Pharmacokinetics in practice (metabolism and excretion)

Question 1

What is first order kinetics?

Answer 1

• Rate of elimination is PROPORTIONAL to the plasma drug concentration (processes involved in elimination do not become saturated)
• A constant % of the plasma drug is eliminated over a unit of time
• If plasma concentration ↑ clearance capacity ↑ too

Question 2

What is zero order kinetics?

Answer 2

• Rate of elimination is NOT proportional to the plasma drug concentration (metabolism processes become saturated)
• A constant AMOUNT of the plasma drug is eliminated over a unit of time

Question 3

What is Cmax?

Answer 3

Maximum plasma concentration

Question 4

What is Tmax?

Answer 4

Time taken to reach Cmax

Question 5

What is clearance (CL)?

Answer 5

rate of drug elimination by all eliminating organs

Question 6

What is half life?

Answer 6

time taken for plasma drug concentration to fall 50%

Question 7

What is half life dependent on?

Answer 7

• Dependent on clearance (CL) of drug from body by all eliminating organs (hepatic, renal, faeces, breath)
• Dependent on volume of distribution (Vd):
  
  • A drug with large Vd will be cleared more slowly than a drug with a small Vd
  • The better a drug distributes = will have a longer half life
    -t1/2 is not dependent on drug dose or drug formulation

Question 8

If a drug is given at 50% of its concentration what will happen to its half life?

Answer 8

Stays the same

Question 9

After how many half lives is a drug basically (97%) cleared from the body?

Answer 9

5

Question 10

What is the steady state in continuous IV infusion?

Answer 10

rate of drug input is equal to rate of drug elimination

Question 11

What is Css in continuous IV infusion?

Answer 11

drug plasma concentration at steady state

Question 12

What does a 50% dose reduction do to Css?

Answer 12

50% reduction (time to Css is unchanged)

Question 13

What does reduced clearance mean for half life?

Answer 13

Reduced clearance means prolonged half life
Therefore Css increases
Need dose reduction

Question 14

How is Css calculated?

Answer 14

rate of infusion/ CL

Question 15

What does repeat IV dosing aim to do?

Answer 15

Aim for Css which lies between the Maximum safe concentration (MSC) and minimum effective concentration (MEC)

Question 16

Why would we need to reduce time to steady state?

Answer 16

In some conditions waiting for steady state could be detrimental

Question 17

What could speed up time to steady state?

Answer 17

A loading dose will speed up time to steady state

Question 18

Which drugs require a loading dose?

Answer 18

• Digoxin
• Vancomycin
• Teicoplanin
• Amiodarone
• Heparin

Question 19

When does zero order kinetics occur?

Answer 19

If an enzyme system that removes a drug is saturated the rate of removal of the drug is constant and unaffected by an increase in concentration

Question 20

What order kinetics does ethanol follow?

Answer 20

Ethanol follows zero order kinetics once alcohol dehydrogenase has been saturated

Question 21

Describe drugs with a narrow therapeutic window

Answer 21

Drugs with a narrow window between MEC and MSC