Alcohol Flashcards
How do you calculate the absolute amount of alcohol?
%ABV x 0.78 = g alcohol/100ml
How do you calculate the units of alcohol?
(%ABV x volume (ml))/1000
Where is alcohol absorbed?
20% in stomach
80% in the intestines
What effect does gastric emptying have on effects of alcohol onset?
Speed of onset of effects of alcohol is proportional to speed of gastric emptying
Why is there this proportional relationship between onset of effects of alcohol and gastric emptying?
Alcohol is far more readily absorbed in small intestine so if you drink on a full stomach, you have a much slower rate of absorption of alcohol because the alcohol is retained in the stomach rather than going into the small intestine where it’s absorbed easily
What percentage of alcohol is metabolised?
90%
What does the breath test for alcohol measure?
Some of the 10% unmetabolised alcohol as it is excreted via the lungs
Where is alcohol metabolised mainly?
Liver
What enzymes are involved in the metabolism of alcohol to acetaldehyde?
Alcohol dehydrogenase (75%) Mixed function oxidase (25%)
Why isn’t metabolism finished when you form acetaldehyde?
Acetaldehyde is toxic so needs to be metabolised as well
How do you develop alcohol tolerance?
Mixed function oxidase is induced if you continually expose yourself to alcohol so the liver becomes more effective at metabolising alcohol- this is reversible
What limits metabolism of alcohol?
The liver is very good at metabolising alcohol but enzymes can be saturated
Why are men better able to tolerate alcohol?
Women have about 50% body water and men have about 60% body water (in terms of fluid in the body for alcohol to be dissolved in) and women have less alcohol dehydrogenase in their stomach.
Alcohol is very water soluble so plasma alcohol concentration will be lower in the average man than woman
How is acetaldehyde metabolised?
Aldehyde dehydrogenase metabolises acetaldehyde to acetic acid
What is disulfiram used for and what does it do?
It is used as an alcohol aversion therapy, it blocks aldehyde dehydrogenase which leads to acetaldehyde accumulation and more negative effects of acetaldehyde will be felt
What is asian flush?
Common genetic polymorphism in the aldehyde dehydrogenase enzyme which means acetaldehyde metabolism isn’t very effective
What is the pharmacological potency of alcohol?
It is low- need a lot more to produce effects in body
What is the general alcohol pharmacodynamics?
It is a depressant- slows down cellular activity
What is the effect of alcohol dependent on?
Degree of CNS excitability at the time, environment, personality, setting
Why is alcohol not very specific?
It is a simple molecule and can bind to lots of different receptors
What are the three major CNS targets of alcohol?
GABA receptors
NMDA receptors
Calcium channels
What effect does alcohol have on GABA function?
It enhances it so is a depressant
How does alcohol affect chloride influx?
It increases allopregnenolone production which is an allosteric modulator of chloride channels and facilitates chloride channel opening hence increasing chloride influx and acting as a depressant
What effect does alcohol have on NMDA receptor function?
Decreases it via some sort of allosteric modulation
Which brain regions are particularly sensitive to alcohol?
Cortical regions- motor and sensory function is impaired
Corpus callous- info passing from left side of brain to right etc
Hypothalamus- appetite, emotions, temperature and pain
Reticular activating system- consciousness
Hippocampus- Memory
Cerebellum- Movement and coordination
Basal ganglia- perception of time
How does alcohol cause flushing?
Vasodilation
Associated with reduced calcium entry and increased prostaglandins
Acetaldehyde is believed to be responsible for most of these vasodilation effects
What effect does alcohol have on heart rate?
It leads to a centrally mediated decrease in baroreceptor which leads to reduced parasympathetic stimulation and reduced inhibition of sympathetic stimulation which causes an acute increase in heart rate
What endocrinological effect does alcohol have?
It is a powerful diuretic- this effect probably is caused by acetaldehyde
It acts on neurohypophysis and inhibits vasopressin release
What is Wernicke-Korsakoff syndrome caused by?
Thiamine deficiency
Why do alcoholics develop Wernicke-Korsakoff syndrome?
They get a lot of their calories from alcohol so tend to have a bad diet and become thiamine deficient
How does thiamine deficiency cause Wernicke-Korsakoff syndrome?
Thiamine is an important co-factor and ATP formation in cells is very dependent on thiamine but this is impaired and the Kreb’s cycle being impaired leads to oxidative stress building up in cells in the brain which causes injury and eventually apoptosis
What is Wernicke’s encephalopathy caused by?
Mitochondrial injury
What is Korsakoff’s psychosis caused by?
Cell apoptosis in the brain that irreversible and will probably cause the patient to die
What is required in the liver for metabolism of alcohol to acetaldehyde?
NAD+
What are the chronic effects of alcohol in the liver?
Build up of NADH will inhibit beta oxidation of lipids so you get fat build up in the liver that interferes with the TCA cycle so you get less ATP been produced
What else can metabolise alcohol apart from alcohol dehydrogenase?
Cytochrome P450
What is the problem with chronically using cytochrome P450 to metabolise alcohol?
You will generate oxygen free radicals which will contribute to damage within the cell- mitochondrial injury and inflammatory changes- this is how you get hepatitis
How is cirrhosis caused in an alcoholic?
Inflammation persists that will lead to recruitment of fibroblasts which lay down connective tissue and this leads to cirrhosis and these patients may require liver transplants
How is chronic alcohol at safe levels good for the cardiovascular system?
It appears to cause an increase in HDL and decrease in platelet aggregation which explains anti-atherogenic effects and reduced mortality
What are the chronic effects of alcohol on the GI tract?
It is very damaging- particularly to the stomach
It can be metabolised which can lead to lots of acetaldehyde building up in the stomach and this directly damages the gastric mucosa. It is also common for chronic alcoholics to get ulcerations
What are the chronic effects of alcohol on endocrine system?
Often presents with cushing’s type symptoms because alcohol causes an increase in ACTH secretion and it can also reduce testosterone secretion
What are the symptoms of a hangover?
Nausea Headache Fatigue Restlessness and muscle tremors Polyuria and polydipsia
When are a lot of the symptoms of a hangover at their worst?
When your blood alcohol concentration reaches zero- drinking a bit when hungover can make you feel a bit better because it increases your BAC from zero
Why does alcohol cause nausea?
It irritates the stomach
Why does alcohol cause a headache?
It is a profound vasoconstrictor
