Alcohol Abuse and Pharmacotherapy of Alcohol DependencePHM462H1Dr. Laurie ZawertailoClinical Neuroscience Section

Class ObjectivesReview physiological and pharmacological aspects of alcohol use, abuse and dependenceReview and discuss various treatments available for alcohol dependenceInterview and discussion with a recovered alcoholic

DefinitionsDrug misuse: use of a drug for other than its prescribed indicationDrug abuse: drug use that deviates from accepted social patterns.Drug dependence: biological adaptation to prolonged drug exposure characterized by a withdrawal syndrome upon abrupt discontinuationDrug 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 AbuseDRUGPharmacological activityAvailabilityPharmacokineticsCostPotency

HOSTHeredityComorbidityPrior drug experiencePropensity for risk taking ENVIRONMENT- social setting- community attitudes

Potency: Definition of a Standard Drink

Pharmacology of AlcoholAbsorptionDistributionMetabolismPeripheral EffectsGICVCNS EffectsDevelopment in uteroNeuroreceptor / neurotransmitter systemsneuroanatomy

Pharmacokinetics

Absorption and DistributionAlcohol is rapidly absorbed unaltered from the GI tract (mostly small intestine) Rate of absorption is affected by Type of beverageStomach contentsAbsorbed into blood and transported directly to the liver

Metabolismmetabolized by the liver at a constant rate of 10 g/hrHeavy drinkers have an increased rate of metabolism

Metabolism of Alcohol alcohol acetaldehyde dehydrogenase dehydrogenaseEthanol Acetaldehyde Acetate CO2 +H2O

Blood Alcohol Levels

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

CNS Depressant Effects of AlcoholrelaxationMild sedationstuporanaesthesiacomadeath

The Psychopharmacology of Reward

glutamate

dopamine

GABA

alcohol/ benzodiazepines

amphetamine/cocaine/cannabis/nicotine

serotonin

nicotine

acetylcholine

opioidpathway

alcohol/PCP

hallucinogens

alcoholopioids

Moderate Alcohol ConsumptionCurrent GuidelinesNo more than 2 standard drinks per dayWeekly consumption limitsFourteen drinks/week for menNine drinks/week for women

When Drinking Becomes a ProblemProblems 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 to1Good response to brief interventions and strategies to reduce drinking.

Alcohol DependenceClinical syndrome characterized by:Very heavy consumptionContinued drinking despite severe social, psychiatric or physical consequencesPre-occupation with alcoholNeglect of responsibilitiesDifficulty moderating drinkingPhysical dependence

Chronic Effects of AlcoholToleranceAcuteRapidChronicPhysiologicalBehaviouralCross-toleranceWithdrawal

WithdrawalAssessment (CIWA-Ar)Nonpharmacological - monitor signs and symptoms - reassurance, supportive nursing care - reality orientation - psychosocial treatment programPharmacological

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.

CAGENeed 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 vomiting1 mild nausea with no vomiting4 intermittent nausea with dry heaves7 constant nausea, frequent dry heaves and vomiting

AGITATION (Observation)0normal activity1 somewhat more than normal activity4moderately fidgety and restless7paces back and forth during most of the interview, or constantly thrashes about

Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar)TREMORArms extended and fingers spread apart (Observation)0no tremor1 not visible, but can be felt fingertip to fingertip234moderate, with patients arms extended567severe, even with arms not extended

Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar)PAROXYSMAL SWEATS (Observation)0no sweat visible1 barely perceptible sweating, palms moist4beads of sweat obvious on forehead7drenching sweats

ANXIETY (Observation)0no anxiety, at ease1 mildly anxious4moderately anxious, or guarded, so anxiety is inferred7equivalent to acute panic states as seen in severe delirium or acute schizophrenic reactions

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

0normal activity1 somewhat more than normal activity4moderately fidgety and restless7paces back and forth during most of the interview, or constantly thrashes about

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

0none1very mild itching, pins and needles, burning or numbness2mild itching, pins and needles, burning or numbness3moderate itching, pins and needles, burning or numbness4moderately severe hallucinations5severe hallucinations6extremely severe hallucinations7continuous hallucinations

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

0not present1very mild harshness or ability to frighten2mild harshness or ability to frighten3moderate harshness or ability to frighten 4moderately severe hallucinations5severe hallucinations6extremely severe hallucinations7continuous hallucinations

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

0not present1very mild sensitivity2mild sensitivity3moderate sensitivity4moderately severe hallucinations5severe hallucinations6extremely severe hallucinations7continuous hallucinations

Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar)HEADACHE, FULLNESS IN HEAD

0not present1very mild2mild3moderate4moderately severe5severe6very severe7extremely 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?

0oriented and can do serial additions1cannot do serial additions or is uncertain about dates2disoriented for date by no more than 2 calendar dates3disoriented for date by more than 2 calendar dates4disoriented for place and/or person

Diazepam Loading Protocol for Alcohol WithdrawalBasic Protocol:Diazepam 20mg po q1-2 h until symptoms abateObserve for 2-4 hours after last doseTake-home medication is generally not requiredThiamine 100mg i.m., then 100mg po for 3 daysDo not give glucose before thiamine (may precipitate Wernickes encephalopathy).

Alcoholic Liver DiseaseFatty liverAlcoholic hepatitisCirrhosis (10-20% of chronic alcoholics develop cirrhosis)

Other ComplicationsMedical (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)

Pharmacotherapy for Alcohol DependenceDisulfiram (Antabuse) *not readily availableNaltrexone (Revia )AcamprosateOndansetronTopiramateIbogaine

Follow-upbooster sessions are required for long-term maintenance of abstinence or moderation of alcohol useSelf-help groups (e.g., Alcoholics Anonymous [AA]) are available in many communities