Pharmacodynamics

Question 1

pharmacodynamics

Answer 1

the study of the relationship between the concentration of a drug and the response obtained in a patient
*how the drug affects the body

Question 2

receptor

Answer 2

the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects

Question 3

ligand

Answer 3

a substance that binds to a receptor

Question 4

agonist

Answer 4

a drug that binds to and ACTIVATES a receptor

Question 5

antagonist

Answer 5

a drug that attenuates the effect of an agonist

Question 6

5 basic mechanisms of transmembrane signaling

Answer 6

1) a lipid-soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor
2) the signal binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic activity of its cytoplasmic domain
3) the signal binds to the extracellular domain of a transmembrane receptor bound to a separate protein tyrosine kinase, which it activates
4) the signal binds to and directly regulates the opening of an ion channel
5) the signal binds to a cell-surface receptor linked to an effector enzyme by a G protein

Question 7

EC50

Answer 7

drug concentration producing HALF-maximal effect
*used in drug concentration-effect relationship curve

Question 8

Emax

Answer 8

maximal effect of a drug
*used in drug concentration-effect relationship curve

Question 9

Bmax

Answer 9

total concentration of receptor sites
*used in curve for relationship of receptor binding & drug concentration

Question 10

Kd

Answer 10

equilibrium dissociation constant
*represents concentration of free drug at which HALF-maximal BINDING is observed
*used in curve for relationship of receptor binding & drug concentration

Question 11

relationship between Kd and affinity

Answer 11

INVERSE
**Kd characterizes the receptor’s affinity for the drug
**if Kd is high, affinity is low

Question 12

competitive antagonists

Answer 12

*bind the SAME receptor at the agonist
*increases EC50 (shift right) but does not affect Emax
*can be overcome by increasing dose of agonist

Question 13

noncompetitive antagonist

Answer 13

*usually bind in irreversible fashion
*decreases Emax; EC50 unchanged
*effects can NOT be overcome by increasing dose of agonist

Question 14

spare receptors

Answer 14

*in reality, maximal biologic response occurs at a concentration of agonist that does NOT occupy all receptors
*demonstrated by adding an increasing concentration of irreversible antagonist

Question 15

negative allosteric modulators

Answer 15

bind to a different site that alters the agonist binding site
*similar effect to non-competitive antagonists

Question 16

alternative nomenclatures for non-competitive antagonists

Answer 16

1) non-competitive antagonist - orthosteric
2) competitive antagonist - irreversible
3)irreversible antagonist (& insurmountable)

Question 17

alternative nomenclatures for negative allosteric modifiers

Answer 17

1) non-competitive antagonist - negative allosteric modifiers
2) non-competitive antagonist (& insurmountable)

Question 18

partial agonists

Answer 18

*drugs that bind to the receptor, but cause LESS THAN MAXIMAL activation
*concentration-effect curve looks like agonist in presence of irreversible antagonist
*“mixed agonist-antagonist”

Question 19

inverse agonists

Answer 19

*bind to a receptor and produce the OPPOSITE pharmacological effect that would be produced by an agonist or by the natural ligand
*DECREASE receptor activity (less than constitutive activity)

Question 20

potency

Answer 20

*concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect
*depends on affinity (Kd) of drug for receptors AND efficiency of drug:receptor interaction

Question 21

relationship between potency and EC50

Answer 21

potency INCREASES as EC50 decreases
*inverse relationship

Question 22

efficacy

Answer 22

the maximal response that the drug can produce
*whichever curve has the highest Emax is the drug with the highest efficacy

Question 23

ED50

Answer 23

dose that causes a therapeutic effect in 50% of the population

Question 24

LD50

Answer 24

dose that causes death in 50% of the population
median lethal dose

Question 25

TD50

Answer 25

median toxic dose

Question 26

therapeutic dose

Answer 26

RATIO between TD50 and ED50
= TD50 / ED50

Question 27

therapeutic window

Answer 27

RANGE of doses that produce a therapeutic effect without causing significant toxic effects

Question 28

do you prefer a high or a low therapeutic index

Answer 28

prefer a HIGH therapeutic index (can give a lot of drug without toxicity)

Question 29

idiosyncratic response

Answer 29

infrequently observed; sometimes makes no sense

Question 30

hyporeactive response

Answer 30

drug’s effect at a given dose are decreased compared to most people

Question 31

hyperreactive response

Answer 31

drug’s effect at a given dose are increased compared to most people

Question 32

tolerance

Answer 32

decreased responsiveness to a drug as a result of continued administration (need to give more of the drug to get the same effect)

Question 33

tachyphylaxis

Answer 33

desensitization (decreased effect) that occurs rapidly with subsequent doses
*rapidly occurring tolerance