Anticholinesterase Flashcards
What are the 3 classes of anticholinesterase and examples of each?
organophosphate insect icide- malathion, chlorpyrifos
carbamate insecticide - carbaryl, carbofuran
nicotinoid insecticide - imidocloprid
Why did these compounds replace organochlorines?
still high mammalian toxicity BUT
readily degraded in alkali or water and have short half life so no residues
What are these insecticides used for in pets and livestock in addition to their agricultural application?
warbles, fleas and other insects
What are sources of poisonings in animals and birds?
consumption of treated grain, mistaken use as feed additive, excessive application, sprayed forage, malicious poisoning
What is the absorption and distribution?
all routes including dermal and resp
rapid distribution to all tissues
no accumulation in fat
What is the metabolism and excretion?
some require metabolic activation (melathion)
hydrolysis reduces toxicity
rapid metabolism
rapid excretion of metabolites in a few days
What is the MOA?
organophosphates and carbamate inhibit acetylcholinesterase and other cholinesterase enzymes
= no acetylcholine breakdown at synapse or NMJ
= parasym and sym affected
what enzymes are affected?
pseudo (plasma) cholinesterase - human and not measured
true (RBC) cholinesterase
- specific to acetylcholine
- excessive NT activity in cholinergic and NM nicotinic sites
- muscarinic much more sensitive
- nicotinic only bind to nicotinic and are less toxic
What is detrimental about organophosphate poisoning?
inhibits acetylcholine –> choline and acetic acid (irreversibly)
- after 1-2 days phosphorylated enzyme is stable and irreversible
What is unique about carbamate poisoning?
hydrolysis of acetylcholine inhibited same way but reversible and can be reactivated
Why is nicotinoid compounds less toxic? e.g. imidacloprid
no inhibition of cholinesterase is observed
- extremely high doses needed to manifest nicotinic signs (muscle tremors, twitching)
How fast do you see clinical signs in organophosphates and carbamates?
5min to 1-2h
no chronic ALL ACUTE
What are the muscarinic effects? are they life threatening?
life threatening
GIT - diarrhea, vomiting, salivation
Resp - dyspnea (bronchocontriction)
CV - decrease HR (cyanosis)
Eye - myosis (constriction)
What are the nicotonic effects?
muscle twitching and tremors
limb rigidity
What are the CNS effects?
depression and convulsions
What is delayed neurotoxcity? which class does it occur with? whats an example?
sydrome developing after 10d to 3m
ONLY with organophosphates
e.g. TOCP (no anticholinesterase activity) - found in lubricants and moonshine
What are the clinical manifestations of delayed neurotoxicity?
begin in distal limb sensory and motor irreversible damage - muscle weakness (hindlimb) - knuckling (cattle) - ataxia to flaccid paralysis - cats unable to retract claws
all other organ systems normal
cholinesterase activity normal
Whats the cause of delayed neurotoxicity?
mechanism not sure
toxic phosphate triester
What is the typical post mortem finding for delayed neurotoxicity?
axonal degen
peripheral neutropathy
degen of myelin sheath
What are DDx for delayed neurotoxicity?
organophosphate TOCP 2, 4 - D mushrooms some plants methyl mercury organic arsenic salt (pigs) chronic Se (pigs)
What is the Dx of delayed neurotoxicity?
histo of SC
chem analysis of tissue
cholinesterase will be normal
a history of exposure for several weeks
What is the PM findings for acute poisoning?
typically negative (few lesions)
mild petechial hemorrhage and congestion on viscera
slight pulmonary edema (dyspnea and bronchocontriction)
if seed grain (undigested grain)
What is the Dx for acute poisoning?
History (sudden death) clinical signs (muscarinic, nicotinic) PM (negative) chem (tissue levels difficult to detect) cholinesterase activity
What kind of blood must be taken to measure cholinesterase activity?
heparinized blood taken when showing clinical signs
