Toxic alcohols

What is the anion gap equation?

anion gap = Na+ - (Cl- + HCO3-)

what is a normal anion gap?

~4-12

What things cause increased anion gap metabolic acidosis?

Methanol

Uremia

DKA, SKA, AKA (diabetic, starvation, alcoholic - acidosis)

Phenformin (metformin), paraldehyde

Isoniazid, INH

Lactate, CO, CN, methemoglobinemia

Ethylene glycol

Salicylates

what are the toxic alcohols?

methanol, ethylene glycol, and isopropanol (isopropyl alcohol)

Clinical presentation of toxic alcohol use

altered mental status (inebriation), GI distress

T/F: there are specific clinical presentation differences between toxic alcohols

true

where is methanol found/used for?

Gas-line antifreeze, windshield washer fluid, denaturants

Does methanol have high volatility?

yes - can be ordered/show up on a volatile’s panel

what is ethylene glycol used for?

automobile coolant, solvents, de-icers, and in air conditioning units

Does ethylene glycol have high voltatility?

No

what are the early features of methanol toxicity?

possible GI distress/inebriation within 0-24 hours of ingestion

what are the early features of ethylene glycol toxicity?

possible GI distress/inebriation that may be more delayed than methanol toxicity

what are the clinical presentations that occurs later in methanol toxicity?

high anion gap metabolic acidosis and visual changes (blindness)

Why can methanol cause blindness

due to the formation of formaldehyde and formic acid (formic acid is extremely toxic to the optic nerve and the retina)

what are the clinical presentations that occurs later in ethylene glycol toxicity?

high anion gap metabolic acidosis, nephrotoxicity, and hypocalcemia 

T/F: the higher the anion gap the more severe the toxicity/the longer it has been since exposure to toxic alcohols

true

T/F: ethanol can inhibit alcohol dehydrogenase

true

T/F: methanol metabolism to formic acid is the biggest toxicity cocern

true

What is methanol metabolized to?

formaldehyde —→ formic acid & formate

what is ethylene glycol metabolized to?

glycolic acid —→ glyoxylic acid —> a bunch of acids (ketoadipic acid, oxalic acid, hippuric acid, benzoic acid)

what is the initial management for methanol and ethylene glycol?

GI contamination (but not very helpful), electrolytes and arterial blood gas, ethanol level, methanol and ethylene glycol levels (delayed in receiving results), measure osmolality, consider ADH inhibition 

why is GI decontamination not helpful for toxic alcohol ingestion?

alcohols are absorbed extremely fast so whole bowel irrigation doesn’t work, and charcoal cannot bind with alcohol

dosing of ethanol for methanol and ethylene glycol overdose

1 g/kg —- IV 10% solution or PO equivalent of 4 shots patron

What is the maintenance dosing for ethanol in methanol/ethylene glycol overdose

up to a BAC of ~100 mg/dL (legal limit is 80 mg/dL)

what are the ADH inhibitor options?

ethanol and fomepizole

MOA of fomepizole

competitive inhibitor of alcohol dehydrogenase

ADRs of foempizole

HA, nausea, dizziness, minor allergic reactions (rare)

dosing of fomepizole

loading dose of 15 mg/kg

second phase of 10 mg/kg Q12h for 4 doses

Maintenance phase of 15 mg/kg Q12h

Why do the dosing phases of fomepizole go from high to low back to high doses?

the medication has autoinduction!

how is fomepizole diluted for administration?

diluted in NS or D5W and infused over 30 minutes

T/F: you need to increase the dose of fomepizole during hemodialysis

true

facts regarding ethanol use compared to fomepizole:

inexpensive, difficult to dose/titrate/prepare (especially oral), hypotonic, limited availability, and ADRs of CNS inebriation, thrombophlebitis, GI sx’s

facts regarding fomepizole use compared to ethanol:

expensive, easy to dose quickly, minimal adverse effects

why is sodium bicarbonate used in ethylene glycol toxicity?

to correct acidosis

why is sodium bicarbonate used in methanol toxicity?

to correct acidosis, reduce ratio of formic acid to formate, and promote ion trapping