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pharmacology > Agonists and dose response curves L2 > Flashcards

Agonists and dose response curves L2 Flashcards

1
Q

what is the sequence of events that agonists cause and give example

A
  1. bind to receptor forming agonist-receptor complex
    - salbutamol binds to B2 adrenoceptor
  2. causes an action
    - increases cAMP levels
  3. causes an effect
    - bronchodilation
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2
Q

what are dose-response curves used for

A

to determine correct dose

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3
Q

describe dose-response curves

A

Y: biological response
X: log of agonist concentration
-semi log as only one factor is in log

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4
Q

describe the two dose-response relationships

A
  1. graded
    - response of a particular (individual) system
    - measured against agonist concentration
  2. quantal
    - drug dose required to produce specific response determined in each member of population
    - tend to look like bell curve
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5
Q

what does a dose-response curve tell us

A
  1. estimation of Emax
  2. estimation of concentration or dose required to produce 50% of maximal response (EC50 or ED50)
  3. Allow efficacy to be determined
  4. potency to be determined
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6
Q

what is Emax

A

maximum effect of agonist

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7
Q

what is EC/ED50

A

estimation of concentration or dose required to produce 50% of maximal response

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8
Q

what is efficacy

A

the size of the effect
- uses Emax to be determined

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9
Q

if there is a high Emax, what is efficacy like

A

high efficacy

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10
Q

what is potency

A

The drug which can produce an effect at lower drug concentrations is “more potent”
use EC50 to work out

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11
Q

if an agonist has lower EC50, what kind of potency does it have

A

high potency

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12
Q

what is affinity

A

the strength with which an agonist/drug binds to a receptor

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13
Q

in the formation of agonist receptor complex, what does K1 and K-1 represent

A

K1: association constant
K-1: dissociation constant
one agonist receptor complex is formed, it either dissociates or produced biological response

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14
Q

how is receptor saturation easily measured

A

Bmax
maximum number of binding sites

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15
Q

what is difficult to get a measure of in terms of receptor saturation

A

how avidly the drug binds – affinity (KD)

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16
Q

how can affinity be determined

A

K1/K-1
- rate of association/ rate of dissociation

17
Q

what does a large value of K1 and a small value of K-1 mean

A

high affinity and low dissociation rate

18
Q

what is Kd

A

equilibrium dissociation constant

19
Q

what does equilibrium dissociation (Kd) show

A

The KD is a physiochemical constant like Avogadros number and is the same for a given receptor and drug combination in any tissue, in any species (as long as the receptor is the same).
can be used to determine
1. unknown receptor
2. quantitatively compare the affinity of different drugs on the same receptor.
Kd is EC50

20
Q

Kd and affinity are inversely proportional
what does a low Kd suggest

A

high affinity

21
Q

on a binding-dose curve there are two curves
- one to the right and one to the left
which curve has the highest affinity

A

the one to the left as it has lower Kd so less agonist needed to get EC50 as it dissociates less readily

22
Q

which will have the higher potency

A

the one to the left

23
Q

what are potent drugs

A

Potent drugs are those which elicit a response by binding to a critical number of receptors at low concentration (high affinity) compared with other drugs acting on the same system with lower affinity
high affinity at low concentrations

24
Q

what 4 factors is potency dependant on

A

1.affinity of drug
2. efficacy of drug
3. receptor density
4. Efficiency of stimulus-response mechanisms used

25
Q

how does EC50 relate to potency

A

lower EC50, higher potency
- lower concentration needed to achieve half of the maximum biological response
agonists which are potent tend to have high affinity

26
Q

why may only a fraction of total receptors may be needed to be stimulated to get maximum response

A

Many receptors can amplify signal duration and intensity
Systems that exhibit this behaviour are said to have spare receptors

27
Q

what is efficacy

A

ability of agonist to activate receptor and evoke an action
determined by the nature of the receptor-effector system
refers to the maximum effect an agonist can produce regardless of dose

28
Q

what are the two types of agonists and what is their efficacy

A
  1. full agonist: high efficacy
    - the maximum response produced corresponds to the maximum response that the tissue can give.
  2. partial agonist: low efficacy
    - maximal response which falls short of the maximal response that the system is capable of producing
29
Q

what is the relationship between type of agonist, efficacy and forming active agonist-receptor complex

A

full agonist mean active complx is likely
- produce a maximum response while occupying only a small % of receptors available
parital agonist means active complex is less likely
- unable to produce a maximum response even when occupying all the available receptors

30
Q

give 3 examples of partial agonists

A
  1. Varenicline
    -Nicotine receptor partial agonist for smoking cessation.
  2. Tamoxifen
    - Estrogen receptor partial agonists for use in estrogen dependent breast cancer.
  3. Aripiprazole
    - Antipsychotic – partial agonists at selected dopamine receptors.
31
Q

describe inverse agonists

A

Have higher affinity for the AR (inactive) state than for AR* (active) state of the agonist receptor complex
Many ‘classical’ competitive antagonists display inverse agonist activity

32
Q

give an example of inverse agonists

A

β-carbolines on GABAA receptors – anxiogenic rather than anxiolytic

33
Q

what effect does the allosteric modulator Benzodiazepines have on GABA receptors

A

Increases KA for GABA
Increase efficacy of GABA

34
Q

what are the two types of allosteric modulators and give examples

A
  1. Positive (PAM)
    Not active alone but increase affinity and/or efficacy of endogenous agonist
    Examples: Diazepam, Propofol, Isoflurane
  2. Negative (NAM)
    Not active alone but decrease affinity and/or efficacy of endogenous agonists
    mGluR5 dipraglurant
35
Q

describe desensitization of receptors

A

Effect of the drug reduces with continual/repeated administration.

36
Q

what term is given to desenitization of receptors

A

tachyphylaxis

37
Q

how does desentisation of receptors happen

A

Conformational changes in receptor
Internalisation of receptors
Depletion of mediators
Altered drug metabolism
Other physiological responses (homeostatic).

pharmacology (13 decks)

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