Pharmacokinetics

Question 1

In its most basic form, what is pharmacokinetics the study of?

Answer 1

What the body does to drugs

Question 2

What are the four major parts of pharmacokinetics?

Answer 2

ADME
Absorption
Distribution
Metabolism
Elimination

Question 3

How do we measure the amount of drug that is actually available in the blood stream? What calculation would you do to calculate it?

Answer 3

Bio availability= serum concentration/ drug dose *100

Question 4

What would the bioavailability be of an IV drug?

Answer 4

100%

Question 5

What factors affect bioavailability of a drug?

Answer 5

Drug formulation and administration
Vomiting, malabsorption
Age
Food eaten at same time as drug

Question 6

What are the major body compartments that a drug could go into?

Answer 6

Extracellular space- includes plasma+ interstitium

Intracellular space

Question 7

What determines how far a drug is distributed in the body?

Answer 7

Regional blood flow
Lipid solubility
Disease
Specific receptor sites in tissues
Protein binding
Drug interactions
Active transport

Question 8

How do we measure how far a drug is distributed in the body (hypothetically)

Why is this “apparent” and not true?

Answer 8

Volume of distribution
Vd= dose/ drug concentration at time 0 in plasma. Eg 100mg gentamicin given. Peak plasma concentration 5mg/L, Vd= 20 litres.

Volume of distribution is apparent because it could theoretically work out to be more than the body’s volume itself eg 200l

Question 9

Why does the degree of protein binding matter?

Answer 9

Highly bound protein drugs displace those which are less tightly bound meaning that the concentration of the less tightly bound drug in the plasma suddenly increases.

Question 10

Where can first pass metabolism occur?

Answer 10

Liver, gut lumen or gut wall

Question 11

Where does phase I and phase II metabolism occur?

Answer 11

In the liver

Question 12

What is the significance of CYP450 enzymes?

Answer 12

They are part of phase I metabolism and break down drugs, being primarily oxidative. They can be induced and inhibited by certain drugs meaning that the metabolism of the drug in question is either sped up or slowed down, so that either concentration in plasma decreases or increases (sometimes into toxic range)

Question 13

What is a prodrug?

Answer 13

A chemical which has no clinically useful function until it is metabolised by the liver where it has active metabolites which are clinically useful.

Question 14

Where are most drugs eliminated?

Answer 14

Via the kidney or bile

Question 15

What affects elimination?

Answer 15

GFR
Passive tubular reabsorption
Active tubular secretion

Question 16

What is 1st order kinetics?

Answer 16

Rate of elimination is proportional to drug level. I.e a constant fraction of a drug is eliminated per unit time, so half life can be defined.

Question 17

What is zero order kinetics?

Answer 17

Rate of elimination is a constant. Normally occurs once all of the active sites of the metabolism enzymes are saturated, then concentration in plasma rises rapidly (often into toxic range)

Question 18

Why do we sometimes need to give a loading dose?

Answer 18

If we need to reach therapeutic dose quickly and the drug has a long half life.
It normally takes 4-5 half lives to reach a steady state
Therefore with a drug with a long half life this is going to take a while
Therefore we need to give a higher concentration of drug to bring them up to steady state. This is called the loading dose.

Question 19

What is half life proportional to?

What is it inversely proportional to?

Answer 19

It is proportional to Vd and inversely proportional to clearance.

Question 20

In what situations would be need to measure the concentration of a drug in plasma?

Answer 20

Monitoring of therapeutic effect
If it had known toxic effects
If the drug had zero order kinetics
If the drug had a long half life
Narrow therapeutic window
Great risk of drug drug interaction

Question 21

How do we calculate the loading dose?

Answer 21

= volume of distribution* concentration of drug required at steady state