Transcript Alcohol-Pharmacology of Detox and Beyond

Alcohol-Pharmacology
of Detox and Beyond
D
Raquin Cherian
Specialty Registrar(ST4)
MRCPsych Course Cambridge
16th October 2012
Aims of Teaching
 Pharmacological treatment in alcoholism and brief
pathophysiology
 Different medications used in detox and indications
 Different treatment regimes used
 Medicines used to treat complications of detox
 Medicines that help maintain abstinence from alcohol
and how do they differ
Importance of Pharmacological
Rx of withdrawal
 Withdrawal is a dangerous time for the brain
 Complications including delirium tremens, seizures,
even death if untreated
 Appears to have long lasting consequences for those
who go through even medicated detox.
 Adequate pharmacological treatment of alcohol
withdrawal critical in preventing and treating
complications during detox.
Action of Alcohol in the Brain
Inhibitory/Excitatory imbalance
GABA
 Potentiates GABA (inhibitory) neurotransmitter at the GABA-A receptor
(Explain why Alcohol is an effective anxiolytic!)
 Brain downregulates GABA receptors and change their response to GABA.
 In withdrawal, the brain is in a hypoGABAergic state, ( explains the profound
anxiety and propensity for seizures during alcohol withdrawal )

When we treat alcohol withdrawal with benzodiazepines we are potentiating
the action of GABA – although BDs attach to a different receptor site on the
GABA chloride channel – the effect is similar.

We use long-acting benzos with active metabolites so the decrease in GABA
potentiation is gradual and the brain can adapt. driest martini!
Inhibitory/Excitatory imbalance
NMDA
 Alcohol antagonises NMDA transmission (glutamatergic) ie.
Excitatory.
 Chronic alcohol intake: increase in NMDA receptors
 withdrawal: hyperglutamatergic state . NMDA transmission
in excess is neurotoxic acting via Calcium.
 Acamprosate : neuroprotective by blocking some NMDA
transmission and rise in glutamate during withdrawal.
Similarly, anticonvulsants such as carbamazepine act via
inhibiting calcium influx, thus mitigating excitatory excess.
CBZ also binds to certain subtypes of the GABA-A receptor.
Alcohol’s effects on endogenous opioids
and the mesolimbic dopamine system
Alcohol Withdrawal
Symptoms of Alcohol Withdrawal
Time of appearance after last drink
Minor sx:insomnia,tremor,mild
anxiety,GI sx;headache,perspiration
and Palpitation
6-12 Hours
Visual,auditory,Tactile hallucinations
12-24 hours(usually resolved within
48 hours)
Withdrawal seizures
24-48 hours(Has been reported early
as 2 hours)
Delerium Tremens
48-72 hours(peaks at 5 days after
cessation)
Aims of Detox medications
 Manage withdrawal
 Relapse prevention and maintain abstinence
 Prevention of complication of withdrawal e.g WE
 Reduction of harm associated with alcohol use
Indications for inpatient detox
 H/o severe withdrawal sx
 H/o seizures/DTs
 Concommitent serious medical/psychiatric conditions
 Multiple past detoxifications(kindling))
 Recent high levels of alcohol consumption
 Lack of reliable social support
 Pregnancy
 Older adults
Kindling
Predictors of severe
/complicated withdrawal
 Recent high amounts of alcohol consumption
 Hx of severe withdrawal
 Hx of seizures or DTs
 Concomitant use of other psychoactive drugs
 Poor physical health
 Coexisting psychiatric disorder
 elderly
Detox Pharmacology
 Drugs that can correct the excitatory/inhibitory
imbalance: Benzos, Carbamazepine etc
 Symptomatic treatment: Metochlopramide, Loperamide,
Sedatives.
 Vitamin Supplements: Thiamine, Vitamin B co forte
 Correct electrolyte imbalance: Mg, PO4, K deficiency
 Treatment of complications
Medicines used for detox
 Benzodiazepines
 Carbamazepine : equally efficacious but not commonly
used in UK
 Clormethiazole
reserved for inpatient settings
Use only after due consideration of its safety
Which Benzos and when
 Diazepam: Immediate onset and long acting-if risk of
seizures high, co-morbid benzo dependence
 Oxazepam: Short acting and delayed onset of actionsevere liver damage
 Lorazepam: intermediate onset of action, short actingseizures and deranged LFT
 Chlordiazepoxide: intermediate onset of action and
long acting, less abuse potential. All other detox
scenarios
Treatment Regimes
 Fixed Dose Regime (Refer to hand out)
Routine use
Used in community and inpatient setting
 Symptom triggered (Refer to hand out)
Only with adequate monitoring (inpatient)
Use a withdrawal rating scale e.g CIWA ar
 Front Loading with Diazepam
Treatment of complications
Seizures
 Benzodiazepines, particularly diazepam, prevent de
novo seizures
 Lorazepam effective in preventing a second seizure
in the same withdrawal episode
 Anticonvulsants : equally as efficacious but no
advantage when combined
Treatment of complications
Delirium
 Benzodiazepines:Diazepam and Chlordiazepoxide(long
half life) prevent Delerium and should be used to treat
 Haloperidol for hallucination
 Correct electrolyte imbalance
 Supportive management
Treatment of complications
WKS
 Thiamine replacement critical
 Parenteral Route for treatment of WE and those at risk
a. > 15SAU/ day for a month or more
b. recent weight loss or vomiting or diarrhoea
c. malnutrition
d. peripheral neuropathy
e. chronic ill- health.
Thiamine-Dose and Route
 Low risk of WE: Oral thiamine >300 mg/day ,during
detoxification.
 Prevention of WE : 250 mg thiamine (one pair of
ampoules Pabrinex®) i.m/ i.v. once daily for 3–5 days
or until no further improvement is seen
 Treatment of WE : Thiamine >500 mg should be given
i.m/i.v for 3–5 days (i.e. two pairs of ampoules
Pabrinex® three times a day for 3-5 days), followed by
one pair of ampoules once daily for a further 3–5 days
depending on response
Abstinence aiding
medications- Acamprosate
 Glutamatergic NMDA antagonist (alcohol dependence and withdrawal
are hyperglutamatergic )-potentially neuroprotective
 ?Anticraving. Anxiolytic ,insomnia
 Should be started during detoxification (BAP). prescribe 6months

Moderately effective in increasing abstinence after detoxification
 Some evidence : also reduce ‘heavy drinking’ after relapse
 Well tolerated.
 Good safety profile even with physical comorbidity
 Use with caution / contraindicated in severe liver and renal
impairment .
Abstinence aiding medication:
Naltrexone
 Non-selective opioid antagonist.
 Reduces alcohol’s rewarding effects and motivation to drink
or ‘craving’ (mu opioid receptor-Dopaminergic activity)
 Impulse control: pathological gambling esp those with a
family history of alcoholism.
 Comorbid cocaine/alcohol dependence reduced cocaine
and alcohol use in men but not women.
 Start soon after detox. Prescribe for 6 months
 Not licensed in the UK but can be used and NICE
recommended
Acamprosate or Naltrexone
 No overall superiority of Naltrexone over Acamprosate
that would apply to the UK patient population. (BAP)
 Acamprosate more effective in preventing a lapse
 Naltrexone prevents better at a lapse from becoming a
relapse.
Abstinence aiding medication
Disulfiram(antabuse)
 blocks aldehyde dehydrogenase- accumulation of acetaldehyde if
alcohol is consumed- nausea, flushing, and palpitations-deters
people from drinking. “deterrent”
 blocks dopamine-b-hydroxylase - increase dopamine and reduce
noradrenaline
 Cautiuos approach: alcohol-antabuse reaction, lasts upto 7 days
after last dose. Pt should be warned.
 should be tried after acamprosate or naltrexone, or where the
patient indicates a preference (NICE).
 Started after alcohol free for at least 24 hr. No guidance on max
duration of prescribing
 Witnessing intake improves compliance - effectiveness
Other Drugs
 Baclofen
 Topiramate
 Pregabalin
 SSRIs: In those without comorbid depression, their use
cannot be recommended (BAP)
Abstinence Medications
Conclusions
 Relapse prevention medication to be considered for everyone who is
alcohol dependent wanting to be abstinent .
 Acamprosate : improve abstinence rates . continued if the person
starts drinking as it reduces alcohol consumption
 Naltrexone :prevents lapse becoming a relapse, better choice if
someone is ‘sampling’ alcohol regularly but wishes to be abstinent.
 Disulfiram effective if intake is witnessed. treatment option for
patients who intend to maintain abstinence, and for whom there are
no contraindications .
 Baclofen :intents abstinence, has high levels of anxiety and not
benefited from/ unable to take acamprosate, naltrexone or disulfiram .
 SSRIs should be avoided, or used with caution in type 2 alcoholism.
Multiple choice questions:1
 Where depression and anxiety are prominent predetoxification features, they:
 should be treated with standard pharmacotherapy
 should receive an ICD diagnosis immediately
 commonly disappear three weeks post-detoxification
 indicate the need for in-patient detoxification
 predict drop-out from detoxification.
MCQ:2
 The following items are part of the Windsor Clinic
Alcohol Withdrawal Assessment Scale that predict
serious withdrawal problems:
 quality of contact
 tremulousness
 thought disturbance
 seizures
 pulse rate.
MCQ:3
 Severe withdrawal is often associated with the
following medical complications:
 Wernicke's encephalopathy
 magnesium deficiency
 hyperglycaemia
 hypotension
 polydrug use.
MCQ:4
 Preparation for detoxification should include:
 checking the patient is at the determination or action
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

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stage of change
planning the post-detoxification week
identifying a support person
agreeing the detoxification regimen
making an after-care appointment.
MCQ:5
 The following can be considered as suitable first-line
drugs for detoxification:
 carbamazepine
 chlordiazepoxide
 clomethiazole
 chlorpromazine
 clonidine.
What have we learnt?
 Importance of detox
 Brief pathophysiology of alcoholism
 Setting,regimes and medication used for detox
 Medicines used to support Relapse prevention
 Some useful resources: NICE guidelines;BAP
Guidelines;management of Alcohol detoxification-APT
2000: Duncan Raistrick
END