Transcript Document
Alcohol Dr Alison Battersby Alcohol has a short half life • “I am not a heavy drinker. I can sometimes go for hours without touching a drop” 10% of the population drink half the alcohol Those pesky neurotransmitters • Significant actions on GABA and glutamate, primary neurotransmitters • Enhances GABA-A receptor function cf BDZ (sedation, relaxation, unsteadiness, amnesia) • High doses mimics barbiturate effect (locks open the channel, coma, respiratory depression) And more… • Alcohol blocks glutamate NMDA-type receptors causing decreased excitation, sedation, amnesia, coma and death • Chronic use, NMDA receptors increase in number creating a hyperexcitable withdrawal state. Acamprosate may reduce this Alcohol withdrawal • Compensatory glutamate receptor up- regulation with loss of magnesium leading to excess brain stimulation • Long term potentiation in the hippocampus is attenuated by alcohol Acamprosate • Withdrawal increases in severity over time. Repeated withdrawal leads to greater glutamate levels and increased mortality. Blocked by acamprosate • Dahchour and De Witte Alcohol and amines • Alcohol, as opiates, stimulants and cannabis release dopamine in brain, ? A common pleasure circuit • Low 5HT function leads to alcohol abuse and chronic use decreases 5HT, SSRIs may reverse this (middle-aged women) • Chronic alcohol damages brain noradrenaline system, leading to dementia Alcohol and endorphins • Brain endorphins system is main site of action of heroin and other opiates. Alcohol releases endorphins this may explain therapeutic effect of naltrexone to reduce relapse and effect in Sinclair method It only takes me one drink to get me drunk. The trouble is, I can’t remember if it’s the thirteenth or fourteenth! Why drink alcohol? • Positive reward or reinforcement: pleasure. Escapism, euphoria, rush • Negative reinforcement: feel normal, anxiolytic, overcome withdrawal • Urge compulsion: cannot control use Alcohol alters perception of self leading to decreased social anxiety Alcohol and its withdrawal drives motivation • I would kill everyone in this room for a drop of sweet beer Blood alcohol Detects recent drinking only, ethanol metabolised at 10g/hour Breath levels correlate closely with blood In a person smelling of alcohol BAC can confirm recent drinking, suggest tolerance if high BAC low impairment Urine alcohol longer window of detection GGT (gammaglutamyltransferase) • Most sensitive blood test that is widely available but only positive in 30% of heavy drinkers in community • Alcohol is the commonest cause of elevation but up to 50% GGT elevations for other reasons eg obesity, medications • Half life 2 weeks • Prognostic value, tool in monitoring Other markers • Aminotransferases AST:ALT ›1.5 suggests alcohol • MCV: slow to return to normal, T1/2 60days, non-specific eg nutritional, drugs, liver disease Alcohol:management of withdrawal and detoxification • Where and when to detoxify? • What are the medical risks? • What setting is appropriate? • What does the service user want from detox? • How to integrate into the bigger treatment picture? Treatment regimens:alcohol detox • Benzodiazepines are efficacious in reducing signs and symptoms of withdrawal and are recommended as the treatment of choice • No particular one except lorazepam or oxazepam in liver failure • Reducing regimen, front loading, symptom triggered Surprise! • Carbamazepine has been shown to be efficacious and can be chosen as an alternative to benzodiazepines • Chlormethiazole is reserved for inpatient settings only after due consideration, risk of respiratory depression with alcohol Seizures • Benzodiazepines, particularly diazepam reduces • • de novo seizures and are recommended for the treatment of withdrawal No advantage in anticonvulsants and benzodiazepines combined To prevent a second seizure in same withdrawal episode the evidence supports the use of lorazepam but does not support the use of phenytoin Delirium Benzodiazepines, particularly those with longer half life prevent delirium and are recommended A cautionary tale! Acamprosate • Increases abstinence rates by double to ≤ 40% after 3, 6 or 12 months • Start during detoxification Neuroprotective • If drink alcohol, less frequent and lower amount Other medications • Naltrexone • Baclofen • Disulfiram • Odansetron ….. 1930s, Blauwe (or Blue) Week Blessed is he who does not drink wine: Russia 1900