PK/PD

Question 1

What is zero order kinetics?

Answer 1

Rate of drug elimination is INDEPENDENT of concentration…Same amount is eliminated per hour. (Very few drugs - ASA, ethanol, phenytoin…)

Question 2

What is first order kinetics?

Answer 2

Rate of drug elimination is DEPENDENT on concentration…half lifes. (most drugs)

Question 3

What is therapeutic index?

Answer 3

The desired range of drug concentration. Calculated - Lethal dose for 50% (LD)/Effective dose for 50% (ED)

Question 4

Which drugs require TDM for narrow TI?

Answer 4

Lithium, digoxin and carbamazepine

Question 5

What are some drugs that require TDM for SE/ADRs?

Answer 5

Phenobarbital, Vancomycin, Aminoglycosides, Dilantin, Flucytosine

Question 6

What is pharmacokinetics?

Answer 6

The study of the ACTION of the drug in the body (Absorption, Distribution, Metabolism, Elimination)

Question 7

What is pharmacodynamics?

Answer 7

The study of the drug’s EFFECT on the biochemical and physiological functions of the body.

Question 8

What is absorption?

Answer 8

How much of the drug and how fast it leaves the site of administration. Described as “bioavailability” or “F”. (F 1.0=100%)

Question 9

What is bioequivalence?

Answer 9

Where two drugs have the same active ingredients, identical in strength, dosage form, route of administration AND F.

Question 10

What are the efflux transporters?

Answer 10

Pgb, MRP2, BCRP

Question 11

What are the influx transporters?

Answer 11

OATP, PEPT, OAT/OCT

Question 12

Antacids can cause a DDI with which meds?

Answer 12

Itraconazole (capsules), ketoconazole, posaconazole, atazanavir, dasatinb, erlotinib and Fe. (All need an acid environment.)

Question 13

Digoxin can cause a DDI with which med?

Answer 13

Amiodarone (Cordarone) because it inhibits the movement of Digoxin into the circulation and can cause toxicity.

Question 14

Fluorquinolones, tetracycline and levothyroxine can cause a DDI with which di- or tri-valent cations?

Answer 14

Ca++, Fe++, Mg++ and Al+++ (Counsel - give supplements 2 hours pre or post or it will effect bioavailability.)

Question 15

What happens in the first phase of distribution?

Answer 15

Drug moves from site of administration to blood.

Question 16

What happens in the second phase of distribution?

Answer 16

Drug moves from the blood to tissue.

Question 17

What is volume of distribution (Vd)?

Answer 17

The estimated volume (size of compartment) needed to account for the total volume of drug in the body if it were the same concentration throughout.

Question 18

Which drugs typically have a low Vd?

Answer 18

water soluble drugs (stay in blood)

Question 19

Which drugs typically have a high Vd?

Answer 19

lipophilic drugs (distribute to tissue)

Question 20

What happens in Phase I metabolism?

Answer 20

oxidation/reduction via an enzyme system (primarily CYP450). Enzymes give a functional group to prepare the drug for Phase II.

Question 21

What is the most common CYP450 (Phase I) enzyme?

Answer 21

CYP3A4 (36% of meds)

Question 22

Which drug is of concern in 2C9 polymorphism?

Answer 22

Warfarin

Question 23

What is a genetic polymorphism?

Answer 23

The patient’s enzyme is changed and drug concentration can go up because the drug does not recognize it for binding.

Question 24

What happens in Phase II metabolism?

Answer 24

Conjugation reactions (by nonmicrosomal enzymes)add a compound to the drug to make it more hydrophilic.

Question 25

What are the Phase II enzymes?

Answer 25

UGT (most common), SALT, NAT, MT enzymes

Question 26

What influences drug elimination from breastmilk?

Answer 26

Lipid solubility Plasma concentration MW (>500 favors elimination) Protein binding (lower protein bound are "free" in plasma and more readily eliminated)

Question 27

Estimates of GFR

Answer 27

CrCl using Cockcroft-Gault (adults) | 24 hours urine

Question 28

Cockcroft-Gault Equation (CrCl)

Answer 28

[(140-age) x kg]/72 x Cr = ml/min (then, multiply x 0.85 if female)

Question 29

What is a normal CrCl for males?

Answer 29

>120 ml/min

Question 30

What is a normal CrCl for females?

Answer 30

>110 ml/min

Question 31

CrCl - use actual body weight or IBW?

Answer 31

If underweight or NOT >20% over IBW, use actual weight. If >20% over IBW, use a range of IBW-actual.

Question 32

Formula: IBW (males)

Answer 32

50 + 2.3 (inches > 60)

Question 33

Formula: IBW (females)

Answer 33

45.5 + 2.3 (inches > 60)

Question 34

CrCl - consideration if >65 yrs, thin or frail and Cr < 1.0

Answer 34

use Cr=1.0

Question 35

"Order" for CrCl calculation

Answer 35

1. kg, height, age, male/female, Cr 2. lbs --> kg 3. Calc IBW using height 4. Is actual body weight >20% over IBW? If so, calculate ABW. 5. Ask, "Cr <1.0. older than 65 and thin/frail? Use Cr=1.0 Plug in numbers to equation. 7. If female, multiply x 0.85

Question 36

Formula: ABW

Answer 36

[(Actual body weight - IBW) x 0.4] + IBW

Question 37

A strong inhibitor increases AUC by how much?

Answer 37

5x (can cause toxicity!)

Question 38

A moderate inhibitor increase AUC by how much?

Answer 38

2x

Question 39

A weak inhibitor increases AUC by how much?

Answer 39

1.25-<2