Absorption of Ethanol

 Readily absorbed p.o.

 20-30% from stomach, remainder upper GI

 rate influenced by concentration and food

 max. BAL approx. 30-90 min after single dose

 Drug distribution

 Distributes in total body water

readily crosses the placenta to affect fetus

and will appear in breast milk
 Metabolism of ethanol

 Metabolism follows zero-order kinetics

 2% - 10% excreted unchanged through lungs,

urine and sweat

 At high BAL, ethanol also metabolized by

P4502E1 enzyme (CYP2E1) and will cause
marked induction of the P4502E1 enzyme
Ethanol metabolism changes
NADH/NAD ratio in liver
NAD NADH
Ethanol Acetaldehyde
ADH NAD
ALDH

NADH
Acetate

ADH = Alcohol Dehydrogenase

ALDH = Aldehyde Dehydrogenase
ALDH genetics and Alcoholism
 Multiple isoforms of human ALDH exist

» ALDH21 is responsible for metabolism of

acetaldehyde by liver mitochondria

» However, a genetically dominant yet

inactive allele, ALDH22 causes
natural protection from alcoholism
 endogenous disulfiram (ANTABUSE) effect
Metabolic changes due to
alcohol metabolism
Metabolism of ethanol can cause
metabolic changes resulting from change
in NADH/NAD ratio in liver

 Hyperlacticacidemia
 Hyperuricemia
 Hypoglycemia
 Hyperlipidemia
 Ketosis
 Acute tolerance (Mellanby effect)
measured by nystagmus

nystagmus ends
nystagmus

BAL
occurs
} Difference is due
to acute tolerance
Predicted loss

- - - + + + + - - - -

Time
 Other acute CNS effects

 Inhibits temperature regulation

 Alters neuroendocrine activity

 diuresis
 Chronic CNS effects

Characterized by neuroadaptive changes

 CNS tolerance

 Physical dependence
» Alcoholism
Effects on cardiovascular
system
 Very little acute effect on circulation
 some peripheral vasodilation

Moderate intake (1-2 drinks/day)

associated with reduced risk of coronary
heart disease

Problem drinking associated with

increased cardiovascular mortality
Effects on gastrointestinal
system

 Low doses increase gastric secretion

 High doses decrease gastric secretion

and motility

 Chronic alcohol use can lead to gastritis,

diarrhea, esophageal dysfunctions, and
malabsorption syndromes
Effects on hepatic system

 Acute alcohol has few direct pharmacological

effect on hepatic functions
 fatty liver may occur with relatively small amounts of
alcohol

 Chronic intake causes persistent fatty liver,

eventually leading to cirrhosis and hepatic
encephalopathy
 Alcohol toxicity

Acute overdose causes stupor, seizures,

coma and respiratory arrest

 Chronic abuse can cause several

toxicities, including cirrhosis, brain
damage, and teratogenesis in newborns
(the fetal alcohol syndrome)
Alcohol ingestion can interact
with the action of other drugs

Anesthetics Antibiotics
Anticoagulants Antidepressants
Antihistamines Antipsychotics
Antiseizure drugs Anxiolytics
 Analgesics (narcotic and non-narcotic)
Cardiovascular drugs NSAIDs
Oral hypoglycemics
Drugs used specifically to alter
alcohol effects

 Disulfiram to suppress drinking

 acts by inhibition of ALDH

 Naloxone to reduce relapse drinking

 antagonist at opiate receptors

 Acamposate - promising new drug for

relapse in alcoholics