Lecture 32

Question 1

What are the three factors that affect plasma concentration of drug?

Answer 1

rate of input of drug into plasma
rate of distribution of drug
rate of elimination

Question 2

a measure of the apparent space in the body availabe to contain the drug

Answer 2

Volume of distribution

Question 3

a measure of body’s ability to eliminate the drug

Answer 3

clearance

Question 4

the fraction of drug absorbed into the systemic circulation

Answer 4

bioavailability

Question 5

What does low Vd mean?

Answer 5

higher drug concentration in plasma than amount of drug in extravascular system (tissue)

Question 6

What does high Vd mean?

Answer 6

higher drug concentration in the body (extravascular system) than drug concentration in plasma

Question 7

Equation for Vd

Answer 7

Vd=Dose/C0

Question 8

Equation for Dose

Answer 8

Dose = Vd * TC (target plasma drug concentration)

Question 9

Equation for clearance

Answer 9

CL = Rate of elimination of drug / plasma drug concentration

Question 10

For a drug eliminated with first-order kinetics, CL is constant, thus the ratio of the rate of elimination to the plasma concentration is the same regardless of plasma concentration. Why is it?

Answer 10

Because physiological mechanisms of drug elimination are not saturated

Question 11

Why is half-life important?

Answer 11

It determines the rate at which blood concentration rises during a constant infusion and falls after infusion is stopped.

Question 12

What is steady-state concentration?

Answer 12

Point where amount administrated per unit time is equal to amount eliminated per unit time

Question 13

For first-order, how many half lives does it take to reach steady state?

Answer 13

4 half lives

Question 14

Half life equation

Answer 14

Half life = (0.693*Vd) / CL

Question 15

For first order, what is the relationship between infusion rate and Css?

Answer 15

Doubling the infusion rate doubles Css, but increasing infusion rate does not influence the time required to reach Css, it still take 4 half lives

Question 16

Factors increasing half life (7) and decreasing half life (1)

Answer 16

incresasing

• obesity & pathologic fluid (effects on Vd)
• ageing, CYP inhibition, cardiac, liver, renal failure (effect on CL)

Decreasing
- CYP induction

Question 17

When is nonlinear kinetics observed?

Answer 17

When drug concentration exceeds Km (zero order)

Question 18

Drugs that exhibit zero order elimination (saturation kinetics) (3)

Answer 18

aspirin at high doses
ethanol
phenytoin

Question 19

Rate of elimination equation for zero order

Answer 19

Drug concentration is much higher than Km (so remove Km)

Rate of elimination = V max

Question 20

Properties of saturation kinetics (zero order)

Answer 20

• rate of elimination is maximal and independent of drug concentration
• a constant amount of drug is eliminated per unit time
  (for first order, a fraction of drug is eliminated)
• plot of plasma concentration vs time is linear.
• CL is not constant, varies with the concentration of drug.
• Half life is not constant

Question 21

Equation for CL in zero order

Answer 21

CL = V max / (Km +C)