Pharmacokinetics

Question 1

TDM

Answer 1

Therapeutic drug monitoring

• predicts a physiologic response of the concentration:response relationship
• individualizes a patient’s dosage regimen based on serum drug concentrations, serving to improve efficacy and minimize toxicity

Question 2

When is TDM used?

Answer 2

When the pharmacokinetics and pharmacodynamics are understood, and when the drug has a low therapeutic index
- ex: electrolytes (bicarb)

Question 3

Elimination is composed of both ______ and ______

Answer 3

Excretion and metabolism

- follows zero-order and first-order processes

Question 4

Zero-order process

Answer 4

Removes a constant amount of drug

• saturated process
• CRI’s, many transdermals and sustained release formulations

Question 5

First-order process

Answer 5

Remove a constant proportion of drug

• applies to most oral and extravascular administrations
• elimination rate constant primarily determines terminal drug concentrations

Question 6

What is dose proportionality?

Answer 6

Occurs when first-order processes exist and as such a change in dose results in a proportional change in plasma concentrations
- ex: 2x increase in dose = 2x increase in plasma concentration

Question 7

Lack of dose proportionality

Answer 7

• saturation (zero order) of absorptive processes –> ex: 2x increase in dose = 1.5x increase in plasma concentration
• saturation (zero order) of elimination processes leading to drug accumulation beyond proportionality –> ex: 2x increase in dose = 3x increase in plasma concentration

Question 8

What does it mean when a drug is said to have “flip-flop” kinetics

Answer 8

Occurs when absorption rate is slower than the elimination rate

• absorption rate constant primarily determines terminal drug concentrations
• many sustained release formulations have flip-flop kinetics

Question 9

What is an elimination half life and how can it be used to estimate the time required to eliminate a drug?

Answer 9

Time it takes for the body to remove 1/2 of the drug present

• zero order processes: half life changes with changing drug concentrations
• first order processes: half life is constant

Question 10

Clinical implications of first order half life

Answer 10

• predict time to nontoxic concentrations after poisoning or accidental overdose
• predict slaughter and milk withdrawal times

Question 11

What is the purpose in pharmacokinetics of a volume of distribution (Vd) term?

Answer 11

The proportionality constant between C and A is the volume of distribution (Vd) of the drug in the body
- units of L/kg or mls/kg

Question 12

Does Vd have physiologic significance?

Answer 12

Mathematical term that may or may not have physiologic significance

Question 13

What does a Vd>1 L/kg signify?

Answer 13

Associated with tissue binding (concentration) of drug

Question 14

Explain the plateau principle (steady state)

Answer 14

When peak and trough concentrations do not vary between dosing intervals

Question 15

How does changing the dose or the dosing interval affect time until steady state?

Answer 15

Dosage changes result in differing peak and trough values, but it still takes the same amount of time to reach steady-state

Dosage interval changes result in differing peak and trough values, but it still takes the same amount of time to reach steady-state

Question 16

Drugs with ______ reach steady state rapidly

Answer 16

Short half-lives

- no or minimal accumulation from prior doses

Question 17

Drugs with ______ take a long time to reach steady state

Answer 17

Long half-lives

Question 18

To reach desired concentrations rapidly for a drug with a long half life, give a ________

Answer 18

Loading (priming) dose

- applicable to IV or rapidly absorbed extravascular routes

Question 19

Assumptions for ratio (proportionality) method

Answer 19

• no change in interval will occur
• kinetic processes are all first-order (dose proportionality exists)
• for drugs with a long half-life one must wait for steady state to occur thru the plateau principle

Question 20

Ratio formula

Answer 20

Old dose/existing concentration = new dose/ desired concentration
OR
New dose = (old dose x desired concentration)/ existing concentration

Question 21

Clearance

Answer 21

Volume of fluid (plasma) totally cleared of drug in a given time
CL = rate of elimination/concentration in plasma

Question 22

What is total body clearance (TBC) the best parameter for describing the overall disposition of a drug

Answer 22

CL addresses both the elimination rate and the Vd