Lecture 8 2/13/24

Question 1

When does plasma protein binding matter?

Answer 1

-quick plasma-tissue equilibrium time
-narrow therapeutic window

Question 2

Which two characteristics of pharmacokinetics are dependent on physiology?

Answer 2

-Vd
-Cl

Question 3

What drives Kel?

Answer 3

-Vd
-Cl

Question 4

What is the equation for half-life?

Answer 4

HL = 0.693/K

Question 5

What is the equation for K?

Answer 5

Cl/Vd

Question 6

What is the main characteristic of hybrid parameters?

Answer 6

depend on other parameters

Question 7

What is a half-life?

Answer 7

time that it takes for the drug concentration in plasma to decline by 50%

Question 8

In which type of process is half-life a constant value?

Answer 8

first order

Question 9

Why does high clearance not always lead to a short half-life?

Answer 9

if a drug distributes extensively in the tissues, there will not be enough drug in the plasma to clear at the high clearance rate

Question 10

What is the limiting factor of high extraction?

Answer 10

blood flow/speed at which a drug is brought to the liver

Question 11

What is the limiting factor of low extraction?

Answer 11

liver capacity for elimination of the drug

Question 12

What are the potential characteristics of long-acting drugs?

Answer 12

-high plasma protein binding
-high volume of distribution
-slow release from administration site

Question 13

What factors play into selecting a dose interval?

Answer 13

-half-life
-therapeutic index
-compliance

Question 14

When is a drug considered to be majority eliminated from the body?

Answer 14

after 4-6 half-lives

Question 15

What is a steady state?

Answer 15

point where the rate of drug coming in is the same as the rate of drug being eliminated

Question 16

What determines the time it takes to reach steady state?

Answer 16

rate of drug elimination

Question 17

What effect does half-life have on steady state?

Answer 17

-a drug with a shorter half-life will reach steady state sooner
-a drug with a longer half life will reacher steady state later

Question 18

Why is steady state irrelevant for drugs with very short half-life values?

Answer 18

the drug does not accumulate with repeat dosing

Question 19

What is a loading dose?

Answer 19

-increased initial dose that helps a drug get into the therapeutic range quickly
-followed up by maintenance dose(s)

Question 20

Which factors impact half-life?

Answer 20

volume of distribution
-clearance

Question 21

Which factors impact systemic exposure?

Answer 21

-clearance
-bioavailability

Question 22

What is clearance in first order systems?

Answer 22

proportionality constant between the rate of elimination and the concentration of drug in the system

Question 23

What is the calculation for intravenous dose?

Answer 23

dose = Cl x AUC

Question 24

What is the calculation for extravascular dose?

Answer 24

dose = (Cl/F) x AUC

Question 25

What is the equation for infusion rate?

Answer 25

Inf. rate = Conc. steady state x Cl

Question 26

What is the equation for loading dose?

Answer 26

LD = Vd x Conc. steady state

Question 27

How can a new dose be calculated from an old dose when half-life is long?

Answer 27

new dose = old dose x (Conc. target min./Conc. measured min.)

Question 28

What is the theoretical equation for clearance?

Answer 28

Cl = Kel x Vd

Question 29

What is the theoretical equation for volume of distribution?

Answer 29

Vd = dose/C0