Pharmacology of Ethanol

Question 1

Absorption of Ethanol

Answer 1

Rapid throughout entire GI tract - extremely rapid in SI
More rapid the ingestion  More rapid the absorption (dependent on concentration gradient)

Presence of food slows absorption
Delays passage to small intestine
Heavy meal can decrease peak concentration by 30%

Question 2

Distribution of Ethanol

Answer 2

Ethanol is water soluble and distributed in TBW

Placenta is permeable to ethanol - factor in FAS

Distribution - equilibration most rapid in areas of high blood flow –>brain, liver, kidney, lung

Initial CNS effects within 5 min

Peak effects within 15-60 min

Fat contains less water –> less alcohol distribution
Women have greater % body fat than men
Given same g/kg dose of ethanol as man of equal weight–> woman will have a higher BAC

Question 3

Meto of etoh

Answer 3

liver

Question 4

Disulfiram (sold under the trade names Antabuse and Antabus)

Answer 4

Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, which means many of the effects of a “hangover” are felt immediately after alcohol is consumed.

Question 5

↑ NADH

Answer 5

↓ Krebs activity-gluconeogenesis–> hypoglycemia

Question 6

You receive a blood chemistry workup on an individual (90 kg male) admitted to the emergency room because of a car accident. The individual seemed disoriented, and you astutely ordered a blood-ethanol level determination along with other tests. The reports indicate a blood alcohol concentration (BAC) of 0.24 gm/dl and a blood pH of 7.15 (acidotic). Which of the following is most likely responsible for the acidotic condition of your patient?

Ethanol’s actions on the GABA system of brain result in suppression of ADH release and fluid retention.
Ethanol inhibits the excretion of organic acids in the urine leading to acidosis.
Ethanol metabolism generates NADH that promotes the production of lactate from pyruvate, leading to lactic acidosis.
Ethanol metabolism generates acetaldehyde that acts to inhibit the kidney acid transport systems.

Answer 6

?

Ethanol metabolism generates NADH that promotes the production of lactate from pyruvate, leading to lactic acidosis.–MAYBE

Question 7

Acute CNS Effects of Ethanol

Sedative-Hypnotic Effects

Answer 7

Dose-dependent CNS depressant effect – similar to barbiturates

Low-moderate dose (0.05-0.250 g/dL)–> ↑ GABA plus ↓ Glutamate neuronal function

Anxiolysis major reinforcing effect leading to abuse

Question 8

Acute CNS Effects of Ethanol

Anticonvulsive Effects

Answer 8

Good anticonvulsant initially, but hyperexcitability upon withdrawal

May precipitate convulsions – contraindicated in epilepsy

Question 9

Organ System Effects of Ethanol

Liver

Answer 9

Fatty liver
etoh heptis

esophageal varices

Question 10

Organ System Effects of Ethanol

GI

Answer 10

Pancreatitis

Question 11

Organ System Effects of Ethanol

CVS

Answer 11

Cardioprotection
=)

Moderate etoh= happy heart

s/s hypothermia, CHF

Question 12

methamphetamine

Answer 12

CNS stimulants

Question 13

heroin

Answer 13

Opioid analgesics

Question 14

diazepam

Answer 14

Benzodiazepines

Question 15

pentobarbital

Answer 15

Barbiturates

Question 16

phencyclidine

Answer 16

Dissociative anesthetics

Question 17

Alcohol’s action on the brain produces a variety of effects. Alcohol intoxication (at lethal dosages) most closely resembles intoxication with which of the following classes of abused drugs?

CNS stimulants (methamphetamine)
Opioid analgesics (heroin)- u 
Benzodiazepines (diazepam)- low dose 
Barbiturates (pentobarbital)- high dose 
Dissociative anesthetics (phencyclidine)- nmda

Answer 17

Barbiturates (pentobarbital)- high dose

Question 18

Which of the following signs is NOT characteristic of the acute alcohol (ethanol) withdrawal syndrome?

Tremor
Anxiety
Somnolence
Agitation
Insomnia

Answer 18

Somnolence

Question 19

What is characteristic of etoh wd

Answer 19

Tremor
Anxiety
Agitation
Insomnia

Question 20

Drug Interactions ETOH

Answer 20

Additive effects with all CNS depressants (acute)
Cross-tolerance to sedative-hypnotic drugs and general anesthetics (chronic use)
Can promote GI bleeding if taken with aspirin
Increase risk of hepatotoxicity with acetaminophen

Question 21

Drug Interactions ETOH

Answer 21

Altered disposition of drugs metabolized by liver

Non-alcoholic  acute alcohol can inhibit metabolism

Alcoholic with normal liver function  faster metabolism via induction of CYP2E1

Reduce concomitant drug effect

Potentiate acetaminophen toxicity

Alcoholic with mild liver disease  normal metabolism

Alcoholic with severe liver disease (hepatitis/cirrhosis)

Slower metabolism (enzyme loss) increasing effects of concomitantly administered drugs

Disulfiram-like symptoms with metronidazole

Question 22

Treatment of Acute Alcohol Intoxication

Answer 22

Support of respiration

Administration of IV fluids - glucose, thiamine, and electrolytes (K+ and Mg++)

No specific antidote available

Question 23

Alcohol Withdrawal Syndrome

Answer 23

Benzodiazepines (chlordiazepoxide, lorazepam)
• Action at GABA receptors prevents emergence of CNS hyperexcitability following withdrawal of alcohol
• Hyperexcitability is due to down-regulation of GABA function and increased glutamate receptor activity
• Benzodiazepines act via principle of cross-dependence
α2 adrenergic agonists (clonidine)
• Effective for signs of autonomic hyperactivity

Question 24

management of acute alcohol intoxication

Answer 24

Support of respiration
Administration of IV fluids - glucose, thiamine, and electrolytes (K+ and Mg++)
No specific antidote available