Alcohol%20Abuse%20and%20Pharmacotherapy%20of%20Alcohol%20Dependence

1
Alcohol Abuse and Pharmacotherapy of Alcohol
Dependence

• PHM462H1
• Dr. Laurie Zawertailo
• Clinical Neuroscience Section

2
Class Objectives

• Review physiological and pharmacological aspects
  of alcohol use, abuse and dependence
• Review and discuss various treatments available
  for alcohol dependence
• Interview and discussion with a recovered
  alcoholic

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Definitions

• Drug misuse use of a drug for other than its
  prescribed indication
• Drug abuse drug use that deviates from accepted
  social patterns.
• Drug dependence biological adaptation to
  prolonged drug exposure characterized by a
  withdrawal syndrome upon abrupt discontinuation
• Drug addiction chronic relapsing disorder of
  compulsive uncontrollable drug use despite
  harmful consequences. An experience dependent
  change in behavior mediated by changes in neural
  systems.

4
Variables Affecting the Onset and Continuation of
Drug Abuse

• DRUG
• Pharmacological activity
• Availability
• Pharmacokinetics
• Cost
• Potency

• HOST
• Heredity
• Comorbidity
• Prior drug experience
• Propensity for risk taking

• ENVIRONMENT
• - social setting - community attitudes

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Potency Definition of a Standard Drink
Type Oz ml. g alcohol absolute alcohol
Absolute alcohol 0.6 17 13.6 100
Spirits 1.5 43 13.6 40
Wine 5 142 13.6 12
Fortified wine (Sherry) 4 85 13.6 18
Beer 12 341 13.6 5
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Pharmacology of Alcohol

• Absorption
• Distribution
• Metabolism
• Peripheral Effects
• GI
• CV
• CNS Effects
• Development in utero
• Neuroreceptor / neurotransmitter systems
• neuroanatomy

Pharmacokinetics
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Absorption and Distribution

• Alcohol is rapidly absorbed unaltered from the GI
  tract (mostly small intestine)
• Rate of absorption is affected by
• Type of beverage
• Stomach contents
• Absorbed into blood and transported directly to
  the liver

8
Metabolism

• metabolized by the liver at a constant rate of 10
  g/hr
• Heavy drinkers have an increased rate of
  metabolism

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Metabolism of Alcohol

• alcohol acetaldehyde
• dehydrogenase dehydrogenase
• Ethanol Acetaldehyde Acetate CO2
  H2O

10
Blood Alcohol Levels
11
Pharmacology

• Sedative / hypnotic or CNS depressant
• Rewarding effects involve multiple receptor
  systems and widespread neuroanatomical sites.
• Degree of depressant effect is dose-dependent.

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CNS Depressant Effects of Alcohol
coma
stupor
relaxation
death
anaesthesia
Mild sedation
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The Psychopharmacology of Reward
                                       
 
opioid pathway
alcohol opioids
GABA
alcohol/ benzodiazepines
alcohol/PCP
dopamine
glutamate  
amphetamine/ cocaine/ cannabis/nicotine
nicotine
serotonin
 
acetylcholine
hallucinogens
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Moderate Alcohol Consumption

• Current Guidelines
• No more than 2 standard drinks per day
• Weekly consumption limits
• Fourteen drinks/week for men
• Nine drinks/week for women

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When Drinking Becomes a Problem

• Problems relating to alcohol consumption exist
  along a continuum.
• Problem drinking is characterized by
• drinking above the guideline limits
• may have one or more problems associated with
  their drinking.
• Outnumbers alcohol dependence 4 to1
• Good response to brief interventions and
  strategies to reduce drinking.

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Alcohol Dependence

• Clinical syndrome characterized by
• Very heavy consumption
• Continued drinking despite severe social,
  psychiatric or physical consequences
• Pre-occupation with alcohol
• Neglect of responsibilities
• Difficulty moderating drinking
• Physical dependence

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Chronic Effects of Alcohol

• Tolerance
• Acute
• Rapid
• Chronic
• Physiological
• Behavioural
• Cross-tolerance
• Withdrawal

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Withdrawal

• Assessment (CIWA-Ar)
• Nonpharmacological
• - monitor signs and symptoms
• - reassurance, supportive nursing care
• - reality orientation
• - psychosocial treatment program
• Pharmacological

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CAGE

• The CAGE is a frequently used four-item screening
  test for alcohol problems and only consists of
  four questions. A yes response to two or more
  questions is considered to show evidence of
  alcohol problems.

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CAGE

• Need to Cut down on drinking?
• Annoyed by criticism about your drinking?
• Guilty about drinking?
• Need a morning drink or Eye-opener?

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• Pulse or heart rate, one minute ______ Blood
  pressure ____/_____
• NAUSEA AND VOMITING (Observation)
• 0 no nausea and no vomiting
• 1 mild nausea with no vomiting
• 4 intermittent nausea with dry heaves
• 7 constant nausea, frequent dry heaves and
  vomiting
• AGITATION (Observation)
• 0 normal activity
• 1 somewhat more than normal activity
• 4 moderately fidgety and restless
• 7 paces back and forth during most of the
  interview, or constantly thrashes about

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• TREMOR Arms extended and fingers spread apart
  (Observation)
• 0 no tremor
• 1 not visible, but can be felt fingertip to
  fingertip
• 2
• 3
• 4 moderate, with patients arms extended
• 5
• 6
• 7 severe, even with arms not extended

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• PAROXYSMAL SWEATS (Observation)
• 0 no sweat visible
• 1 barely perceptible sweating, palms moist
• 4 beads of sweat obvious on forehead
• 7 drenching sweats
• ANXIETY (Observation)
• 0 no anxiety, at ease
• 1 mildly anxious
• 4 moderately anxious, or guarded, so anxiety is
  inferred
• 7 equivalent to acute panic states as seen in
  severe delirium or acute schizophrenic reactions

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• AGITATION (Observation)
• 0 normal activity
• 1 somewhat more than normal activity
• 4 moderately fidgety and restless
• 7 paces back and forth during most of the
  interview, or constantly thrashes about

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• TACTILE DISTURBANCES
• 0 none
• 1 very mild itching, pins and needles, burning or
  numbness
• 2 mild itching, pins and needles, burning or
  numbness
• 3 moderate itching, pins and needles, burning or
  numbness
• 4 moderately severe hallucinations
• 5 severe hallucinations
• 6 extremely severe hallucinations
• 7 continuous hallucinations

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• AUDITORY DISTURBANCES
• 0 not present
• 1 very mild harshness or ability to frighten
• 2 mild harshness or ability to frighten
• 3 moderate harshness or ability to frighten
• 4 moderately severe hallucinations
• 5 severe hallucinations
• 6 extremely severe hallucinations
• 7 continuous hallucinations

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• VISUAL DISTURBANCES
• 0 not present
• 1 very mild sensitivity
• 2 mild sensitivity
• 3 moderate sensitivity
• 4 moderately severe hallucinations
• 5 severe hallucinations
• 6 extremely severe hallucinations
• 7 continuous hallucinations

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• HEADACHE, FULLNESS IN HEAD
• 0 not present
• 1 very mild
• 2 mild
• 3 moderate
• 4 moderately severe
• 5 severe
• 6 very severe
• 7 extremely severe

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Clinical Institute Withdrawal Assessment for
Alcohol Scale (CIWA-Ar)

• ORIENTATION AND CLOUDING OF SENSORIUM
• - Ask What day is this? Where are you? Who am
  I?
• 0 oriented and can do serial additions
• 1 cannot do serial additions or is uncertain
  about dates
• 2 disoriented for date by no more than 2 calendar
  dates
• 3 disoriented for date by more than 2 calendar
  dates
• 4 disoriented for place and/or person

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Diazepam Loading Protocol for Alcohol Withdrawal

• Basic Protocol
• Diazepam 20mg po q1-2 h until symptoms abate
• Observe for 2-4 hours after last dose
• Take-home medication is generally not required
• Thiamine 100mg i.m., then 100mg po for 3 days
• Do not give glucose before thiamine (may
  precipitate Wernickes encephalopathy).

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Alcoholic Liver Disease

• Fatty liver
• Alcoholic hepatitis
• Cirrhosis (10-20 of chronic alcoholics develop
  cirrhosis)

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Other Complications

• Medical (e.g., blackouts, Wernicke-Korsakoff
  syndrome, Pseudo-Parkinsonism)
• G.I. (e.g., alcoholic liver disease, alcoholic
  gastritis, alcoholic pancreatitis)
• Hematological (e.g., anemia)
• Endocrine (e.g., diabetes, sexual dysfunction)
• Cardiovascular (e.g., cardiomyopathy)

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Pharmacotherapy for Alcohol Dependence

• Disulfiram (Antabuse) not readily available
• Naltrexone (Revia )
• Acamprosate
• Ondansetron
• Topiramate
• Ibogaine

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Follow-up

• booster sessions are required for long-term
  maintenance of abstinence or moderation of
  alcohol use
• Self-help groups (e.g., Alcoholics Anonymous
  AA) are available in many communities