Organophospates - Carbamates Flashcards
(32 cards)
what is the MOA of organophosphates?
irreversibly inactivate acetylcholinesterase = persistent acetylcholine activity
what are the common exposure routes for organophosphates?
- contaminated feed or drinking water
- use of empty pesticide containers for feeding/watering animals
- dusting, spraying of animals or animal grounds or housing
- sheep dip
- flea treatment, meds
- overdose
- intentional poisoning
Why are organophosphates more toxic after 1-2 years in storage?
subject to storage activation
are organophosphates lipo or hydrophilic?
lipophilic - readily absorbed through the skin and mucus membranes, GIT, and inhalation
how are organophosphates normally metabolized?
in liver - excretion/bioactivation
Which organophosphate requires lethal synthesis?
thiophosphate
- liver enzymes (CYP450) metabolize or bioactivate
what can happen with continued low dose/chronic exposure of OPs?
- can lead to adaptation to decreased acetylcholinesterase - homeostatic response
- enzyme induction or increased acetylcholinesterase production
- receptor down regulation or decrease in acetylcholine receptor
thiophosphates are biologically inactive until transformed by?
the liver to -oxon metabolites
what is the major route of elimination for thiophosphates?
paraoxonase - a serum bound enzyme –> hydrolysis of paraoxon
what is the MOA of OPs? (plus primary - tertiary)
Irreversible inhibition of cholinesterases! (end result = increase in acetylcholine!)
- OP binds to cholinesterase
- aging = conformational change in OP-AChesterase complex that results in increased or irreversible binding of complex over time
primary: muscarinic receptor over stimulation
seconary: nicotinic receptor over stimulation (neuromuscular and CNS stim)
tertiary: nicotinic blockage (neuromuscular blockade, CNS depression)
what is the result of high exposure with OPs?
paralysis of diaphragm leading to pulmonary edema, asphyxia, and death due to respiratory failure
delayed neurotoxicity is possible with what OP?
thiophosphates
“OP induced delayed polyneuropathy”
what are the muscarinic effects of OP toxicity?
DUMBELLS
- diarrhea
- urination
- miosis
- bronchospasm
- emesis
- lacrimation
- salivation
what are the CNS effects of OP toxicity?
- cross the BBB
- increase sensory and behavioral distrubances, incoordination, depressed motor function, and resp depression
- resp paralysis
- increased pulmonary secretions coupled with resp failure = USUAL CAUSE OF DEATH
what is the normal cause of death in a patient with OP toxicity?
- increased pulmonary secretions coupled with respiratory failure
what is OP-induced delayed polyneuropathy?
- develops 10-14 days after exposure
- distal degeneration of long/large diameter motor and sensory axons of peripheral nerves and spinal cord
- clinical signs = muscle weakness, ataxia, rear limb paralysis
- chickens most sensitive
what is OP-induced intermediate syndrome?
- occurs 2-4 days after acute cholinergic effect and signs of the acute effects are no longer obvious
- symptoms and signs occur after apparent recovery from acute effects
- NO muscarinic signs or muscle fasciculations
- weakness of resp muscles and accessory muscles
what is the pathology of OP toxicity?
- acute death, no specific lesions
non specific lesions
- pulm edema
- congestion
- cyanosis
- hemorrhages
- edema of various organs
- necrosis of skeletal muscle
delayed effects: degeneration and demyelination of peripheral and spinal motor neurons
what lab diagnosis can we use for OPs?
- plasma achetylcholinesterase activity level
- <50% is suspicious, <25% is diagnostic!
what test can we run to see if an animal has been exposed to OPs?
atropine response test
- if the test is POS (dry MM, increased HR, dilated pupils) = LOW LIKELY OP poisoning!
- if the test is NEG (no signs seen) = LIKELY OP POISONING
what DRUG do we use to treat OP poisoning?
Atropine
- specific ACh
antagonist
- repeat with decreasing doses 3-6 hours based on clinical response
what is the main goal for atropine therapy with OP poisoning?
to suppress or dry pulmonary secretions
main concern with OP tox is resp failure from excessive airway secretions
How can we treat OP poisoning with 2-PAM?
- it is a cholinesterase reactivator - “oximes”
- binds to OP-inactivated acetylcholinesterase and reverses the binding
Carbamate pesticides are derived from?
carbamic acid
