pharmacology of ethanol

Question 1

Absorption of ethanol

Answer 1

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%)

Question 2

Ethanol distribution

Answer 2

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

Question 3

How long does it take for initial and peak effects of alcohol

Answer 3

initial: CNS effects within 5 minutes. Peak effects within 15-60 minutes

Question 4

compare ethanol distribution in males vs females

Answer 4

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

Question 5

elimination of ethanol

Answer 5

2-10% expired unchanged in air and urine. 90-98% metabolized by liver

Question 6

kinetics of ethanol metabolism

Answer 6

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)

Question 7

Enzymes involved in metabolism of ethanol

Answer 7

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

Question 8

Asians and ethanol

Answer 8

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

Question 9

NADH in ethanol metabolism

Answer 9

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

Question 10

Hepatic metabolic disruption with ethanol

Answer 10

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

Question 11

Effects of ethanol on CNS

Answer 11

Dose dependent CNS depressant. Initially, depression of inhibitory cortical neurons occurs which results in relative stimulation prior to depressiv eaction

Question 12

Which blood alcohol levels are the limits for DWAI and DUIs in colorado

Answer 12

DWAI: 0.05-0.08. DUI: 0.08-0.2

Question 13

physiological reaction at BAC of 0-0.05

Answer 13

loss of inhibitions, impaired judgment

Question 14

physiological reaction at BAC of 0.05-0.08

Answer 14

impaired driving ability

Question 15

physiological reaction at BAC of 0.08-0.2

Answer 15

inability to operate motor vehicle

Question 16

physiological reaction at BAC of 0.2-0.3

Answer 16

emesis, respiratory depression, danger of death with other CNS depressants

Question 17

physiological reaction at BAC of >0.3

Answer 17

unconciousnes, severe respiratory-CVS

Question 18

highest known BAC

Answer 18

2.1- in chronic alcoholic

Question 19

Ethanol MOA

Answer 19

At 0.05-0.250 BAC, potentiation of GABA and inhibition of glutamate NMDA receptors occurs.

Question 20

ethanol reinforcing effect

Answer 20

anxiolysis-leads to abuse

Question 21

Acute effects of alcohol

Answer 21

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)

Question 22

ethanol effects on other organs

Answer 22

fatty liver, hepatitis, cirrhosis, esophageal varices, pancreatitis, hypothermia, congestive heart failure,

Question 23

ethanol tolerance

Answer 23

Occurs, but limited relative to opioids. Cross tolerance occurs with other CNS depressants such as benzos.

Question 24

Ethanol withdrawal symptoms and time course

Answer 24

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)

Question 25

List the chronic CNS effects of ethanol

Answer 25

Wernickes disease, korsakoffs psychosis, cerebral atrophy and cerebellar atrophy. All are due to ethanol toxicity and malnutrition

Question 26

Wernickes disease signs

Answer 26

confusion, diplopia, nystagmus, ataxia, peripheral neuropathy

Question 27

korsakoff’s psychosis signs

Answer 27

disorientation, amnesia, confabulations

Question 28

cerebral atrophy signs

Answer 28

frontal lobe degeneration, personality disintegration, dementia (irreversible)

Question 29

cerebellar atrophy signs

Answer 29

irreversible ataxia

Question 30

criteria for fetal alcohol syndrome

Answer 30

Prenatal or postnatal growth retardation AND altered morphogenesis (especially facial dysmorphology) AND CNS involvement – developmental delay, learning disabilities

Question 31

Effects of ethanol on fetus by trimester

Answer 31

1st: major morphologic abnormality. 2nd: Increased risk of spontaneous abortions. 3rd: Decreased fetal growth

Question 32

Treatment of acute alcohol intoxication

Answer 32

Respiration support, IV fluids with glucose, thiamine, and electrolytes. No specific antidote

Question 33

Treatment of alcohol withdrawal syndrome

Answer 33

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

Question 34

Function of disulfiram

Answer 34

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

Question 35

Function of Naltrexone

Answer 35

aka revia- opioid antagonist that Reduces alcohol craving, consumption, and relapse rates in combination with psychotherapy

Question 36

function of acamprosate

Answer 36

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