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AlcoholismAlcoholismAlcoholismAlcoholism

Winemaking Tradition Requiring

the Fermentatio

n of the Sugar in

Grapes with Yeast to

Form Alcohol

Engraving of ‘Gin Lane’ by

William Hogarth (1697-

1764) showing the popular opinion that the ‘lower

classes’ drank gin and got

drunk.

• In the 18 months since the US invaded Iraq, over 1,000 American military personnel have been killed. Make you think twice about a military career?

• Every academic year 1,400 American college students die from alcohol-related unintentional injuries, and another 500,000 are injured? Make you think twice about using alcohol? Or Going to college?

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What is Alcohol?

• Ethyl Alcohol (Grain Alcohol)– Booze, hooch, juice, brew– Used in medicine and beverages– Colorless, mixes with water, solvent– Product of sugar fermentation by yeast– Many cough & mouthwash contain up to

25% or 50 proof with antihistamines!• NyQuil (25% etoh) Listerine (26.9%)• Formula 44D (20% etoh) Cepacol (14.5%)

Other Alcohols

• Methyl alcohol (wood alcohol or antifreeze)

• Isopropyl alcohol (rubbing alcohol)

• Butyl alcohol• Amyl alcohol• Very toxic when taken orally!

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Ethyl Alcohols’ Local Effect

• Denatures proteins by precipitation and dehydration

• Basis for use topically:– Germicide– Irritant– Astringent

• Injection– Pain, sloughing of tissues, nerve

damage and anesthesia

Ethyl Alcohol’s Overview Effect

• CNS depressant – Appears to be a stimulant from the

depression of the higher faculties of the brain and represents the loss of inhibitions

– Decreases mental & physical ability– Given amounts affect individuals differently

• Excess consumption will cause bodily damage– Has calories

• Time is the way to sober up

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Systemic EffectsCNS

• Interferes with nerve transmission at synapses

• Progressive• Variable

– Size– Tolerance– Outside stimuli

CNS Progressive EffectsBAC (mg%)

Changes Brain Impaired

10-50 Relax, sense of wellness, loss ofinhibition

CerebralCortex

AlertnessJudgement

60-100 Pleasure, numb feelings, sleep

Cc and forebrain

Fine coordinat,Visual tracking

110-200 Mood swing, sad anger, mania

Cc,fb, cerebellum

Reason, obnox,perceptions

210-300 Aggression, stupor, depress

Cc,fb,cere, brainstem

Slurred speech, blance, temp

310-400 Unconsci, coma, death poss

Cc,fb,cere,bs, entire brain

Lossbladder,dif breath, slowHR

410 + Death

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Central Nervous System

• Acute Brain Damage• Alcohol Induced Brain Damage• Chronic Brain Damage

– Atrophy– Dementia– Nutritional Deficit Damage– Encephalopathy

Alcohol Induced

Brain Damag

e

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CV GIT• Dilation blood

vessels– Heat loss– Increase Pulse– Lower BP

• Chronic Use– Cardiomyopathy– HTN, dysrhythmias– MI (J-curve)

• Stimulate GI acid– Dissolves mucosal

lining– Hemorrhagic lesions

• Chronic Use– Pancreatitis– Diabetes or reactive

hypoglycemia– Hepatic cellular

damage• Fibrosis & scarring• Cirrhosis & hepatitis

– Nutritional Deficit

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Renal Liver

• Increase urine due to increase fluid!

• Acts as a diuretic– Inhibits ADH

• Large chronic use– Renal damage

• Liver Failure– Leading cause is

alcoholism– Cirrhosis, Cancer– Alcoholic Hepatitis

• Liver Transplant– 10% on

recovering alcoholics

– Non renewable resource

Effect of Chronic EtOH on the LiverHealthy Fatty Cirrhotic

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Pharmacokinetics of Ethanol

• Administration and absorption– Oral & does not require digestion

• 80% absorption from upper intestine– Rate limiting factor is stomach emptying– Total absorption is unaffected by food

– Both water and fat soluble, distributes to every tissue• 90%+ access to all body compartments

OverviewMetabolism of Alcohol

• Alcohol is converted by alcohol dehydrogenase to acetaldehyde

• Acetaldehyde is converted by aldehyde dehydrogenase to acetic acid then to CO2 and water

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Metabolism and Excretion

• Liver Metabolism– 95% of alcohol is metabolized by alcohol

dehydrogenase enzyme and CYP450– 85% of that metabolism occurs in the

liver– Balance eliminated via lungs and

kidneys– All women, alcoholic or not, have 60%

less stomach alcohol dehydrogenase than men

– Women appear to be even more vulnerable than men to intoxication and chronic effects

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Pharmacodynamics

• Inhibits glutamate release and action at the receptors– Increase glutamate release during

withdrawal is excitotoxic

• Alcohol is a GABA & Dopamine agonist (stimulator!)– Result is super sized combo of DA

positive & GABA negative reinforcement

French Paradox?

• CV benefits from 1 glass of wine/day

• Disappear at equiv. 3 glasses/day

• Same benefits– 6 glasses grape

juice– Flavinoids not Etoh

• CV disease– Cumulative– Multiple factors– Prior to 1960s French diet lower in saturated fats than American diet

Selective Significant Drug Interactions with Alcohol

Substances Mechanism Possible Effect

Antihistamines, antidepressants, opioids, sed-hyp, antianxiety, antipsychotic drugs

Additive Enhanced CNS depressant effects

Disulfirammetronidazole

Accumulation of acetaldehyde

n/v/flushing, HA, sweating, inc HR hypotension,

ASANSAIDs

Additive GI bleeding

Fetal Alcohol Syndrome

• Teratogenic• Mental Retardation• Low Birth Weight• Neurological

Craniofacial MalformationsNormal Exposed to

Alcohol

Symptoms of Alcohol Dependence

• Job performance• Behavioral

– Blackouts– Depression– Insomnia– Disappearing– Frequent Bathroom breaks

• Sleeping a lot• Emotional flares• Slurred speech• Use of mints &

mouthwash

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Alcohol Withdrawal Symptoms

• Acute Infrequent Ingestion– Hangover

• HA, n/v, malaise

• Chronic Ingestion 48-72 hours into withdrawal

– Mental disturbances• Anxious, confusion• Nightmares, sweats• Hallucinations, fear

• Perception Distortions– Spinning, floor moves– Injury from falls

• Delirium Tremens (DTs)– Tachycardia.

Increased temperature

– Convulsions– Tonic-Clonic Activity– Tremors

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Avenues of TreatmentNon-Pharmacologic

• Life long disease– Motivated client– Complete abstinence

• Controlled Drinking?

– Behavioral and psychosocial support• AA mainstay of treatment

– Concurrent diseases (Co-morbidity)• Depression, anxiety

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Pharmacologic Support

• Aversion Therapy

– Works by making patients sick with nausea and vomiting if they drink alcohol.

– Disulfiram (Antabuse)

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Agents

• Campral (acamprosate) Glutamate agonist• Antabuse (disulfiram) Aversion therapy• ReVia (naltrexone) Opiate antagonist• Topamax (topiramate) Craving reduction• Benzodiazepines for withdrawal• Antidepressants for depression• Antipsychotics for hallucinations

dangerous

Kindling Model