Pharmacodynamics

Question 1

Receptors determine quantitative relationship between dose of a drug and pharmacological effect

Answer 1

Binding affinity determines concentration required to form drug-receptor complexes, maximal effect of a drug is limited by number of receptors

Question 2

Receptors are responsible for selectivity of drug action

Answer 2

Drug structures determine affinity for receptor classes, non-selective drugs can cause side effects

Question 3

Receptors mediate actions of pharmacologic agonists and antagonists

Answer 3

Drugs binding to receptors can activate or interfere with normal physiological processes

Question 4

Occupancy theory

Answer 4

Intensity of a drug’s response is proportional to the amount of receptors are occupied by that drug, maximal response is achieved when all receptors are occupied

Question 5

Lock and key model

Answer 5

Shape of the drug must fit the shape of the receptor

Question 6

Induced fit model

Answer 6

The receptor undergoes conformational change upon binding to better fit the shape of the drug, depending on the change, a better fit will increase drug-receptor affinity and drug efficacy, better fit explains potency

Question 7

Spare receptor concept

Answer 7

Physiologically, maximal effect can be obtained when only a fraction of the receptors are occupied, spare receptors increase sensitivity for drug binding, less drug is needed to activate effectors for response

Question 8

Affinity

Answer 8

Low Kd = high affinity (inversely proportional), Kd = free drug concentration at which 50% of the drug is bound

Question 9

Potency

Answer 9

Depends on the affinity and efficacy, requires two-drug comparison, EC50 = free drug concentration at which 50% of the maximal effect is achieved

Question 10

Efficacy

Answer 10

Maximal response that can be produced by the drug

Question 11

Kd

Answer 11

Free drug concentration at which 50% of the drug is bound

Question 12

EC50

Answer 12

Free drug concentration at which 50% of the maximal effect is achieved

Question 13

Reversible antagonist

Answer 13

Antagonist does not activate receptor, but competes with the agonist for the binding site

Question 14

Irreversible antagonist

Answer 14

Antagonist binds to allosteric site to cause conformational change to the receptor

Question 15

Competitive antagonist

Answer 15

Competes with the agonist for the binding site, more agonist is required to overcome the antagonism, changes potency

Question 16

Non-competitive antagonist

Answer 16

More agonist cannot overcome the antagonism, antagonist disables receptors so the agonist cannot achieve the full effect, changes efficacy

Question 17

Functional antagonist

Answer 17

Shows the same kinetic response as non-competitive antagonism, binds to another receptor and antagonizes the response, agonist-receptor effect may reach 100% but is antagonized by a separate receptor and does not get 100%

Question 18

Partial agonist

Answer 18

May be more or less potent than a full agonist, do not reach 100% efficacy, can be used clinically to blunt the physiological response in a diseased population

Question 19

Reason for use of partial agonists over full agonists or antagonists

Answer 19

The body will compensate to full agonists and antagonists by upregulation of the receptors, leading to tolerance of the drug, partial agonists do not generate drug tolerance

Question 20

ED50

Answer 20

Dose at which 50% of subjects exhibit a therapeutic response to a drug

Question 21

TD50

Answer 21

Dose at which 50% of subjects exhibit a toxic response to a drug

Question 22

LD50

Answer 22

Dose at which 50% of subjects die

Question 23

Therapeutic index

Answer 23

relates the dose of a drug required to produce a desired effect to that which produces an undesired effect, narrow TI is more dangerous, wider TI is more favorable

Question 24

Equation for therapeutic index

Answer 24

Therapeutic index = TD50 / ED50

Question 25

Margin of safety

Answer 25

Refined from therapeutic index, margin of safety = TD1 / ED99

Question 26

Factors affecting dose-response curve

Answer 26

Body size, weight, age, sex, route of administration, time of administration, pathological state, tolerance, genetic factors, presence of other drugs