Pharmacology 15 - Alcohol

Question 1

Describe epidemiology of alcohol consumption

Answer 1

• Alcohol consumption is high in western europe (Ireland has highest consumption)
• Therefore this is where effects are highest

Question 2

Describe dosing of alcohol

Answer 2

• % ABV (alcohol by volume) x 0.78 - g alcohol/100ml
• %ABV x volume (ml)/1000 is one unit (10mg or 8g of absolute alcohol)
• Safe level is less than 14 units a week
• Binge drinking is more than 8 units in one sitting (binge drinking in 16-24 year olds is falling)

Question 3

How is alcohol absorbed?

Answer 3

• Orally
• Stomach (20% on full stomach)
• Small intestine (80%)
• Alcohol has a more powerful affect when drank on an empty stomach, as the alcohol remains in the stomach longer when you are full, and it is less likely to be absorbed

Question 4

Describe the metabolism of alcohol

Answer 4

• 90% of the alcohol you drink is metabolised, it is metabolised better when drank in small doses
• Broken down in the liver (85%)
• 75% alcohol dehydrogenase
• 25% mixed function oxidase (upregulated when you drink regularly)
• Converted to acetaldehyde (toxic)
• 15% alcohol metabolised in the stomach lining to acetaldehyde by alcohol dehydrogenase
• Acetaldehyde to acetic acid via aldehyde dehydrogenase

Question 5

Describe the difference in male and female blood alcohol levels

Answer 5

• Women have less alcohol dehydrogenase in the stomach lining, so more alcohol enters the systemic circulation.
• Women have more body fat than men, and therefore as a proportion have less water
• Therefore, the alcohol is diluted more in the men than in alcohol

Question 6

What is disulfiram?

Answer 6

• Blocks aldehydehydrogenase, and therefore acetaldehyde will build up and have toxic effects
• Therefore, you will not want to drink alcohol due to it making you feel bad

Question 7

What are the effects of alcohol dependent on?

Answer 7

• Alcohol has low pharmacological potency, but can bind to many receptors. A high dose is needed to see effects.
• Depressant effect is dependent on degree of CNS excitability (altered by environment and personality)
• Low dose alcohol causes CNS excitability

Question 8

How does alcohol affect the CNS on a molecular level?

Answer 8

• Decreases NMDA receptors (allosteric modulation) and Ca2+ channels
• Positive effect on GABA (on the GABA receptors coupled to chloride, which can promote chloride influx. Presynaptically increases allopregnenolone which also binds to GABA receptors)

Question 9

How does alcohol cause euphoria?

Answer 9

• Binds to mu receptor which inhibits GABA release at the VTA
• Therefore removes inhibition in the VTA causing dopamine release at the NAcc

Question 10

How does alcohol affect CVS?

Answer 10

• Causes cutaneous vasodilation decreased Ca2+ entry
• May be influence on prostaglandins
• Due to acetaldehyde
• Chronic alcohol use causes centrally mediated decrease in baroreceptor sensitivity, which causes increase in heart rate and blood pressure

Question 11

How does alcohol cause polyurea?

Answer 11

• Diuresis
• Suppresses vasopressin
• May be via acetaldehyde

Question 12

List the chronic effects of alcohol

Answer 12

• Lack of thiamine in the diet due to high calories from alcohol, which therefore reduces brain function. More thiamine is needed the more alcohol drank.
• Impaired metabolism in brain regions with high demand resulting in dementia (cortical atrophy) and ataxia (cerebellar cortex degeneration)
• Wernicke-Korsakoff syndrome
• Liver damage
• Damage to gastric mucosa (15% alcohol metabolised in GIT)
• Increased ACTH and decreased testosterone secretion (leading to development of female characteristics)

Question 13

What is wernicke-korsakoff syndrome?

Answer 13

• Thiamine deficiency
• Wernickes encephalopathy (hypothalamus/thalamus - reversible)
• Korsakoffs psychosis (hippocampus - irreversible)

Question 14

How does alcohol chronically affect the liver?

Answer 14

• Consumption of NAD+ and production of NADH+ due to alcohol metabolism, and there is no NAD+ to metabolise triglycerides
• Increased glycerol and fatty acids while NAD+ is low
• Decrease in hepatocyte mitochondria
• Hepatitis (due to cytokine changes and free radicals)
• Cirrhosis (fibroblasts increase, hepatocyte regeneration decreases and active liver tissue decreases as the fibroblasts replace hepatocytes)
• Results in toxic chemical build up in the blood

Question 15

List the beneficial effects of alcohol

Answer 15

• Decreased mortality from coronary artery disease
• Increased HDL
• Increased tPA and decreased platelet aggregation

Question 16

What is the genetic polymorphism relating to alcohol metabolism?

Answer 16

• Asians tend to have lack of fuctional aldehyde dehydrogenase
• Therefore aldehyde dehydrogenase will build up and have its negative effects

Question 17

How does alcohol affect the brain acutely?

Answer 17

• Affects RAS (conscioussness)
• Hippocampus (memory)
• Cerebellum (movement and coordination)
• Basal ganglia (perception of time)
• Hypothalamus (appetite, emotions, temperature)
• Corpus collosum (passes information between the left and right half)

Question 18

How does alcohol affect the GIT?

Answer 18

• High acetaldehyde due to 15% metabolism in the GIT
• Therefore, there is damage to gastric mucosa
• Carcinogenic

Question 19

How does alcohol affect testosterone?

Answer 19

• Increases ACTH secretion
• Decreases testosterone secretion
• Results in feminine qualities developing

Question 20

List the symptoms of hangover. What can be done to reduce symptoms?

Answer 20

• Symptoms peak as blood alcohol concentration falls to 0
• Nausea due to acetaldehyde (Irritant -> Vagus -> Vomiting center)
• Headache (Vasodilation due to acetaldehyde)
• Fatigue (sleep deprivation, rebound excitation as BAC falls, waking up due to polyurea)
• Restlessness and muscle tremors
• Polyuria and polydipsia (↓ ADH secretion)
• To help resolve this, sleeping and drinking water are important