Alcohol

Alcohol intro

dependence: 3/7 conditions over 12 months:
- tolerance, w/drawal sympts, ingestion of larger amounts, persistent desire, spending incring time drinking/recovering, abandoning social/work activities, continued use despite problems
NB %ABV X 0.78 = g alcohol/100ml
legal driving limits:
- 80mg/100ml blood
- 35mg/100ml breathe
- 107mg/100ml urine

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absorption
- 80% in duodeum/jejunum
- simple diffusion
- rate of absorption is conc-dependent and related to stomach emptying
distribution
- rapidly distrib b/c rich blood supply= fast effect
- crosses BBB easily
- Vd equal to total body water (0.6 L/kg)
  - affects women more b/c of higher body fat thus high conc in remaining water
  - similarly fatter people get higher relative blood conc
metabolism
- ethanol > (alcohol dehydrogenase/ADH)> acetaldehyde >(acetaldehyde dehydrogenase/ALDH)> acetate > CO2 + H2O
- ADH is rate limiting step enzyme levels under genetic variation
- clearance rate ~6g/hr
excretion - 2% not metabolised excreted unchanges in urine and breathe- use for detection

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CNS depressant via:
- GABA-A potentiation
- NMDA antagonist
- serotonin, opiod, dopaminergic NTs - reward centres
drug interactions
- CNS drugs
  - incr crowsiness, incr sedation
  - e.g. phenothiazines, TCAs, antiH, benzodiazepines
- antihypertensives/CV drugs
  - enhanced hypotensive
- warfarin
- metronidazole/ketoconazole
  - inhibts aldehyde dehydrogenase- get anatabuse (disulfiram) effect
  - disulfiram reactions = acetaldehyde accumulation = sickness
alcohol Rx in methanol/ethylene glycol poisoning (fomepizole also same effect)
- competitive inhibition of ADH prevents metabolism to toxic formic acid/formate

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neuro:
- periph neuropathy, cerebellar degen, cerebral haem, Wernicke's encephalopathy, dementia
hepatic:
- fatty change and cirrhosis >ca
GI:
- oesophagitis, gastritis, pancreatitis, Oesoph ca., Mallory-Weiss syndrome, varices
Resp:
- pulm Tb, pneumonia
skin:
- spider naevi, palmar erythema, Duputren's contracture
cardiac: cardiomyopathy, HTN, arrythmias
msk: myopathy, #s
endocrine/metabolic: pseudo-cushing's syndrome, hypoglycaemia, gout
repro: hypogonadism, fetal alcohol syndome, infertility, impotence

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Dx
- FBC- macrocytosis
- U&E- low urea
- LFT - incr transaminases , gamma GT - elevated
- INR - prolonged
withdrawal
- 6-12 hrs: insomnia, anxiety, GI upset, palpitations, tremulousness
- 12-24 hrs: alcoholic hallucinosis (visual, auditory, tactile)
- 24-48 hrs: generalised tonic-clonic
- 4-72 hrs: delirium tremens- hallucinations, tachy, incr BP, agitation, diaphoresis (sweating)
Mx of withdrawal
- benzodiazepines (chlordiazepoxide or diazepam)
- reactive or prophylactic for seizures and symptoms
prevention/Rx of encephalopathy
- Pabrinex - high dose vit B (thiamine[B1], riboflavin[B2}, pyroxidine[B6], nicotinamide, vitC)
- followed by oral thiamine 200-300mg daily +/- vit b complex tablets TDS

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