Alcohols and Glycols Flashcards
What is the chemical metabolism of methanol?
methanol -> formaldehyde (by ADH; rate limiting) -> formic acid -> CO2 +water
* toxicity is caused by formic acid (methanol is nontoxic)
How does methanol cause toxicity
toxicity is caused by formic acid (methanol is nontoxic)
- metabolic acidosis by inhibits mitochondrial respiration
- damages retina by inhibiting mitochondrial resp and depleting glutathione
What is the clinical presentation of methanol poisoning
First few hours: inebriated, gastritis
After latent period of 12-24 hrs: vision disturbance, parkinsons-like symptoms. hyperventilation (secondary to metabolic acidosis), CNS depression
What are sources of methanol and sources of ethylene glycol
methanol: industrial solvents, windshield wiper fluid
ethylene glycol: antifreeze, industrial solvent
What causes the toxicity in ethylene glycol
parent compound is non-toxic
ethylene glycol is metabolised to glycoaldehyde by ADH, then to glycolic acid by ALDH which causes severe metabolic acidosis.
eventually turns into oxalic acid –> precipitates into calcium oxalate damaging kidneys
What is the clinical presentation of ethylene glycol poisoning
Initial CNS depression
then renal failure, metabolic acidosis,
hypocalcemia
tetanic contractions
multiorgan failure
What is the clinical presentation of ethylene glycol poisoning
Initial CNS depression
after 4-12 hrs: hypocalcemia with tetanic contractions, renal failure, metabolic acidosis, multiorgan failure
What are the main treatments for methanol and ethylene glycol poisoning? what are some limitations
Treat with ethanol or fomepizole (competes for ADH, preventing the parent compounds from being metabolized into toxic metabolites) and eliminate parent compound by dialysis
limitations: adverse drug effects in majority of cases for ethanol, as well as difficult to dose; fomepizole is safer but very expensive, can cause bradycardia occasionally
What are some adjunctive treatments for MetOH and ethylene glycol poisoning
Methanol: folic catalyzes the reaction of formic acid to CO2 and water
Ethylene glycol: pyridoxine, thiamine, magnesium
How is acidosis corrected?
Sodium bicarb
methanol: formic acid (undissociated) is very toxic, while formate (dissociated formic acid) is less toxic, bicarb shifts eq to favour formate
What is the general steps of treatment for both methanol and Eglycol
- inhibit metabolism, ethanol or fomepizole
- dialysis to remove parent compound
- adjunctive treatment (folic acid; pyridoxime, thiamine)
- correct acidosis with bicarb
What are sources of diethylene glycol and propylene glycol? What are the toxicities like? how are they diagnosed?
diethylene glycol: antifreeze, brake fluid (more toxic than ethylene glycol; treatment same, renal failure permanent)
- double gap screening
propylene glycol: antifreeze, solvent for some IV pharmaceuticals (lower toxicity; can cause coma, seizures after large amounts)
- propylene glycol is metabolized to lactate -> serum lactate elevated (treat with supportive care)
- double gap + elevated lactate
definitive testing for both is still GC (also for methanol and ethylene glycol)
What toxins can cause double gap (anion and osmole gaps)
methanol, ethylene glycol, diethylene glycol, propylene glycol
Describe definitive testing, screening tests (osmole gap, anion gap, lactate gap, POC testing, Urine testing) in methanol and ethylene glycol poisoning
Definitive for both: GC, but time consuming, expensive, not readily available, so we typically use screening tests, but these are challenging to interpret (low sens and spec)
urine fluorescence (ethylene glycol) : BAD low sensitivity and specificity
urine crystals (ethylene glycol): poor sensitivity and specificity
POC testing (methanol): immunochromatographic test; can cross react with ethanol which is typically also ingested in patients, so unreliable
lactate gap (ethylene glycol): glycolic acid is interpreted as lactate on some blood gas analyzers, so there will be a gap between analyzer and standard lab analysis of lactate; only works on a specific analyzer
Osmole gap: good sensitivity, awful specificity (2Na + urea + glucose +1.25 ethanol);only the parent compound increases osmole gap, so if already metabolized, it may not show
Anion gap: low sensitivity and low specificity
osmole gap and anion gap are used to screen, but GC testing is needed for managing patients poisoned by these agents
What are some lab testing issues that can result in elevated osmole gap?
use of anticoagulants in collection tube
delay in analyzing tests
use of vapour pressure osmometry
