Pharmacodynamics

Question 1

Drug/receptor binding may…

Answer 1

1) do nothing
2) lead to undesired effect
3) lead to desired therapeutic effect

Question 2

Binding reaction driven by…

Answer 2

Chemical/physical forces

Question 3

Binding strength determined by…

Answer 3

Size, shape, charge, hydrophobicity etc.

Small changes can greatly change binding characteristics

Question 4

Drug receptor

Answer 4

Site of binding and initial effect for any drug

Pre-existing receptor whose normal function is signaling in response to an endogenous ligand

Broad - Drug can bind to enzyme, structural element, DNA, protein etc.

Specific - Cell receptors bind drugs and then transduce and amplify intracellular signal that changes cell function

Question 5

Agonist

Answer 5

Mimic endogenous ligand and activate receptor

Intrinsic activity

Question 6

Antagonist

Answer 6

Bind receptor but do not activate it
Block agonist response
May bind with greater affinity
No intrinsic activity

Question 7

Drug action

Answer 7

Molecular mechanism

Question 8

Drug effect

Answer 8

Physiological change

Question 9

Potency

Answer 9

If drug binds tightly it will be a potent modulator of activity

Amount of drug needed to produce a certain response
X axis

Lower doses have higher affinity and are more potent

Question 10

Intrinsic activty

Answer 10

Ability to activate the receptor

Question 11

Law of mass action

Answer 11

Drug binding to receptor is a reversible reaction

From this reaction equation an dissociation constant can be derived (Kd)

Question 12

Low Kd

Answer 12

High affinity for the receptor

Question 13

Kd

Answer 13

Drug concentration at which 50% of receptors are bound

As you increase concentration, there is more drug available to bind receptors until receptors reach a saturation point

Question 14

EC50 or ED50

Answer 14

Amount of drug needed to reach 50% maximum effect
May equal Kd but usually doesn’t

Provides some measure of affinity (potency)

Drug effect is proportional to number of receptors occupied

Question 15

Limitations of dose-receptor/effect curves

Answer 15

Not all drugs activate receptors

Sometimes activation makes it so not all receptors have to be bound to have 100% effect

Question 16

Dose vs Concentration

Answer 16

In vitro = concentration

In vivo = dose (amount that actually reaches the receptor in unknown)

Question 17

Efficacy

Answer 17

Capacity of a drug to produce a pharmacological response

Question 18

Full agonist

Answer 18

Able to produce maximal response

Question 19

Partial agonist

Answer 19

Also termed partial antagonist (takes up/compete for receptors from full agonists but also produce some level of response)
Produce any degree of efficacy between the two extremes

Question 20

LDR Curve slope

Answer 20

Steeper slope increases risk of adverse consequences

Question 21

Graded response

Answer 21

Any action or effect of drug that is continuously variable

Limited in its application to patients due to the great amount of variability in their ability to absorb, distribute, and metabolize the drug as well as their sensitivity to the drug

Question 22

Quantal response

Answer 22

Specified effect or response
“yes or no”
Used to establish safety and efficacy in a large population

Question 23

Cumulative frequency distribution

Answer 23

Quantal dose-response curve

Looks at % of total individuals experiencing quantal response at that dose or lower

Helps to compare desired effect and undesired side effect
What dose is effective for a majority of the population but has bad side effect for a low proportion of the population

Question 24

LD50

Answer 24

Dose that kills 50% of population

More important for animal models

Question 25

TD50

Answer 25

Dose that is toxic to 50% of the population

Some toxic effect happens at lower doses, these are listed as side effects (risk vs benefit)

More important for human trials

Question 26

Drugs with high therapeutic index

Answer 26

Can still produce lethal effects

Minimum dose producing desired effect in 100% of population would be lethal to some members of population

Question 27

Drug selectivity

Answer 27

No drug is “specific” but they can be selective for a receptor

Drugs can bind a subtype of receptor anywhere in the body it is found - this produces wanted effects as well as extra unwanted effects

A drug may prefer one receptor over another but at higher doses the unwanted receptor will be increasingly bound

Question 28

Hyperreactive to drug

Answer 28

Respond to unexpectedly low dose

Question 29

Hyporeactive to drug

Answer 29

Require unexpectedly high dose

Question 30

Hypersensitive to drug

Answer 30

Allergic rxn

Question 31

Tolerance to drug

Answer 31

Hyporeactivity that is acquired

Question 32

Negative intrinsic activity

Answer 32

Antagonist can block normal response causing a decrease in activity that is seen as an effect

These drugs are efficacious but still don’t have intrinsic activity

Question 33

Competitive antagonism

Answer 33

Most antagonists bind reversibly
Agonist must compete for open receptors
**LDR shifts to the right
High concentrations of agonist will overcome antagonist (use this concept to treat overdose)

Question 34

Noncompetitive antagonism

Answer 34

Few antagonists bind irreversibly - function of agonist depends on how many spare receptors are left
**LDR shifts right and decrease maximum/change curve
Effects of these drugs are more prolonged

Question 35

Signal transduction

Answer 35

A single agonist can bind several receptors and convey a different intracellular signal in each one

Question 36

Amplification

Answer 36

Steps in the signaling cascade that multiply the intensity of the signal
Increases sensitivity of the signal and allows for points of regulation

Question 37

Strong input and prolonged input and cell sensitivity

Answer 37

Cell decreases sensitivity and decreases number of receptors

Uncouple g-protein, desensitize ion channel, down regulate receptor formation

Question 38

Diminished input and cell sensitivity

Answer 38

Cell increases sensitivity and increases number of receptors

If input rapidly increases, cell will go cray