Organophosphates and Carbamates Flashcards
Use of OPs?
pesticides, nerve agents, solvents and plasticizers
Exposure routes of OPs
contaminated feed/water use of empty containers to feed/water animals lawn treatment flea treatment or meds overdosing intentional poisoning
What is storage activation?
if sealed and stored 1-2y, becomes more toxic
Toxicokinetics of OPs
lipophilic - readily absorbed through skin, MM, GIT, inhalation
well distributed in body
metabolized in liver
lethal synthesis - liver CYP450 metabolize/bioactivate thiophosphate OPs
Chemical properties of OPs
degrade quickly when exposed to environment
subject to storage activation
drug-drug interactions
Two types of OPs
thiophosphates and phosphates
T/F: thiophosphates are biologically active while phosphates require hepatic bioactivation
false, other way around
Major route of elimination of thiophosphates via ______, a serum bound enzyme.
paraoxonase
MoA of OPs
Irreversible inhibition of cholinesterases
Primary - muscarinic over-stimulation
Secondary - nicotinic overstimulation (CNS stim)
Tertiary - nicotinic blockade (CNS depression)
Ach increases throughout CNS - overstimulation of nicotinic and muscarinic receptors
Muscarinic effects of OPs
overstimulation of PSNS - DUMBELLS diarrhea urination miosis bronchospasm emesis lacrimation salivation
Nicotinic effects of OPs
Ach accumulation at neuromuscular auction - fasciculations in muscle groups –> depolarization and paralysis
SNS stimulation - sweating, hypertension, tachycardia
CNS effects of OPs
crosses BBB
incoordination, depressed motor function, resp depression
impairment of diaphragm + thoracic skeletal m –> resp paralysis
increased pulmonary secretions –> resp failure = usual cause of death
Recovery of OP poisoning depends on
generation of new enzyme or Ach-esterase in critical tissues
2 delayed effects of thiophosphates
organophosphate-induced delayed polyneuropathy
organophosphate induced intermediate syndrome
describe organophosphate induced delayed polyneuropathy
10-14d post exposure
distal degeneration of long motor and sensory axons of peripheral nerves and spinal cord
CS: muscle weakness, ataxia, rear limb paralysis
chickens most sensitive
describe organophosphate-induced intermediate syndrome
2-4d after acute effects no longer obvious
symptoms and signs occur after apparent recovery
no muscarinic signs or muscle fasciculations
weakness of resp muscles, neck muscles and proximal limb muscles
Lesions expected with OP poisoning
acute death, no specific lesions
pulmonary edema, congestion, cyanosis, hemorrhages, edema in various organs including brain, necrosis of skeletal mm.
degeneration and demyelination of peripheral and spinal motor neurons
pancreatitis reported in some dogs
Lab diagnosis of OPs
direct detection in stomach or on skin
may find residues in fat or liver with more lipophilic OPs
plasma ACHesterase activity level
use whole blood
Describe the atropine response test
give atropine 1-2mg IV wait 15 ins
if atropine + –> dry skin and MM, increased HR, moderately dilated pupils, low likelihood of OP poisoning
if atropine - –> no signs seen, high likelihood of OP poisoning
How do you treat OP poisoning
Decontaminate (wash, induce emus, activated charcoal), support avoid drugs that depress respiration (opioids) and phenothiazines, ahminoglycosides, muscle relaxants Atropine as physiologic antagonist cholinesterase reactivates (oximes)
Main concern with OP toxicity is
A) resp failure from excessive airway secretions
B) CNS stimulation resulting in muscle tremors
C) no concern
A - resp failure from airway secretions
How does atropine treat OP toxicity?
atropine therapy suppresses or dries pulmonary secretions (remember this was our main concern with OP toxicity because resp failure from excessive secretions)
Prognosis of OP toxicity
guided - wide variety in response to treatment
Most toxic of the carbamates?
Aldicarb
T/F: Carbamates undergo storage activation
false
T/F: carbamates require hepatic bioactivation
false
MoA of carbamates
Reversible inhibition of acetylcholinesterase (competitive inhibition)
Clinical signs of carbamate poisoning
SLUD signs salivation lacrimation urination diarrhea
Death from carbamate toxicity usually due to?
resp failure and hypoxia due to bronchoconstriction leading to tracheobronchial secretion and pulmonary edema
Lab Diagnosis of carbamate poisoning?
cholinesterase levels
Treatment of carbamates
atropine
T/F oximes are effective in treating OP and carbamate toxicity
false , not effective against carbamates
