Pharm - Pharmacokinetics/-dynamics (Enzyme kinetics, Pharmacokinetics, & Dosage calculations)

Question 1

What are the axes of the Michaelis-Menten kinetics graph?

Answer 1

x-axis: [S] = concentration of substrate, y-axis: Velocity (V)

Question 2

Draw the Michaelis-Menten kinetics graph, graph a reaction, including and labeling the following: (1) Km (2) Vmax (3) 1/2 Vmax (4) Saturation.

Answer 2

See p. 238 in First Aid 2014 for graph at top

Question 3

How does Km relate to affinity of enzyme for its substrate?

Answer 3

Km is inversely related to the affinity of the enzyme for its susbstrate

Question 4

How does Vmax relate to enzyme concentration?

Answer 4

Vmax is directly proportional to the enzyme concentration

Question 5

What kind of curve do most enzymatic reactions exhibit? What does this mean?

Answer 5

Most enzymatic reactions follow a hyperbolic curve (follow Michaelis-Menten kinetics)

Question 6

What causes an enzymatic reaction to exhibit a sigmoid curve? Give an example of such a reaction.

Answer 6

Enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (i.e.., hemoglobin)

Question 7

What are the axes of the Lineweaver-Burk plot?

Answer 7

x-axis: 1/[S], y-axis: 1/V

Question 8

Draw the Lineweaver-Burk plot, graph a reaction, including and labeling the following: (1) 1/-Km (2) 1/V max (3) slope = Km/Vmax.

Answer 8

See p. 238 in First Aid 2014 for middle graph

Question 9

What is the slope of the Lineweaver-Burk plot?

Answer 9

slope = Km/Vmax

Question 10

What happens to Vmax as the y-intercept of the Lineweaver-Burk plot is increased?

Answer 10

increase y-intercept, decrease Vmax

Question 11

On the Lineweaver-Burk plot, what does it mean to move the x-intercept to the right (in terms of numerical value)? What effect does this have on Km and affinity?

Answer 11

The further to the right the x-intercept (i.e., closer to zero), the greater the Km and the lower the affinity

Question 12

Graph the following lines on the Lineweaker-Burk plot: (1) Competitive inhibitor (2) Noncompetitive inhibitor (3) Uninhibited.

Answer 12

See p. 238 in First Aid 2014 for bottom graph

Question 13

How do competitive versus noncompetitive inhibitors interact with their own kind?

Answer 13

Competitive inhibitors cross each other competitively, whereas noncompetitive inhibitors do not

Question 14

Does each of the following resemble substrate: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?

Answer 14

(1) Yes (2) Yes (2) No

Question 15

Is each of the following overcome by increasing [S]: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?

Answer 15

(1) Yes (2) No (3) No

Question 16

Does each of the following bind the active site: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?

Answer 16

(1) Yes (2) Yes (3) No

Question 17

What effect does each of the following have on Vmax: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?

Answer 17

(1) Unchanged (2) Decrease (3) Decrease

Question 18

What effect does each of the following have on Km: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?

Answer 18

(1) Increase (2) Unchanged (3) Unchanged

Question 19

What effect does each of the following have on potency/efficacy: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?

Answer 19

(1) Decrease potency (2) Decrease efficacy (3) Decrease efficacy

Question 20

In general, what does pharmacokinetics study? Give 4 specific examples.

Answer 20

The effects of the body on the drug; (1) Absorption (2) Distribution (3) Metabolism (4) Excretion; Think: “ ADME”

Question 21

In general, what does pharmacodynamics study? Give 4 specific examples of concepts.

Answer 21

The effects of the drug on the body; Includes concepts of (1) receptor binding (2) drug efficacy (3) drug potency (4) toxicity.

Question 22

Define Bioavailability. What is its abbreviation?

Answer 22

Bioavailability (F): Fraction of administered drug that reaches systemic circulation unchanged

Question 23

What is the bioavailability of an IV dose?

Answer 23

For an IV dose, F = 100%

Question 24

What is the bioavailability of an oral dose, and why?

Answer 24

Orally: F typically < 100% due to incomplete absorption and first-pass metabolism

Question 25

Define Volume of distribution (Vd)

Answer 25

Theoretical volume occupied by the total absorbed drug amount at the plasma concentration.

Question 26

What alters the apparent Vd of plasma protein-bound drugs?

Answer 26

Apparent Vd of plasma-protein bound drugs can be altered by liver and kidney disease (decreased protein binding, increased Vd)

Question 27

What is a minor but important consideration in calculating volume of distribution?

Answer 27

Drugs may distribute in more than one compartment

Question 28

What is the equation for Vd?

Answer 28

Vd = amount of drug in the body / plasma drug concentration

Question 29

Into what compartment do drugs with a low Vd distribute? What characterizes such drugs?

Answer 29

Blood (4-8 L); Large/charged molecules, Plasma protein bound

Question 30

Into what compartment do drugs with a medium Vd distribute? What characterizes such drugs?

Answer 30

ECF; Small hydrophilic molecules

Question 31

Into what compartment do drugs with a high Vd distribute? What characterizes such drugs?

Answer 31

All tissues including fat; Small lipophilic molecules, especially if bound to tissue protein

Question 32

What defines half-life (t 1/2)?

Answer 32

The time required to change the amount of drug in the body by 1/2 during elimination (or constant infusion)

Question 33

Of what type of elimination is half-life a property?

Answer 33

Property of first-order elimination

Question 34

What is the equation for half-life?

Answer 34

t 1/2 = (0.693 x Vd) / CL

Question 35

At the following half-lives, what percentage of drug remains: (1) 1 (2) 2 (3) 3 (4) 4?

Answer 35

(1) 50% (2) 25% (3) 12.5% (4) 6.25%

Question 36

Define Clearance (CL).

Answer 36

The volume of plasma cleared of drug per unit time

Question 37

What are 3 factors/conditions that may impair clearance.

Answer 37

Clearance may be impaired with defects in cardiac, hepatic, or renal function.

Question 38

What is the equation for Clearance (CL)?

Answer 38

CL = rate of elimination of drug / plasma drug concentration = Vd x Ke (elimination constant)

Question 39

What is the equation for the loading dose?

Answer 39

Loading dose = (Cp x Vd) / F; Cp = target plasma concentration at steady state,

Question 40

What is the equation for the maintenance dose?

Answer 40

Maintenance dose = (Cp x CL x tao) / F; Cp = target plasma concentration at steady state, tao = dosage interval (time between doses), if not administered continuously

Question 41

What happens to maintenance versus loading doses in renal or liver disease?

Answer 41

In renal or liver disease, maintenance dose decreases and loading dose is usually unchanged

Question 42

On what factor does time to steady state depend? Of what 2 factors is it independent?

Answer 42

Time to steady state depends primarily on t 1/2 and is independent of dose and dosing frequency

Question 43

In Michaelis-Menten kinetics, what is Km?

Answer 43

Km is [S] at 1/2 V max