Anticholinesterase and Anticholinergic Toxicants Flashcards
(32 cards)
What is intermediate syndrome (IMS)?
syndrome of organophosphate toxicity seen in dogs/cats 24-96 hours after ingestion of highly lipophilic OP, repetitive exposure to low doses, or prolonged dermal exposure that causes decreased AChE activity and nicotinic receptor mRNA expression
What 6 organophosphates are responsible for intermediate syndrome? Carbamate?
- chlorpyrifos
- diazinon
- malathion
- parathion
- phosmet
- bromophos
carbofuran
What 3 chemicals cause organophosphate-induced delated polyneuropathy (OPIDP)? What animals are most affected?
- TOCP
- EPN*
- leptophos
chickens
What is characteristic of organophosphate-induced delated polyneuropathy (OPIDP)? What causes this?
distal degeneration of long and large diameter motor and sensory axons of both peripheral and spinal cord nerves
inhibition of neuropathy target esterase (NTE) and degeneration of axons/myelin sheaths
What are the 3 most common clinical signs of organophosphate-induced delated polyneuropathy (OPIDP)?
- weakness
- ataxia
- limb paralysis
What are 5 ways organophosphate and carbamate toxicoses are diagnosed?
- history of access to or treatment with OP/CM
- clinical signs
- no atropinization on atropine test
- ChE activity in heparinized whole blood
- chemical residues in stomach contents, vomitus, hair, and bait by GC-MS
What is atropinization? How is the atropine test performed?
appearance of typical signs of atropine administration, like increased heart rate and mydriasis (dilation)
- obtain baseline heart rate from patient
- administer a preanesthetic dose of atropine to patient (0.02-0.04 mg/kg IV for dogs and cats)
- ATROPINIZATION = OP/CM toxicity unlikely
- NO ATROPINIZATION = OP/CM toxicity likely
Why does no atropinization on the atropine test point toward organophosphate or carbamate toxicity?
a much higher dose (10x preanesthetic) is required to resolve the mucarinic signs (DUMBELS) of OP/CM poisoning
What 8 syndromes should be considered as differential diagnoses with organophosphate and carbamate toxicosis?
- tremorgenic mycotoxicosis
- amitraz toxicosis
- pyrethrin/pyrethroid toxicosis
- pancreatitis
- garbage intoxication
- blue-green algae toxicosis
- muscarinic mushroom toxicosis
- cationic surfactant intoxication
In what 3 ways can a patient be stabilized in the case of organophosphate and carbamate toxicosis?
- induce emesis for recent oral exposure (<2 hr) and administer activated charcoal and cathartics
- gastric/enterogastric lavage for ingestion of large amounts before emesis has occur or if emesis is contraindicated
- for dermal exposure, wash animal in warm water and mild dishwashing detergent (Dawn) without scrubbing
What are 2 antidotes for organophosphate and carbamate toxicosis? How do they work?
- Atropine - blocks muscarinic ACh receptors and relieves muscarinic (NOT NICOTINIC) signs to control bradycardia and secretions
- Pralidoxime (2-PAM) - reactivates AChE before aging; ineffective on carbamates
In what 2 ways can symptomatic support be given for organophosphate or carbamate toxicosis?
- Diazepam or short-acting barbiturates to control convulsions
- artificial respiration to mitigate effects of respiratory paralysis
How is intermediate syndrome typically treated?
mostly SUPPORTIVE
- feed animal parenterally or by pharyngotomy tube
- correct dehydration and electrolyte imbalances
- bathe upon dermal exposure
Atropine is not indicated, but many patients will respond to Pralidoxime (2-PAM)
What is the main source of anatoxin-a(s)?
blue-green algae (cyanobacteria), like Anabaena, Aphanizomenon, and Oscillatoria spp.
What conditions favor conditions for anatoxin-a(s) toxicosis?
algal blooms in stagnant, eutrophic (high nutrients, NO3, SO4, PO4) water bodies when temperatures are warm, weather is calm, and when wind pushes the blooms to the shoreline
(green discoloration in water)
What leads to anatoxin-a(s) absorption? What is the mechanism of toxicity?
- cyanobacteria are ingested with water
- cells lyse in acidic stomach and release toxins
- toxins absorbed in the small intestine
- toxicosis
irreversibly inhibits acetylcholinesterase in PNS
What is the characteristic clinical signs of anatoxin-a(s) toxicosis? What leads to lethal cases?
acute onset DUMBELS
nicotinic signs
In what 5 ways can anatoxin-a(s) toxicosis be diagnosed?
- history and confirmation of exposure
- clinical signs
- algae identification in water, on skin samples, and in gastric contents
- detection of toxins in water and GI contents by HPLC or LC-MS
- mouse inoculation bioassay (not commonly available)
What are the best 3 treatments of anatoxin-a(s) toxicosis?
- give Atropine - Pralidoxime INEFFECTIVE
- provide symptomatic and supportive therapy with emesis, activated charcoal, cathartic, and bath
- remove animals from contaminated water source
How can water be treated to kill the algae causing anatoxin-a(s) toxicosis?
copper sulfate
What are the most common clinical signs of parasympathetic cholinergic blockage?
SYMPATHETIC SIGNS
- mydriasis
- tachycardia
- hypertension
- hyposalivation
- thirst/dry mouth
- decreased GI motility
- rapid pulse
- constipation/urinary retention
- hyperthermia
- seizures
- altered levels of consciousness (coma, delirium)
What are 5 common ways that signs of parasympathetic cholinergic blockade is described?
- hot as a hare/pistol - hyperthermia
- dry as a bone - dry skin
- red as a beet - flushed
- blind as a bat - mydriasis
- mad as a hatter - delirium
What is the mechanism of toxicity of anticholinergic drugs? What do they have no effect on?
(Atropine, Scopolamine, Ipratropium, Trimethaphan)
competitively antagonizes ACh at postsynaptic muscarinic receptors and autonomic ganglia
NMJ - only have nicotinic receptors
What kind of plants have anticholinergic effects? What causes this?
members of the Solanaceae family (nightshades/potato)
contain tropane alkaloids very similar to Atropine (hyoscyamine) and Scopolamine
