20. Metabolism of Alcohol Flashcards
What the body does to a drug is known as what?
Pharmacokinetics = What the body does to a drug → Absorption, Distribution, Metabolism, Excretion (ADME).
Pharmacodynamics = What the drug does to the body.
What is the Pharmacodynamics of Alcohol?
Pharmacodynamics = What the drug does to the body = CNS Depressant
What is the chemical component in alcoholic drinks?
Alcohol drinks = Ethanol = Ethyl alcohol = C2H5OH
Note: Ethanol is not the same as Methanol
Where is alcohol absorbed?
How is alcohol absorbed?
Does the presence of food in the stomach affect absorption?
Alcohol is absorbed from both the stomach (20%) and the duodenum (80%) by passive (simple) diffusion.
Passively diffuses across the GIT epithelium into interstitial space then capillaries which drain into veins and head towards the liver.
The presence of food in the stomach retards (delays) gastric emptying and reduces absorption.
“Don’t drink on an empty stomach” advice.
What determines how alcohol is distributed in the body?
(Ie. Into which tissues does it move and why?)
Compared to other drugs like warfarin how easily can alcohol distribute into tissues?
Alcohol - Distribution
- Alcohol is soluble in water but practically insoluble in fats and oils
- After absorption it is quickly distributed throughout total body water - it distributes readily from the blood into water within the tissues.
- The concentration of alcohol in a tissue is dependent on the relative water content of the tissue.
- Distribution is by passive (simple) diffusion.
- There is no plasma protein binding of alcohol - ie.
- The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse.
Explain why a woman will have a higher BAC compared to a man of the same weight and height.
BAC - Men vs. Women
- The same dose of alcohol per unit of body weight can produce different BACs in different individuals.
- Concentrations are determined by variations in the proportion of fat and water in the body, and metabolism.
- Women generally have a smaller volume of distribution for alcohol than men because of their higher percentage of body fat.
- More fat = Less H20 for alcohol to distribute into
- Women will generally have higher peak blood alcohol levels than men when given the same dose (g/kg) of alcohol
Which type of kinetics are most drugs eliminated by?
Explain the half-life and amount of drug eliminated.
Elimination - First Order Kinetics
- For most drugs the time taken to go from a blood level of 100μg/ml to 50μg/ml is the same time to go from 50μg/ml to 25μg/ml, and the same time to go from 25μg/ml to 12.5μg/ml etc
- The blood level halves every half-life, but the actual amount of drug eliminated each half-life varies.
- The rate of elimination is proportional to the drug concentration.
- This is called first order kinetics, and this applies to the vast majority of drugs
Which type of kinetics is alcohol eliminated by?
Elimination - Zero Order Kinetics
- Alcohol is excreted by zero-order kinetics.
- A few compounds are excreted from the body by zero-order kinetics.
- With zero-order kinetics a constant amount of drug is excreted per unit of time.
- The rate of excretion is constant and independent of the amount of drug present in the body at the time.
How much alcohol can the average person metabolise per hour?
How many grams of alcohol is in a standard drink?
The average person can metabolise around 8 to 10 grams of alcohol per hour.
A standard drink contains 10 grams of alcohol.
What is alcohol metabolised to?
(Equation + Enzymes involved)
Metabolism of Alcohol
- • Alcohol is metabolised to acetaldehyde (mostly by alcohol dehydrogenase but also 2 other minor pathways) which is then metabolised to acetate by aldehyde dehydrogenase
- Acetate then converted to CO2 and water by the Krebs cycle
Where is Alcohol metabolised?
What is Disulfiram? How does it work?
What causes facial flushing in some people when consuming alcohol?
Liver
Ethanol → Acetaldehyde → Acetate (Acetic Acid → CO2 + H20 in Krebbs
Enzymes:
- Ethanol → Acetaldyhde = Alcohol dehydrogenase
- Acetaldehyde → Acetate = Aldehyde dehydrogenase
Disulfiram = inhibits aldehyde dehydrogenase - prevents conversion of acetyaldehyde to acetate
Build up of Acetyladelhyde causes toxicity
What causes alcohol to be eliminated by zero order kinetics?
Metabolism of Alcohol - Zero Order Kinetics
- The majority of alcohol is metabolised to acetaldehyde by alcohol dehydrogenase.
- Alcohol dehydrogenase becomes saturated at relatively low alcohol concentrations - mainly due to a lack of NAD+
- The saturation of alcohol dehydrogenase means that a constant amount of alcohol is metabolised per unit of time, and this amount is independent of the actual amount of alcohol present at the time.
What are 2 alternative pathways for the metabolism of alcohol to acetyladehyde?
Metabolism of Alcohol - Alternate Pathways
- The cytochrome P450 2E1 (CYP2E1) enzyme can also metabolise alcohol to acetaldehyde
- However, CYP2E1 it is only active after a person has consumed large amounts of alcohol
- Catalase can also convert a small fraction of the alcohol present to acetaldehyde
Is all alcohol metabolised?
Where is it eliminated?
How does a breathylser work? What BAC does a breath alcohol concentration reflect?
Alcohol - Elimination
- A small amount of alcohol is not metabolised and is eliminated from the body in the expired air, urine and sweat.
- The breathalyser test for measuring BAC is based on the fact that alcohol diffuses from the pulmonary arterial blood into the alveolar air.
- The alcohol in the breath is in equilibrium with the alcohol dissolved in the blood.
- The ratio of alcohol in the blood to the alveolar air is about 2100:1
- Therefore, the amount of alcohol in 1mL of blood is the same as the amount of alcohol in 2.1L of expired air
- Why you need to wait 15mins after drinking to be breathlysed or the concentration will just reflect the oral and throat amount not the concentration in the alveolar air (& BAC).
What is the rate of alcohol metabolism & elimination per hour?
By how much does the BAC reduce each hour?
How does this relate to the driving limit?
Alcohol is metabolised and eliminated at an average rate of 0.015 g/100mL/hour, which is the same as reducing the blood alcohol concentration (BAC) by 0.015 per hour.
0.015 BAC = 1 standard drink
Driving limit = 0.05
Therefore, 0.05/0.015 = ~3 standard drinks
How many standard drinks are in:
- 100ml of 11% V/V wine
- 150ml of 14.5% V/V wine
Standard Drink Calculations
100ml of 11% V/V wine has:
100 x 0.11 x 0.787 g of alcohol = 8.6g (0.86 standard drinks)
150ml of 14.5% V/V wine has:
150 x 0.145 x 0.787 g of alcohol = 17.1g (1.71 standard drinks)
How much alcohol does the average Australian consume?
The average Australian drinks just under 10 litres of pure alcohol annually, equivalent to about 15 standard drinks a week
How have the rates of beer, wine, sprits, and cider consumption changed since 1961?
What are 5 Clinical Features of Foetal Alcohol Syndrome?
Foetal Alcohol Syndrome - Clinical Features
- Abnormal facial development, with wide-set eyes, short palpebral fissures and small cheekbones
- Reduced cranial circumference
- Retarded growth
- Mental retardation and behavioural abnormalities, often taking the form of hyperactivity and difficulty with social integration
- Other anatomical abnormalities, which may be major or minor e.g. congenital cardiac abnormalities, malformation of the eyes and ears
