Response to Antagonists

Question 1

antagonist

Answer 1

drug that binds to a receptor but does not
activate it
* intrinsic efficacy= 0
* Antagonist reduces affinity and/or intrinsic efficacy of
agonist

no response but prevents agonist from binding

Question 2

types of antagonism

Answer 2

Competitive antagonists - reversible
Insurmountable antagonists – irreversible, allosteric
Physiological (a.k.a functional) antagonists

These antagonists counteract the effects of an agonist by producing a physiological response that opposes the agonist’s action. This is not due to direct competition for receptor binding.

Question 3

Competitive Antagonists

Answer 3

• Bind to the same site as the agonist on a receptor
• Bind reversibly to receptor binding site

Question 4

Insurmountable Antagonism

Answer 4

Includes irreversible and some forms of allosteric antagonism (equations do not apply)
* Irreversible antagonism
* Antagonist binds irreversibly (covalently) or with very slow dissociation (very high affinity)
* Effect cannot be reversed by increasing agonist dose

Antagonist binds to a different site from agonist and reduces
receptor activation (intrinsic efficacy) as well as agonist
binding (affinity)

Question 5

Insurmountable Allosteric Antagonism
And other Allosteric antagonism

Answer 5

Mechanism: Antagonist binds to a different site (allosteric site) from the agonist, Reduces agonist binding affinity, reduces receptor activation (intrinsic efficacy).
The antagonist’s effect is insurmountable because increasing the agonist dose cannot reverse the inhibition.

Other Allosteric Antagonism:
Affects only affinity.
The receptor can still achieve full activation and efficacy once the agonist binds.

• Antagonist binds to a different site from agonist and reduces agonist binding (affinity) WITHOUT AFFECTING receptor activation (intrinsic efficacy)
• i.e. negative allosteric modulation

Question 6

Physiological antagonism (functional antagonism)

Answer 6

• agonists with opposing physiological effects on the same tissue
• e.g. Acetylcholine will contract bronchial smooth muscle while salbutamol will relax it

Question 7

Partial antagonism (partial agonist; partial antagonists;
mixed agonist-antagonist)

Answer 7

• properties of both agonists and antagonists (intrinsic
  activity > 0; < 1)
• not 100% max. response even at 100% receptor
  occupancy
• both slope and max. response
  may be different

Question 8

Chemical antagonism

Answer 8

• When two substances combine to form an inactive
  compound

direct chemical interaction between an antagonist and an agonist, leading to the inactivation of the agonist

• e.g. heavy metals with dimercapterol
• e.g. infliximab and tumour necrosis factor (TNF)

Question 9

K_B (Affinity) and pA2 (Potency)

Answer 9

1. K_B is the equilibrium dissociation constant for an antagonist. It reflects the affinity of the antagonist for its receptor.
   A lower K_B value indicates a higher affinity, meaning the antagonist binds more tightly to the receptor.
2. pA2 is a measure of the potency of a competitive antagonist.
   pA2 = -logKb, where the antagonist concentration is the concentration required to cause a twofold shift in the agonist’s dose-response curve.
   == A higher pA2 value indicates a more potent antagonist, meaning it requires a lower concentration to effectively block the receptor.