Drug Elimination

Question 1

Pharmacokinetic parameters of elimination for a specific drug describe the ____ and ______ of elimination

Answer 1

rate, extent

Question 2

How is rate measured?

Answer 2

Half life (t1/2) or clearance

Question 3

How is extent measured?

Answer 3

not measured, all of drug dose will ultimately be eliminated from the body

Question 4

Clinical relevance of the steady state equation

Answer 4

Question 5

How does blood flow to the liver effects hepatic clearance?

Answer 5

Low extraction drugs - clearance is not significantly influenced

High extraction drugs - changes have a major influence on clearance

Question 6

What affects intrinsic hepatic metabolic activity?

Answer 6

subject to coadministration of inducers and inhibitors

Question 7

3 factors that hepatic clearance varies with

Answer 7

1. blood flow to liver
2. intrinsic metabolic activity (inducers/inhibitors)
3. Protein-drug binding (only free drugs metabolized)

Question 8

What is used to monitor kidney function?

Answer 8

Serum creatinine (SCr), Creatinine Clearance (CrCl)

Question 9

In first order kinetics what is the rate of elimination proportional to?

Answer 9

Rate is proportional to a rate constant X the Cp raised to the first power

Question 10

Most clinically utilized drugs are eliminated by _____ order kinetics when given in therapeutic doses

Answer 10

first (99%)

Question 11

Hepatic metabolism and renal excretion are ____ order processes

Answer 11

First

Question 12

Describe first order kinetics

Answer 12

constant percent of drug eliminated per time, rate of drug eliminated is proportional to Cp and constantly changing

Question 13

A drug eliminated by 1st order kinetics will generate straight line with a slope of ______, and the y intercept is ____

Answer 13

slope is Ke - the elimination rate constant
y intercept is Cp0 plasma concentration at time 0

Question 14

What is half life and how is it determined?

Answer 14

Time required to eliminate half of the drug, used to describe rates of elimination

t1/2 = 0.693/ke

Question 15

Half life is _______ proportional to clearance, and ________ proportional to Vd

Answer 15

inversely, directly

increase clearance = decrease half life
increase Vd = increase half life (and vice versa)

Question 16

Half life is ______ of the total amount of drug present

Answer 16

independent

Question 17

What determines the degree of fluctuation in plasma levels between doses?

Answer 17

The number of half lives in the dosing interval, mor half lives = more fluctuation

Question 18

As a rule of thumb estimate, how long does it take for a drug to reach steady state when administered continuously?

Answer 18

4-5 half lives

Question 19

As a rule of thumb estimate how long does it take a drug to be eliminated after the last dose?

Answer 19

4-5 half lives

Question 20

What is zero order kinetics most often due to?

Answer 20

saturation of hepatic metabolism, especially in phase II conjugations

Question 21

Describe zero order kinetics

Answer 21

The amount of drug eliminated per time is constant and independent of the plasma concentration, seen with very few drugs at therapeutic doses and many drugs at toxic doses

Question 22

The amount of fluctuation in Cp tolerated for any dug is related to its __________ __________

Answer 22

Therapeutic Window

Question 23

How can you slow absorption of a drug and blunt the fluctuations in Cp?

Answer 23

extended release preps

Question 24

Calculate the degree of fluctuation for a drug if t1/2 = 24 hrs and the drug is dosed every 3 days

Answer 24

(T/t1/2) Dosing time/half life = 72hrs/24hrs = 3 –> 2^3 = 8