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

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

Question 7

What proportion of alcohol is metabolised?

Answer 7

90% (the remaining 10% stays unmetabolised and is excreted via eg lungs hence breath test works)

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 to acetaldehyde

Answer 9

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

Question 10

What is an important feature of mixed function oxidase?

Answer 10

It can be upregulated if you constantly expose yourself to alcohol – it is 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

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 12

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

Answer 12

The stomach contains alcohol dehydrogenase, which is responsible for15% 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 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 14

Describe the metabolism of acetaldehyde.

Answer 14

Acetaldehyde is toxic and 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 – 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 16

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

Answer 16

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 17

Describe the pharmacological potency of alcohol and its selectivity

Answer 17

Low pharmacological potency (low affinity and efficacy)

Low selectivity

Question 18

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

Answer 18

GABA – its presynaptic function is that alcohol increases allopregnenolone production (which facilitates the opening of chloride channels) – thus enhancing GABA action. It also directly enhances GABA function post synaptically and allows more Cl- influx
NMDA – alcohol decreases NMDA receptor function via allosteric modulation
Ca2+ channels – alcohol reduces Ca2+ channel function meaning that there is less calcium 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 and NMDA will increase dopaminerelease
However, alcohol enhances GABA and reduces NMDA activity

Question 20

Name a few specific parts of the brain that contribute to the ACUTE CNS effects of alcohol

Answer 20

Corpus callosum - L and R brain more disconnected
Hypothalamus – controls appetite, emotions, temperature. Alcohol suppresses this
Reticular activating system – impairs consciousness
Hippocampus – amnesic effects
Cerebellum – movement and coordination (alcohol suppresses this)
Basal ganglia – perception of time (alcohol suppresses)

Question 21

Describe and explain the effects of alcohol on cutaneous vasculature.

Answer 21

Alcohol causes vasodilation (this is thought to be due to acetaldehyde)
It causes decrease calcium influx and increased prostaglandins –> vasodilation

Question 22

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

Answer 22

Alcohol decreases the sensitivity of baroreceptors
This means decreased baroreceptor firing –> decreased parasympathetic firing + decreased inhibition of sympathetic firing –> INCREASED HEART RATE

Question 23

Describe the ACUTE effects of alcohol on the endocrine system.

Answer 23

Alcohol inhibits vasopressin release from the neurohypophysis
This means that alcohol is a powerful diuretic hence alcohol makes u piss

Question 24

How can chronic alcohol abuse lead to dementia?

Answer 24

Chronic alcohol caused cortical atrophy and 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

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
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
The syndrome comprises two parts:
Wenicke’s Encephalopathy – REVERSIBLE brain damage caused by mitochondrial injury
Korsakoff’s Psychosis –IRREVERSIBLE brain damage as a result of cell apoptosis in the brain due to lack of ATP (thiamine deficient)

Question 28

What are the chronic effects of alcohol on the liver?

Answer 28

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 glycolysis and 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 (lactic acidosis)
Acetyl CoA is converted to ketone bodies

Question 29

How can chronic alcohol abuse cause hepatitis?

Answer 29

Liver is constantly exposed to acetaldehyde and depleted of NAD+.

• Acetaldehyde = pro-inflammatory
• NAD+ depletion=deranged metabolic processes= ROS leakage= pro-inflammatory
• There are also increase in pro-inflammatory cytokines in both liver and blood

Question 30

How can chronic alcohol abuse cause cirrhosis?

Answer 30

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

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
NOTE: it is thought that 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)
The acetaldehyde can directly damage the gastric mucosa leading to ulceration
There is some evidence that 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 (causes 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

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

Question 35

Summarise a list of the acute and chronic effects of alcohol

Answer 35

Acute effects:
CNS - different brain areas involved. Main effect is depressant via interaction with 3 main types of receptors/channel (GABA, NMDA, Ca2+)
CVS - cutaneous vasodilation and increased HR
Endocrine- diuresis

Chronic effects:
CNS - Wernicke-Korsakoff syndrome
Liver - cirrhosis
CVS - some beneficial effects (decreases CHD risk)
GIT - gastric ulceration
Endocrine- increased ACTH and decreased Testosterone