Alcohol Flashcards
1
Q
Alcohol is not very potent:
- Standard Dose:
- Consumption:
A
- Standard “dose” is about 14 g:
- 12 ounce beer
- 5 ounce wine
- 1.5 ounce 80 proof liquor
- Consumption:
- Blood alcohol concentration of 30 mg/deciliter
- 30 mg%
- 0.03% w/v
- Equal to 7 mM
- Blood alcohol concentration of 30 mg/deciliter
2
Q
Pharmacokinetics:
Absoprtion
A
- Small, water soluble molecule which is absorbed rapidly from GI tract after oral administration
- Primarily absorbed from small intestine
-
Rate of absorption influenced by:
- ethanol concentration, rate of consumption and composition of gastric contents
- Absorption is decreased if gastric emptying is delayed
3
Q
Pharmacokinetics:
Distribution
A
- Distributed to total body water (Vd = volume of total body water)
- Distribution depends on degree of tissue vascularization
- amount of blood flow
-
Freely membrane permeable
- Including INTO the alveolae from the lung
capillaries - This is the basis for the breathalizer test of expired air
- Including INTO the alveolae from the lung
4
Q
Metabolism/ Biotransformation:
General issues
A
-
Significant first pass effect in liver
- 90-98% of ethanol ingested is metabolized to acetaldehyde
5
Q
Alcohol Dehydrogenase Pathway (ADH):
A
-
Primary pathway for ethanol oxidation to acetaldehyde
- rate limiting
- Primarily in the liver, but also present in other tissues
- Kinetics of ethanol elimination by this pathway are zero-order
- 10 g/hr in 70 g person at the concentrations of ethanol consumed
- since one drink is about 14g ⇒ 1.5 hours to metabolize the drink
6
Q
Microsomal Ethanol Oxidizing System (Mixed Function
Oxidase System) (MFOS):
A
-
High Km - little contribution at concentrations below 100 mg/dl
- low affinity
-
Induced in alcoholics
- CYP2E1 - influences metabolism of other drugs
7
Q
Acetaldehyde Metabolism:
A
- Mitochondrial aldehyde dehydrogenase (ALDH)
- Oxidizes acetaldehyde to acetate
- Genetic polymorphisms
- Inhibition by disulfiram
8
Q
Ethanol Metabolism: Consequences
A
Two major metabolic consequences
-
Increased NADH results in inhibition of TCA cycle
- Reduced gluconeogenesis
- Decreased oxidation of fats
-
Increased acetaldehyde
- Generation of protein adducts
- Decreased glutathione
- Inhibits microtubules
9
Q
Mechanism of Action in the CNS:
A
- Affects function of several ion channels
- In particular, activates GABA receptor-ligand gated Cl-channel
- Disturbs balance between excitatory and inhibitory neurotransmission
10
Q
Acute Effects of Ethanol in CNS:
A
Ethanol is a dose-dependent, CNS depressant:
- BAC: 50-100 (mg/dl) ⇒ Sedation, subjective “high,” increased reaction times
- BAC: 100-200 (mg/dl) ⇒ Impaired motor function, slurred speech, ataxia
- BAC: 200-300 (mg/dl) ⇒ Emesis, stupor
- BAC: 300-400 (mg/dl) ⇒ Coma
- BAC: > 500 (mg/dl) ⇒ Respiratory depression, death
11
Q
Consequences of Chronic Alcohol Consumption
Liver and GI tract
A
-
Liver
- Steatosis - fatty liver
- Hepatitis C - often co-morbid
- Alcoholic cirrhosis - due to necrosis and chronic inflammation
-
GI Tract
- Chronic gastritis
- Pancreatitis
- Diarrhea
- Malabsorption of Vitamins
12
Q
Consequences of Chronic Alcohol Consumption:
Nervous System
A
-
Tolerance
- Adaptive neuronal changes
- Metabolic tolerance
-
Dependence
- Psychological dependence - craving
- Physical dependence - withdrawal is dangerous, can get seizures
-
Neurotoxicity
- Neuralgias and peripheral nerve injury
- Cerebral/Cerebellar Atrophy
- Wernicke’s Encephalopathy
- Korsakoff’s Psychosis
- Psychiatric Disorders
13
Q
Teratogenic Effects / Fetal Alcohol Syndrome:
A
- Associated with chronic maternal alcohol abuse
-
Characterized by:
- retarded body growth
- microcephaly
- poor coordination
- facial abnormalities
- minor joint abnormalities
-
Mechanism of Teratogenic Effect
- direct inhibitory effect of ethanol or acetaldehyde on embryonic cellular proliferation
-
Severity ⇒ dose-dependent
- minimum dose not known
- advise abstinence
14
Q
Alcohol-Drug Interactions:
A
- Effects of ethanol augmented by other CNS depressants
- Barbiturates; benzodiazepines; opiates; neuroleptics
-
Ethanol can also interfere with drug metabolism
- Acute, high doses inhibit CYP2E1 mediated metabolism
- Chronic ethanol induces CYP2E1 enzymes therefore accelerates metabolism of some drugs
- Acetaminophen liver toxicity worse in alcoholic or during acute ethanol intoxication
15
Q
Management of Acute Intoxication:
A
- Goal ⇒ prevention of severe respiratory depression and aspiration of vomitus
- Lethal concentration - generally above 400 mg/dl
- Metabolic alterations may require treatment of hypoglycemia, ketosis and electrolyte imbalance
16
Q
Define alcohol withdrawal:
A
- Syndrome - agitation, anxiety, insomnia, seizures, mood swings
- Severity - proportional to degree and duration of alcohol abuse
17
Q
What are the objectives of drug therapy for alcohol withdrawal?
A
prevention of seizures, delirium and arrhythmias
-
Benzodiazepines – Diazepam (Diastat® / Dizac™ / Valium®), Chlordiazepoxide (Librium®)
- Gradual reduction of dose “tapering off”
18
Q
Pharmacotherapy of Alcoholism:
A
-
Naltrexone (Depade® / Re Via® / Vivitrol™)
- Therapeutic Use - reduces “urge to drink”; increases control
- Mechanism of Action - opioid receptor antagonist
- Best together with psychosocial therapy
-
Acamprosate (Campral®)
- Decreases drinking frequency and reduces relapse
- Mechanism of action - GABA mimetic
- Well tolerated - primary side effect is diarrhea
-
Disulfiram (Antabuse®)
- Therapeutic Use - Aversion Therapy
- Mechanism of Action - inhibition of aldehyde dehydrogenase
- Pharmacologic Effects - acetaldehyde syndrome
- Not very effective
