Drugs of Abuse 3 – Alcohol Flashcards
What equation is used to determine the number of grams of alcohol per 100 ml?
ABV% x 0.78 = g/100 mL
What equation is used to calculate the number of units in a given volume of alcohol?
ABV% x volume (ml)/1000
What is the recommended weekly allowance of alcohol for men and women?
<14 units
What is the legal driving limit for alcohol?
80 mg/100 ml
Where is alcohol absorbed in the GI tract?
20% - stomach
80% - small intestine
What determines the speed of onset of the effects of alcohol?
The speed of onset of the effects of alcohol is proportional to the rate of gastric emptying
What proportion of alcohol is metabolised?
90% (the remaining 10% stays unmetabolised)
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
State two enzymes in the liver that are involved in metabolising alcohol.
Alcohol dehydrogenase
Mixed function oxidase
NOTE: these both convert alcohol to acetaldehyde
What is an important feature of mixed function oxidase?
It can be induced if you constantly expose yourself to alcohol – it is the reason for alcohol tolerance
Why would one large dose of alcohol give a higher plasma ethanol concentration than several small doses?
The liver enzymes that are responsible for metabolising alcohol are saturable
Giving a large dose at once is more likely to saturate the enzymes
Describe the metabolism of alcohol in the stomach. How does this differ in women compared to men?
The stomach contains alcohol dehydrogenase, which is responsible for15% of alcohol metabolism
Women have 50% less alcohol dehydrogenase in their stomachs than men
State one other reason why women, in general, can’t tolerate alcohol as well as men?
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
Describe the metabolism of acetaldehyde.
Acetaldehyde is toxic and must be metabolised further
It is metabolised by aldehyde dehydrogenase to produce acetic acid
Name a drug that is used as an alcohol aversion therapy. Explain why it is used for this purpose.
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
Why do some people (particularly Asians) tend to tolerate alcohol badly?
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
Describe the pharmacological potency of alcohol.
Low pharmacological potency
What are the three major CNS targets of alcohol and what effectsdoes alcohol have on these targets?
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
Explain the counter-intuitive effects of alcohol on the central reward pathway.
GABA will reduce dopamine release and NMDA will increase dopaminerelease
However, alcohol enhances GABA and 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.
Hypothalamus – controls appetite, emotions, temperature
Reticular activating system – impairs consciousness
Hippocampus – amnestic effects
Cerebellum – movement and coordination
Basal ganglia – perception of time
Describe and explain the effects of alcohol on cutaneous vasculature.
Alcohol causes vasodilation (this is thought to be due to acetaldehyde)
It causes decrease calcium influx and increased prostaglandins –> vasodilation
Describe and explain the effects of alcohol of alcohol on heart rate.
Alcohol decreases the sensitivity of baroreceptors
This means decreased baroreceptor firing –> decreased parasympathetic firing + decreased inhibition of sympathetic firing –> INCREASED HEART RATE
Describe the effects of alcohol on the endocrine system.
Alcohol inhibits vasopressin release from the neurohypophysis
This means that alcohol is a powerful diuretic
How can chronic alcohol abuse lead to dementia?
Chronic alcohol caused cortical atrophy and a loss of cerebral white matter –> dementia
How can chronic alcohol abuse lead to ataxia?
Chronic alcohol can cause cerebellar cortex degeneration
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
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
What are the chronic effects of alcohol on the liver?
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
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 and inflammatory changes
How can chronic alcohol abuse cause cirrhosis?
If the inflammation persists, fibroblasts could be recruited, which lay down connective tissue and cause cirrhosis
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
NOTE: it is thought that 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)
The acetaldehyde can directly damage the gastric mucosa leading to ulceration
There is some evidence that alcohol can be carcinogenic in the stomach
Describe the chronic effects of alcohol on the endocrine system.
Alcohol can increase ACTH secretion (causes 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
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
