Toxicants Affecting the Nervous System III (8) Flashcards
What are the muscarinic signs?
SLUDGE or DUMBELS
What are the nicotinic signs?
MATCH
Cholinesterase inhibitors are
nicotinic and muscarinic stimulators
(cholinesterases degrade ACh, so if they are inhibited, then ACh accumulates)
Do nicotinic or muscarinic signs first show up with cholinesterase inhibitors?
muscarinic
What do organophosphates do?
acts as an AChE inhibitor
absorbed through the GI, respiratory tract, or skin
What is the structure of organophosphates?
How do organophosphates interfere with acetylcholine degradation?
binds to the esteric site of acetylcholinesterase
With organophosphate poisoning, what does it chronically inhibit and what happens?
inhibition of neuropathic esterase
Wallerian-type degeneration in distal CNS and PNS
Organophosphate-Induced Delayed Neuropathy
With organophosphate poisoning, what does it acutely inhibit and what happens?
AChE
accumulation of ACh at muscarinic and CNS receptors = acute cholinergic syndrome
excess ACh at NMJ leading to downregulation of ACh receptors = intermediate syndrome
What does 2-PAM do?
binds and gets phosphate off of acetylcholinesterase
Along with 2-PAM treating organophosphates. what also treats this toxicity? How?
atropine - muscarinic antagonist
When can you treat with atropine or 2-PAM?
nonaged (early therapeutic window)
What are carbamates?
in insecticides, herbicides, and fungicides
What is the difference between organophosphates and carbamates?
carbamates block both sites of AChE - 2-PAM can’t get it off
have to wait for body to degrade it
What is atropine?
anti-cholinergic
What does atropine cause?
- drying of secretions
- ILEUS
- mydriasis
- arrhythmias
- flushing
- confusion, hallucination
How do you treat OP/carbamate?
low test dose of atropine
If you see an animal having meiosis and urinating with a low-dose of atropine, is the animal in a cholinergic crisis?
yes - atropine should be blocking the muscarinic i.e. parasympathetic responses, but this animal is still showing clinical signs
Which species should you be cautious of when treating with atropine for organophosphate or carbamate toxicity? Why?
horses
atropine can cause fatal ileus due to it blocking motility of the gut (parasympathetic actions)
What are examples of organochlorine pesticides?
DDT, DDE, endrin
How do organochlorine pesticides cause problems?
interfere with inactivation of Na+ / K+ channels = remain in depolarized state
How do organochlorines act?
act mainly on the nerve axon by interfering (excitatory, blocking) with Na+ & K+ conductance gating
What are nicotinic signs of neurotoxicity?
What toxin is in chrysanthemum plants?
pyrethrins / pyrethroids (synthetic form)
A cat started having seizures, and the owner noticed it had eaten this plant. Toxin and plant?
pyrethrin
chrysanthemum
How do pyrethrins cause issues?
block sodium channels (left in depolarized state)
What are clinical signs of pyrethrin toxicity?
profuse drooling, vomiting, tremoring, hyperexcitability, agitation, seizures, weakness, difficulty breathing
What are these seeds from?
the strychnos nux-vomica tree
What is the toxicant in strychnos nux-vomica?
strychnine
What does strychnine do?
antagonist of glycine (inhibitory NT) - blocks it itself (not like tetanus)
What is the toxic agent in chocolate, mulches, and caffeine?
methylxanthines - paraxantine, theophylline, theobromine
How do methylxanthines cause issues?
phosphodiesterase inhibitors
unable to degrade cAMP to AMP
What are the clinical signs of methylxanthine toxicity?
presents as highly sympathetically stimulated
What can methylxanthines also block?
adenosine - constrictor of smooth cells (vasculature)
What is tick paralysis?
caused from neurotoxin produced in the salivary gland of female ticks
What are clinical signs of tick paralysis?
LMN deficits
How do you treat tick paralysis?
take the tick off - insecticide bath
