29. Drugs against ectoparasites (except macrocyclic lactones) 1. (organophosphates, carbamates, pyrethroids, amitraz)

Question 1

Ectoparasiticids. Drug list (organophosphates, carbamates, pyrethroids, amitraz)

Answer 1

Organophospates:
- Diazinon
- Coumaphos
- Phoxim

Carbamates:
- Propoxur

Pyrethroids:
- Permethrin
- Deltamethrin
- Flumethrin
- Tetramethrin

Amitraz

Question 2

Damage caused by ectoparasites:

Answer 2

• causing stress
• anaemia (blood sucking)
• wounds, tissue injuries -> serious infections, myasis
• vectors and intermediate hosts of viral, bacerial and parasitic diseases

Question 3

Role of vectors and intermediate hosts

Answer 3

• fleas -> Dipylidium caninum (cucumber seed like tapeworm of dog
• ticks -> Ixodes - Lyme disease, Dermacentor -> babesiosis, anaplasmosis, Rhipicephalus -> ehrlichiosis
• mosquitos -> dirofilariasis (heart worm disease)
• sand fly -> leishmaniasis

Question 4

Classification of ectoparasiticides

Answer 4

• adulticides - neurotoxins (target is the nervous syste of the parasite). Can be contact poisons or systemic agents (must be digested by parasite, e.g. by sucking blood with drug)
• insect growth regulators - acting only on parasites with metamorphosis. Will not kill the parasite but stop their development
• repellents - drugs that keep parasites away

Question 5

Explain selective toxicity of ectoparasiticides

Answer 5

PK:
- metabolism in mammals is much faster than in parasites
- BBB -> prevention of CNS signs (but careful with MDR1 mutation)
- slow absorption -> less toxicity

PD:
- e.g. GLuCl channels (depolarization or hyperpolarization) - not present in warm-blooded animals
- nACh receptor sensitivity (similar target, affinity to parasitic receptors is much higher than to our patients’)

Question 6

Dermal absorption

Answer 6

• usually ectoparasiticides are large, lipophilic molecules
• slow but good absorption -> low plasma conc -> low toxicity for patient
• poor to moderate amount of the drug crosses BBB
• duration of action: collars - 4-8 months (least toxic); spray, bathing - days; spot on - 4-12 weeks (can be most toxic because absorption is the fastest -> plasma conc is high)

Question 7

Organophosphates. Drugs

Answer 7

• Diazinon (=dimpylate in USA) - mostly for sheep dipping
• Coumaphos - mites
• Phoxim - mites

Question 8

Organophosphates. PK

Answer 8

• good lipophilicity
• sensitive to alkaline pH
• good absorption: oral 35% (considered bad for oral), dermal 2-14% (considered good for dermal)
• excellent distribution (special barriers, BBB)
• metabolism - partial activation - makes subsctance more active and more toxic (much longer half-life)
• excretion: 80% urine, 20% feces
• cats are very sensitive! forbidden in cats!

Question 9

Organophosphates. Mechanism of action

Answer 9

• contact poisons
• irreversible inhibition of AChE -> organophosphates toxicosis = ACh toxicosis
• first muscarinic ACh receptors are affected, then nicotinic, then CNS
• antidote - pralidoxim. Enzyme reactivation. Pralodoxime higher affinity to the binding site of AChE than organophososphates - but only can work as antidote within 1 day because of aging of binding and it can’t be reversed anymore)

Question 10

Organophosphates. SE

Answer 10

Muscarinic ACh receptors:
- SLUDGE - salivation, lacrimation, urination, diarrhea, GI pain, emesis
- also bronchoconstriction, bradycardia, miosis
- can be reversed with atropin

Nicotinic ACh receptors:
- muscle tremors, spasms
- hyperthermia, brain oedema
- atropin won’t be effective here
- anticonvulsives needed, cooling down the animal

CNS:
- seizures, coma, death
- uncounciousness with miosis

Question 11

Organophosphates. Usage

Answer 11

Diazinon
- broad spectrum in ost species. Fleas, ticks, lice, mites, myasis
- mostly for dipping (sheep)

Coumaphos
- varroosis of honey bees (sucks haemolyph of bees)

Question 12

Carbamates

Answer 12

• Propoxur - only in SAM
• reversible
• much safer than organophosphates
• less lipophilic than organophosphates
• fleas, ticks
• collars, aerosol sprays, shampoos

Question 13

Pyrethroids. Drugs

Answer 13

• PERmethrin
• DELTAmethrin
• FLUmethrin (Foresto)
• TETRAmethrin - 1st gen, cheaper but more toxic

Question 14

Pyrethroids. Mechanism of action

Answer 14

• opening of Na+ channels -> constant depolarization -> “knock-down effect”, “hot-feet effect”
• contact poison + repellent

Question 15

Pyrethroids. Usage

Answer 15

• ticks: still ok (Rhipocephalus is not that affected)
• fleas: resistance is common
• poor efficacy against mange mites
• fly control
• moderate efficacy against varroa mites (resistance!) (photo)
• combination with macrocyclic lacones
• usually not used in cats but but collar (Foresto) can be used for cats

Question 16

Pyrethroids. Toxicity

Answer 16

• safe in warm-blooded animals (CATS! - tremors, seizures, excitation)
• fish are especially sensitive (careful with waste)
• NO antidote
• Intralipid - pharakokinetic antidote, in blood strea preventing from crossing BBB
• Favourable prognosis in most cases
• local irritation, allergic reactions at the site of application may appear
• midriasis, consciousness !

Question 17

How to distinguish organophosphates toxicosis and pyrethroids toxicosis?

Answer 17

Organophosphates - miosis, unconscious
Pyrethroids - midriasis, conscious

Question 18

Amitraz

Answer 18

• MAO (monoamine oxidase) inhibitor + alpha-2 agonist (sedaiton, bradycardia, hypothermia, emesis, hyperglycemia side effects)
• only against 8-legged ectoparasites
• octopamine (exclusively found in 8-leg parasite, selective toxicity), dopamine, noradrenaline, inhibition of serotonin reuptake
• increase of energy demand! (esp. in bees)
• temperature! optimal is 14-18 degree
• moderate absorption (1-3% dermal)
• spectrum: mange mites , demodex, ticks
• dipping, collar, strips (bees)
• small TI: not in horses, chihuahua, cats