AlcoholAlcohol

Dr Alison BattersbyDr Alison Battersby

Alcohol has a short half lifeAlcohol has a short half life

• ““I am not a heavy I am not a heavy

drinker. I can sometimes go drinker. I can sometimes go

for hours without touchingfor hours without touching

a drop”a drop”

10% of the population drink 10% of the population drink half the alcoholhalf the alcohol

Those pesky Those pesky neurotransmittersneurotransmitters• Significant actions on GABA and Significant actions on GABA and

glutamate, primary glutamate, primary neurotransmittersneurotransmitters

• Enhances GABA-A receptor function Enhances GABA-A receptor function cf BDZ (sedation, relaxation, cf BDZ (sedation, relaxation, unsteadiness, amnesia)unsteadiness, amnesia)

• High doses mimics barbiturate effect High doses mimics barbiturate effect (locks open the channel, coma, (locks open the channel, coma, respiratory depression)respiratory depression)

And more…And more…

• Alcohol blocks glutamate NMDA-type Alcohol blocks glutamate NMDA-type receptors causing decreased receptors causing decreased excitation, sedation, amnesia, coma excitation, sedation, amnesia, coma and deathand death

• Chronic use, NMDA receptors Chronic use, NMDA receptors increase in number creating a increase in number creating a hyperexcitable withdrawal state. hyperexcitable withdrawal state. Acamprosate may reduce thisAcamprosate may reduce this

Alcohol withdrawalAlcohol withdrawal

• Compensatory glutamate receptor Compensatory glutamate receptor up-regulation with loss of magnesium up-regulation with loss of magnesium leading to excess brain stimulationleading to excess brain stimulation

• Long term potentiation in the Long term potentiation in the hippocampus is attenuated by hippocampus is attenuated by alcoholalcohol

AcamprosateAcamprosate

• Withdrawal increases in severity over Withdrawal increases in severity over time. Repeated withdrawal leads to time. Repeated withdrawal leads to greater glutamate levels and greater glutamate levels and increased mortality. Blocked by increased mortality. Blocked by acamprosateacamprosate

• Dahchour and De WitteDahchour and De Witte

Alcohol and aminesAlcohol and amines

• Alcohol, as opiates, stimulants and Alcohol, as opiates, stimulants and cannabis release dopamine in brain, ? A cannabis release dopamine in brain, ? A common pleasure circuitcommon pleasure circuit

• Low 5HT function leads to alcohol abuse Low 5HT function leads to alcohol abuse and chronic use decreases 5HT, SSRIs and chronic use decreases 5HT, SSRIs may reverse this (middle-aged women)may reverse this (middle-aged women)

• Chronic alcohol damages brain Chronic alcohol damages brain noradrenaline system, leading to noradrenaline system, leading to dementiadementia

Alcohol and endorphinsAlcohol and endorphins

• Brain endorphins system is main site Brain endorphins system is main site of action of heroin and other opiates. of action of heroin and other opiates. Alcohol releases endorphins this may Alcohol releases endorphins this may explain therapeutic effect of explain therapeutic effect of naltrexone to reduce relapse and naltrexone to reduce relapse and effect in Sinclair methodeffect in Sinclair method

It only takes me one It only takes me one

drink to get me drunk.drink to get me drunk.

The trouble is, I can’tThe trouble is, I can’t

remember if it’s the remember if it’s the

thirteenth or fourteenth!thirteenth or fourteenth!

Why drink alcohol?Why drink alcohol?

• Positive reward or reinforcement: Positive reward or reinforcement: pleasure. Escapism, euphoria, rushpleasure. Escapism, euphoria, rush

• Negative reinforcement: feel normal, Negative reinforcement: feel normal, anxiolytic, overcome withdrawalanxiolytic, overcome withdrawal

• Urge compulsion: cannot control useUrge compulsion: cannot control use

Alcohol alters perception of Alcohol alters perception of self leading to decreased social self leading to decreased social anxietyanxiety

Alcohol and its withdrawal Alcohol and its withdrawal drives motivationdrives motivation

• I would kill everyone in this room for I would kill everyone in this room for a drop of sweet beera drop of sweet beer

Blood alcoholBlood alcohol

Detects recent drinking only,Detects recent drinking only, ethanol metabolised at ethanol metabolised at 10g/hour10g/hourBreath levels correlate Breath levels correlate closely with bloodclosely with bloodIn a person smelling of In a person smelling of alcohol BAC can confirm alcohol BAC can confirm recent drinking, suggest recent drinking, suggest tolerance if high BAC tolerance if high BAC low impairmentlow impairmentUrine alcohol longer Urine alcohol longer window of detectionwindow of detection

GGT GGT (gammaglutamyltransferase)(gammaglutamyltransferase)

• Most sensitive blood test that is widely Most sensitive blood test that is widely available but only positive in 30% of available but only positive in 30% of heavy drinkers in communityheavy drinkers in community

• Alcohol is the commonest cause of Alcohol is the commonest cause of elevation but up to 50% GGT elevation but up to 50% GGT elevations for other reasons eg elevations for other reasons eg obesity, medicationsobesity, medications

• Half life 2 weeksHalf life 2 weeks• Prognostic value, tool in monitoringPrognostic value, tool in monitoring

Other markersOther markers

• Aminotransferases AST:ALT Aminotransferases AST:ALT ›1.5 ›1.5 suggests alcoholsuggests alcohol

• MCV: slow to return to normal, T1/2 MCV: slow to return to normal, T1/2 60days, non-specific eg nutritional, 60days, non-specific eg nutritional, drugs, liver diseasedrugs, liver disease

Alcohol:management of Alcohol:management of withdrawal and detoxificationwithdrawal and detoxification

• Where and when to detoxify?Where and when to detoxify?

• What are the medical risks?What are the medical risks?

• What setting is appropriate?What setting is appropriate?

• What does the service user want What does the service user want from detox?from detox?

• How to integrate into the bigger How to integrate into the bigger treatment picture?treatment picture?

Treatment regimens:alcohol Treatment regimens:alcohol detoxdetox

• Benzodiazepines are efficacious in Benzodiazepines are efficacious in reducing signs and symptoms of reducing signs and symptoms of withdrawal and are recommended as withdrawal and are recommended as the treatment of choicethe treatment of choice

• No particular one except lorazepam No particular one except lorazepam or oxazepam in liver failureor oxazepam in liver failure

• Reducing regimen, front loading, Reducing regimen, front loading, symptom triggeredsymptom triggered

Surprise!Surprise!

• Carbamazepine has been shown to Carbamazepine has been shown to be efficacious and can be chosen as be efficacious and can be chosen as an alternative to benzodiazepinesan alternative to benzodiazepines

• Chlormethiazole is reserved for Chlormethiazole is reserved for inpatient settings only after due inpatient settings only after due consideration, risk of respiratory consideration, risk of respiratory depression with alcoholdepression with alcohol

SeizuresSeizures

• Benzodiazepines, particularly diazepam Benzodiazepines, particularly diazepam reduces de novo seizures and are reduces de novo seizures and are recommended for the treatment of recommended for the treatment of withdrawalwithdrawal

• No advantage in anticonvulsants and No advantage in anticonvulsants and benzodiazepines combinedbenzodiazepines combined

• To prevent a second seizure in same To prevent a second seizure in same withdrawal episode the evidence supports the withdrawal episode the evidence supports the use of lorazepam but does not support the use of lorazepam but does not support the use of phenytoinuse of phenytoin

DeliriumDelirium

Benzodiazepines, Benzodiazepines,

particularly those with particularly those with

longer half life preventlonger half life prevent

delirium and are delirium and are

recommendedrecommended

A cautionary tale!A cautionary tale!

AcamprosateAcamprosate

• Increases abstinence rates by double Increases abstinence rates by double to to ≤ 40% after 3, 6 or 12 months≤ 40% after 3, 6 or 12 months

• Start during detoxification Start during detoxification NeuroprotectiveNeuroprotective

• If drink alcohol, less frequent and If drink alcohol, less frequent and lower amountlower amount

Other medicationsOther medications

• NaltrexoneNaltrexone

• BaclofenBaclofen

• DisulfiramDisulfiram

• Odansetron …..Odansetron …..

1930s, Blauwe (or Blue) 1930s, Blauwe (or Blue) Week Week

Blessed is he who does not Blessed is he who does not drink wine: Russia 1900drink wine: Russia 1900