Drugs of Abuse 3 – Alcohol

Question 1

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

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

Where is alcohol absorbed in the GI tract?

Answer 4

20% - stomach

80% - small intestine

Question 5

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

Answer 5

The speed of onset of the effects of alcohol is proportional to the rate of gastric emptying

Question 6

What proportion of alcohol is metabolised?

Answer 6

90% (the remaining 10% stays unmetabolised)

Question 7

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

Answer 7

85% - Liver

15% - Stomach

Question 8

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

Answer 8

Alcohol dehydrogenase
Mixed function oxidase
NOTE: these both convert alcohol to acetaldehyde

Question 9

What is an important feature of mixed function oxidase?

Answer 9

It can be induced if you constantly expose yourself to alcohol – it is the reason for alcohol tolerance

Question 10

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

Answer 10

The liver enzymes that are responsible for metabolising alcohol are saturable

Giving a large dose at once is more likely to saturate the enzymes

Question 11

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

Answer 11

The stomach contains alcohol dehydrogenase, which is responsible for 15% of alcohol metabolism

Women have 50% less alcohol dehydrogenase in their stomachs than men

Question 12

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

Answer 12

Women have a body water composition of about 50%

Men have a body water composition of about 59-60% so a given amount of alcohol will be more dilute in a man compared to a woman

Question 13

Describe the metabolism of acetaldehyde.

Answer 13

Acetaldehyde is toxic and must be metabolised further

It is metabolised by aldehyde dehydrogenase to produce acetic acid

Question 14

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

Answer 14

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

Question 15

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

Answer 15

There is a common genetic polymorphism in the aldehyde dehydrogenase gene meaning that some people (particularly Asians) can’t convert acetaldehyde to acetic acid as efficiently so acetaldehyde builds up and makes them feel bad

Question 16

Describe the pharmacological potency of alcohol.

Answer 16

Low pharmacological potency

Question 17

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

Answer 17

GABA – alcohol increases allopregnenolone production (which facilitates the opening of chloride channels) – thus enhancing GABA action

NMDA – alcohol decreases NMDA receptor function

Ca2+ channels – alcohol reduces Ca2+ channel function meaning that there is less calcium influx, which negatively affects neurotransmitter exocytosis

Question 18

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

Answer 18

GABA will reduce dopamine release and NMDA will increase dopamine release

However, alcohol enhances GABA and reduces NMDA activity - less dopamine released

Question 19

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 19

Hypothalamus – controls appetite, emotions, temperature

Reticular activating system – impairs consciousness

Hippocampus – amnestic effects

Cerebellum – movement and coordination

Basal ganglia – perception of time

Corpus callosum – information from left—>right

Question 20

Describe and explain the effects of alcohol on cutaneous vasculature.

Answer 20

Alcohol causes vasodilation (this is thought to be due to acetaldehyde)

It causes decrease calcium influx and increased prostaglandins –> vasodilation

Question 21

Describe and explain the effects of alcohol of alcohol on heart rate.

Answer 21

Alcohol decreases the sensitivity of baroreceptors

This means decreased baroreceptor firing –> decreased parasympathetic firing + decreased inhibition of sympathetic firing –> INCREASED HEART RATE

Question 22

Describe the effects of alcohol on the endocrine system.

Answer 22

Alcohol inhibits vasopressin release from the neurohypophysis

This means that alcohol is a powerful diuretic

Question 23

How can chronic alcohol abuse lead to dementia?

Answer 23

Chronic alcohol caused cortical atrophy and a loss of cerebral white matter –> dementia

Question 24

How can chronic alcohol abuse lead to ataxia?

Answer 24

Chronic alcohol can cause cerebellar cortex degeneration

Question 25

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

Answer 25

Wernicke-Korsakoff Syndrome

Question 26

Describe and explain how chronic alcoholism can cause this syndrome. (Wernicke-Korsakoff )

Answer 26

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

The lack of thiamine impairs the Krebs’ cycle and leads to the build up of oxidative stress within the cells

The oxidative stress can cause mitochondrial damage and apoptosis

Wenicke’s Encephalopathy – caused by mitochondrial injury

Korsakoff’s Psychosis – cell apoptosis in the brain – this is irreversible and the patient will probably die

Question 27

What are the chronic effects of alcohol on the liver?

Answer 27

Alcohol metabolism in the liver uses up NAD+ so it depletes the liver’s NAD+ stores and increases NADH

This inhibits beta-oxidation of lipids in the liver so you get an accumulation of fat in the liver

It also interferes with the Krebs’ cycle because, without NAD+, glucose can’t be converted to pyruvate, and pyruvate can’t be converted to Acetyl CoA

Pyruvate is converted to lactate

Acetyl CoA is converted to ketone bodies

Question 28

How can chronic alcohol abuse cause hepatitis and cirrhosis?

Answer 28

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

If the inflammation persists, fibroblasts could be recruited, which lay down connective tissue and cause cirrhosis

Question 29

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

Answer 29

Decreased mortality from coronary artery disease

Increase HDL

Increase tPA/decreased platelet aggregation

NOTE: it is thought that polyphenols are responsible for these effects

Question 30

Describe the chronic effects of alcohol on the GI tract.

Answer 30

Alcohol is partly metabolised in the GI tract to generate acetaldehyde (toxic)

The acetaldehyde can directly damage the gastric mucosa leading to ulceration

There is some evidence that alcohol can be carcinogenic in the stomach

Question 31

Describe the chronic effects of alcohol on the endocrine system.

Answer 31

Alcohol can increase

ACTH secretion (causes Cushing’s type appearance)

Decrease testosterone

Question 32

Why do you get the following symptoms when hungover:

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

Answer 32

a. Nausea
Gastric irritation –> vagus –> vomiting centre

b. Headache
Vasodilation

c. Restlessness and muscle tremors
Rebound increase in CNS activity once the alcohol (depressant) wears off

d. Polyuria and polydipsia
Inhibition of ADH secretion