Alcohol
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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