Neuro Emerg 28: Neurological toxicities

Question 1

Are cutaneously absorbed toxins usually hydrophilic or lipophilic?

Answer 1

lipophilic

Question 2

At what time frame post toxin ingestion is colonic lavage indicated?

Answer 2

4-6 hours after ingestion

Question 3

Name two toxins tracking more rapidly through the GI tract, indicating earlier colonic lavage

Answer 3

• organophosphates
• carbamates

Question 4

Name the types of toxins that are not absorbed by activated charcoal

Answer 4

• Alcohols
• strong acids or alkalis
• dissociable salts and metals (e.g., iron, lithium)
• petroleum products

Question 5

Explain the MOA of sorbitol

Answer 5

cathartic –> decreases transit time of toxins through GI tract –> reduces toxin absorption

Question 6

What are the two broad categories of neurotoxins?

Answer 6

• neuroexcitatory
• neuroinhibitory

Question 7

What is the mechanism of action of bromethalin toxicity

Answer 7

• 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

Question 8

What are the two different clinical pictures of bromethalin toxicity?

Answer 8

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)

Question 9

What class of medication is ivermectin?

Answer 9

avermectins or macrocyclic lactones

Question 10

What breeds are more sensitive to ivermectin toxicity and why?

Answer 10

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

Question 11

What is the mechanism of action of macrocytic lactones?

Answer 11

agonist for GABA(A)-gated chloride channels in the CNS

Question 12

Are benzodiazepines contraindicated in ivermectin toxicity?

Answer 12

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

Question 13

What is the mechanism of action of lead toxicity

Answer 13

• 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

Question 14

What would you see on a blood smear cytology in case of lead toxicity

Answer 14

nucleated red blood cells and basophilic stippling

Question 15

Name chelation options for lead toxicity

Answer 15

Succimer PO
Ca-EDTA SQ or IV
D-Penicillamine

Question 16

Why is MgSO4 indicated in lead toxicity

Answer 16

PO –> cathartic and binds to lead forming insoluble lead sulphate, that cannot be absorbed

Question 17

What is the MOA of methaldehyde toxicity

Answer 17

• decreases levels of GABA - inhibitory neurotransmitter
• increased monoamine oxidase activity
• decreased noradrenaline and serotonin levels (5-HT)

Question 18

What is the MOA of chocolate toxicity?

Answer 18

methylxanthine (contains theobromine)
phosphodiesterase inhibitor –> increases levels of cyclic AMP/cAMP
–> increased IC Ca levels –> neuromuscular excitability + positive inotropic effects

Question 19

What are the most common tremorgenic mycotoxins?

Answer 19

• Penitrem A
• Roquefortine

Question 20

What is the MOA of tremorgenic mycotoxins?

Answer 20

• unknown, but glycine inhibition is suspected

Question 21

What is the MOA of nicotine toxicity?

Answer 21

• low doses –> acts on nicotinic acetylcholine receptors –> neuroexcitatory
• higher doses –> neuromuscular blockage, persistent depolarization
• stimulates the emetic chemoreceptor trigger zone

Question 22

What medications should be avoided in nicotine toxicity?

Answer 22

H2-blockers or PPIs – alkalination of the stomach increases absorption

Question 23

What is the MOA of organochloride toxicity?

Answer 23

• unknown
• suspected: opening on Na channels in neurons –> repetetive firing of action potential
• suspected: GABA inhibition

Question 24

What is the mechanism of action of organophosphate and carbamate toxicity and what are the three different groups of clinical signs?

Answer 24

inhibits ACh-esterase –> ACh accumulates at cholinergic synapses

CS:
* Cholinergic signs (SLUDGE + bronchospasms and respiratory signs)
* CNS toxicity
* nicotinic toxicity (muscle tremors and weakness)

Question 25

What are the three different types of organophosphate toxicity clinical presentation?

Answer 25

1) Acute toxicity 2) Intermediate syndrome 3) organophosphate-induced delayed neuropathy

Question 26

How do organophosphates and carbamate differ in their mechanism of toxicity?

Answer 26

Organophosphates bind permanently to AChE Carbamates bind reversible to AChE - shorter duration of CS

Question 27

Explain specific treatments for organophosphate and carbamate toxicity

Answer 27

* Atropine for cholinergic signs * 2-PAM (Pralidoxime) --> reactivates phosphorylated cholinesterase (for severe nicotinic signs)

Question 28

What is the MOA fo permethrin toxicity?

Answer 28

* slow the opening and closing of voltage-gated Na-channels --> leads to repetetive impulse firing

Question 29

What is the MOA of strychnine?

Answer 29

glycine inhibition --> glycine is an inhibitory neurotransmitter prevents the release of glycine from Renshaw cells

Question 30

What is the MOA of metronidazole neurotoxicity?

Answer 30

mechanism of action unknown suspected: inhibition of neuronal protein synthesis by binding to RNA + thiamine antagonism

Question 31

List 5 types of toxins found in snake venom

Answer 31

1. Neurotoxins 2. Procoagulants 3. Anticoagulants 4. Hemolysins 5. Myotoxins

Question 32

Why should you avoid hypothermia in permethrin toxicity?

Answer 32

hypothermia may enhances intracellular Na movement --> worsens clinical signs