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- Prof. David W. Craig
- Dept. of Chemistry
- Hobart and William Smith Colleges
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- With 1 to 2 drinks (.01-.05 g/dL BAC) -- euphoria and perceived
reduction in anxiety
- With 3 to 5 drinks (.06-.10 g/dL BAC) -- judgement and motor
coordination impaired, sometimes
increased aggression
- With 10 to 13 drinks (.20-.25 g/dL BAC) -- sedation
- With 0.30 g/dL BAC -- memory
impairment and loss of consciousness
- With 0.40 to .50 g/dL BAC --
depressed respiration , coma, death
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- Number of Drinks Consumed
- Body Size and Build
- Sex
- Time
- Past Drinking Experiences
- Is Stomach Empty or Full?
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- Rate of absorption is dependent on:
- concentration gradient between gut and blood
- surface area of contact
- degree of vascularization
- Effect of Food on Absorption
- food dilutes alcohol in the digestive system
- fatty foods are slow to digest and slow to move from the stomach to the
small intestine
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- Ethanol clearance is zero order … the rate of clearance is independent
of the ethanol concentration
- Average ethanol clearance rates
- For moderate drinkers - .017 g/dL/hr
- Drinkers consuming >60 drinks/month - .020 g/dL/hr
- 80% of adult population > .012 g/dL/hr
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- Women are smaller than men
- Women have lower total body water content (49%) than men (58%) of
comparable size
- Gastric ADH lower in women
- virtually nonexistent in alcoholic women
- declines in men over 50
- Fluctuations in gonadal hormone levels during the menstrual cycle may
affect the rate of alcohol metabolism
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- Isoenzymes in Alcohol DH (ADH)
- Beta1 in Caucasian has Km 0.00023 g/dL
- Beta2 in Asian has Km 0.0043 g/dL
- Beta3 in 15% African Amer. has Km .165 g/dL
- 50% Chinese and Japanese Asians have inactive mito. Aldehyde DH (ALDH)
resulting in facial flushing, palpitations, dizziness, and nausea
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- Metabolic Tolerance
- But….This is not the whole story….more to come
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- With 1 to 2 drinks (.01-.05 g/dL BAC) -- euphoria and perceived
reduction in anxiety
- With 3 to 5 drinks (.06-.10 g/dL BAC) -- judgement and motor
coordination impaired, sometimes
increased aggression
- With 10 to 13 drinks (.20-.25 g/dL BAC) -- sedation
- With 0.30 g/dL BAC -- memory
impairment and loss of consciousness
- With 0.40 to .50 g/dL BAC --
depressed respiration , coma, death
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- Potentiates GABA receptor function
- Inhibits Glutamate receptor function
- Increases Dopamine concentration
- Increases Seratonin release
- Stimulates Opiate Neuropeptide Release
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- Dopamine stimulates pleasure centers and functions in positive
reinforcement
- alcohol increases Dopamine concentrations in nucleus acumbens and other
reward centers
- Serotonin functions in mood, sleep and positive reinforcement
- alcoholics and thrill seekers
have low serotonin levels and alcohol consumption ( and thrill
activities) brings theses levels up to normal.
- Serotonergic drugs have reduced alcohol consumption by alcoholics.
- Endorphins and Enkephalins are natural neural peptides that bind to
opiate receptors and produce euphoric effects.
- Endorphins and Enkephalins are released by the brain when exposed to
alcohol
- Euphoria seems to stimulate further drinking
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- GABA is major inhibitory neurotransmitter controlling “arousal state”
and sensory and motor activity
- Alcohol Potentiates GABA receptor function
- GABA receptor is site of action of
- sedative/anesthetic barbiturate,
pentobarbitol
- sedative/anxiolytic benzodiazipines
- RO 15-4513 overcomes motor impairment
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- Glutamate is major excitatory neurotransmitter
- Alcohol inhibits NMDA glutamate receptor function
- Impaired NMDA Glutamate Receptor Function Causes:
- cognitive impairment and amnesia
- inability to learn new information
- Alcohol parallels action of PCP or “angel dust”
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- Tolerance
- changes in number and types of GABA receptors
- Increase in number of glutamate receptors
- Withdrawal
- increased Anxiety within hours -- GABA
- seizures -- Glutamate
- Dependence
- changes in Dopamine and Seratonin function appear to be long lasting
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- Pounding Headache
- Caused by reduced blood pressure in cranial vessels
- General Lethargy
- Caused by buildup of lactic acid and acidosis by release of acetic acid
- Hypersensitivity to Light and Sound
- Alcohol withdrawal leads to increased excitability, depressed mood, and
sensitivity to stimuli
- Queasy Stomach
- Empty stomach, overly acidic
- Also due to withdrawal
- What about taking a drink to relieve hangover symptoms?
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- Physiological responses
- Erections slower to rise and quicker to fall
- Reduction in vaginal lubrication
- Psychological Perceptions
- 45% of men and 68% if women say alcohol enhances sexual enjoyment
- Rutgers study (2-3 standard drinks)
- Subjects who thought they drank alcohol were most highly aroused (those
that did not actually get alcohol were slightly less aroused)
- Subjects who expected tonic but actually got alcohol were less aroused
than those that expected alcohol but did not.
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- Ethyl ester of Cocaine
- potentiates cocaine “high”
- Aspirin and Cimetidine Inhibits
Gastric ADH
- Liver Drug Detoxification Impaired
- Depleted NAD impairs livers ability to clear other drugs
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- Ethyl esters of Fatty Acids and Cholesterol
- may cause heart damage, impair energy metabolism, disrupt cell
membranes
- Protein Modification by Acetaldehyde
- enzymes inactivated by imine adducts
- Ethanol can also be oxidized by MEOS/Cytochrome P450
- MEOS oxidation produces harmful free radicals
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- High NADH/NAD ratio:
- Impaired Energy Metabolism and increased production of lactic acid
- Inhibits Lipid Degredation in Liver
- Stimulation of fat synthesis and increases in LDL and HDL levels
- Inhibition of oxidative steps in testosterone synthesis
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- Risk becomes significant when alcohol consumption exceeds
- 6.2oz/day for men
- 1.55oz/day for women
- Caused by
- Free radical rx in fatty liver
- Cytokine stimulated differentiation of Ito cells into collagen
myofibroblasts
- Increased levels of Acetaldehyde due to lower levels of Aldehyde
dehydrogenase
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- Suppresses proliferation of lymphocytes in blood, spleen, and thymus
- Reduced B cell antibody production
- Natural Killer (NK) cells have reduced activity
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- Reduced risk of CAD with <=2 drinks/day
- increased HDL, inhibition of platelet activity
- Reduction in Cerebral Vascular Disease (Stroke)
- reduced platelet activity
- 50% greater risk of hypertension with 3-4 drinks/day
- Cardiomyopathy (weakened heart muscle)
- impaired protein metabolism, free radicals
- Arrhythmias caused by alcohol effect on sinoatrial node
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