Download 10/6/2014 Alcohol

10/6/2014
Alcohol
Numerous types of alcohols are commercially used. When referring to “alcohol” that is consumed, this implies ethanol.
Alcohol Physicochemical Properties
Ethanol has both hydrophobic and hydrophilic groups:
thanol has both hydrophobic and hydrophilic groups:
CH3CH2OH
so is membrane permeable and water soluble (at all concentrations).
Alcohol is a small molecule (18 g/mol) which further facilitates solubility and permeability.
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Alcohol Pharmacokinetics – Absorption Alcohol is readily absorbed, primarily through the small intestine.
Some absorption (ca. 20%) occurs through stomach.
Factors Affecting Alcohol Absorption
Food slows ethanol absorption and decreases amount absorbed.
1. Gastric emptying delayed – hence, alcohol resides in stomach longer
2. Enzymes in the GI metabolize alcohol, so decreasing the rate of absorption results in lower blood alcohol content (BAC).
Carbonation speeds up alcohol absorption
Carbonation forces fluids into small intestine more rapidly.
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Carbonation of Beverages
carbonic acid
carbonic acid
bicarbonate
proton
Carbonation decreases pH to 4‐5 due to carbonic acid formation.
Carbon dioxide (CO2) is significantly more soluble in water than nitrogen (N2).
Alcohol Pharmacokinetics – Distribution Ethanol is more water soluble than fat soluble, so distributes more into aqueous environments.
Alcohol crosses all membranes in the human body, including the BBB and placenta.
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Alcohol Pharmacokinetics – Metabolism Approximately 95% of ethanol is metabolized
Approximately 95% of ethanol is metabolized.
85% of metabolism occurs in liver; 15% of metabolism occurs in GI tract.
5% is excreted unchanged via the lungs. Breathalyzer analyzes for ethanol (not metabolite(s)).
Alcohol Metabolism Alcohol metabolism follows zero‐order (linear) kinetics.
10‐14 mL ethanol / hour metabolized ‐ roughly 1 drink per hour. NAD+ cofactor supply limits ethanol metabolism. Acetaldehyde metabolite is toxic – buildup can cause nausea, vomiting, headache, flushing
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Alcohol Metabolism Continued Acetate is converted to acetyl‐CoA
Acetate is converted to acetyl
CoA and enters the Kreb cycle (citric acid cycle).
Series of metabolic steps convert it to H2O, CO2, and ______________.
Alcohol Metabolism Gender Differences
Considering men and women of similar age, weight and fitness:
Men: Higher percentage of water in the body, so more dilute BAC
Women: Higher body fat; since fat is less vascularized, more concentrated BAC
Men: Greater amount of ALD enzyme in GI tract, hence, increased metabolism
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Alcohol Metabolism Variability
Chronic drinkers: Increased metabolism of ethanol due to production of an ADH variant.
Certain sub‐populations: mutation in ALDH enzyme causes “alcohol flush reaction” due to buildup of acetaldehyde.
Alcohol Pharmacology
Ethanol primarily effects the CNS
p
y
Graded, reversible depression of behavior, mental functioning, and cognition.
CNS effects are additive with those of other sedative‐hypnotic compounds.
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Alcohol Pharmacology – GABAergic Effects
Ethanol enhances GABA inhibitory neurotransmission.
GABA neurotransmission results in flow of Cl‐ ions into cell, causing hyperpolarization and decreased likelihood of action potential firing.
• Sedation
• Muscle relaxation
• Inhibition of motor and cognitive skills
• Reduced anxiety
gamma‐aminobutyric acid (GABA)
Major inhibitory neurotransmitter
Alcohol Pharmacology – Glutaminergic Effects
Ethanol inhibits the NMDA subtype of glutamate receptors in specific brain regions:
thanol inhibits the NM A subtype of glutamate receptors in specific brain regions:
hippocampus, amygdala, striatum.
•Decreased response of NMDA receptors to glutamate neurotransmitter
• Cognitive impairments in learning and memory at high BAC levels
glutamate (Glu)
Major excitatory neurotransmitter
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Alcohol Pharmacology – Indirect Effects on CNS
•Increased opiod
I
d i d release triggering dopamine release
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ti
i d
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•Increased serotonin activity
•Increased endocannabinoid release
O
HO
dopamine (DA)
N
H
serotonin (5‐HT)
anandamide
Alcohol Pharmacology – Systemic Effects
• Anticonvulsant ‐
A ti
l t withdrawal from chronic high doses can lead to seizures
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h i hi h d
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• Dilation of blood vessels – flushing, decrease in body temperature
• Cardiovascular benefits at low doses – increased HDL, decreased LDL, reduced stroke risk
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Ethanol is Not Considered a Therapeutic Drug
Exception – poisoning due to consumption of other alcohols
Exception –
poisoning due to consumption of other alcohols
Denatured Alcohol
Methanol added to industrial ethanol to discourage recreational use.
Denatured alcohol is labeled as such, and a dye may be added to the solution.
Denatured alcohol is tax exempt.
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Toxicity of Denatured Alcohol
Metabolites of methanol are toxic.
Treatment for methanol poisoning?
Toxicity of Denatured Alcohol
Alcohol dehydrogenase oxidizes several alcohols (non‐specific enzyme).
Administer ethanol – block methanol from metabolism by enzyme.
or
Administer alcohol dehydrogenase inhibitor.
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