

Safety and toxicity of BZDs

Answer 15

Milk of treated animals not recommended
Overall safe
Slaughter clearance times required

Question 16

Levamisole (imidazothiazoles)

Answer 16

Used world wide and oldest
Highly water soluble and formulation flexibility
In cats, dogs, sheep, cattle, goats, swine, poultry

Question 17

MOA of levamisole

Answer 17

Nicotinic AChR agonist that causes spastic paralysis of muscle

Question 18

PK of levamisole

Answer 18

Rapidly absorbed (2 hrs)
Distributed in all tissues and metabolized in the liver

Question 19

Formulations of levamisole

Answer 19

Drinking water for pigs and poultry
Injectable in cattle
IM/SC phosphate salt preferred
NEVER IV

Question 20

Safety and toxicity of levamisole

Answer 20

Not used in dairy cows
Avoid in horses
2-11 day slaughter clearance time

Question 21

Pyrantel and morantel (tetrahydro-pyrimididines)

Answer 21

Adult stages of GI nematodes
Sustained release bolus of morantel tartrate for dairy and beef cattle
Equine tapeworms

Question 22

Pyrantel pamoate

Answer 22

Used against A. perforliata (tapeworm/ cestode) treatment

Question 23

Piperzaine

Answer 23

Blocks transmission by hyperpolarizing nerve membranes @ NMJ leading to flaccid paralysis
Mainly ascarids in dogs, cats, horses, pigs and poultry

Question 24

Diethylcarbamazine citrate (DEC)

Answer 24

Heterocyclic compounds
Used for microfilaria in dogs

Question 25

Adulticide therapy (heartworm)

Answer 25

Doxycycline and ivermectin prior to 3 dose regimen of melarsomine
Used micocycline if doxy not available

Question 26

Therapeutic failures

Answer 26

Inadequate integration between management strategies and drug therapy
Incorrect use of drugs
Host-related factors
Drug resistance

Question 27

Parasites resistance mechanisms

Answer 27

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

Question 28

Optimize the use of antinematodal therapy

Answer 28

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