Antiparasitics Flashcards
antiparasitics can be broadly classified in 3 ways
endoparasiticides, ectoparasiticides, endectocides
2 ways drugs are different than pesticides: how are they identified? which can be used extra-label?
drugs: DIN, can be prescribed, extra-label permitted
pesticides: PCP (Pest Control Products Act) registration number, can’t be used extra-label
what are 3 main reasons for anti parasitic treatment failure
resistance!!
also failure to integrate drug treatment with mgmt strategies and incorrect use due to lack of knowledge
what NT activates nicotinic receptors
acetylcholine, ACh
where are nicotinic receptors found in mammals
SNS and PSNS ganglia, muscel, CNS
where are nicotinic receptors found in nematodes
muscle, neurons
where are nicotinic receptors found in insects
CNS
both curare and snake alpha-neurotoxin contain _______ which acts as a neuromuscular blocker causing [not red]
nAchR antagonist (block Ach interacting with nicotinic receptors)
myasthenia graves results in destruction of nAchRs at NMJ. what does treatment involve, and how does it work
administration of acetylcholinesterase antagonist:
ok. so. Ach acts at nAchRs of spinal cord ganglion of SNS; myasthenia gravis destroys these receptors so that signals.
AchE breaks down Ach. if AchE is INHIBITED, then more Ach stays in synapse, so nerve impulses keep going.
[the drug isn’t helping the destroyed receptors, but it keeps the Ach levels up]
give MOA for levamisole and pyrantel
nAch agonists and AchE inhibitors, causing spastic paralysis of nematode muscles.
[weak agonists for mammalian nAchRs and strong agonists of nematode nAchRs]
this drug toxicity looks similar to organophosphate poisoning: see muscarinic and nicotinic effects. the is drug is given PO, parenterally, or topically. effective against mature ruminant parasites.
what is the drug? what is the class?
levamisole, an imidazothiazole
what are signs of NICOTINIC overstimulation
muscle tremors (first head, then body), tetany, weakness, tachycardia, myadriasis (due to SNS activation by nicotinic overstimulation)
what are signs of MUSCARINIC overstimulation
diarrhea, urination, miosis, bradycardia, bronchospasms, emesis, lacrimation, loss muscle strength, salivation, sweating. DUMBBELLSS
this drug has same MOA as imidazothiazoles (eg. levamisole), is poorly absorbed from the GIT and is generally very safe, safer than levamisole, acts directly on the worms in GIT. it is only available orally and has lots of resistance.
what is the drug? what is the class?
pyrantel, a tetrahydropyrimidine
organophosphates and carbamates are pesticides commonly used in agriculture. toxicosis can occur.
what is the mechanism of toxicity for each?
acetylcholinesterase inhibition (acetylcholine excess)
organophosphate = irreversible
carbamate = reversible
organophosphate and carbamate toxicosis acute syndrome: what are the 3 broad categories of clinical signs that can occur?
muscarinic, nicotinic, CNS. C/S vary between cases
(specifically:
- Muscarinic (DUMBBELLS): Diarrhea, Urination, Miosis, Bronchorrhea (also bronchospasm), Bradycardia, Emesis, Lacrimation, Lethargy, Salivation/sweating
- Nicotinic: Muscle tremors (first head, then body), tetany, weakness, tachycardia and mydriasis (because of sympathetic activation by nicotinic receptor overstimulation)
- CNS: Anxiety, restlessness, hyperactivity, depression, seizures, depressed respiration, and coma)
organophosphate and carbamate toxicosis acute syndrome: death occurs due to what?
respiratory failure!
massive respiratory secretions, bronchiolar constriction, and intercostal and diaphragm muscle paralysis
describe intermediate syndrome of organosphosphate/carbamate toxicosis: what does it results from? what is it caused by/ what do clinical signs relate to?
chronic exposure to single exposure to very lipophilic compound. may follow acute crisis or be the only effect
due to development of Ach tolerance: down regulation of muscarinic Ach receptors, therefore C/S relate to nicotine overstimulation
organophosphate and carbamate toxicosis: what are clinical signs in large animals
similar to small animals: nicotinic, muscarinic, and CNS effects. delayed polyneuropathy weeks to months after exposure (weakness, ataxia, progressing to paralysis with loss of tail, anus, and bladder tone) acutely, bloat in cattle
organophosphate and carbamate toxicosis: describe treatment
severe muscarinic signs require emergency treatment with atropine!
reactivate AchE in organophosphate toxicity
decontamination: emesis or washing with dish soap
increasing the influx of sodium through VGNaCs in axons (excessively) leads to what
excessive depolarization and cell death
pyrethrin and pyrethroid MOA
increasing the influx of sodium through VGNaCs in axons leading to excess depolarization and cell death in insect nervous system
why is pyrethrin/pyrethroid toxicosis primarily a problem in cats
metabolism of the insecticide requires glucoronidation can cats are bad at it
