L8 Pharmacodynamics I

Question 1

What are the three main phases of drug action?

Answer 1

1. Pharmaceutical phase
2. Pharmacokinetic phase
3. Pharmacodynamic phase

Question 2

Receptor responses to drugs are graded; what does this mean?

Answer 2

Increasing the dose increases the response (up to some maximal point)

Question 3

What is the difference between a binding site and a receptor?

Answer 3

Binding sites can bind a substance but are not themselves capable of initiating a subsequent response; receptors are capable of initiating a response

Question 4

What is a pharmacophore?

Answer 4

The part of a receptor that recognizes and binds the drug (structural specificity)

Question 5

What is the stereospecificity of a receptor?

Answer 5

The isomers of a drug may differ in their potency or maximal activity at the same receptor; they may also preferentially activate different receptors

Question 6

Describe the concept of saturability as it relates to receptors.

Answer 6

Receptors exist in finite numbers and can be saturated by high doses of drugs

Question 7

There is a quantitative relationship between the magnitude of the response and what property of the receptors?

Answer 7

The total number of receptors occupied

Question 8

The response to a drug binding at a receptor depends on what three things?

Answer 8

1. Amount of drug reaching its site of action
2. Specific drug-receptor interaction at the site (coupling efficiency)
3. Functional status of the receptor and/or target cell (desensitization or supersensitivity)

Question 9

True or false - receptors are subject to regulation.

Answer 9

True

Question 10

What are the four major chemical forces that contribute to drug binding?

Answer 10

1. Electrostatic
2. Hydrogen binding
3. Van der Waal’s forces
4. Hydrophobic forces

Question 11

True or false - most drug binding interactions are irreversible.

Answer 11

False - most are reversible

Question 12

True or false - drugs interact with both unoccupied and occupied receptors.

Answer 12

False - they only interact with free/unoccupied receptors; drug displacement generally does not occur in drug receptor interactions

Question 13

The binding of drugs to receptors is dictated by the ___ equation.

Answer 13

Fractional occupancy

Question 14

Fractional occupancy = ?

Answer 14

1/[1+(Kd/[D])]

Question 15

What does receptor fractional occupancy depend on?

Answer 15

1. Drug affinity (Kd)
2. Drug concentration [D]
   NOT receptor number (density)

Question 16

Kd = ?

Answer 16

[D][R]/[DR] = koff/kon

Question 17

What is the Kd value (affinity constant)?

Answer 17

A measure of the propensity of that drug of bind to a given receptor; the concentration of a drug required to occupy 50% of a receptor population

Question 18

As Kd increases, drug affinity ___.

Answer 18

Decreases

Question 19

The magnitude of the response to receptor binding = ?

Answer 19

f[(Fractional occupancy)(Receptor density)]

Question 20

Upon what does drug selectivity depend?

Answer 20

The relative affinities of a drug for various receptors (various Kds)

Question 21

As drug dose increases, selectivity ___.

Answer 21

Decreases

Question 22

It takes at least ___ log units of concentration of a drug to occupy 1-91% of receptors.

Answer 22

3

Question 23

What is the correspondence between the amount of drug and the magnitude of effect?

Answer 23

Dose-response relationship

Question 24

Increasing the dose ___ the effect in a graded manner

Answer 24

Increases

Question 25

What is potency?

Answer 25

The concentration or dose of drug needed to produce 50% of that drug’s maximal response (EC50/ED50)

Question 26

Drug potency depends on what two things?

Answer 26

1. Affinity for the receptor

2. Efficiency with which the receptor activation is coupled to the response

Question 27

What is maximal efficacy?

Answer 27

The maximal response produced by the drug (aka intrinsic activity)

Question 28

What is the intrinsic activity of a full agonist?

Answer 28

1

Question 29

What is the intrinsic activity of a partial agonist?

Answer 29

<1

Question 30

What is the intrinsic activity of a neutral antagonist?

Answer 30

0

Question 31

What is the intrinsic activity of an inverse agonist (negative antagonist)?

Answer 31

<0

Question 32

True or false - efficacy and potency are independent properties of a drug.

Answer 32

True

Question 33

The clinical effectiveness of a drug depends on its ___, not ___.

Answer 33

Maximal efficacy; potency

Question 34

Systems in which maximal response is achieved by doses of agonists that occupy only a small % of receptors are considered to have ___.

Answer 34

Spare receptors

Question 35

What leads to receptor reserve?

Answer 35

Degree of response amplification following any given drug receptor interaction

Question 36

Describe the effects of competitive antagonists on the DR curve, ED50, and Emax.

Answer 36

1. DR curve shifts right
2. ED50 increases
3. Emax is unchanged

Question 37

Describe the effects of non-competitive antagonists on the DR curve, ED50, and Emax.

Answer 37

1. DR curve does not shift along the x-axis
2. No change in ED50
3. Emax decreases

Question 38

How do partial agonists affect response?

Answer 38

Partial agonists reduce the effectiveness of full agonists.

Question 39

What are the three non-pharmacological means of antagonizing drug effects?

Answer 39

1. Chemical (chemical inactivation of a drug)
2. Physiologic (use of opposing pathways to antagonize the effects of the drug)
3. Biologic (one drug affects the metabolism of another)