Toxidromes Flashcards
How is methanol poisonous?
- direct toxic effects of methanol - CNS depressant
- 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
What are the symptoms of methanol poisoning?
- CNS depression (direct effect)
- headache, dizziness, nausea, lack of coordination, and confusion.
- later (hours)
- blurring, loss of vision, acidosis due to effects of formate
Sufficiently large doses can cause unconsciousness and death.
How do you treat methanol poisoning?
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
What is ethylene glycol?
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.
How is ethylene glycol toxic?
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
What are the features of ethylene glycol poisoning?
hyperventilation metabolic acidosis cardiovascular dysfunction acute kidney failure - calcium oxalate crystals in the urine ***
What is the treatment for ethylene glycol poisoning?
Ethanol or Fomipezole
- Competitively inhibits alcohol dehydrogenase which metabolises ethylene glycol to its toxic metabolites
- Same principal as methanol poisoning
What are organophosphates?
Esters of phosphoric acid
- found in pesticides, solvents
e.g. Malathion, Parathion, Sarin (nerve gas)
How does organophosphate poisoning occur?
Organophosphates irreversibly inhibit acetylcholinesterases leading to accumulation of acetylcholine at central and peripheral muscarininic and nicotinic receptors
- cholinergic syndrome = parasympathetic overdrive
What are the signs and symptoms of organophosphate poisoning?
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
What is the treatment for organophosphate poisoning?
Muscarinic antagonists - Atropine
- blocks effects of acetylcholine
Benzos for seizures
What are the symptoms of an anticholinergic toxidrome?
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
What are the symptoms of a sympathomimetic toxidrome?
Fever, tacycardia, hypertension
agitation, rhabdomyolysis, lactic acidosis, diaphoresis, flushing, increased RR, arrythmias, cardiomyopathy, MI, stroke, aortic dissection
What are symptoms of a sedative toxidrome?
decreased LOC respiratory depression hypotension bradycardia ataxia nystagmus *opitates and barbituates cause miosis and hypothermia
What are symptoms of salicylate overdose?
Tinnitus Vertigo nausea, vomiting, diarrhoea Air hunger, hyperventiation altered mental state non cardiogenic pulmonary odema
Acid base in salicylate overdose?
inital respiratory alkalosis
followed by high anion gap metabolic acidosis due to production of organic acids
*leads to a mixed picture of above
What is the treatment of salicylate overdose?
Alkalinise the urine with sodium bicarobnate
haemodialysis
glucose administration as salicylates induce neuroglycopenia even with normal serum glucose
What are the distinguishing features of serotonin syndrome?
lower limb hyper-reflexia and clonus flushing increased bowel sounds early onset dose related
What are the distinguishing features of NMS?
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
What are medications that commonly precipitate serotonin syndrome?
SSRIs/MAOIs most common
addition of tramadol, lithium, fentanyl, pethidine, amphetimines, st johns wort
What medications typically precipitate NMS?
dopamine antagonists
- typical and atypical antipsychotics
- antiemetics (dopaminergic - metoclopramide etc.)
Treatment for NMS?
Dantrolene
supportive management
Treatment for serotonin syndrome?
supportive
cyproheptadine
avoid haloperidol as it can cause decreased sweating and increased agitation
- benzos for agitation
