Pharmacodynamics Flashcards

1
Q

Pharmacology

A

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

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2
Q

pharmacokinetics

A

dose -> blood concentration -> receptor site concentration

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

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3
Q

pharmacodynamics

A

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

  • what happens once you get to point of action
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4
Q

pharmacology steps

A

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

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5
Q

physiological receptors

A

= 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
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6
Q

steps starting with binding

A

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

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7
Q

classical receptor theory

A

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

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8
Q

modified classical theory

A

-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

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9
Q

result of modified classical theory

A

EC50 lower than apparent Kd for brining

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10
Q

why can cell amplify

A

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

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11
Q

full agonist

A

agonist that produces maximum response from a tissue

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12
Q

partial agonist

A

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

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13
Q

Efficacy

A
  • reflects ability to convert to activated state; related to max response
  • determined by extent of conversion of receptor to activated state by agonist
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14
Q

partial agonist efficacy

A

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

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15
Q

potency

A

reflected by Ec50

  • determined by binding affinity
  • concentration dependence, high potency = high affinity
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16
Q

antagonist efficacy and potency

A

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

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17
Q

partial agonists are also

A

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

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18
Q

partial agonists therapeutic uses

A

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

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19
Q

biased agonism

A

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

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20
Q

opiate receptors and bias agonism

A

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

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21
Q

competitive antagonist

A

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
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22
Q

inverse agonist

A

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

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23
Q

inverse agonist and basal activity

A

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

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24
Q

add competitive agonist to basal receptor activity ->

A

no change

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25
2 state model
basal activity equilibrium between active and inactive conditions generally most receptors = inactivated but some receptors in basal activity state in absence of ligand
26
agonist pulls to
activated state (have higher affinity for activated state than resting, inactive state)
27
inverse agonist pulls to
reduce basal activity bc have higher affinity for inactive state than active state
28
antagonist
affinity for both inactive and active receptor so have no effect on receptor with basal activity
29
effect of competitive antagonist on inverse agonist is
to antagonize its effect which in turn increase apparent activity of a receptor in presence of inverse agonist
30
full and partial agonists and basal activity
will activate receptor with basal activity
31
basal activity
activity level in absence of ligand
32
allosteric modification
bind to site other than transmitter or hormone binding site to affect receptor response
33
negative allosteric modulator
effect of binding is inhibition of agonist response | - aka a noncompetitive antagonist
34
positive allosteric modulator
if binding of an allosteric modulator does not inhibit agonist activation
35
noncompetitive antagonists
bind to receptor whether or not agonist is bound and inhibit activation and response
36
noncompetitive antagonists and agonists
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
37
noncompetitive antagonists and EC50
maximum response is reduced with increasing concentrations of noncompetitive antagonist so no effect on EC50
38
positive allosteric modulators
- 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
39
affect of positive allosteric modulators
- no effect on their own but increase potency of agonists with no effect on efficacy; decrease EC50 of agonist
40
sites of drug action
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
41
physiological receptors
include G protein-coupled receptors, enzyme-linked receptors, nuclear receptors, and ligand-gated ion channels
42
enzymes
ex. acetycholine, cyclooxygenase, angiogensin converting enzyme
43
transporters/ carriers/ pumps
ex. norepinephrine transporter, weak acid carrier, Na+/K+ ATPase
44
ion channels
ex. voltage gated Na+ channels, voltage gated Ca++ channels
45
interactions of drugs with drug receptors share three chracteristics of physiological receptor interactions
- specificity - saturation - reversiblity
46
specificity
ligand is structurally complementary to the receptor, producing a structurally specific and high affinity interaction
47
saturablity
finite number of receptors per cell
48
reversiblity
after being to receptor ligand dissociated in unchanged form
49
actions of drugs on drug receptors include
- physiological receptors - enzymes - transporters/ carriers/ pumps - ion channels
50
physiological receptors
full and partial agonism; inverse agonist; competitive, noncompetitive, and uncompetitive antagonism; allosteric potentiation
51
enzymes
competitive and noncompetitive inhibition
52
transporters/ carriers/ pumps
competitive inhibition and allosteric modulation
53
ion channels
allosteric modulation, including inhibition and activation
54
population or quantal dose effect curve
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
55
median effective dose
dose of drug required to produce desired effect in 50% of animals (ED50)
56
width of frequency distribution
reflects variability in population
57
slope of cumulative frequency distribution
related to width of frequency distribution curve
58
cumulative freqnecy distribution
generated by adding together all animals responding at or below each dose
59
population or quantal dose-effect curve
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
60
slope of population dose effect curve
expression of variability in population rather than of responsiveness of receptor system
61
median toxic dose
dose of drug required to produce toxic or adverse effects in 50% of animals
62
toxic dose
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
63
therapeutic index
comparison of median effective dose and median toxic dose | therapeutic index= TD50/ED50
64
therapeutic index is indication of
how selective drug is in producing desired effect vs its toxic or adverse effects
65
LD50
median lethal dose; can do a therapeutic index which is LD50/ED50
66
overlaps of ED50 curve and LD50 curve
very consequential