Drugs of Abuse 3 – Alcohol Flashcards by Georgia Leggett

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

ABV% x 0.78 = g/100 mL

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

ABV% x volume (ml)/1000

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

< 14 units

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What is the legal driving limit for alcohol?

80 mg/100 ml

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Where is alcohol absorbed in the GI tract?

20%: stomach

80%: small intestine

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

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

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What proportion of alcohol is metabolised?

90% (remaining 10% stays unmetabolised)

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

85%: Liver

15%: Stomach

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

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

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What is an important feature of mixed function oxidase?

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

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

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

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

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

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

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

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Describe the metabolism of acetaldehyde.

Acetaldehyde is toxic + must be metabolised further

It is metabolised by aldehyde dehydrogenase to produce acetic acid

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

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

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

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

Describe the pharmacological potency of alcohol.

Low pharmacological potency

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

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

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

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

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

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

Describe and explain the effects of alcohol on cutaneous vasculature.

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

Describe and explain the effects of alcohol on heart rate.

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

Describe the effects of alcohol on the endocrine system.

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

How can chronic alcohol abuse lead to dementia?

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

How can chronic alcohol abuse lead to ataxia?

Chronic alcohol can cause cerebellar cortex degeneration | decrease volume of cerebral white matter

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

Wernicke-Korsakoff Syndrome

Describe and explain how chronic alcoholism can cause this syndrome.

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

What are the chronic effects of alcohol on the liver?

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

How can chronic alcohol abuse cause hepatitis?

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

How can chronic alcohol abuse cause cirrhosis?

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

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

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

Describe the chronic effects of alcohol on the GI tract.

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

Describe the chronic effects of alcohol on the endocrine system.

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

Why do you get the following symptoms when hungover: a. Nausea b. Headache c. Restlessness and muscle tremors d. Polyuria and polydipsia

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

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

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

What is the primary effect of alcohol?

Depressant | Depends on CNS excitability which is influenced by personality + environment