Organophosphate Toxicosis Flashcards
What is the site of action of organophosphates?
widespread (CNS and PNS) cholinergic transmission —> complex clinical picture
What is the mechanism of action of organophosphates?
acetylcholinesterase inhibition, leading to ACh accumulation and overstimulation of the PNS and CNS cholinergic receptors = cholinergic crisis
Organophosphate mechanism of action?
How does organophosphate action compare to carbamate action?
OP = form a strong covalent bond with AChE that is initially reversible, but becomes irreversible after aging (loss of alkyl group)
CB = form weaker bonds with AChE making it reversible; no aging occurs
What are the main clinical signs of organophosphate toxicosis? What is death usually a result of?
combination of muscarinic, nicotinic, and CNS signs (NOT ALL will be seen in all animals; signs vary over time)
respiratory failure - bronchoconstriction, bronchorrhea, paralysis of respiratory muscles, central respiratory depression
What test is used to diagnose organophosphate toxicosis? What results indicate toxicosis?
ATROPINE TEST - low pre-anesthetic dose of atropine is given
NO atropinization - no tachycardia or mydriasis, reduced glandular secretions, etc.
In what animals do we avoid using the atropine test to diagnose organophosphate toxicosis?
horses —> causes ileus
What acetylcholinesterase activity is indicative of organophosphate toxicosis?
> 50% decrease = exposure
> 75% decrease = diagnostic, clinical signs
What things can be tested for the presence of organophosphate to diagnose toxicosis? What is seen on necropsy?
rumen/stomach contents, liver, skin, wool, urine
usually non-specific, may see pulmonary changes
What is the first step to treating organophosphate toxicosis?
stabilize the patient
- secure airway and ventilate if necessary
- administer supplemental oxygen
- secure venous access and collect blood for lab tests
- administer isotonic IV fluids to support perfusion and blood pressure
- control seizures (Diazepam)
When can emesis be induced for organophosphate toxicosis? What is recommended to use to induce emesis in dogs and cats?
recent (<1 hr) oral exposure if no contraindications exist
DOGS:
- hydrogen peroxide: local irritation of oropharynx and gastric lining
- Apomorphine: centrally acting to stimulate dopamine receptors in CTZ
CATS:
- Xylazine: centrally acting to stimulate α2-adrenergic receptors in CTZ
- Dexmedetomidine: centrally acting to stimulate α2-adrenergic receptors in CTZ
What is regarded as the “universal antidote” in the treatment of toxicosis?
activated charcoal - highly porous material with enormous surface area that reversibly adsorbs substances with weak bonds
What are the 2 major cathartics used for toxicosis? Which one is typically avoided?
- Sorbitol - accelerates toxicant transit though GI and decreases absorption time
- saline (Mg or Na) - stimulate GI motility
Mg saline —> CNS depressant effect
Why are cathartics not usually necessary for organophosphate toxicosis?
patients are typically already experiencing diarrhea
When is gastric/enterogastric lavage indicated for organophosphate toxicosis?
- ingestion of a large amount of OP before emesis has occured
- emesis in contraindicated
(may need scout radiograph to assess presence or absence of ingesta if substantial amount of time has elapsed since ingestion)
How does Atropine work as an antidote to organophosphate toxicosis?
(much higher dose than pre-anesthetic dose) - competes with ACh for muscarinic receptors and blocks them, causing the accumulation of ACh to have no effect since they cannot bind
very little effect at nicotinic sites
How does 2-Pralidoxime work as an antidote to organophosphate toxicosis? In what 3 ways does it differ from Atropine?
combines with OP and removes it from AChE, reactivating it
- only works on OPs, not CMs (can make it worse)
- must be given early, prior to aging
- can quickly reverse nicotinic signs
