ALCOHOL ABUSEMedical Review

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

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)

BODY ALCOHOL CONCENTERATIONS

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.

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

PHARMACOKINETICS

TCATCA

ATP

CO2

H2O

NAD+NADH

NAD+NADH

NAD+

NADH

NAD+

NADH

electron transportelectron transport

Energy Yield: 7 Kcals/g

CH3CH2OH(mM)

ADHADH

CH3CHO(μM)

NAD+ NADHNAD+ NADH

ALDH1ALDH1

CH3CHOALDH2ALDH2

CH3COOH(mM)

CH3COOH

CH3COOH(mM)

CYTOSOL

NADH Shuttle

NAD+ NADH

Metabolism in Hepatocyte

PHARMACOKINETICS

Elimination

• 90% to 98% is removed in the liver, and the remainder is excreted by the kidneys, lungs, and skin.

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

Blood Ethanol Levels

Signs:

• Heavy recurrent alcohol use and/or intoxication• Other drug use or unexpected drug responses or

interactions • Trauma• Absenteeism, presenters• Personal neglect

Symptoms:

• Nausea, vomiting • Unexplained diaphoresis • Tachycardia• Seizures, hallucinations • Withdrawal, tremors, blackouts• Depression, anxiety, sleep disturbance• Erectile dysfunction in men

Initial Laboratory Evaluation of Suspected Alcoholic Patient

• Blood alcohol (drug screen)• LFT’s (GGTP)• elevated MCV• elevated triglycerides

Medical Complications

• Nervous system: Brain:encephalopathy, Wernicke-Korsakoff syndrome(thiamine deficiency), cerebellar degeneration, central pontine myelinolysis, dementia, Neuritis

Medical Complications

• GI tract/Liver: Fatty liver, hepatitis, cirrhosis, esophagitis, gastritispancreatitis, cancers

Medical Complications

• Nutrition: Deficiencies of Vitamins: Folate, thiamine, pyridoxine, niacin, riboflavinMinerals: Magnesium, zinc, calciumProtein

• Metabolites and electrolytes: Hypoglycemia, ketoacidosis, hyperlipidemia, hyperuricemia, hypomagnesemia, hypophosphatemia

Medical Complications

• Endocrine: Pseudo-Cushing's syndrome, testicular atrophy, amenorrhea, DM, Osteopenia/osteoporosis

• Cancers (i.e., breast, Prostate)

• Traumatic injury

• Fetal alcohol syndrome

• Impotency

DSM-IV Criteria

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

Medications Used

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. 

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 

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.

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.

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

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

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.

2nd Stage

• Drug use and abuse• Crimes and violent behavior• Suicidal and Homicidal behavior• Child neglect and abuse• Birth Defect (Physical & Mental)

THANK YOU !