week 3 drugs

Page 1

Benzimidazoles (BZs) – white drenches

Mode of action: inhibits polymerization of tubulin

Primary BZ: thiabendazole

Secondary BZ’s: oxibendazole

Tertiary BZ’s: Albendazole, oxfendazole, fenbendazole etc.

Probenzimidazole: febantel converted to FBZ in gut

Spectrum: broad Safety

index: >10

Use:

administration: orally, drench, pastes, tablets, powder, intra-ruminal injection

ruminants: -3º BZ’s in widespread use

-drug “depot” in rumen

-kill barber’s pole worm, ‘scour worms’, adult liver fluke, nodule worm, & lungworms

-kill inhibited larvae & migrating larvae

-non-toxic

-widespread resistance in GINs of sheep

Page 2

Levamisole – clear or yellow drenches

Mode of action:

cholinergic agonists at synaptic and extrasynaptic nicotinic acetylcholine receptors (motor end plates)

depolarisation causes spastic paralysis

Activity:

broad spectrum

all GINs & lungworms

NOT effective against inhibited larvae and flatworms

Immunomodulatory effect at lower doses (2-3mg/kg)

Pharmakokinetics:

soluble, clear yellow liquid, “clear” drench

absorbed rapidly; peak plasma concentration after 30 min

excreted in urine within 6 h

Safety index: 5** (NOT OVICIDAL)**

Use:

administration: orally, S/C injection, intraruminal injection; topically

cattle: 8 mg/kg in a single dose oral, S/C or intraruminal pour-on (10 mg/kg), temperature and rain effect absorption, no effect against inhibited Ostertagia

sheep: pour-on for newly shorn sheep only usually given orally (8 mg/kg) resistance widespread in GINs**

goats: require higher dose rate than sheep

Page 3

Macrocyclic lactones – MLs (ivermectin, moxidectin)

Mode of action: paralysis by binding to GABA gated Cl-ion channels in neurons

Activity:

all GINs, arthropods

NOT cestodes or trematodes**

extremely potent, doses in µg/kg

Pharmacokinetics:

oral, injectable or pour-on

absorbed rapidly

short half life after oral administration

parenteral administration: half life of ivermectin 14 days

half life of moxidectin 28 days

(moxidectin long-acting 3 months)

Safety index: 20X

Use:

sheep: widely used, mainly oral formulation widespread resistance in GINs

cattle: widely used, mainly as injectible and pour-on kills inhibited Ostertagia resistance only to Cooperia can only use eprinomectin in lactating dairy cattle Cooperia - dose limiting species

Environmental effects: persists in faeces, kills arthropods, moxidectin has less effect on dung beetles

Page 4

Amino-acetonitrile derivatives (AAD’s) – monepantel

Mode of action:

a nematode-specific ACR-23 nicotinic acetylcholine receptor subunit only found in nematodes

causes flaccid paralysis

Activity:

effective against most GINs in ruminants, except lungworms

dose rate for goats 2X sheep dose rate

Safety index: > 30

Page 5

Organophosphates (Naphthalophos, dichlorovos)

Mode of action: inhibits acetylcholinesterase – spastic paralysis

Activity:

highly effective against Haemonchus

higher doses needed to kill Trichostrongylus, Ostertagia

Use:

used only in sheep

no resistance

used in combination where resistance is a problem

Page 6

Salicylanilides (closantel)

Mode of action: uncouples oxidative phosphorylation

Pharmakokinetics:

soluble, given orally

absorbed, binds to plasma proteins

persists for 4-6 weeks

Activity:

inactive against most nematodes

cannot penetrate cuticle

highly effective against blood feeders

“narrow spectrum” anthelmintic

Safety index: low, 5X

Use:

sheep: drug of choice for Haemonchus resistance limited but spreading

dogs: effective against hookworms but rarely used

Page 7

Biological control - Nematophagous fungi – Duddingtonia flagrans

When fed to grazing animals, the thick walled spores pass through the digestive system remaining inert and out into the manure.

When the infective larvae become active within the manure, the fungus sporulates forming a fungal web that captures, paralyses and consumes infective larvae.

BioWorma® and Livamol® with BioWorma® contain the natural fungus Duddingtonia flagrans.

Reduction in parasites – 50% including multi-drug resistant parasites

Page 8

Tests for anthelmintic resistance

Laboratory test:

-larval development test - Drenchrite test

Drenchrite test

send 1 kg of faeces to lab

eggs extracted, test in 96-well microtitration plate

-larval differentiation to identify genera

cheap

determines level of resistance for BZ and LEV only

depends on access to lab

cannot test other mixtures

Field test

Faecal egg count reduction test - relies on fact that anthelmintic should reduce FEC to zero

groups of 12-15 unweaned lambs

check FEC - >250 epg

treat each group with anthelmintic

leave one group as a control

collect faeces for FEC 7-10 days later

calculate FECR: ( C - T)/C or 1 - T/C ( T = treatment; C = control)

resistance present if less than 95% reduction or lower 95% confidence interval is less than 90

crude test, figures >96% may indicate low level resistance

measures anthelmintic efficacy

expensive

by time detected, frequency of resistance genes > 80%