Drug Receptors and Pharmacodynamics

Question 1

Simple explanation of Pharmacodynamics

Answer 1

What the drug does to the body

Question 2

Drugs must interact with a _____ to exert an effect

Answer 2

molecular target

Question 3

_____: 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

Answer 3

Receptors

Question 4

Drug interaction with molecular targets is the initiating event in a multistep process that ultimately alters ______ function

Answer 4

Tissue

Question 5

Receptors (regulatory proteins) that are targets for drugs can also be the targets
for ______, such as neurotransmitters and hormones

Answer 5

endogenous substances

Question 6

______ - measure of how tightly or strongly a drug (ligand) binds to a receptor

Answer 6

Affinity

Question 7

Receptors mediate the actions of pharmacologic _____ and _____

Answer 7

agonists and antagonists

Question 8

______- drugs that bind to receptors and produce some effect or signal from the tissue. It is similar to the response produced by endogenous agents. They posses intrinsic activity

Answer 8

Agonists

Question 9

______- drugs that bind to receptors but do not produce an effect or signal. They possess no intrinsic activity. They block responses from the tissue

Answer 9

Antagonists

Question 10

______- the ability of a drug to evoke a response or effect in a target by altering some activity in the target

Answer 10

Intrinsic activity

Question 11

______- the strength of a single drug-receptor interaction that evokes a response

Answer 11

Efficacy

Question 12

_____- the concentration or dose of a drug required to produce 50% of the drug’s max effect

Answer 12

Potency

Question 13

Types of receptors (4)

Answer 13

• Regulatory proteins- best-characterized receptors
• Enzymes- generally inhibited by drug binding
• Transport proteins- can be useful drug targets
• Structural proteins

Question 14

Two types of dose response curves:

Answer 14

1) Graded dose-response curve
-drug concentration v. percentage of maximal effect
- log of drug concentration v. percentage of max. effect
2) Quantal dose-response curve

Question 15

Maximal response that can be produced by a drug on a graded dose-response curve

Answer 15

Emax

Question 16

The concentration of drug that produces 50% of maximal effect on a graded dose response curve

Answer 16

EC50

Question 17

What does the logarithmic graded dose response curve accomplish?

Answer 17

Expands the scale at lower concentration and compresses the scale at higher concentrations (sigmoid curve)

Question 18

T/F If Kd is low, binding affinity is high

Answer 18

T

Question 19

Which of these drugs is the most potent?

Answer 19

B

Question 20

Therapeutic index - the ratio of the ____ to ____

Answer 20

TD50 to ED50

Question 21

______: the range between the minimum toxic dose and the minimum therapeutic dose

Answer 21

Therapeutic window

Question 22

What do ED50, TD50 and LD50 illustrate?

Answer 22

• ED50- dose at which 50% of individuals exhibit the specified quantal event (median effective dose)
• TD50- median toxic dose
• LD50- median lethal dose

Question 23

T/F all receptors have to be occupied to exhibit a full response

Answer 23

F - you cannot directly correlate physiological responses to binding

Question 24

An antagonist that binds to the receptor in a reversible mass-action manner is referred to as a ____ ____

Answer 24

competitive antagonist

Question 25

What is happening in the graph on the left?

Answer 25

* Reversible binding to the receptor * Can be overcome by increasing the agonist concentration * The maximal response of the agonist is not decreased * The agonist dose-response curve in the presence of a competitive antagonist is displaced to the right

Question 25

the degree of inhibition produced by a competitive antagonist depends on the ____ of the antagonist

Answer 25

Concentration

Question 26

the clinical response to a competitive antagonist depends on the concentration of the competing _____

Answer 26

Agonist

Question 27

_____ Bind irreversibly to receptors

Answer 27

Non-competitive antagonists

Question 28

What does an allosteric antagonist do?

Answer 28

* Bind at a site on the receptor different than the agonist binding site * + or - effect

Question 29

Chemical vs. Physiologic antagonists

Answer 29

Chemical- does not utilize receptors - Example: heparin (Neg charge) can be counteracted by protamine (Pos charge). It makes the other drug unavailable for interactions with blood clotting proteins. * Physiologic- between endogenous regulatory pathways. less specific, harder to control than receptor specific antagonist - Example: glucocorticoid hormones v. insulin

Question 30

What do partial agonists do?

Answer 30

Produce a lower response, at full receptor occupancy, than full agonists * Competitively inhibit the responses produced by full agonist

Question 31

How do lipid soluble agents work?

Answer 31

Move directly through the plasma membrane into the cell - intracellular receptors - Steroids, thyroid hormone (receptors stimulate transcription of genes) - lag time to onset of effects - effects persist longer

Question 32

How do ligand-regulated transmembrane proteins work?

Answer 32

Regulates intracellular enzyme activity - Example: insulin, epidermal growth factor

Question 33

How do cytokine receptors work?

Answer 33

Have extracellular and intracellular domains and form dimers Examples: growth hormone, erythropoietin, types of interferon

Question 34

What is this an example of?

Answer 34

Cytokine receptor

Question 35

What is this an example of?

Answer 35

Ligand-regulated transmembrane

Question 36

How do ion channels work?

Answer 36

Many of the most useful drugs act on ion channels * Drugs can mimic or block the actions of natural agonists Examples: acetylcholine, serotonin, GABA, glutamate

Question 37

What is this channel called?

Answer 37

Ion channels

Question 38

How do G proteins and 2nd messangers work?

Answer 38

Extracellular ligands that increase the intracellular concentration of 2nd messengers

Question 39

3 components of transmembrane signaling

Answer 39

-agonist binding -activation of G protein -G protein changes activity of effector enzyme/ion channel

Question 40

______: caused by genetic differences in metabolism or by immunologic mechanisms, including allergic reactions

Answer 40

Idiosyncratic drug response

Question 41

_____: responsiveness diminishes rapidly

Answer 41

Tachyphylaxis

Question 42

What does clinical selectivity mean with regards to drugs?

Answer 42

No drug causes only a single, specific effect * Unlikely that a drug binds only to a single type of receptor * Biochemical processes are coupled to many other biochemical functions

Question 43

Clinically, selectivity is considered by separating effects into

Answer 43

1) beneficial or therapeutic 2) toxic or adverse