Antagonists and dose-response curves Flashcards

1
Q

What is an antagonist?

A

A drug that blocks the response to an agonist

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2
Q

Antagonist examples

A

Terfenadine at the H1 receptor.

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3
Q

What are pure antagonists?

A

Do not by themselves cause any action by binding to the receptor

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4
Q

General classes of antagonists

A

Chemical
Physiological
Pharmacological

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5
Q

Chemical antagonists

A

Binding of 2 agents to render active drug, inactive.

Commonly called chelating agents

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6
Q

Example of a chemical antagonist

A

Protamine binds (sequesters) heparin

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7
Q

Physiological antagonists

A

Two agents with opposite effects cancel each other out

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8
Q

Example of physiological antagonist

A

Glucocorticoids and insulin

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9
Q

Pharmacological antagonists

A

Binds to a receptor and blocks the normal action of the agonist on receptor responses.

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10
Q

Types of active binding site receptor antagonists

A

Reversible (Competitive antagonist)

Irreversible (Non-competitive active site antagonist)

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11
Q

Type of allosteric site receptor antagonists

A

Reversible and irreversible (Non-competitive antagonists)

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12
Q

Efficacy and antagonists

A

Pure antagonists do not by themselves cause any ‘action’ by binding to the receptor.
Antagonists (no efficacy) - AR* doesn’t exist.

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13
Q

Competitive pharmacological antagonism

A

Binds and prevents agonist action but can be overcome with increased agonist concentration
Causes parallel shift to the right of the agonist response curve.

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14
Q

The dose ratio

A

Agonist plus increasing concentrations of competitive antagonist
(Agonist + antagonist EC50 (x) / Agonist EC50 (y) )

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15
Q

Schild plot for competitive antagonists

A

r - 1 = [B] / Kb
r = Dose ratio
[B] = Antagonist concentration
Kb = Antagonism dissociation constant

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16
Q

What do pA2 values describe?

A

The activity of a receptor antagonist in simple numbers

17
Q

pA2 =

A
  • Log Kb
18
Q

Irreversible (Non-competitive active site) pharmacological antagonism

A

Bind and forms irreversible covalent bonds with receptors.

Causes parallel shift to the right of the agonist-response curve and reduced maximal asymptote.

19
Q

Partial agonist or irreversible antagonist?

A

An antagonism on its own will do nothing, has to have an agonist as well. Agonists will work on their own.

20
Q

Non-competitive (allosteric site) pharmacological antagonism.

A

Signal transduction rather than receptor effects.
Downstream responses are blocked (EG Nifedipine blocks Ca2+ influx)
Reduces slope and maximum dose-response curve

21
Q

Therapeutic window/index

A

Risk:benefit ratio
TD50 / ED50
or
LD50 / ED50