Lecture 6 2/6/24

Question 1

What is clearance?

Answer 1

-overall ability of the living organism to eliminate a drug
-most important pharmacokinetic parameter

Question 2

What is the formal definition of clearance?

Answer 2

rate of drug elimination scaled by plasma concentration

Question 3

What is the operational definition of clearance?

Answer 3

volume of plasma cleared by time unit

Question 4

What impacts the amount of drug contained in the cleared volume?

Answer 4

the concentration/dose of the drug

Question 5

What is the rate of elimination for first order pharmacokinetics?

Answer 5

rate of elimination = constant x concentration

Question 6

How does clearance differ between first order and zero order?

Answer 6

-clearance is constant in first order
-clearance is not constant in zero order

Question 7

What can a clinician control in order to impact clearance?

Answer 7

dosage regimen
-administration route
-dose
-frequency

Question 8

What are the components of clearance?

Answer 8

-blood flow to the organ
-unbound drug fraction
-intrinsic clearing capacity of the organ

Question 9

How does clearance relate to blood flow and organ extraction?

Answer 9

clearance = blood flow x organ extraction

Question 10

How does clearance relate to dose and area under the curve?

Answer 10

clearance = dose/AUC

Question 11

What is capacity dependent clearance?

Answer 11

clearance dependent on what the machinery within a clearance organ can do

Question 12

What is capacity independent clearance?

Answer 12

clearance dependent on how quickly blood flow can bring the substance to the clearance organ

Question 13

What are the dependent factors for high extraction?

Answer 13

blood flow to organ

Question 14

What are the dependent factors for intermediate extraction?

Answer 14

-blood flow to organ
-intrinsic clearing capacity
-protein binding

Question 15

What are the dependent factors for low extraction?

Answer 15

-intrinsic clearing capacity
-protein binding

Question 16

What is the equation for extraction?

Answer 16

Ebody = body clearance/cardiac output

Question 17

What can impact high extraction?

Answer 17

-variations in renal and liver blood flow
-anything else that alters blood flow

Question 18

What can impact low extraction?

Answer 18

-enzymatic metabolism induction or inhibition
-altering capacity
-changes in protein binding

Question 19

What is CL/F?

Answer 19

clearance for routes other than IV admin.

Question 20

Which drug molecules are involved in equilibrium?

Answer 20

only those NOT bound to plasma proteins

Question 21

Why is free fraction not the same as free concentration?

Answer 21

drugs released from plasma protein binding will quickly distribute into the rest of the body fluids

Question 22

What is the reality of protein binding in low extraction?

Answer 22

-clearance increases in parallel to the increase in free fraction
-bound drug concentration decreases while free concentration barely changes

Question 23

In which situation can free concentration increase with increased displacement?

Answer 23

high extraction drugs that are highly bound to plasma proteins, exhibit quick plasma-tissue equilibration time, and have a narrow therapeutic window

Question 24

What truly happens if one drug displaces another?

Answer 24

-unbound fraction increases
-more free drug is available for distribution and elimination
-total drug concentration is lower
-free drug concentration returns to original value

Question 25

What are the three things that can lead to a drug being long-acting?

Answer 25

-highly protein bound: creates storage pool
-high volume of distribution: gets drug into the tissues quickly so it is not in the plasma to be eliminated
-slow release from site of administration