Pharmacokinetics In Practice lecture

Question 1

Why is ethanol the perfect drug?

Answer 1

1. Soluble in water- in order to absorb
2. Not charged- can pass through membranes
3. Small molecule
4. Not subject to changes in molecular structure as a result of changes in the acidity (pH)
5. Soluble in fatty substances (lipids)
   - Can pass through the lipid membrane barriers in the body
   (stomach into the blood or from intestines into the blood) (readily absorbable)

Question 2

Calculate the molar concentration of alcohol in the blood for the UK drive limit

Information given:
EtOH= 46.07g/l

A. 30mg/100ml
B. 50mg/100ml
C. 80mg/100ml
D. 200mg/100ml

Answer 2

C. 80mg/100ml for england

B. 50mg/100ml for scotland

Use Mass = moles x concentration

46.07g per 1litre per 1M concentration

Therefore:
80mg per 100ml per 0.0176M

Question 3

What are the factors that may effect absorption when it comes to ethanol?

Answer 3

1. Rate of consumption
2. Volume consumed
3. Concentration of ethanol in the drink (strength, different %)
4. Presence or absence of carbonation (e.g. carbonation increases rate of absorption like in champagne there’s bubbles)
5. The presence or absence of food in the stomach (food delays absorption)
6. Taking any medications that can interfere with GI motility

Question 4

Calculate the volume of distribution in an average man 70kg man?
Total body H2O?
Extracellular Fluid?
Intracellular Fluid?
Interstitial fluid?
Plasma?

Answer 4

1. H2O= 0.6 x 70 = 42 Litres (Large Vd)
2. Extracellular (1/3)= 14 litres
3. Intracellular (2/3)= 28 litres
4. Interstitial fluid (11.2 litres)
5. As plasma is 2.8 litres (approximately 3 litres) (Small Vd)

Question 5

What percentage of ethanol is metabolised in the liver?

Answer 5

95%

Question 6

Explain first order kinetics and zero order kinetics in relation to ethanol metabolism?

Answer 6

First order is where the actual plasma concentration dictates the rate of elimination: threshold is 10mg/dl (decilitre)
Enzymes can no longer work to eliminate amount of ethanol

Zero order kinetics there after

Question 7

How is ethanol metabolised in the liver?

Answer 7

Ethanol is converted to Acetaldehyde which is converted to Acetate

1. Ethanol to Acetaldehyde
   (Alcohol dehydrogenase)
   - NADPH => NADP
   - NAD+ => NADH
2. Acetaldehyde to Acetate
   - Disulfiram (Aldehyde dehydrogenase inhibitor)
   - NAD+ to NADH
   -

Question 8

How is ethanol excreted in the liver? And how is it allowed to determine blood alcohol levels?

Answer 8

1. 5% is excreted unchanged
2. Allows for breathalysers to determine blood alcohol levels, everyones is different though. (Has to be absorbed into the blood stream though)
3. Ratio of 2100:1 of breath alcohol to blood alcohol

Question 9

What are the classic symptoms that are linked to the consumption of ethanol and explain how they occur?

Answer 9

1. Sedative
   - GABA receptor increased inhibition
   - Glycine receptors
2. Ataxia (random muscle movements
   - Acetylcholine receptors
3. Nausea
   - Acetylcholine receptors on the gut

Question 10

Will this man be below the drink legal limit?
- man drinks 375mL of standard whisky (40% alcohol)
- Has blood concentration 250mg/dl at 12am
- T1/2 = 1 hour
- 10ml/hour
- Wakes up to drive to work at 8am
Work it out?

Answer 10

Zero order kinetics as over 10mg/dl

40% of 375mL = 150mL of ethanol

Correlates with the 250mg/1dl

Therefore the T1/2 = 1 hour isn’t needed as the reaction is zero order

10ml/hour is the rate at which ethanol is excreted per hour

116mg per ml is the final therefore he’d be over the limit