Pharmocokinetics 2 and 3

Question 1

What is rate of elimination proportional to?

Answer 1

plasma kinetics

Question 2

Equation for rate of elimination?

Answer 2

a constant (L/h) x conc

Question 3

definition of the constant?

Answer 3

This constant is known as the clearance (L/h) and is a measure of the efficiency of elimination

Question 4

define clearance?

Answer 4

Clearance is the volume of plasma irreversibly cleared of drug per unit time.
Plasma CL is the sum of clearances of individual organs

Question 5

There are two bodies, one body is bigger than the other. Both bodies have the same clearance and concentration, so what will be the same and what will be different?

Answer 5

rate of elimination the same, time to eliminate all the drug different for the larger guy

Question 6

How does volume influence steady state?

Answer 6

Volume influences the time to get to steady state but not the magnitude of Css. This is because the concentration at steady state is like the height of the bath and the two tubs can achieve the same height. So volume can affects time to reach steady state but not the steady state itself.

Question 7

What does the slope of Ln conc vs time

after single iv dose tell you?

Answer 7

Slope = CL / V

= k ( elimination rate constant )

Question 8

What is the equation of half life?

Answer 8

T½ = 0.7 V/CL

Question 9

What does half life depend on?

Answer 9

if the Vol increases, T½ increases

if clearance increases, T½ decreases

Question 10

What does the accumulation and elimination half life graph tell you?

Answer 10

Elimination mirrors accumulation. allows you to predict when the maximum effect would be felt.

Question 11

When do you reach steady state in first order kinetics?

Answer 11

After 4 half lives.

Question 12

When does accumulation occur?

Answer 12

Accumulation will occur if :

dose rate in > elimination rate

Question 13

Equation of concentration of steady state?

Answer 13

Css = F x Dose/
DI x CL

F- bioavailability
We can only change the dose and the dose given
F and CL are set for the patient

Question 14

What happens if you give a drug every half life?

Answer 14

The ratio between trough crest wont be greater than two

Question 15

When there is no compliance with the drug what happens?

Answer 15

peak is four times the trough

Question 16

What model do the majority of drugs follow?

Answer 16

1 compartment model

Question 17

What is the two compartment model?

Answer 17

There is a control compartment with a large blood supply. There is distribution of drugs from central compartment to the peripheral compartment.
It is a 2 phase profile with distribution and elimination phase. Concentration drops steeply mainly due to distribution.

Question 18

In zero order kinetics what is half life dependent on?

Answer 18

concentration.

Question 19

In zero order kinetics what happens to elimination

Answer 19

A constant amount is eliminated / time unit

• cf 1st order, where a constant fraction eliminated / time unit

Question 20

In zero order kinetics what does equation At equilibrium
Css = Km x RI / (Vmax - RI)
Where RI = rate in mean

Answer 20

Km - concentration giving you half of the v.mx conc

As rate in approaches Vmax, Css increase therefore drug elimination becomes less possible. because as concentration increases you lose hte direct proportional relationship between rate of elimination and concentration due to saturation of elimination mechanism like enzymes.

Question 21

In zero order kinetics after a single dose what is the time course of pharmacological effect?

Answer 21

Most drugs have greatest effect when Css has been achieved but not for zero order kinetics. This may be because relation between concentration and effect is generally non linear. Observed pharmacological effect may be indirect and take time to develop. Drug at site of action may not be in equilibrium with drug in plasma.