Pharmacokinetics: clinical

Question 1

What determines plasma concentration of drug and target site concentration

Answer 1

Dynamic interactions among drug ADME

Question 2

Fundamental tenet of clinical pharmacokinetics is a

Answer 2

relationship exists between a drugs pharmacological effects and concentration of drug in blood or plasma

Question 3

Four key parameters govern drug disposition (PK) and dosage regimens

Answer 3

-Bioavailability (%F)……..previously discussed
-Volume of distribution (Vd)…….previously discussed
-Clearance………previously discussed
-Elimination half-life (t1/2 )

Question 4

Eliminatory drug processes are usually __________ processes

Answer 4

First-order; a constant fraction of the drug in the blood (body) is eliminated per unit time

Question 5

How many half-lives is drug considered essentially eliminated from blood

Answer 5

4-5 half-lives

Question 6

Elimination half-life

Answer 6

Time required for blood drug concentrations to decrease by 50%

Question 7

True of false: Half-life depends on dose or blood drug concentration

Answer 7

False: does NOT depend on dose or blood drug concentration

Question 8

MEC

Answer 8

minimum effective concentration

Question 9

What happens if duration is prolonged above MEC for desired effect by increasing dose

Answer 9

May produce peak concentration that yields adverse effects

Question 10

Prolonged eddicacy is usually achieved by

Answer 10

administering multiple small doses of drug maintaining drug concentration above MEC for desired effects

Question 11

Do drugs with short half-lives accumulate

Answer 11

Do not unless administered frequently

Question 12

Drug given after every half life: when is steady state reached

Answer 12

Drug accumulation is greater when drug given every half life; plateau or steady state is reached
after ~5 half lives ie. drug input equals drug eliminated

Question 13

Elimination half-life provides clinicians with information regarding

Answer 13

frequency of drug administration needed to maintain blood drug levels in the therapeutic range

Question 14

Elimination half-life equation

Answer 14

t1/2 = (0.693 x Vd)/CL

Question 15

The goal of most dosing regimens is to

Answer 15

Maintain plasma drug
level in the therapeutic range for the duration of therapy

Question 16

Dosing regimens consist of the following:

Answer 16

• Dose (amount of drug given in mg)
• Route of administration
• Frequency of administration eg q12 hrs
• Duration of therapy eg. 3 days

Question 17

Loading doses can be used to

Answer 17

Achieve target therapeutic drug levels quickly

Question 18

Dose loading equation

Answer 18

DoseLoading = Vd x Csteady state / %F

Question 19

Maintenance doses are given to

Answer 19

maintain drug levels in the target therapeutic range

Question 20

Maintenance dose equation

Answer 20

Dosemain = CL x Csteady state / %F

Question 21

Factors (physiologic, disease and drug factors) will have effects predominately on elimination t1/2 through changes in……..

Answer 21

-Volume of distribution
-Clearance

Question 22

Alteration to PKs can result clinically in adverse drug effects

Answer 22

-achieving too high drug levels in the blood and toxicity
-failure to achieve adequate drug levels in the blood and subtherapeutic failure

Question 23

What factors decrease volume of distribution (either increase or decrease) and how this affects half-life

Answer 23

Aging: decrease distribution (decrease muscle mass) –> decrease half-life

Obesity: Increase distribution (increase adipose mass) –> increase half-life

Pathologic fluid: increase distribution –> increase half-life

Question 24

What factors affect clearance and how does this affect half-life

Answer 24

Cytochrome P450 induction (increase metabolism) –> decrease half-life

Cytochrome P450 inhibition (decrease metabolism) –> increase half-life

Cardiac failure (decrease clearance) –> increase half-life

Hepatic failure (decreased clearance) –> increase half-life

Renal failure (decreased clearance) –> increase half-life

Question 25

Drug interaction

Answer 25

change in the magnitude or duration of a pharmacologic effect of a drug due to the presence of another drug, food or environment factor

Question 26

Incidence of drug interactions…

Answer 26

-Increases with number of drugs given ie polypharmacy
-Increases with duration of use

Question 26

Pharmaceutical interactions occur

Answer 26

Before the drug is absorbed by the patient
— -Usually when combined in same syringe or IV fluids
— -Can also occur in the GI tract lumen
— -Affects total dose available for absorption if given orally, or for injection if given by the IV route

Question 27

Result of alterations in physicochemical properties of the affected drug

Answer 27

-Drug-drug interactions most common….aka drug incompatabilities
-Less commonly drug-environment or drug-diet interactions

Question 28

Most drug interactions of clinical significance are due to changes in

Answer 28

Drug pharmacokinetics

Question 29

Absorption interacions

Answer 29

• stomach pH
• GI motility
• P-glycoprotein (MDR-efflux pump), and GI CYP450’s

Question 30

Distribution interactions

Answer 30

• Plasma protein binding or tissue protein binding displacement
• Changes in tissue blood flow

Question 31

Metabolism interactions

Answer 31

• Metabolizing enzymes (CYP450); phase I MFOs; inhibition and induction

Question 32

Excretion interactions

Answer 32

• Urine pH
• Tubular secretion
• Renal blood flow

Question 33

Induction or inhibition is usually not planned resulting in

Answer 33

an adverse drug effect

Question 34

Occasionally inhibition can be planned resulting in

Answer 34

desired therapeutic effect

Question 35

Induction of P450 enzymes produces ________ primarily through _______

Answer 35

increase in the expression of the enzyme, primarily thru increased gene transcription (mRNA)

Question 36

Consequences of induction include

Answer 36

Increased metabolism of the inducing drug

Question 37

How long does induction take to be realized clinically

Answer 37

Usually days or weeks

Question 38

The clinical significance of induction

Answer 38

is a reduced elimination half life and decreased blood drug levels necessitating increased dosage adjustments to accommodate the induction effect

Question 39

Clinical significance of inhibition relative to induction

Answer 39

Opposite; necessitating
decreasing dosage to accommodate the inhibition effect

Question 40

Onset of inhibition effects on other co-administered drugs PKs is

Answer 40

Must faster than occurs with induction