Transcript September 30, 2004

Alcohol Abuse and
Pharmacotherapy of Alcohol
Dependence
PHM462H1
Dr. Laurie Zawertailo
Clinical Neuroscience Section
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
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.
Variables Affecting the Onset and
Continuation of Drug Abuse
• DRUG
• HOST
– Pharmacological
activity
– Availability
– Pharmacokinetics
– Cost
– Potency
–
–
–
–
Heredity
Comorbidity
Prior drug experience
Propensity for risk
taking
• ENVIRONMENT
- social setting
- community attitudes
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
Pharmacology of Alcohol
•
•
•
•
Absorption
Distribution
Metabolism
Peripheral Effects
Pharmacokinetics
– GI
– CV
• CNS Effects
– Development in utero
– Neuroreceptor / neurotransmitter systems
– neuroanatomy
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
Metabolism
• metabolized by the liver at a constant rate of
10 g/hr
• Heavy drinkers have an increased rate of
metabolism
Metabolism of Alcohol
Ethanol
alcohol
acetaldehyde
dehydrogenase
dehydrogenase
Acetaldehyde
Acetate
CO2 +H2O
Blood Alcohol Levels
4
3.5
3
2.5
# drinks/hr
2
males
females
1.5
1
0.5
0
30
50
BAL (mg/100 ml)
80
Pharmacology
• Sedative / hypnotic or CNS depressant
– Rewarding effects involve multiple receptor
systems and widespread neuroanatomical sites.
– Degree of depressant effect is dose-dependent.
CNS Depressant Effects of
Alcohol
death
coma
Mild sedation
The Psychopharmacology of
Reward
opioid
pathway
alcohol
opioids
GABA
alcohol/
benzodiazepines
alcohol/PCP
dopamine
glutamate
nicotine
amphetamine/
cocaine/
cannabis/nicotine
serotonin
hallucinogens
acetylcholine
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
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.
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
Chronic Effects of Alcohol
• Tolerance
–
–
–
–
–
Acute
Rapid
Chronic
Physiological
Behavioural
• Cross-tolerance
• Withdrawal
Withdrawal
• Assessment (CIWA-Ar)
• Nonpharmacological
- monitor signs and symptoms
- reassurance, supportive nursing care
- reality orientation
- psychosocial treatment program
• Pharmacological
CAGE
• The CAGE is a frequently used fouritem 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.
CAGE
•
•
•
•
Need to Cut down on drinking?
Annoyed by criticism about your drinking?
Guilty about drinking?
Need a morning drink or Eye-opener?
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
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 patient’s arms extended
5
6
7 severe, even with arms not extended
Clinical Institute Withdrawal Assessment
for Alcohol Scale (CIWA-Ar)
0
1
4
7
PAROXYSMAL SWEATS (Observation)
no sweat visible
barely perceptible sweating, palms moist
beads of sweat obvious on forehead
drenching sweats
ANXIETY (Observation)
0
1
4
7
no anxiety, at ease
mildly anxious
moderately anxious, or guarded, so anxiety is inferred
equivalent to acute panic states as seen in severe delirium or acute
schizophrenic reactions
Clinical Institute Withdrawal Assessment
for Alcohol Scale (CIWA-Ar)
AGITATION (Observation)
0
1
4
7
normal activity
somewhat more than normal activity
moderately fidgety and restless
paces back and forth during most of the interview, or constantly
thrashes about
Clinical Institute Withdrawal Assessment
for Alcohol Scale (CIWA-Ar)
TACTILE DISTURBANCES
0
1
2
3
4
5
6
7
none
very mild itching, pins and needles, burning or numbness
mild itching, pins and needles, burning or numbness
moderate itching, pins and needles, burning or numbness
moderately severe hallucinations
severe hallucinations
extremely severe hallucinations
continuous hallucinations
Clinical Institute Withdrawal Assessment
for Alcohol Scale (CIWA-Ar)
AUDITORY DISTURBANCES
0
1
2
3
4
5
6
7
not present
very mild harshness or ability to frighten
mild harshness or ability to frighten
moderate harshness or ability to frighten
moderately severe hallucinations
severe hallucinations
extremely severe hallucinations
continuous hallucinations
Clinical Institute Withdrawal Assessment
for Alcohol Scale (CIWA-Ar)
VISUAL DISTURBANCES
0
1
2
3
4
5
6
7
not present
very mild sensitivity
mild sensitivity
moderate sensitivity
moderately severe hallucinations
severe hallucinations
extremely severe hallucinations
continuous hallucinations
Clinical Institute Withdrawal Assessment
for Alcohol Scale (CIWA-Ar)
HEADACHE, FULLNESS IN HEAD
0
1
2
3
4
5
6
7
not present
very mild
mild
moderate
moderately severe
severe
very severe
extremely severe
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
1
2
3
4
oriented and can do serial additions
cannot do serial additions or is uncertain about dates
disoriented for date by no more than 2 calendar dates
disoriented for date by more than 2 calendar dates
disoriented for place and/or person
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 Wernicke’s encephalopathy).
Alcoholic Liver Disease
• Fatty liver
• Alcoholic hepatitis
• Cirrhosis (10-20% of chronic alcoholics
develop cirrhosis)
Other Complications
• Medical (e.g., blackouts, WernickeKorsakoff 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)
Pharmacotherapy for Alcohol
Dependence
•
•
•
•
•
•
Disulfiram (Antabuse®) *not readily available
Naltrexone (Revia ®)
Acamprosate
Ondansetron
Topiramate
Ibogaine
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