Alcohol Abuse and Pharmacotherapy of Alcohol Dependence

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

3. 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. DRUG Pharmacological activity Availability Pharmacokinetics Cost Potency HOST Heredity Comorbidity Prior drug experience Propensity for risk taking Variables Affecting the Onset and Continuation of Drug Abuse • ENVIRONMENT • - social setting - community attitudes

5. Potency: Definition of a Standard Drink

6. Pharmacology of Alcohol • Absorption • Distribution • Metabolism • Peripheral Effects • GI • CV • CNS Effects • Development in utero • Neuroreceptor / neurotransmitter systems • neuroanatomy Pharmacokinetics

7. 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

9. Metabolism of Alcohol alcohol acetaldehyde dehydrogenase dehydrogenase EthanolAcetaldehyde 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.

12. CNS Depressant Effects of Alcohol coma stupor relaxation death anaesthesia Mild sedation

13. The Psychopharmacology of Reward opioid pathway alcohol opioids GABA alcohol/ benzodiazepines alcohol/PCP dopamine glutamate amphetamine/ cocaine/ cannabis/nicotine nicotine serotonin acetylcholine hallucinogens

14. 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

15. 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.

16. 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

17. Chronic Effects of Alcohol • Tolerance • Acute • Rapid • Chronic • Physiological • Behavioural • Cross-tolerance • Withdrawal

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

19. 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.

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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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).

31. Alcoholic Liver Disease • Fatty liver • Alcoholic hepatitis • Cirrhosis (10-20% of chronic alcoholics develop cirrhosis)

32. 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)

33. Pharmacotherapy for Alcohol Dependence • Disulfiram (Antabuse®) *not readily available • Naltrexone (Revia ®) • Acamprosate • Ondansetron • Topiramate • Ibogaine

34. 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