Tolerance: due to pharmacodynamic and pharmacokinetic (eg enzyme induction) processes
Cross-tolerance, eg alcohol and BZDs
Physical dependence: Withdrawal syndrome on abstinence
Psychological dependence: Emotional need to compulsively take a drug (even if no physical withdrawal syndrome)
Characterised by: tolerance (CNS adaptation and pharmacokinetic), narrowing of drinking pattern (stereotyped drinking), amnesic blackouts, withdrawal symptoms, awareness of loss of control, failed attempts at abstinence, preoccupation with drinking, drinking to relieve withdrawal symptoms
Look for: compulsive binges with frequency, stereotyped drinking, intake over 60 g ethanol/day, chronic social and health problems, neurological problems
Use CAGE questions to assess dependency: Have you ever tried to Cut Down, Annoyed by others telling you to cut down, Guilt, Eye-opener
Hazardous Drinking. Heavy drinking with no “obvious” problem
Characterised by prolonged (eg 5 years or more), regular (eg almost daily, or weekend binges), excessive consumption with a high risk of physical mental and social implications, but no dependency features – but maybe some tolerance and occasional amnesic blackouts, may not be associated with acute intoxication
Look for: episodic heavy social drinking to intoxication, increasing psychosocial problems, accidents, inflammation of stomach, liver, pancreas
Problem Drinking: problems related to alcohol without dependency and with or without excessive regular consumption. May result from isolated acute intoxication or drinking with medical contraindication – injury, aggression, binge drinking, family, financial, occupational problems
Remember: Drug abusers often abuse multiple drugs (eg alcohol, BZDs, and marijuana)
Assessment
For liver and pancreatic effects see Topic: Alcoholic Liver Disease
Differential of drowsiness/confusion in alcoholic:
Alcohol intoxication
Sedatives
Post-ictal (eg seizures with alcohol withdrawal)
Wernicke‟s encephalopathy
Subdural haematoma: grow slowly, compounded by global atrophy due to alcohol
Hepatic encephalopathy
Alcoholic hypoglycaemia
Assessment of co-existing disease is vital:
Other drug use (BZD, sedatives, opioids ® also have withdrawal features)
Primary depressive disorder (in addition to alcohol-induced depression which resolves quickly)
Gastro disorders: oesophagitis, pancreatitis, liver disease, small bowel dysmotility
Blood and nutritional: macrocytosis, folate and iron deficiency, impaired leucocytes, hypocalcaemia, hypokalaemia, electrolyte disturbances
Investigations:
Alcohol levels
LFT
FBC (anaemia)
Glucose (® ?hypoglycaemic)
Coagulopathy: INR
Other drugs, eg BZD
Pathological Effects of Alcohol on the Brain
Cerebral atrophy:
Common. Seen in over ¼ of long term alcoholics at post-mortem
Ventricular dilation, widening of the cerebral and cerebellar sulci
No specific cortical changes have been described. No classical changes of multi-infarct dementia or Alzheimer‟s
Wernicke-Korsakov Syndrome:
Due to ¯Vitamin B1 (Thiamine) – Marmite and Cereals are good sources
Thiamine is not stored in the body, signs of deficiency can appear within a month – especially in beer drinkers (high carbohydrate intake ® thiamine requirement)
Rare triad of:
VI nerve palsy (®vertical/horizontal nystagmus)
Ataxia (vestibular dysfunction)
Confusion
Pathology:
Acute: petechial haemorrhages in the grey matter surrounding the third and fourth ventricles and aqueduct
Chronic: shrinkage and haemosiderin staining (especially of mamallory bodies)
If prolonged leads to Korsakov‟s amnesic psychosis
Vitamin B12 (cobalamin) deficiency:
Leads to:
Peripheral neuropathy, demyelination and degeneration of the posterior and lateral columns of the spinal cord
Variety of confusional, amnestic and psychotic alterations
Ie, lots of potential neurotransmitter targets in reward pathways to ¯cravings, etc
Antabuse (disulphram):
Blocks second step of metabolism pathway ® acetaldehyde ® flush, vomiting, ¯BP
Takes 12 hours to block enzyme system. Has effect within ½ hour of a drink (one drink is enough)
Contraindications: heart disease (can‟t cope with ¯BP), makes depression/psychosis worse
Administration needs to be supervised: if taken at own discretion then little impact on abstinence
Acamprosate (Campral): ¯craving, must be taken 3 times daily (a pain!), start 7 days post detox. Not in elderly, pregnant, liver or renal disease. No hypnotic, anxiolytic or antidepressant effects
For non-drug treatment, Treatment of Substance Abuse
Alcohol Withdrawal
Most common drug withdrawal state. Can be life threatening (unlike opioid withdrawal)
Detoxification is only the first step in treatment
Aetiology of alcohol withdrawal syndrome poorly understood
Features of withdrawal:
A spectrum. Delirium Tremens describes severe withdrawal only
Minor withdrawal (peaks at day 2): restlessness, anxiety, nausea, disordered sleep, headache, tachycardia, hypertension, tremor
Major withdrawal (peaks at day 5): Agitation, behavioural disorders, confusion, sweating, fever, paranoia, hyperventilation
Seizures: if they occur, are most likely on day 1 – 3, usually only one, usually grand mal, status rare
Hallucinations: usually visual (auditory unlikely), on day 2 – 4
Management:
Get pre-detoxification blood alcohol level. Helps with assessment (how tolerant are they?). Avoid too much sedative if high. Alcohol metabolised at 20 mg/dl/hour (4 mmol/L/hour) – can predict when it will reach zero
Previous withdrawal severity good indicator of likely current severity. Other indicators of severity: > 15 standard drinks a day, early morning drinking, hypokalaemia, intercurrent illness
If likely to be severe, or if co-existing medical, psychiatric illness or other addiction, withdrawal should be medically supervised (ie admit them). Mattress on the floor with constant nursing attention. If dehydration or constant sweating then iv fluids
Otherwise at home or outpatients if good social support
Parental thiamine followed by short oral course (25 mg po twice daily)
Treat withdrawal with drugs which have cross-tolerance with alcohol (ie BDZs) once they’re nolonger intoxicated
Use BZDs or chlormethiazole
Give sedatives with extreme caution if measurable blood alcohol levels
Diazepam 10 – 20 mg/4 hourly for moderate withdrawal, 20 mg/2 hourly iv for severe. Resist protracted sedatives, otherwise ® addiction. If liver disease then reduce dose
Oral chlormethiazole 1 gm 6 hourly
Additional treatments:
b blockers for tremor, hypertension (except if CORD or CV disease).
Haloperidol 1 – 5 mg 6 hourly if hallucinations
Sodium Valproate (Epilim) 600 mg stat po, then 400 mg 8 hourly for 5 days, if history of seizures – care if liver disease. Likely to occur early in withdrawal, especially if history of seizures with previous withdrawal
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