Elimination

Question 1

Describe first order kinetics

Answer 1

Decline of plasma drug level (elimination) is proportional to drug level - constant fraction of drug is eliminated in unit time.
Linear
Curve if normal, line on log scale
Constant fraction of drug eliminated

If the concentration of drug rises, the rate of elimination rises

Question 2

Describe zero order kinetics.

Answer 2

Rate of decline of plasma drug level is constant.

Non-linear
Rate of elimination is constant and is not dependent on concentration of drug present.
Constant amount of drug is eliminated.

Question 3

When does zero order kinetics occur?

Answer 3

Occurs when the transporters/enzymes are saturated and so will occur for all drugs at high concentrations, although some drugs exhibit zero order kinetics at therapeutic concentration.

Drug elimination also becomes zero order in the elderly and those who are very ill (renal, cardiac or hepatic complications that slow down drug metabolism), it is also more likely to occur in polypharmacy – if drugs either compete for or inhibit cytochrome enzymes or renal transporters

Question 4

What drugs require close monitoring?

Answer 4

0 order drugs need careful monitoring as do those with long half-lives, narrow therapeutic windows and those at greater risk of drug-drug interactions.

0 order drugs are more dangerous as their plasma concs can rise rapidly unpredictably and lead to toxicity and no half-life can be calculated whereas 1st order stay in control as concs increase so does the elimination rate.

Question 5

What factors affect half life? Equation?

Answer 5

Half-life is affected by Vd and Cl unsurprisingly so anything that affects these also affects half-life so (HRH) heart, renal and hepatic factors will play a role.

Half-life = 0.693 x Vd/ Clearance

Question 6

How are steady states achieved?

Answer 6

Repeated dosing of a drug. A balance of the absorption and distribution, and the metabolism and elimination must be achieved. You are aiming for a concentration in the therapeutic window, so as to get a therapeutic effect but not have high risk of toxicity

SS target conc=dose rate/clearance

Question 7

How many half-lives to reach a steady state?

Answer 7

4-5 - only in first order kinetics

Question 8

How to reach steady state more quickly?

Answer 8

Give a loading dose (fill compartments that make up volume of distribution.

Loading dose = volume of distribution x steady state target connotation