Toxidromes

Question 1

How is methanol poisonous?

Answer 1

1. direct toxic effects of methanol - CNS depressant
2. Metabolism in the liver to formic acid
   methanol -> (alcohol dehydrogenase) formaldehyde -> (aldehyde dehydrogenase) formate
   - formate inhibits cytochrome c oxidase causing cellular hypoxia and metabolic acidosis

Question 2

What are the symptoms of methanol poisoning?

Answer 2

1. CNS depression (direct effect)
2. headache, dizziness, nausea, lack of coordination, and confusion.
3. later (hours)
   - blurring, loss of vision, acidosis due to effects of formate

Sufficiently large doses can cause unconsciousness and death.

Question 3

How do you treat methanol poisoning?

Answer 3

Fomipezole or ethanol
- competitively inhibit alcohol dehydrogenase so it is excreted by the kidney and not metabolised into toxic metabolites (formic acid)

IV bicarb for metabolic acidosis
Dialysis
Folic/Folinic acid to enhance the metabolism of formate

Question 4

What is ethylene glycol?

Answer 4

an organic compound primarily used as a raw material in the manufacture of polyester fibers and fabric industry, and polyethylene terephthalate resins (PET) used in bottling. A small percent is also used in industrial applications like antifreeze formulations and other industrial products. It is an odorless, colorless, syrupy, sweet-tasting liquid.

Question 5

How is ethylene glycol toxic?

Answer 5

Ethylene glycol -> (alcohol dehydrogenase) glycol acid (toxic) -> oxalic acid (toxic)

• metabolites cause encephalopathy or cerebral oedema
• metabolic acidosis due to glycol acid
• renal impairment due to glycol acid
• oxalic acid binds to calcium causing calcium oxalate crystals which deposit and damage tissue in the heart, brain, kidneys

Question 6

What are the features of ethylene glycol poisoning?

Answer 6

hyperventilation
metabolic acidosis
cardiovascular dysfunction
acute kidney failure
- calcium oxalate crystals in the urine ***

Question 7

What is the treatment for ethylene glycol poisoning?

Answer 7

Ethanol or Fomipezole

• Competitively inhibits alcohol dehydrogenase which metabolises ethylene glycol to its toxic metabolites
• Same principal as methanol poisoning

Question 8

What are organophosphates?

Answer 8

Esters of phosphoric acid
- found in pesticides, solvents

e.g. Malathion, Parathion, Sarin (nerve gas)

Question 9

How does organophosphate poisoning occur?

Answer 9

Organophosphates irreversibly inhibit acetylcholinesterases leading to accumulation of acetylcholine at central and peripheral muscarininic and nicotinic receptors
- cholinergic syndrome = parasympathetic overdrive

Question 10

What are the signs and symptoms of organophosphate poisoning?

Answer 10

Cholinergic syndrome:
- arises from either acetylcholinesterase enzyme inhibition (organophosphates) or direct agonist action at muscarinic or nicotinic receptors.

S - Salivation
L - Lacrimation
U - Urination: relaxation of the internal sphincter muscle of urethra, and contraction of the detrusor muscles
D - Diaphoresis:
G - GI upset: Smooth muscle tone changes causing gastrointestinal problems, including diarrhea
E -Emesis
M - Miosis: stimulation of pupillary constrictor muscles

Muscle fasciculations, bradycardia

Question 11

What is the treatment for organophosphate poisoning?

Answer 11

Muscarinic antagonists - Atropine
- blocks effects of acetylcholine

Benzos for seizures

Question 12

What are the symptoms of an anticholinergic toxidrome?

Answer 12

Blind as a bat
Mad as a hatter
Full as a flask
Dry as a bone
Red as a beat
Most prominent feature is tacycardia
Ileus and reduced bowel sounds

Question 13

What are the symptoms of a sympathomimetic toxidrome?

Answer 13

Fever, tacycardia, hypertension
agitation, rhabdomyolysis, lactic acidosis, diaphoresis, flushing, increased RR, arrythmias, cardiomyopathy, MI, stroke, aortic dissection

Question 14

What are symptoms of a sedative toxidrome?

Answer 14

decreased LOC
respiratory depression
hypotension
bradycardia
ataxia
nystagmus
*opitates and barbituates cause miosis and hypothermia

Question 15

What are symptoms of salicylate overdose?

Answer 15

Tinnitus
Vertigo
nausea, vomiting, diarrhoea
Air hunger, hyperventiation
altered mental state
non cardiogenic pulmonary odema

Question 16

Acid base in salicylate overdose?

Answer 16

inital respiratory alkalosis
followed by high anion gap metabolic acidosis due to production of organic acids
*leads to a mixed picture of above

Question 17

What is the treatment of salicylate overdose?

Answer 17

Alkalinise the urine with sodium bicarobnate
haemodialysis
glucose administration as salicylates induce neuroglycopenia even with normal serum glucose

Question 18

What are the distinguishing features of serotonin syndrome?

Answer 18

lower limb hyper-reflexia and clonus
flushing 
increased bowel sounds
early onset 
dose related

Question 19

What are the distinguishing features of NMS?

Answer 19

later onset
hyporeflexic
raised CK more often
more rigidity and higher temperatures
usually occurs within first few weeks of starting meds but can occur at any time
idosyncratic

Question 20

What are medications that commonly precipitate serotonin syndrome?

Answer 20

SSRIs/MAOIs most common

addition of tramadol, lithium, fentanyl, pethidine, amphetimines, st johns wort

Question 21

What medications typically precipitate NMS?

Answer 21

dopamine antagonists

• typical and atypical antipsychotics
• antiemetics (dopaminergic - metoclopramide etc.)

Question 22

Treatment for NMS?

Answer 22

Dantrolene

supportive management

Question 23

Treatment for serotonin syndrome?

Answer 23

supportive
cyproheptadine
avoid haloperidol as it can cause decreased sweating and increased agitation
- benzos for agitation