Neuro Emerg 28: Neurological toxicities Flashcards
Are cutaneously absorbed toxins usually hydrophilic or lipophilic?
lipophilic
At what time frame post toxin ingestion is colonic lavage indicated?
4-6 hours after ingestion
Name two toxins tracking more rapidly through the GI tract, indicating earlier colonic lavage
- organophosphates
- carbamates
Name the types of toxins that are not absorbed by activated charcoal
- Alcohols
- strong acids or alkalis
- dissociable salts and metals (e.g., iron, lithium)
- petroleum products
Explain the MOA of sorbitol
cathartic –> decreases transit time of toxins through GI tract –> reduces toxin absorption
What are the two broad categories of neurotoxins?
- neuroexcitatory
- neuroinhibitory
What is the mechanism of action of bromethalin toxicity
- uncoupling of oxidative phosphorylation –> less ATP available
- –> decreased function of Na-K-ATPase pumps –> increased intracellular Na
- water accumulating in cellls –> cerebram edema –> increased ICP
What are the two different clinical pictures of bromethalin toxicity?
High dosages –> acute hyperexcitability (2-24 hours after exposure) –> seizures, hyperaesthesia, tremors
More common –> delayed ataxia, paresis, decreased conscious proprioception (1-3 days after exposure)
What class of medication is ivermectin?
avermectins or macrocyclic lactones
What breeds are more sensitive to ivermectin toxicity and why?
Collies and related breeds (Australian Shepherds, Border Collies, Shetland Sheepdogs, other herding dogs)
MDR1 mutation –> inefficient blood-brain barrier efflux pumps –> increased accumulation of the drug in the CNS
What is the mechanism of action of macrocytic lactones?
agonist for GABA(A)-gated chloride channels in the CNS
Are benzodiazepines contraindicated in ivermectin toxicity?
Historically thought to be contraindicated - due to drugs proximity to same GABA binding site
now postulated that this is actually not the case - can use benzos
What is the mechanism of action of lead toxicity
- leads binds to sulfhydryl groups and interferes with sulfhydryl-containing enzymes –> interference in haem synthesis, RBC fragility, basophilic stippling
- neurotoxic mechanisms unclear, proposed: GABA-interferences, capillary damage leading to cerebral hemorrhage + cerebral necrosis, Ca-inhibition, dopamine-interference
What would you see on a blood smear cytology in case of lead toxicity
nucleated red blood cells and basophilic stippling
Name chelation options for lead toxicity
Succimer PO
Ca-EDTA SQ or IV
D-Penicillamine
Why is MgSO4 indicated in lead toxicity
PO –> cathartic and binds to lead forming insoluble lead sulphate, that cannot be absorbed
What is the MOA of methaldehyde toxicity
- decreases levels of GABA - inhibitory neurotransmitter
- increased monoamine oxidase activity
- decreased noradrenaline and serotonin levels (5-HT)
What is the MOA of chocolate toxicity?
methylxanthine (contains theobromine)
phosphodiesterase inhibitor –> increases levels of cyclic AMP/cAMP
–> increased IC Ca levels –> neuromuscular excitability + positive inotropic effects
What are the most common tremorgenic mycotoxins?
- Penitrem A
- Roquefortine
What is the MOA of tremorgenic mycotoxins?
- unknown, but glycine inhibition is suspected
What is the MOA of nicotine toxicity?
- low doses –> acts on nicotinic acetylcholine receptors –> neuroexcitatory
- higher doses –> neuromuscular blockage, persistent depolarization
- stimulates the emetic chemoreceptor trigger zone
What medications should be avoided in nicotine toxicity?
H2-blockers or PPIs – alkalination of the stomach increases absorption
What is the MOA of organochloride toxicity?
- unknown
- suspected: opening on Na channels in neurons –> repetetive firing of action potential
- suspected: GABA inhibition
What is the mechanism of action of organophosphate and carbamate toxicity and what are the three different groups of clinical signs?
inhibits ACh-esterase –> ACh accumulates at cholinergic synapses
CS:
* Cholinergic signs (SLUDGE + bronchospasms and respiratory signs)
* CNS toxicity
* nicotinic toxicity (muscle tremors and weakness)
What are the three different types of organophosphate toxicity clinical presentation?
1) Acute toxicity
2) Intermediate syndrome
3) organophosphate-induced delayed neuropathy
How do organophosphates and carbamate differ in their mechanism of toxicity?
Organophosphates bind permanently to AChE
Carbamates bind reversible to AChE - shorter duration of CS
Explain specific treatments for organophosphate and carbamate toxicity
- Atropine for cholinergic signs
- 2-PAM (Pralidoxime) –> reactivates phosphorylated cholinesterase (for severe nicotinic signs)
What is the MOA fo permethrin toxicity?
- slow the opening and closing of voltage-gated Na-channels –> leads to repetetive impulse firing
Why should you avoid hypothermia in permethrin toxicity?
hypothermia may enhances intracellular Na movement –> worsens clinical signs
List 5 types of toxins found in snake venom
- Neurotoxins
- Procoagulants
- Anticoagulants
- Hemolysins
- Myotoxins
What is the MOA of strychnine?
glycine inhibition –> glycine is an inhibitory neurotransmitter
prevents the release of glycine from Renshaw cells
What is the MOA of metronidazole neurotoxicity?
mechanism of action unknown
suspected: inhibition of neuronal protein synthesis by binding to RNA + thiamine antagonism
