Antagonism and Dose response relationships and Principles of Therapeutics Flashcards Preview

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Flashcards in Antagonism and Dose response relationships and Principles of Therapeutics Deck (56)
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1

inhibit or block the effects of an agonist

Antagonists

2

Type of antagonist that combines with the agonist and thereby disallows interaction with its site of action

Chemical

3

Physiological agonists:

1. Activates an opposing physiological input
2. Could be an agonist

4

eg. Acetylcholine and norepinephrine are _________ of each other with respect to regulation of heart rate.

physiological antagonists

5

Blocks the effects of the agonist at its site of action (i.e. receptor)

Pharmacological

6

Binds to exactly the same site as the agonist

Competitive pharmacological antagonist

7

EC50’ is

the EC50 for the agonist in the presence of a given concentration of antagonist;

8

K-sub-I is

the K-sub-D of the antagonist for the receptor

9

EC50’ =

EC50 (1+ ([antagonist]/ K1))

10

Binds to exactly the same site as the agonist

Competitive pharmacological antagonist

11

The ability of the agonist to produce a response in the presence of a competitive, equilibrium
antagonist is dependent upon

the affinity of the antagonist for the receptor and its concentration

12

R + D RD--> Effect
+
A --> AR No Effect
The ability of the antagonist to be effective is dependent upon both

its concentration and the concentration of agonist that is present

13

R + D RD--> Effect
+
A --> AR No Effect
All else being equal, the antagonist with highest affinity for the receptor will

produce the greatest inhibition

14

Binds to the agonist binding site in a covalent or very slowly reversing manner

Irreversible, competitive antagonist

15

Once the receptors are bound by this type of antagonist, they cannot be activated by agonist. This reduces the receptor pool

Irreversible, competitive antagonist

16

Irreversible, competitive antagonist :
When we look at the effect of the agonist in the presence of a non-equilibrium antagonist, the EC50 value _________ but the Emax is ________.

does not change
reduced

17

Therapeutic implications of using a non-equilibrium antagonist
(i) New receptor synthesis is ....
(ii) The degree of inhibition produced is not influenced very much by ....

-the only way to overcome the effects of the antagonist
-the concentration of agonist present

18

a) Blocks the activation of the receptor by an agonist at a site other than the agonist binding site;

Noncompetitive pharmacological antagonist

19

blocks the signal transduction step

Noncompetitive pharmacological antagonist

20

D + R DR --X--> Effect

Noncompetitive pharmacological antagonist

21

Noncompetitive pharmacological antagonist:
The agonist concentration curves look steeper/same as the effect of an irreversible, competitive antagonist

Same

22

Noncompetitive pharmacological antagonist:
Emax is _________ for non-competitive inhibitor
EC50 does/does not change
Is/is not influenced by presence of spare receptors

reduced
does not
is not

23

Noncompetitive pharmacological antagonist:
Antagonist effect is dependent or independent of agonist concentration at the receptor

independent

24

Noncompetitive pharmacological antagonist:
Can be used to inhibit the effects of multiple agonists that use

the same signal transduction cascade (eg. inhibition of voltage operated calcium channels)

25

Partial agonist/partial antagonist (PA)
1. Ligands that have affinity for the receptor and an intrinsic activity between

1 and 0

26

When a partial agonist is present alone, one sees an

agonist effect

27

when a partial agonist is present in combination with a full agonist, one sees an

antagonist-like effect

28

receptors are in equilibrium between

actively signaling (Ra) and inactive (Ri) forms

29

An agonist shifts the equilibrium of Ra and Ri relationship towards

more receptors in the Ra form

30

__________ has no effect, and therefore does not affect this equilibrium at all

A true antagonist