Clinical Applications of Pharmacokinetics

Question 1

For IV infusion, rate of entry (R0, in units of mL/min) into the body is constant with

Answer 1

Time

Question 2

This means that absorption by IV infusion is said to follow

Answer 2

Zero-order kinetics

Question 3

The rate of exit, or loss from the body, however, is said to follow

Answer 3

First-order kinetics

Question 4

In fact, the rate of loss is always equal to the

Answer 4

Total body clearance

Question 5

Upon starting an IV infusion, the plasma concentration rises until the rate of loss equals the rate of

Answer 5

Input

Question 6

Thereafter, the plasma concentration reaches a steady state in which drug in = drug out. The steady-state plasma concentration is denoted

Answer 6

Css

Question 7

The achievable steady state plasma concentration depends solely on the

Answer 7

Infusion rate

Question 8

Not achieved any faster if the infusion rate is doubled

Answer 8

Plateau

Question 9

A general rule of thumb is that in order to approximate the steady state condition, we need how many half-lives to elapse?

Answer 9

4

Question 10

Directly proportional to the infusion rate (R0) and inversely proportional to the total body clearance

Answer 10

Css

Question 11

The rate of approach to steady state is independent of R0, but rather depends solely on

Answer 11

kd or t 1/2

Question 12

What are 2 salient considerations for a discontinuous drug regimen?

Answer 12

Half-life and therapeutic index

Question 13

A commonly employed intravenous regimen is to start with a loading dose that is

Answer 13

2X effective dose of drug

Question 14

Then, follow with a maintenance dose that is equal to the effective dose every

Answer 14

Half-life

Question 15

The maintenance dose replaces the amount of drug lost within the

Answer 15

Dosing interval (t*)

Question 16

If the drug is to be administered orally rather than IV, the dosing rate need only be adjusted for the

Answer 16

Oral bioavailability of the drug

Question 17

The most common pattern of drug administration

Answer 17

Fixed dose-Fixed time discontinuous drug regimen

Question 18

In the fixed dose-fixed time regimen, the drug accumulates until

Answer 18

Input = output

Question 19

Drugs are eliminated

Answer 19

Exponentially

Question 20

Therefore, drug accumulates until its concentration increases to a point where the rate of loss = the

Answer 20

Input rate

Question 21

During the dosing interval, we want to know the

Answer 21

Average amount of drug at steady state (Abavg)

Question 22

For patients with renal disease, the sensitivity to drugs is

Answer 22

Unchanged (i.e. plasma concentration of drug that produces the desired effect is the same as in normal patients)

Question 23

However, due to renal disease, we do see impairment of

Answer 23

Elimination

Question 24

Smaller due to renal disease

Answer 24

Kd

Question 25

Due to renal disease, kd is smaller and, thus, we have a larger

Answer 25

t 1/2

Question 26

The degree of impairment is determined by

Answer 26

Severity of renal disease and contribution of renal clearance to total body clearance

Question 27

If a drug is eliminated entirely by renal mechanisms, then impairment of renal clearance will be evident in the form of a decline proportional to that observed in

Answer 27

Creatinine clearance

Question 28

Recall from physiology that creatinine clearance is used as an endogenous measure of

Answer 28

Renal function

Question 29

Specifically, the renal component of drug clearance declines linearly with a decline in

Answer 29

Creatinine Clearance

Question 30

However, the hepatic (metabolic) component of drug clearance remains

Answer 30

Unchanged

Question 31

If t½ is doubled due to renal impairment (i.e., t½-ri = 2t½), then the normal regimen would result in a CSS at

Answer 31

2X the normal level

Question 32

In this situation, in order to avoid toxicity, you must either

Answer 32

1. ) Reduce dose by one-half (o.5Do) | 2. ) Double dosing interval (2t*)