Alcohol

Question 1

Ethanol

Answer 1

Absorption: primarily oral and rapid, from small intestine mostly and increased with increased gastric emptying (carbonated beverages and decreased with food), rate influenced by ethanol concentration and rate of ethanol consumption
Distribution: volume of distribution approximates total body water (small molecule, water soluble) and crosses membrane freely (to alvelolae from lung capillaries so breathelizer test works)
Distribution to individual organs depending on degree of tissue vascularization; amount of blood flow
Metabolism: 90-98% to acetaldyehyde (two enzymatic routes)
Significant first pass effect (gastric and liver alcohol dehydrogenases)
Remainder eliminated unchanged by breath, sweat, saliva

Question 2

Ethanol Metabolism

Answer 2

1. Alcohol Dehydrogenase–> primary pathway oxidation to acetaldehyde and is rate limiting; primarily in the liver and zero order
2. Microsomes Ethanol Oxidizing System–> induced in alcoholics CYP2E1 and influences metabolism of other drugs
3. From acetaldehyde via aldehyde dehydrogenase to acetate (genetic polymorphisms)

Question 3

Ethanol MOA and Effects

Answer 3

Activates GABA receptor ligand gated CL- channel and inhibits NMDA cation channel

Effects: dose dependent and CNS depressant
Liver and GI: alcoholic liver disease and GI pathologies (chronic gastritis, pancreatitis, diarrhea, malabsorption of vitamins)
Nervous System: tolerance (adaptive neuronal changes and metabolic tolerance) and dependence (craving and physical); Neurotoxicity( neuralgias, cerebral/cerebellar atrophy, wernike’s encephalopathy, Korsakoff’s Psychosis, Psychiatric disorders)
Teratogenic Effects: fetal alcohol syndrome (low body growth, microencephaly, poor coordination, facial abnormality, minor joint abnormality) through direct inhibition on embryonic cell proliferation
High doses acute: inhibit CYP 2E1
Chronic will induce CYP 2E1

Question 4

Benzodiazepines

Answer 4

Diazepam, Chlordiazepoxide
Used for alcohol withdrawal syndrome
Prevention of seizure, delirium, and arrhythmias
Tapering off slowly

Question 5

Acamprosate

Answer 5

Treat alcoholism
Decrease drinking frequency and reduce relapse
GABA mimetic
Well tolerated- side effect is diarrhea

Question 6

Naltrexone

Answer 6

Alcoholism treatment
Reduce “urge to drink”
Opioid receptor antagonist

Question 7

Disulfiram

Answer 7

Alcoholism treatment- aversion therapy
Inhibition of aldehyde dehydrogenase
Accumulate acetaldehyde and effects are not good