Pharmacodynamics

Question 1

Pharmacology

Answer 1

study of how function of living systems is affected by chemical agents study of physical and chemical properties and absorption and elimination of chemical agensts

Question 2

pharmacokinetics

Answer 2

dose -> blood concentration -> receptor site concentration

- this is getting drug to site action and what body does to drug distribution and elimination

Question 3

pharmacodynamics

Answer 3

receptor site concentration -> pharmacological réponse -> clinicat response therapeutic outcome

• what happens once you get to point of action

Question 4

pharmacology steps

Answer 4

dose -> blood concentration -> receptor site concentration -> pharmacological response -> clinical response therapeutic outcome

Question 5

physiological receptors

Answer 5

= subset of drug receptors defined by two properties

1. Recognition: binds ligands reversibly with high affinity and specificity
2. Transduction: structure-dependent conversion of binding into cellular response, reflected in activity or efficacy

Question 6

steps starting with binding

Answer 6

binding -> transduction -> response (cell response -> organ response -> body response)

Question 7

classical receptor theory

Answer 7

1: 1 between agonist concentration and % binding or max response
- can be true for some measured response like when recording current flow through ligand, gated ion channel

Question 8

modified classical theory

Answer 8

-bc of signal transduction cascades the original activated receptor response can be amplified and a maximum response can be produced w/o full occupation (saturation) of receptor

Question 9

result of modified classical theory

Answer 9

EC50 lower than apparent Kd for brining

Question 10

why can cell amplify

Answer 10

because response is downstream from binding so cell can amplify the response amplification meaning separation between binding event and response event so can get full response w/o activation all response

Question 11

full agonist

Answer 11

agonist that produces maximum response from a tissue

Question 12

partial agonist

Answer 12

agonist that produces less than the maximum tissue response at full saturation
- binds at higher affinity which doesn’t interfere with its ability to activate

Question 13

Efficacy

Answer 13

• reflects ability to convert to activated state; related to max response
• determined by extent of conversion of receptor to activated state by agonist

Question 14

partial agonist efficacy

Answer 14

convert less of bound receptor to activated state and thus produce lower maximum response

Question 15

potency

Answer 15

reflected by Ec50

• determined by binding affinity
• concentration dependence, high potency = high affinity

Question 16

antagonist efficacy and potency

Answer 16

has zero efficacy but has potency bc bind with affinity but doesn’t lead to change

Question 17

partial agonists are also

Answer 17

partial antagonists bc in presence of full agonist higher concentration of partial agonist will decrease response until maximum response of partial agonist is reached if the concentration of partial agonist vs full agonist is high enough

Question 18

partial agonists therapeutic uses

Answer 18

use partial agonist which turns system down not off bc partial agonists block full response of full agonist

Question 19

biased agonism

Answer 19

multiple independent responses can be generated from different conformations of the receptor; structurally diff agonists can produce diff functional effects by inducing different fxnional effects by inducting diff receptor conformations and activating different intracellular signaling pathways; receptors activating secondary messenger systems can activate more than one effector pathway; different agonists can activate pathways differentially with bias for one pathway over another
- especially true for GPCRs

Question 20

opiate receptors and bias agonism

Answer 20

opiate receptors act by activating Gi/o and binding arrestin Gi/o = analgesic arrestin can -> respiratory distress; hope is find conformation that favors Gi/o to get analgesic effect without as much respiratory distress

Question 21

competitive antagonist

Answer 21

increase the EC50 of agonist w/o affecting its maximum response

• occupy receptor w/o activation and decrease apparent potency of agonist (bc can only have one thing bound at a time); dnt affect efficacy of agonist just potency, increase concentration agonist to overcome this
• can be overcome with higher concentration of agonist and therefore maximum response to agonist is still attainable but requires higher concentrations of agonists

Question 22

inverse agonist

Answer 22

decrease the resting or basal activity of receptor by converting receptors that are active under resting conditions to inactive state; occurs only for receptor that display constitutive activity but even in absence of constitutive activity inverse against will reduce response to an agonist

Question 23

inverse agonist and basal activity

Answer 23

reduces basal activity binds to receptor and changes activity of receptor when there is no ligand;

Question 24

add competitive agonist to basal receptor activity ->

Answer 24

no change

Question 25

2 state model

Answer 25

basal activity equilibrium between active and inactive conditions generally most receptors = inactivated but some receptors in basal activity state in absence of ligand

Question 26

agonist pulls to

Answer 26

activated state (have higher affinity for activated state than resting, inactive state)

Question 27

inverse agonist pulls to

Answer 27

reduce basal activity bc have higher affinity for inactive state than active state

Question 28

antagonist

Answer 28

affinity for both inactive and active receptor so have no effect on receptor with basal activity

Question 29

effect of competitive antagonist on inverse agonist is

Answer 29

to antagonize its effect which in turn increase apparent activity of a receptor in presence of inverse agonist

Question 30

full and partial agonists and basal activity

Answer 30

will activate receptor with basal activity

Question 31

basal activity

Answer 31

activity level in absence of ligand

Question 32

allosteric modification

Answer 32

bind to site other than transmitter or hormone binding site to affect receptor response

Question 33

negative allosteric modulator

Answer 33

effect of binding is inhibition of agonist response | - aka a noncompetitive antagonist

Question 34

positive allosteric modulator

Answer 34

if binding of an allosteric modulator does not inhibit agonist activation

Question 35

noncompetitive antagonists

Answer 35

bind to receptor whether or not agonist is bound and inhibit activation and response

Question 36

noncompetitive antagonists and agonists

Answer 36

noncompetitive antagonists decrease the maximum response of agonists the decrease can't be overcome with high concentration of agonist bc antagonist binding to diff site

Question 37

noncompetitive antagonists and EC50

Answer 37

maximum response is reduced with increasing concentrations of noncompetitive antagonist so no effect on EC50

Question 38

positive allosteric modulators

Answer 38

- agonist binds and increase affinity agonist -> positive modulation - can bind to receptor whether or not agonist is bound; increases affinity of receptor for agonist and still allowing activation of receptor by against

Question 39

affect of positive allosteric modulators

Answer 39

- no effect on their own but increase potency of agonists with no effect on efficacy; decrease EC50 of agonist

Question 40

sites of drug action

Answer 40

broadly termed drug receptors: 4 most common type drug receptors are proteins including - physiological receptors - enzymes - transporters/ carriers/ pumps - ion channels - some drugs can act by binding to structural proteins like tubulin or DNA

Question 41

physiological receptors

Answer 41

include G protein-coupled receptors, enzyme-linked receptors, nuclear receptors, and ligand-gated ion channels

Question 42

enzymes

Answer 42

ex. acetycholine, cyclooxygenase, angiogensin converting enzyme

Question 43

transporters/ carriers/ pumps

Answer 43

ex. norepinephrine transporter, weak acid carrier, Na+/K+ ATPase

Question 44

ion channels

Answer 44

ex. voltage gated Na+ channels, voltage gated Ca++ channels

Question 45

interactions of drugs with drug receptors share three chracteristics of physiological receptor interactions

Answer 45

- specificity - saturation - reversiblity

Question 46

specificity

Answer 46

ligand is structurally complementary to the receptor, producing a structurally specific and high affinity interaction

Question 47

saturablity

Answer 47

finite number of receptors per cell

Question 48

reversiblity

Answer 48

after being to receptor ligand dissociated in unchanged form

Question 49

actions of drugs on drug receptors include

Answer 49

- physiological receptors - enzymes - transporters/ carriers/ pumps - ion channels

Question 50

physiological receptors

Answer 50

full and partial agonism; inverse agonist; competitive, noncompetitive, and uncompetitive antagonism; allosteric potentiation

Question 51

enzymes

Answer 51

competitive and noncompetitive inhibition

Question 52

transporters/ carriers/ pumps

Answer 52

competitive inhibition and allosteric modulation

Question 53

ion channels

Answer 53

allosteric modulation, including inhibition and activation

Question 54

population or quantal dose effect curve

Answer 54

determine effective dose of a drug and its variably in population of animals plot # animals responding to each dose of drug as function of log of the dose producing frequency distribution

Question 55

median effective dose

Answer 55

dose of drug required to produce desired effect in 50% of animals (ED50)

Question 56

width of frequency distribution

Answer 56

reflects variability in population

Question 57

slope of cumulative frequency distribution

Answer 57

related to width of frequency distribution curve

Question 58

cumulative freqnecy distribution

Answer 58

generated by adding together all animals responding at or below each dose

Question 59

population or quantal dose-effect curve

Answer 59

resembles sigmoid shape of concentration-response curve - usually # animals responding normalized to total # animals in study and y axis is expressed as percentage of animals responding

Question 60

slope of population dose effect curve

Answer 60

expression of variability in population rather than of responsiveness of receptor system

Question 61

median toxic dose

Answer 61

dose of drug required to produce toxic or adverse effects in 50% of animals

Question 62

toxic dose

Answer 62

just bc drug has therapeutic effect for animal animal at certain part of curve does not mean it will have toxic or adverse effect at same level of that curve

Question 63

therapeutic index

Answer 63

comparison of median effective dose and median toxic dose | therapeutic index= TD50/ED50

Question 64

therapeutic index is indication of

Answer 64

how selective drug is in producing desired effect vs its toxic or adverse effects

Question 65

LD50

Answer 65

median lethal dose; can do a therapeutic index which is LD50/ED50

Question 66

overlaps of ED50 curve and LD50 curve

Answer 66

very consequential