Drugs of Abuse 3 – Alcohol

Question 1

What equation is used to determine the number of grams of alcohol per 100 ml?

Answer 1

ABV% x 0.78 = g/100 mL

Question 2

What equation is used to calculate the number of units in a given volume of alcohol?

Answer 2

ABV% x volume (ml)/1000

Question 3

What is the recommended weekly allowance of alcohol for men and women?

Answer 3

< 14 units

Question 4

What is the legal driving limit for alcohol?

Answer 4

80 mg/100 ml

Question 5

Where is alcohol absorbed in the GI tract?

Answer 5

20%: stomach

80%: small intestine

Question 6

What determines the speed of onset of the effects of alcohol?

Answer 6

Speed of onset of the effects of alcohol is proportional to rate of gastric emptying

Question 7

What proportion of alcohol is metabolised?

Answer 7

90% (remaining 10% stays unmetabolised)

Question 8

Out of the alcohol that is metabolised, what proportion is metabolised in the liver? Where does the rest of the metabolism take place?

Answer 8

85%: Liver

15%: Stomach

Question 9

State two enzymes in the liver that are involved in metabolising alcohol.

Answer 9

Alcohol dehydrogenase (75%)
Mixed function oxidase (25%)
Both convert alcohol to acetaldehyde

Question 10

What is an important feature of mixed function oxidase?

Answer 10

Can be upregulated with constant exposure to alcohol= the reason for alcohol tolerance

Question 11

Why would one large dose of alcohol give a higher plasma ethanol concentration than several small doses?

Answer 11

Liver enzymes responsible for metabolising alcohol are saturable
Giving a large dose at once is more likely to saturate the enzymes

Question 12

Describe the metabolism of alcohol in the stomach. How does this differ in women compared to men?

Answer 12

Stomach contains alcohol dehydrogenase, responsible for 15% of alcohol metabolism
Women have 50% less alcohol dehydrogenase in their stomachs than men

Question 13

State one other reason why women, in general, can’t tolerate alcohol as well as men?

Answer 13

Women: body water composition ~ 50%
Men body water composition: ~60%
so a given amount of alcohol will be more dilute in a man compared to a woman

Question 14

Describe the metabolism of acetaldehyde.

Answer 14

Acetaldehyde is toxic + must be metabolised further

It is metabolised by aldehyde dehydrogenase to produce acetic acid

Question 15

Name a drug that is used as an alcohol aversion therapy. Explain why it is used for this purpose.

Answer 15

Disulfiram: an aldehyde dehydrogenase inhibitor so promotes build up of acetaldehyde, which is responsible for most of the negative feelings associated with drinking

Question 16

Why do some people (particularly Asians) tend to tolerate alcohol badly?

Answer 16

A common genetic polymorphism in the aldehyde dehydrogenase gene means some people (esp. Asians) can’t convert acetaldehyde to acetic acid as efficiently so acetaldehyde builds up + makes them feel bad

Question 17

Describe the pharmacological potency of alcohol.

Answer 17

Low pharmacological potency

Question 18

What are the three major CNS targets of alcohol and what effects does alcohol have on these targets?

Answer 18

GABA: alcohol increases allopregnenolone release (which facilitates opening of cl- channels) thus enhancing GABA action
NMDA: alcohol decreases NMDA receptor function
Ca2+ channels: alcohol reduces Ca2+ channel function, decreases Ca2+ influx, which negatively affects neurotransmitter exocytosis

Question 19

Explain the counter-intuitive effects of alcohol on the central reward pathway.

Answer 19

GABA will reduce dopamine release + NMDA will increase dopamine release
Alcohol enhances GABA + reduces NMDA activity

Question 20

Name a few specific parts of the brain that are affected by alcohol and state how they are responsible for features of alcohol intoxication.

Answer 20

Corpus callosum: transfers info between left + right sides of brain
Hypothalamus: controls appetite, emotions, temperature + pain sensation
Reticular activating system: consciousness
Hippocampus: memory
Cerebellum: movement + coordination
Basal ganglia: perception of time

Question 21

Describe and explain the effects of alcohol on cutaneous vasculature.

Answer 21

Alcohol causes vasodilation (thought to be due to acetaldehyde)
Causes decreased Ca2+ influx + increased prostaglandins –> vasodilation

Question 22

Describe and explain the effects of alcohol on heart rate.

Answer 22

Alcohol decreases sensitivity of baroreceptors
Results in decreased baroreceptor firing –> decreased parasympathetic firing + decreased inhibition of sympathetic firing –> INCREASED HR

Question 23

Describe the effects of alcohol on the endocrine system.

Answer 23

Alcohol inhibits vasopressin release from the neurohypophysis
So alcohol is a powerful diuretic

Question 24

How can chronic alcohol abuse lead to dementia?

Answer 24

Chronic alcohol causes cortical atrophy + a loss of cerebral white matter –> dementia

Question 25

How can chronic alcohol abuse lead to ataxia?

Answer 25

Chronic alcohol can cause cerebellar cortex degeneration

decrease volume of cerebral white matter

Question 26

State an important syndrome that is caused by chronic alcohol use.

Answer 26

Wernicke-Korsakoff Syndrome

Question 27

Describe and explain how chronic alcoholism can cause this syndrome.

Answer 27

Wernicke-Korsakoff syndrome is caused by thiamine (vitamin B1) deficiency
Chronic alcoholics tend to have a bad diet
Thiamine is an important cofactor in the generation of ATP within cells
Lack of thiamine impairs the Krebs’ cycle + leads to the build up of oxidative stress within cells
Oxidative stress can cause mitochondrial damage + apoptosis
Wenicke’s Encephalopathy: caused by mitochondrial injury
Korsakoff’s Psychosis: cell apoptosis in the brain: irreversible + patient will probably die

Question 28

What are the chronic effects of alcohol on the liver?

Answer 28

Alcohol metabolism in the liver uses up NAD+ so depletes liver’s NAD+ stores + increases NADH
This inhibits B-oxidation of lipids in the liver, so fat accumulates in the liver
Interferes with Krebs’ cycle because, without NAD+, glucose can’t be converted to pyruvate, + pyruvate can’t be converted to Acetyl CoA
Pyruvate is converted to lactate –> Acidosis
Acetyl CoA is converted to ketone bodies –> Ketosis

Question 29

How can chronic alcohol abuse cause hepatitis?

Answer 29

Chronic use of cytochrome P450 enzymes in metabolising alcohol can generate oxygen free radicals, which can cause mitochondrial injury + inflammatory changes

Question 30

How can chronic alcohol abuse cause cirrhosis?

Answer 30

If inflammation persists, fibroblasts could be recruited, which lay down connective tissue, reducing the number of hepatocytes, decreases ability of liver to metabolise anything, toxins accumulate in blood

Question 31

What are the potentially beneficial effects of chronic alcohol use at moderate levels?

Answer 31

Decreased mortality from coronary artery disease
Increase HDL
Increase tPA/ decreased platelet aggregation
It’ thought polyphenols are responsible for these effects

Question 32

Describe the chronic effects of alcohol on the GI tract.

Answer 32

Alcohol is partly metabolised in the GI tract to generate acetaldehyde (toxic)
Acetaldehyde can directly damage gastric mucosa leading to ulceration
Some evidence suggests alcohol can be carcinogenic in the stomach

Question 33

Describe the chronic effects of alcohol on the endocrine system.

Answer 33

Alcohol can increase ACTH secretion (cause Cushing’s type appearance)
Decrease testosterone

Question 34

Why do you get the following symptoms when hungover:

a. Nausea
b. Headache
c. Restlessness and muscle tremors
d. Polyuria and polydipsia

Answer 34

Nausea: Gastric irritation –> vagus –> vomiting centre
Headache: Vasodilation
Fatigue: sleep deprivation + rebound excitation of CNS
Restlessness + muscle tremors: Rebound increase in CNS activity once the alcohol (depressant) wears off
Polyuria + polydipsia: Inhibition of ADH secretion

Question 35

How does drinking on a full stomach influence your blood alcohol level?

Answer 35

Alcohol will remain in the stomach longer
Finds it harder to come into contact with the stomach walls where it would be absorbed
Slowly pulses into small intestine
Delays effects

Question 36

What is the primary effect of alcohol?

Answer 36

Depressant

Depends on CNS excitability which is influenced by personality + environment