M&R Pharmacokinetics

Question 1

What are the different way to administer a drug?

Answer 1

Formulation of the drug can be a solid (rate depends on dissolution) or liquid

Site of administration:

• local eg eye, skin, inhalation
• systemic (enteral eg oral rectal, parenteral eg IM, IV, transdermal, subcutaneous)

Question 2

Define oral bioavailability

Answer 2

The proportion of a dose given orally (or any route other than IV) than reaches the systemic circulation in an unchanged form. Can be expressed as amount or rate

Question 3

What is the therapeutic ratio?

Answer 3

A measure of how dangerous the drug is - the more narrow the therapeutic window the more dangerous
The max tolerated dose / min effective dose
LD50 (lethal dose to 50% of people) / ED50 (effective dose in 50% of people)

Question 4

What is the first pass effect?

Answer 4

Substances absorbed from the ileum enter the venous blood which drains into the hepatic portal vein straight into the liver.
The liver is the main site of drug metabolism so drugs are extensively metabolised when they first pass they liver - the first pass effect.
IM, IV, rectal and sublingual routes avoid it

Question 5

What is drug distribution?

Answer 5

The theoretical volume which a drug has distributed assuming this occurred instantaneously.
Obtained by extrapolation of plasma levels to 0 time

Question 6

What are protein binding drug interactions?

Answer 6

Drugs can be free (active) or bound to proteins
When the drug displaces from binding sites it causes protein binding drug interactions. Important when the drug:
- highly bound to albumin (>90%)
- small volume of distribution
- low therapeutic ratio

Class 1 drug is used at a lower dose than number of albumin binding sites. Class 2 drug is used at a greater dose and displaces class 1 drug

Question 7

How are drugs eliminated?

Answer 7

Metabolised in the liver

• oxidised/ reduces
• conjugated

Excretion (predominantly renal)

• only free fraction filtered
• reabsorption depends of pH (only non ionised moiety is lipid soluble and crosses membranes)

Question 8

What is the difference between 1st and 0 order kinetics?

Answer 8

1st order kinetics: rate of elimination proportional to drug level. Most common. Half life can be defined Predictable and reliable

0 order kinetics: rate of elimination constant. Rare

Question 9

How long does it take to achieve a steady state?

Answer 9

During repeated drug administration a steady state is achieved in 5 half lives (irrespective of dose or frequency)

Question 10

When do drug interactions in metabolism matter clinically?

Answer 10

• drugs with low therapeutic ratio
• drugs used a min effective conc eg OC pill
• drug metabolism follows 0 order kinetics

Question 11

Describe the renal excretion of drugs

Answer 11

Weak acids - acidic urine increases absorption and alkaline urine decreases reabsorption

Weak bases - acidic urine decreases absorption and alkaline urine increases absorption

eg in aspirin overdose acids are given to aid elimination of the drug