pharmacology of ethanol Flashcards
Absorption of ethanol
rapid throughout GI, expecially small intestine. The more rapid the ingestion, the more rapid the absorption b/c increased concentration gradient. Presence of food slows absorption by delaying passage to small intestine (heavy meal can decrease peak conc by 30%)
Ethanol distribution
water soluble, thus ethanol distributes in total body water and can cross the placenta. Equilibration is most rapid in areas of high blood flow such as brain, liver, kidney,lung
How long does it take for initial and peak effects of alcohol
initial: CNS effects within 5 minutes. Peak effects within 15-60 minutes
compare ethanol distribution in males vs females
Women have greater % body fat than men. Given same g/kg dose of ethanol as man of equal weight, woman will have higher blood alcohol content
elimination of ethanol
2-10% expired unchanged in air and urine. 90-98% metabolized by liver
kinetics of ethanol metabolism
Mainly zero order kinetics (constant rate of 7-10g alcohol per hour or 0.015-0.020% BAC reduction per hour, regardless of how much alcohol is consumed). Maximum rate of 220 g/day (can increase 50-60% in chronic alcoholics)
Enzymes involved in metabolism of ethanol
Alcohol dehydrogenase and CYP2E1 which accounts for 10-25% of ethanol metabolism at higher BACs. Both convert ethanol into acetaldehyde. Aldehyde dehydrogenase converts acetyaldehyde into acetate
Asians and ethanol
90% of Asian population have Aldehyde dehydrogenase with increased activity. Asians are also missing the high affinity form of aldehyde dehydrogenase, allowing acetaldehyde to build up and causing aversive flushing reaction
NADH in ethanol metabolism
NADH is formed when acetaldehyde is converted to acetate. NADH must be oxidized to NAD, but mitochondrial oxidation is insufficient with increased levels of NADH. This leads to disruptions in hepatic metabolic pathways
Hepatic metabolic disruption with ethanol
elevated levels of NADH causes decreased Krebs activity-gluconeogenesis leading to hypoglycemia. Increased blood lactate leads to acidosis, behavioral disturbances. Increased Mg++ excretion can lead to convulsions. Increased Acetyl CoA leads to increased F.A. synthesis + decreased fat breakdown causing fatty liver. Decreased uric acid excretion may precipitate gout attacks
Effects of ethanol on CNS
Dose dependent CNS depressant. Initially, depression of inhibitory cortical neurons occurs which results in relative stimulation prior to depressiv eaction
Which blood alcohol levels are the limits for DWAI and DUIs in colorado
DWAI: 0.05-0.08. DUI: 0.08-0.2
physiological reaction at BAC of 0-0.05
loss of inhibitions, impaired judgment
physiological reaction at BAC of 0.05-0.08
impaired driving ability
physiological reaction at BAC of 0.08-0.2
inability to operate motor vehicle
physiological reaction at BAC of 0.2-0.3
emesis, respiratory depression, danger of death with other CNS depressants
physiological reaction at BAC of >0.3
unconciousnes, severe respiratory-CVS
highest known BAC
2.1- in chronic alcoholic
Ethanol MOA
At 0.05-0.250 BAC, potentiation of GABA and inhibition of glutamate NMDA receptors occurs.
ethanol reinforcing effect
anxiolysis-leads to abuse
Acute effects of alcohol
anticonvulsive (but hyperexcitability upon withdrawal), may precipitate convulsions (avoid in epilepsy), analgesia, suppression of stage IV-REM, vomiting, hangover (alcohol or acetaldehyde or contamination product)
ethanol effects on other organs
fatty liver, hepatitis, cirrhosis, esophageal varices, pancreatitis, hypothermia, congestive heart failure,
ethanol tolerance
Occurs, but limited relative to opioids. Cross tolerance occurs with other CNS depressants such as benzos.
Ethanol withdrawal symptoms and time course
anxiety, tremor, anorexia and insomnia occur from 0-48 hrs post alcohol, with peak at 24-36 hrs. Seizures are possible 6-48 hrs after onset of alcohol withdrawal syndrome. Disorientation, confusion and disordered sensory perception can occur 24-150 hrs post alcohol and are potentially life threatening (but no seizures occur during this late phase)
List the chronic CNS effects of ethanol
Wernickes disease, korsakoffs psychosis, cerebral atrophy and cerebellar atrophy. All are due to ethanol toxicity and malnutrition
Wernickes disease signs
confusion, diplopia, nystagmus, ataxia, peripheral neuropathy
korsakoff’s psychosis signs
disorientation, amnesia, confabulations
cerebral atrophy signs
frontal lobe degeneration, personality disintegration, dementia (irreversible)
cerebellar atrophy signs
irreversible ataxia
criteria for fetal alcohol syndrome
Prenatal or postnatal growth retardation AND altered morphogenesis (especially facial dysmorphology) AND CNS involvement – developmental delay, learning disabilities
Effects of ethanol on fetus by trimester
1st: major morphologic abnormality. 2nd: Increased risk of spontaneous abortions. 3rd: Decreased fetal growth
Treatment of acute alcohol intoxication
Respiration support, IV fluids with glucose, thiamine, and electrolytes. No specific antidote
Treatment of alcohol withdrawal syndrome
Benzodiazepines (chlordiazepoxide, lorazepam)- Acts at GABA to prevent CNS hyperexcitability (which is due to down regulation of GABA and increased glutamate receptor activity). Alpha 2 adrenergic agonists (clonidine)- effective for autonomic hyperactivity
Function of disulfiram
aka antabuse- alcohol sensitizing drug which inhibits aldehyde dehydrogenase, resulting in 5-10 fold increase in acetaldehyde levels and nausea/vomiting, convulsions, respiratory and cardio collapse
Function of Naltrexone
aka revia- opioid antagonist that Reduces alcohol craving, consumption, and relapse rates in combination with psychotherapy
function of acamprosate
aka camprasal- NMDA receptor drug that has Some reduction in alcohol craving and relapse rate in combo with psychotherapy. May mitigate glutamate hyperexcitability during withdrawal
