Toxic Alcohols
Alcohols include:
- Ethanol
- Methanol
- Ethylene Glycol
In toxicity:
- All present with symptoms of alcohol intoxication
- All contribute to the osmolar gap
- Different toxicities occur due to the different metabolites
Ethanol
Ethanol is a weak alcohol with a complicated mechanism of action similar to volatile anaesthetic agents:
- Enhanced GABA-mediated inhibition
This is reversible with flumazenil. - Inhibition of Ca2+ entry
- Inhibition of NMDA function
- Inhibition of adenosine transport
| Property | Drug |
|---|---|
| Dosing | One unit is ~8g/10ml of pure ethanol |
| Absorption | Rapid PO absorption |
| Metabolism | Saturatable kinetics at >4mmol.L-1 due to high doses requiring extensive NAD+ for oxidation, limiting metabolism to ~1 unit per hour. Low (0.2) extraction ratio, so high portal vein concentrations from rapid absorption (e.g. shots) causes a greater pharmacological effect. Ethanol is metabolised by alcohol dehydrogenase to acetylaldehyde, which is metabolised by aldehyde dehydrogenase to acetyl CoA. |
| Elimination | 10% eliminated unchanged in air and urine |
| Resp | Respiratory depression |
| CVS | Vasodilatation increasing heat loss, reduced cardiovascular disease mortality due to increased HDL and inhibition of platelets. Alcoholic cardiomyopathy in abuse. |
| CNS | Slurred speech, intellectual impediment, motor impediment, euphoria, dysphoria, increased confidence. Dementia, encephalopathy, peripheral neuropathy, and cerebellar atrophy with chronic use. |
| Endocrine | Stimulates ACTH release and 'pseudo-Cushing's syndrome'. Inhibits testosterone release. May cause lactic acidosis and hypoglycaemia in toxicity. |
| Renal | Inhibition of ADH release, causing diuresis. Ethanol is osmotically active and contributes to the osmolar gap. |
| GIT | Gastritis. Fatty liver, progressing to hepatitis, necrosis, fibrosis and cirrhosis |
| GU | Tocolytic effect |
| Haeme | Inhibition of platelet aggregation |
| Metabolic | High energy content comparable with fat (29kJ.g-1) |
| Other | Synergistic with other CNS depressants. Metabolic interactions with warfarin, phenobarbitone, and steroids |
Methanol
- Metabolised by alcohol dehydrogenase to formaldehyde and then formic acid
- Formic acid is neurotoxic
Damages retina and the optic nerve.
Ethylene Glycol
- Metabolised by alcohol dehydrogenase to glycoaldehyde, and (via several intermediate steps) to oxalic acid
- Oxalic acid binds calcium, which causes:
- Hypocalcaemia
- Long QT
- Acute renal failure
- Hypocalcaemia
References
- Rang HP, Dale MM, Ritter JM, Flower RJ. Rang and Dale's Pharmacology. 6th Ed. Churchill Livingstone.
- Holford NH. Clinical pharmacokinetics of ethanol. Clin Pharmacokinet. 1987 Nov;13(5):273-92.
- LITFL- Toxic Alcohol Ingestion