Alcohol

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  • Created by: z
  • Created on: 17-03-16 19:14

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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Alcohol pharmacokinetics

  • 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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Effect of alcohol

  • 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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Consequences of chronic alcohol misuse

  • 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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Alcohol problems

  • 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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Abstinence pharmacology

  • acamprosale
    • stabilises glutamate and GABA- reduces cravings
  • naltrexone
    • opiod antagonist - reduces rate of relapse
  • nalmefene
    • opiod R modulator- reduces consumption
  • disulfiram (antabuse)
    • inhibits ALDH- causes flushing, sweating, nausea
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