#9 Pharmacodynamics I

Question 1

receptors

Answer 1

interacts with drugs or endogenous substances and is capable of initiating a subsequent response

Question 2

Kd

Answer 2

the equilibrium dissociate or affinity constant. (K2/K1)

inversely proportional to affinity

represents the concentration of the drug that will occupy 50% of a receptor population

Question 3

receptor fractional occupancy

Answer 3

1/(1+(kd/[D])) depends only on affinity and concentration

indenpendent of the number of receptors present

Question 4

total number of receptors occupied

Answer 4

depends on the faction of the receptor population occupied and the number of receptors in a given tissue

the response is related to the total number of receptors occupied

Question 5

selectivity

Answer 5

the ability of a drug to interact with one type of receptor versus other receptors.

Selectivity decreases as dose increases

Question 6

simple occupancy theory

Answer 6

predicts that there is a one to one relationship between receptor occupation and response

1. magnitude of the effect is linearly proportional to the number of receptors occupied by the drug
2. the maximum response is obtained only when all receptors are occupied

does not describe most medications

Question 7

modified occupancy theory

Answer 7

1. response is some positive function of the receptor occupancy (not necessarily linear)
2. max effects could be produced by an agonist occupying only a small portion of receptors
3. different drugs may have varying capacities to initiate a response

Question 8

efficacy (intrinsic activity)

Answer 8

the limit or plateau of the does-response curve on the response axis

Question 9

full agonist intrinsic activity

Answer 9

1

Question 10

neutral antagonists intrinsic activity

Answer 10

0 (bind the receptor but have no biologic effects)

Question 11

potency

Answer 11

the concentration or does of a drug necessary to produce 50% of that drugs maximal response and is expressed as a ED50 value

depends on 1. affinity and 2. efficiency with which drug-receptor interaction is coupled to a response.

Question 12

clinical effectiveness of a drug depends on

Answer 12

maximal efficacy (Emax)

Question 13

spare receptors (receptor reserve)

Answer 13

when a max response can be obtained by activating only a fraction of the available receptors

on a graded dose response curve the max efficacy is reached prior to 3 log units (more narrow curve)

Question 14

competitive antagonism

Answer 14

antagonist bind but do not elicit a response. Higher concentrations of agonist are required to reach Emax.

Emax does not change but ED50 increases

Question 15

non-competitive angtagonists

Answer 15

removed the receptor from available sites. Therefore if there is no receptor reserve Emax will decrease but ED50 (and Kd since affinity for the drug does not change) will remain the same.

Question 16

antagonism by partial agonists

Answer 16

when given with a full agonist they will reduce the max response. As more partial agonist is added the Emax will approach that of the partial agonist

Question 17

chemical antagonist

Answer 17

chemical inactivation of a drug

Question 18

physiological antagonism

Answer 18

the used of opposing regulatory pathways to antagonize the effects of a drug. These effects are less specific and less easy to control than the effects of a receptor specific antagonist

Question 19

therapeutic index

Answer 19

estimate of the safety of a drug. it is the ratio of the TD50 (or LD50) to the ED50 (median toxic/ median effective)

Question 20

therapeutic window

Answer 20

the dosage range between the minimum effective therapeutic dose and the minimum toxic dose. this is more clinically relevant index of safety.

Question 21

median effective dose

Answer 21

ED50 (different meaning) in the quantal dose response curve. it is the dose at which 50% of the individuals will exhibit a specific effect.