CHAPTER 2- Drug Receptor Interaction Pharacodynamics

Question 1

Agonist

Answer 1

drug that binds to receptor and ACTIVATES it FULLY, induces a biological response
- same action as endogenous molecules

Question 2

Partial Agonist

Answer 2

drugs that binds to receptor and PARTIALLY ACTIVATES it, induces biological response
- mimics the action of endogenous molecules in our body

Question 3

Antagonist

Answer 3

drug binds to receptor and BLOCKS it, reduces biological response/inhibit activity

Question 4

Receptor Families (4)

Answer 4

Ligand-gated ion channels, G protein-coupled receptors, Enzyme-linked receptors, Intracellular receptors

Question 5

Ligand-gate Ion Channels

Answer 5

drug binding site regulates opening of the pore
- channel closed until activated by agonist, then channel opens
EX) Ach opens nicotinic receptors

Question 6

G protein-coupled Receptors

Answer 6

extracellular portion contains ligand binding site, intracellular portion interacts w G protein when activated
- made of alpha, beta, and gamma subunits
- a subunit goes somewhere to activate/inhibit another effector

Question 7

G proteins; Gs, Gi, and Gq

Answer 7

Gs: activates adenylyl cyclase, inc cAMP
Gi: inhibits adenylyl cyclase, dec cAMP
Gq: activates phospholipase C, inc IP3, inc DAG (secondary messengers)

Question 8

Enzyme-linked receptors

Answer 8

receptor has a conformational change when activated by ligand, results in ic intracellular enzyme activity
ex) insulin receptor, triggers production of glucose transporters
ex) extracellular receptor binds, intracellular enzyme acts

Question 9

Intracellular receptors

Answer 9

ligand must have sufficient lipid solubility to diffuse into cell and react w receptor
- transcription factors activated and inactivated

• steroid receptors: endogenous molecule passes through membrane, binds, moves into nucleus for gene transcription

Question 10

Signal transduction (2 aspects)

Answer 10

-signal amplification
-desensitization and down-regulation of receptors

Question 11

Signal Amplification

Answer 11

ability to amplify the signal intensity and duration through the signal cascade effect
- ex) activated G proteins longer durations than the original agonist-receptors

Question 12

Desensitization and down/up-regulation of receptors “defense mechanisms”

Answer 12

repeated/continuous agonist can change the responsiveness of the receptor
- becomes DESENSITIZED/not response to drug

down-regulation: transmembrane receptors internalize, not available to agonist

up-regulation: repeated exposure to ANTAGONIST, receptor reserves are inserted into membrane and inc number of receptors available

Question 13

Graded Dose-Response relationship
- potency and EC50

Answer 13

graded= how much
- tells us the drug potency, EC50 shows the concentration of the drug producing 50% of the maximum effect to determine potency

Question 14

which drug is more potent? one with a higher EC50 and steeper curve, or higher EC50 and less steep curve?

Answer 14

the one with the steeper curve is more potent. it reaches that EC50 (50% of max effect) faster than another drug. therefore it is more POTENT

Question 15

potency vs. efficacy

Answer 15

potency- measure of amount of drug necessary to produce an effect, expressed by EC50

efficacy- magnitude of response a drug causes when it interacts w a receptor, HEIGHT of the curve
- Emax is max efficacy of a drug

Question 16

potency, what does EC50 show you?

Answer 16

a smaller EC50 means the drug has a greater potency.
a larger EC50 means the drug has lower potency. it takes longer for that drug to reach 50% of its max effect, so it is not as potent as something that takes a shorter amount of time to reach that threshold.

Question 17

how do you reach Emax, max efficacy?

Answer 17

when all receptors are BOUND/OCCUPIED
-higher curve=greater effect/efficacy

Question 18

intrinsic activity

Answer 18

determines ability of drug to activate to the receptors and its max effect, drug categorized according to this and its Emax values

Question 19

drug categories

Answer 19

agonists and antagonists

Question 20

Agonist (3)

Answer 20

full, partial, and inverse agonists

Question 21

Antagonist (2)

Answer 21

competitive, non competitive (irreversible and allosteric)

Question 22

Full Agonist
- definition
-intrinsic activity

Answer 22

produce MAX biological effect, mimics response to the endogenous molecucle

intrinsic activity=1

Question 23

Partial Agonist
- definition
-intrinsic activity

Answer 23

produce LESS THAN max effect compared to full

intrinsic activity >0 and<1

• causes a conformational change of target once binded but not exact like the full agonist

Question 24

full agonists with partial antagonists

Answer 24

may be coupled with an agonist to occupy binding sites and REDUCE the activity of the full agonist

Question 25

Inverse Agonists

Answer 25

reverse the spontaneously active receptor into an INACTIVE form

intrinsic activity <0
- produces an effect OPPOSITE to the agonist

Question 26

difference between inverse agonists and antagonists?

Answer 26

inverse agonists inactivate the receptor and produces an effect OPPOSITE to the agonist.
antagonists produce no effects, but simply block the activity that was being produced before and decrease the effect

Antagonists will never produce an OPPOSITE EFFECT

Question 27

Antagonists

Answer 27

bind to a receptor with a high affinity, possess ZERO intrinsic activity
-NO effect on biological function, can DEC effect of an agonist when present

Question 28

Competitive Antagonists

Answer 28

bind to the SAME site on receptor as the agonist REVERSIBLY
intrinsic activity=0

Question 29

how do you overcome inhibition with competitive antagonists?

Answer 29

• inc conc of agonist relative to antagonist can OVERCOME inhibition, displaces the antagonist

Question 30

Non-Competitive Antagonists

Answer 30

bind PERMANENTLY to the receptor , reduces number of receptors available to the agonist

Question 31

can you overcome inhibition with non-competitive antagonists?

Answer 31

no you cannot. increasing the conc of agonists doesn’t make a difference to the antagonist effect

Question 32

non-competitive antagonists: Irreversible

Answer 32

bind to the same site as the agonist

-irreversibly=covalent bonds (strong bonds)

Question 33

non-competitive antagonists: allosteric

Answer 33

bind to a site OTHER than agonist binding site, can result in conformational change in binding site
makes it not possible for the agonist to bind

Question 34

Quantal Dose-Response relationship

Answer 34

relationship between the DOSE of the drug and the proportion of patients that respond to it

Question 35

quantal dose: 3 effects we look at

Answer 35

all done in PRECLINICAL TRIALS:

therapeutic effect- ED50
toxic effecct- TD50
lethal effect-LD50

Question 36

Quantal dose: therapeutic effect

Answer 36

the effective dose in 50% of the population

Question 37

Quantal dose: toxic effect

Answer 37

the dose that induces toxic effects in 50% of the population

Question 38

Quantal dose: lethal effect

Answer 38

the dose that induces lethal effects in 50% of the population

Question 39

quantal dose: Therapeutic Index (TI)
what is it? what does it measure?

Answer 39

it is a measure of DRUG SAFETY

the ratio of the TD50 (produces toxicity) over the ED50 (produces the clinically desired/effective response)

Question 40

therapeutic index: relationship

Answer 40

higher TI=safer drug
when the TD50 is a larger amount than the ED50 this means it gives us a very large range between the effective and toxic doses to administer that drug
- gives more room to inc conc of the drug before reaching TD50 and experiencing ADVERSE EFFECTS!!!

Question 41

why is a low TI (therapeutic index) bad?

Answer 41

lower TI indicates that the TD is lower than the ED. this indicates a smaller range between ED dose and TD dose resulting in a difficult range to administer drug doses without crossing over into that toxic range