Medical Review of Alcohol Abuse and Its Treatment
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Medical Review of Alcohol Abuse and Its Treatment
- 2. INTRODUCTION • The alcohol in alcoholic beverages is ethyl alcohol commonly known as ethanol. Available Beverages • Malted Liquors: Fermentation of Barley- Beers (3-6%). • Wines: Fermentation of Grapes, Apples etc. − No Distillation <15% − Fortified(port) – up to 22% − Champagne – 12-16% • Spirits – Rum, Whisky, Brandy, Gin & Vodka − 40-55% v/v − Standard 42.8% v/v
- 3. INTRODUCTION • Most people abstain or drink moderately placing them at low risk for alcohol use disorders. In general, Moderate Drinking is up to 2 drinks/day for men; up to 1 drink/day for women. • A ―binge‖ is a pattern of drinking alcohol that brings blood alcohol concentration (BAC) to 0.08 gm% or above. For the typical adult, this pattern corresponds to consuming 5 or more drinks (male) or 4 or more drinks (female) in about 2 hours. (USDA/HHS Dietary Guidelines, 2005)
- 5. PHARMACOKINETICS Absorption • The rate of absorption is extremely variable depends on several factors: • Volume, type and alcohol concentration of the beverage - less concentrated solutions are absorbed more slowly, however very concentrated solutions can inhibited gastric emptying. • Rate of drinking - the faster you drink, the faster the absorption. • Food - food has a major effect on alcohol absorption. The amount, timing and type of food all have an effect.
- 6. PHARMACOKINETICS Distribution • The distribution of alcohol is into total body water. • There are gender differences in body composition, with women having a lower proportion of total body water compared to men, even if they have the same weight. • 25% enters the bloodstream from the stomach, 75% from the intestine
- 7. PHARMACOKINETICS TCATCA ATP CO2 H2O NAD+ NADH NAD+ NADH NAD+ NADH NAD+ NADH electron transport electron transport Energy Yield: 7 Kcals/g CH3CH2OH (mM) ADHADH CH3CHO (μM) NAD+ NADHNAD+ NADH ALDH1ALDH1 CH3CHO ALDH2ALDH2 CH3COOH (mM) CH3COOH CH3COOH (mM) CYTOSOL NADH Shuttle NAD+ NADH Metabolism in Hepatocyte
- 8. PHARMACOKINETICS Elimination • 90% to 98% is removed in the liver, and the remainder is excreted by the kidneys, lungs, and skin.
- 9. PHARMACODYNAMYICS • Actions of alcohol : − Local Rubifacient and counterirritant to skin Irritant soft skin and mucus membrane Pain, − inflammation and necrosis − injection Astringent: Antiseptic (20 – 90%) 100% is dehydrating No action on spores
- 11. Signs: • Heavy recurrent alcohol use and/or intoxication • Other drug use or unexpected drug responses or interactions • Trauma • Absenteeism, presenters • Personal neglect
- 12. Symptoms: • Nausea, vomiting • Unexplained diaphoresis • Tachycardia • Seizures, hallucinations • Withdrawal, tremors, blackouts • Depression, anxiety, sleep disturbance • Erectile dysfunction in men
- 13. Initial Laboratory Evaluation of Suspected Alcoholic Patient • Blood alcohol (drug screen) • LFT’s (GGTP) • elevated MCV • elevated triglycerides
- 14. Medical Complications • Nervous system: Brain:encephalopathy, Wernicke-Korsakoff syndrome(thiamine deficiency), cerebellar degeneration, central pontine myelinolysis, dementia, Neuritis
- 15. Medical Complications • GI tract/Liver: Fatty liver, hepatitis, cirrhosis, esophagitis, gastritis pancreatitis, cancers
- 16. Medical Complications • Nutrition: Deficiencies of Vitamins: Folate, thiamine, pyridoxine, niacin, riboflavin Minerals: Magnesium, zinc, calcium Protein • Metabolites and electrolytes: Hypoglycemia, ketoacidosis, hyperlipidemia, hyperuricemia, hypomagnesemia, hypophosphatemia
- 17. Medical Complications • Endocrine: Pseudo- Cushing's syndrome, testicular atrophy, amenorrhea, DM, Osteopenia/osteoporosis • Cancers (i.e., breast, Prostate) • Traumatic injury • Fetal alcohol syndrome • Impotency
- 18. DSM-IV Criteria
- 19. TREAMENT PRINCIPLES • Combining Medications and Behavioral Interventions (COMBINE) -Benefit medications/counseling combined • Medications usually prescribed for 6 to 12 months • Twice weekly brief counseling efficacious
- 20. Medications Used
- 21. DISULFIRAM • It has been used to treat alcohol dependence for more than 50 years. Disulfiram is an aversive agent that inhibits aldehyde dehydrogenase and prevents the metabolism of alcohol's primary metabolite, acetaldehyde. • Drinking alcohol while taking disulfiram results in the accumulation of acetaldehyde in the blood, causing unpleasant effects such as sweating, headache, dyspnea, lowered blood pressure, flushing, sympathetic over activity, palpitations, nausea, and vomiting. The experience of these symptoms associated with drinking is intended to discourage further alcohol consumption • It is initially dosed at 500 mg/day for one to two weeks, followed by an average maintenance dose of 250 mg/day with a range from 125-500 mg based on the severity of adverse effects. The medication should not be used by patients with current alcohol intoxication.
- 22. NALTREXONE • Naltrexone exerts its principal pharmacological effects through blockade of the mu-opioid receptor. Endogenous opioids are involved in modulating the expression of alcohol's reinforcing effects. Naltrexone also modifies the hypothalamic-pituitary-adrenal axis to suppress ethanol consumption. • If opioids are required to treat pain, naltrexone should be discontinued. Naltrexone is contraindicated in acute hepatitis or liver failure. • Oral naltrexone — The usual dose of naltrexone is 50 mg/day, but some trials have used up to 100 mg/day
- 23. ACAMPROSATE • It’s principal anti-drinking neurochemical effect has been attributed to the modulation of glutamate neurotransmission at metabotropic-5 glutamate receptors • The usual dose is 666 mg three times daily. Lower doses should be considered for some patients, including those with renal impairment, body weight less than 60 kg, or a history of response to a lower dose.
- 24. TOPIRAMATE • It has not been approved by the US FDA for this indication. Topiramate has two principal mechanisms of action that may contribute to its anti-drinking effects: • Antagonizing alpha-amino-3-hydroxy-5-methylisoxazole-4- propionic acid receptors and kainate glutamate receptors . • Facilitating inhibitory GABA(A)-mediated currents at non- benzodiazepine sites on the GABA(A) receptor. • It should be titrated up gradually over several weeks. It is generally initiated at 50 mg/day and increased to a maximum dose of 150 mg twice daily.
- 25. OTHER MEDICATIONS • Ondansetron —a 5-HT3 receptor antagonist. • Selective serotonin reuptake inhibitors — A meta-analysis of seven trials found that selective serotonin reuptake inhibitors (SSRI) do not effectively treat alcohol dependence in patients who do not have a comorbid mental disorder. • Nalmefene — an opioid antagonist. • Baclofen —a GABA receptor agonist. • Combination Therapies
- 26. PSYCHOLOGICAL TREATMENT • Suspect the problem • Emphasis on the things that can be done. • Motivational interviewing • Alcoholics Anonymous 12 Steps Group • religious counseling • Career of Professional threat
- 27. ADAPTATIONS FOR THE OFFICE • Avoid placement in jobs where the alcoholic must be alone, e.g., as a traveling buyer or sales executive. • Use supervision but not surveillance. • Keep competition with others to a minimum. • Avoid positions that require quick decision-making on important matters (high-stress situations). In general, commitment to abstinence and avoidance of situations that might be conducive to drinking are most predictive of a good outcome.
- 28. 2nd Stage • Drug use and abuse • Crimes and violent behavior • Suicidal and Homicidal behavior • Child neglect and abuse • Birth Defect (Physical & Mental)
- 29. THANK YOU !
Editor's Notes
- Thus, if a woman and a man, who both have the same weight, consume the same amount of alcohol, the woman would achieve higher blood alcohol levels compared to the man.
- The major pathway for the metabolism of alcohol is found in the liver and involves the enzyme alcohol dehydrogenase (ADH). Alcohol is metabolized to acetaldehyde, a highly reactive and potentially toxic molecule. In most circumstances, acetaldehyde is rapidly metabolized by another enzyme, aldehyde dehydrogenase (ALDH) to acetate. Because of the rapid enzymatic conversion of acetaldehyde to acetate, the concentration of acetaldehyde in the cell is typically a thousand-fold lower than that of alcohol, and the eventual product of this pathway, acetate. Both alcohol and acetate are found at millimolar levels following drinking, while acetaldehyde is found at micromolar concentrations. [The legal intoxicating blood alcohol level in all states in the U.S. is 80 mg%, which is 17.4 mM. The normal baseline level for acetaldehyde in humans is 9 µM, or 40 µgram%. After alcohol ingestion, the acetaldehyde level in most individuals will increase to 20-30 µM, or 90 – 130 µgram%. Metabolism of a dose of alcohol achieving a blood alcohol concentration of 80 mg% may result in elevation of tissue acetate levels by 100 mg%.] When the level of acetaldehyde increases, an individual may experience very dysphoric feelings and the potential for toxic reactions with various cellular components increases.
- http://pubs.niaaa.nih.gov/publications/10report/chap08b.pdfThe most important consideration for the clinician is to Suspect the problem early and take a nonjudgmental attitude, although this does not mean a passive one. The problem of denial must be faced, preferably with significant family members at the first meeting. This means dealing from the beginning with any enabling behavior of the spouse or other significant people. Enabling behavior allows the alcoholic to avoid facing the consequences of his or her behavior.There must be an emphasis on the things that can be done. This approach emphasizes the fact that the clinician cares and strikes a positive and hopeful note early in treatment.Valuable time should not be wasted trying to find out why the patient drinks; come to grips early with the immediate problem of how to stop the drinking.Although total abstinence should be the ultimate goal, a harm reduction model indicates that gradual progress toward abstinence can be a useful treatment stratagem.Motivational interviewing, a model of counseling that addresses both the patient’s contradiction and motivation for change, may contribute to reduced consumption over time.B. SocialGet the patient into Alcoholics Anonymous and the spouse into Al-Anon.Success is usually proportionate to the utilization of Alcoholics Anonymous, religious counseling, and other resources.The patient should be seen frequently for short periods and charged an appropriate fee.Do not underestimate the importance of religion, particularly since the alcoholic is often a dependent person who needs a great deal of support. Early enlistment of the help of a concerned religious adviser can often provide the turning point for a personal conversion to sobriety.One of the most important considerations is the patient’s job—fear of losing a job is one of the most powerful motivations for giving up drink.In the latter case, some specific recommendations to employers can be offered: