ethanol (alcohol and alcohol withdrawal)

see also:

• ethanol intoxication
• cirrhosis
• Western Health policies (intranet only):
  • alcohol withdrawal
  • alcohol withdrawal scale

• ethanol is primarily a CNS depressant acting by stimulating GABA_A receptor in the CNS.
• from 1996-2005 throughout Australia, each year, an average of over 80,000 were hospitalised, and over 3,000 died from alcohol attributable injury and disease caused by risky/high risk drinking - mainly due to alcohol dependence, falls, assaults and alcohol abuse¹⁾
• current advice suggests no more than 2 glasses alcohol per day long term, and no more than 4 glasses alcohol on any one occasion.
• middle aged men who drink more than 3 standard drinks a day have faster cognitive decline with age, speeding up memory loss by up to 6 years ²⁾

• rapidly absorbed, peak 30-90min from time of last drink, delayed with food
• initial “overshoot” as distrib. to brain before muscle - minimised by exercise;
• uniformly distributed in all body tissues Vd=0.6-0.9L/kg (0.1 less in females);
• air:blood part. coeff. 2100:1 (ie. same amount in 2100ml air if 5.26% CO₂ → 216mg CO₂ as 1ml blood) & after taking into account the decreased resp. quotient due to alcohol ingestion, thus the amount ethanol accompanying 190ml exp. CO₂ = that in 1ml blood;
• 90-98% oxidised by liver cytosol alcohol dehydrogenase (Km=7.4mg/dl) using NAD ⇒ acetaldehyde which is converted via aldehyde dehydrogenase to acetyl CoA.
  • genetic polymorphism of both alcohol & aldehyde dehydrogenase;
  • NB. up to 25% metab. by hep. microsomal NADPH/cytoch.P450 oxidising system which may be induced 5-fold by chronic intake → 2x overall increase in ethanol metabolism rate;
• rate of elimination: 80-150mg/kg b.wt/hr with mean of 100 (= 7g/hr in 70kg man)

• see also ethanol dependence

• induction of microsomal system → 2x elimination rate;

• effects greater in rising than falling or constant level phase;
• diuretic effect, CNS “intoxication”;
• cross-tolerance occurs (see below);

• ? behaviourally augmented tolerance - a learned ability to cope;
• mainly for low doses only; higher doses near lethal range no tolerance!
• cross-tolerance occurs to CNS depressants;

• 1st effects those processes that depend on training & previous experience & that usually make for sobriety & self-restraint.
• Memory, concentration & insight are dulled & then lost;
• confidence abounds, personality ⇒ expansive & vivacious;
• uncontrolled mood swings & emotional outbursts may occur;
• sensory & motor disturbances ⇒ sedation with resp. depression;
• effects are generally proportional to blood [ethanol] but greater when rising than falling;

• (cortical then limbic then cerebellar & finally brain stem):
  • [ ] < 0.02%
    • ⇒ euphoria, some disorder of cognitive & motor function
    • ⇒ disinhibition and increased sexual desire (but impaired sexual responsiveness)
    • ⇒ decreased seizure threshold
    • ⇒ inhibition of ADH release in proportion to [ethanol]
      • (but only when it is [ethanol] is rising!) → diuresis
  • [ ] > 0.2%
    • ⇒ cerebellar ataxia, memory impairment
    • ⇒ narcosis, decreased CO2 drive
      • ⇒ risk of mononeuropathy due to prolonged nerve compression
  • [ ] > 0.3-0.4%
    • ⇒ risk of coma & fatal respiratory arrest

• vasodilatation (unless severe intoxication affecting vasomotor centre)
  • ⇒ hypothermia, mild hypotension
• increased exercise-induced angina if IHD

• increased adrenal medulla catecholamine release
  • ⇒ hyperglycaemia, pupillary dilatation, slight increase BP;
• increased gastric secretions & irritative to mucosa if 40% alcohol
  • ⇒ increased risk peptic ulceration
• acute fatty liver within a few days of even modest alcohol consumption
• acute hepatitis +/- steatorrhoea in bouts of heavy drinking:
  • most cases are probably subclinical
  • spectrum ranges from minimal nausea, vomiting & abdo. pain to acute liver failure
    • ⇒ tachycardia, fever, hypotension, RUQ tenderness, +/- jaundice
    • ⇒ LFT's: elevated AST, ALT usually < 10x normal with ALT < AST
    • ⇒ FBE: neutrophilia of 10000-20000 common
    • check PT, U&E, acid-base for alcoholic ketoacidosis, deranged electrolytes & liver dysfunction
    • may need to exclude viral hepatitis, pancreatitis, gastritis, CBD obstruction (see hepatobiliary imaging)
  • Mx is primarily supportive:
    • correct fluid & electrolyte imbalance
    • antiemetics
    • watch for & Rx hypoglycaemia
    • give thiamine 100mg IV BEFORE any glucose to avoid inducing acute Wernicke's enceph.
    • give empirical magnesium replacement Rx unless C/I by renal failure or known hypermagnesaemia
    • high-calorie, vitamin supplemented diet
    • restrict protein if evidence of cirrhosis or incipient encephalopathy
    • H2 antagonists &/or antacids to Rx coexisting gastritis
    • look for & Rx GIT bleeding
    • admission to hospital generally NOT required unless concern over:
      • degree of fluid & electrolyte abnormality
      • ability to retain oral intake
      • coexistent diagnoses/complications
      • patient's social situation
• acute fiber rhabdomyolysis
• acute pancreatitis

• Liver:
  • fatty change (steatosis) most likely due to diminished NAD+/NADH ratio which favors TG production
    • direct function of the duration & amount of alcohol consumed
    • in general, is reversible with cessation of alcohol
    • ⇒ benign, usually painless hepatomegaly
  • alcoholic cirrhosis
    • ⇒ portal hypertension → oesophageal varices
    • ⇒ hypoalbuminaemia → oedema & ascites
    • ⇒ impaired production of clotting factors
    • ⇒ impaired metabolism of drugs
    • ⇒ hepatic encephalopathy
• CNS:
  • ? cerebral atrophy
  • Korsakoff's encephalopathy - memory impairment, confabulation
  • adolescent alcohol intoxication gives ~5x risk of young onset dementia in men (median age onset 54yrs), this increases to 20x risk if combined with 2 other risk factors such as depression, antipsychotic use, substance abuse, FH father with dementia, or being in lower 1/3rd percentiles for cognition or height.³⁾
• Heart:
  • irreversible congestive cardiomyopathy
• Sk.muscle:
  • chronic fiber rhabdomyolysis → myopathy
• Testes:
  • atrophy → sterility
  • decreased testosterone production, increased metabolism, & increased oestrogen production → gynaecomastia, impotence
• Pancreas:
  • chronic pancreatitis
• GIT:
  • peptic ulceration
  • constipation or diarrhoea
  • impaired absorption esp. of thiamine
• Blood:
  • sideroblastic & megaloblastic anaemia; thrombocytopenia;
  • decr. leukocyte migration → decr. inflamm. response to infection;
• Thiamine or other nutritional deficiency (due to poor food intake & impaired absorption):
  • CNS:
    • Wernicke's encephalopathy - ataxia, confusion, ophthalmoplegia
    • cerebellar degeneration
  • PNS:
    • peripheral neuropathy - demyelination