Chemical Control Flashcards
Organophosphates
Inhibit acetylchoiline esterase, binding reversible.
Persistence- short (24 hours- 12 weeks), broken down in the environment, non-cumulative
(Antidote- atropine)
Topical or oral administration.
WHO: Damalinia ovis, Damalinia caprae, Gasterophilus, Oestrus ovis, Hypoderma, Melophagus ovinus, Musca vestustissima, Ctenocephalides felis or canis, Argas persicus, Haematobia exigua
** HAEMONCHUS, High doses needed to kill Trichostrongylus and Ostertagia
** only used in sheep in combination when resistance is a problem.
** examples- Dichlorovos (flea collars, sheep), Naphthalophos, malathion (flea shampoo), diazinon (jetting sheep for blowfly control), cythioate (orally for flea control)
Repellents
DEET (N,N-diethyl-m-toluamide), dipropyl isocinchomeronate, piperonyl butoxide, citronella
Chlorinated hydrocarbons
DDT, Lindane, Dieldrin, Endrin (persistent insecticides- banned for use in food animals)
Carbamates
Similar mode of action to OPs. Inhibit Acetylcholine esterase. Persistent for 4-6 weeks. Examples: Carbaryl- powder or spray for fleas, used in flea collars. And propoxur- powder, spray, flea collars
Formamidines
Inhibit mono-amine oxidase. Example: Amitraz- used for Boophilus microplus, demodex, Psoroptes ovis
Pyrethroids
Pyrethrin derived from Chrysanthemum flowers, persist for only 24 hours. Synthetic pyrethroids persist for 7-14 days.
Act on sodium channels.
Administration: topical
Low toxicity, except fish.
Examples: permethrin- scabies in humans, cypermethrin, deltamethrin (lice in sheep- backline), cyhalothrin- lice on sheep (plunge or dip)
Macrocytic Lactones
Paralysis by binding to GABA gated Cl-ion channels in neurons. Paralysis in pharyngeal pump and somatic musculature– therefore death in nematodes and arthropods. Secreted by soil inhabiting Streptomyces spp. Major groups: 1) Avermectins- ivermectin, abamectin, and selamectin. 2) Milbemycins- moxidectin.
Extremely potent
Administration: topical, parenteral (14 day half life), oral (shorter half life orally)– absorbed rapidly.
Saftey index: 20X
WHO: Linguatula serrata, Gasterophilus, Oestrus ovis, Haematobia exigua, Chorioptes, Felicola substratus, Boophilus microplus, Demodex
STRONGYLOIDES, INHIBITED OSTERTAGIA
(Cooperia is resistant and Cyathostomum, some resistance in trichostrongyles, be careful in dairy cattle due to long lasting- can use moxidectin)
sheep- widely used, mainly oral, limited resistance in trichostrongyles
Cattle- widely used as injectible and pour on, kills inhibited Ostertagia, resistance to Cooper, can only use eprinomectin in lactating dairy cattle
Horses- widely used, mainly oral formulation, ivermectin only kills 10% of inhibited cyathostomes, moxidectin kills up to 80%; resistance in cyathostomes
Dogs and cats- oral (milbemycin) or topical (selamectin)
Environmental effects: persists in faeces, kills arthropods, moxidectin has less effect on dung beetles
Neo-nicotinoids
Synthetic, block receptors, non-toxic
Administration: topical
Translocated in skin.
Examples: imidacloprid- blocks nicotinic receptors (Advantage), nitenpyram (Capstar), fipronil (blocks GABA receptors- FRONTLINE),
** FLEA CONTROL
What kind of control is used on Damalinia gallinae?
Malathion (OP)- as an aerosol
How would you treat Protostrongylus rufescens?
imidazothiazoles (Levamisole). Safety index of 5 however
How would you treat hookworms and lungworms in dogs and cats?
Imidazothiazoles (Levamisole). Safety index of 5 however
Febantel (BZ), pyrantel (tetrahydropyrimidines), selamectin (ML)
Special regime for pregnant dogs with A. Caninum
Benzimadazoles (BZs)
Inhibits polymerization of tubululin.
Primary BZ: TBZ active against all GINs i.e. broad spectrum- NOT GOOD FOR INHIBITED LARVAE. TBZ kills migrating larvae of S. vulgaris at 10x dose rate. 5 daily doses kills inhibited larvae of Ostertagia. Efficacy increases with high dose rates and prolonged contact.
Secondary BZs: oxibendazole
Tertiary BZs: ABZ, FBZ, OXF (OFZ), MBZ- Highly effective against inhibited Ostertagia. Probenzimidazole- febantel converted to FBZ in gut. Kills all strongyles, trichostrongyles, and lungworms, and inhibited larvae and migrating larvae. Non-toxic. HOWEVER WIDESPREAD RESISTANCE IN TRICHOSTRONGYLES IN SHEEP and Cyathostomes. Kills S. vulgaris in horses.
Safety index > 10
- form depot in rumen
- oral admin only
- metabolized to sulphoxide in the liver and to sulphone- anthelmintic activity
- metabolites in blood diffuse across gut wall
- excreted in urine (ABZ excreted in bile)
- OVICIDAL
How would you kill inhibited larvae of Ostertagia?
Probenzimidazole- Febantel converted to FBZ in gut. Tertiary BZ.
What would you use to kill S. vulgaris in horses?
BZs.
Imidazothiazoles- Levamisole
Laevo isomer of tetramisole, dextro isomer not active- toxic. Mode of action: cholinergic agonists at synaptic and extra synaptic nicotinic acetylcholine receptors (motor end plates), depolarisation causes spastic paralysis.
BROAD spectrum, all GINs and lungworms. NOT effective against inhibited larvae and flatworms. Immunomodulatory effect at low doses (2-3 mg/kg)
Excreted in urine within 6 hours. Absorbed rapidly- peak plasma concentration after 30 minutes.
Safety index- 5!!! ***
Admin: orally, submit injection, intramural injection, topically
Cattle: 8 mg/kg in a single dose oral- sub cut or intramural pour on- 10 mg/ kg, temperature and rain affect absorption. No effect against inhibited Ostertagia
Sheep: pour on for newly shorn sheep only, usually given orally (8 mg/kg), resistance widespread in trichostrongyles
Horses: NOT USED CAUSES EXCITEMENT
Dogs and cats: effective against hookworms and lungworms (5-10 mg/kg)
Tetrahydropyrimidines- Morantel, Pyrantel
Mode of action: depolarize motor end plates in muscle, same site of action as levamisole.
Activity: Most GINs, NOT lungworms, no effect on inhibited larvae
Pharmakokinetics: soluble, administered orally, rapidly absorbed, excreted in urine
Safety index: 7X
Sheep- resistance in trichostrongyles, cross resistance with levamisole, if resistant to morantel, still susceptible to levamisole
Cattle- morantel capsule (releases drug for 90 days), widely used in Europe, resistance in trichostrongyles
horses- not effective against Cyathostomums
Dogs and cats- pyrantel rather than morantel used- removes hookworms, used with octantal to kill whipworms
What would you use to control Haemonchus?
Organophosphates. Drug of choice is Salicylanilides (narrow spectrum- must check for other parasites)- but resistance is spreading. BZs and the latest is monopatel.
Heterocyclic compounds
Piperazine (diethylene diamine)
Mode of action: agonist of GABA receptors- flaccid paralysis, relies on peristaltic action to remove worms
Activity: narrow spectrum- ascarids and nodular worms, orally, low toxicity
Horses- removes adult strongyles, does not kill inhibited cyathostomes
Dogs and cats- effective against hookworms
Pigs- active against Oesophagostomum spp.
How would you control Oestophagostomum in pigs?
Heterocyclic compounds- Piperazine
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: 5X LOW
sheep- drug o choice for Haemonchus resistance limited but spreading
Dogs- effective against hookworms but rarely used
Octadepsipeptides
Emodepside- secreted by mycelium of Mycelia sterile from leaves of Camellia japonica. Mode of action: causes flaccid paralysis by binding to the latrophilin receptors in parasitic nematodes, at same site as latroxin (venom of black widow spider)
Used: currently used in product for dogs and cats
Amino-acetonitrile derivatives (AADs)
Monepantel
Mode of action: a nematode specific ACR 23 nicotinic acetylcholine receptor sub-unit only found in nematodes, causes flaccid paralysis
Pharmacokinetics: very little absorbed, converted to S0 in liver, most passed out in faces
Activity: effective against most GINs in ruminants, except lungworms. Dose rate for goats 2X sheep
Safety index: 30X
Derquantel
A spiroindole- 2- desoxyparaherquadmide
Mode of action: nicotinic antagonist causing flaccid paralysis- does not kill nematodes
Activity: not highly effective- Ostertagia, Oesophagostomum, Chabertia
* Effective Dictyocaulus
Available only combined with abamectine to overcome lack of efficacy against some species
* marketed as “medium spectrum”
Use: sheep, too costly in cattle, toxicity in horses
How do you control encysted Larvae of small strongyles (encysted small strongyles of horses only– S. edentatus is an example but there are many)?
Fenbendazole at 10 mg/kg/day for 5 days
Moxidectin at 0.4 mg/kg
Deworming regimen for young dogs and pregnant bitches
Pups
- Treatment every 2 weeks prior to weaning
- Treatment every 4 weeks after weaning
- Treatment every 3 months after 6 months of age
Pregnant bitches
* Fenbendazole an 50 mg/kg/day from 3 weeks prepartum to 2 days postpartum
What is resistance?
Whenever an anthelmintic is used, some nematodes will have mechanisms to survive- may be a single gene or multiple genes. Initial frequency will be very low, and will increase after a lag period. May not be the case on a single closed property. There is single, double, multiple, and “side resistance”
What host species have the largest problem with resistance?
Sheep and goats
What species of parasite are mainly involved with resistance?
Trichostrongylus, Ostertagia, and Haemonchus (insignificant resistance in Nematodirus, Chabertia, Oesophagostomum, Trichuris)– some resistance in Cooperia oncophora in cattle to BZs and avermectins
Factors which influence development of resistance
Polymorphism in nematode population, initial frequency of resistance alleles, number of genes involves, fecundity and length of life cycle, resistance genes dominant or recessive, treatment frequency, refugee, pharmacokinetic profile of drug “tail selection”
How did resistance in sheep become such a big problem in AUS?
Monthly drenching with anthelmintics. Most properties have a low level resistance which is not evident clinically. Fewer properties have a high level of resistance and see outright drench failures.
Laboratory tests for anthelmintic resistance
- egg hatching inhibition using benzimidazoles
- tubulin binding assay using benzimidazoles
- larval paralysis test using levamisole/ML
- larval development test- Drenchrite test
Drenchrite test
send 1 kg of faeces to lab, eggs extracted, test 96 well micro titration plate, larval differentiation to ID genera (cheap, determines level of resistance to BZ and LEV only, depends on access to lab, cannot test other mixtures)
Field test for anthelmintic resistance
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%
Management of anthelmintic resistance
- check timing and administration of drenches (weight of sheep, calibration of drenching gun)
- Check management practices- timing of treatments, pasture management
- Double doses of anthelmintics- no use in BZs, temporarily effective with LEV
- Use of rotations and mixtures- mixtures preferable but increases costs
- Quarantine drenches for all introduced sheep
- Use of monepantel- minimizing the development of anthelmintic resistance– for sheep in AUS
What is the FECR test? What is the alternative test?
Faecal sample and egg count and Treat day zero–> then 14 days later perform again (in vivo)
Or in vitro- culture eggs –> flotation technique (isolate from faces)–> larval development and in the incubator for one week in presence and absence of drug (control). If larval have developed with drug then resistant
