[GENERAL PRINCIPLES] Drug Receptor Interaction

● Affinity

● Intrinsic activity

Features of a ligand include:

Affinity

This is the ability of a ligand to bind to a receptor (attraction).

Intrinsic activity

This is the ability of a ligand to activate the receptor.

● Agonist

● Antagonist

Classes of Ligands include:

Agonist

[CLASSES OF LIGANDS]

This is a ligand that BINDS (AFFINITY) to a receptor and ACTIVATES (INTRINSIC ACTIVITY) it, producing a biological response.

Full agonist

[CLASSES OF LIGANDS]

The intrinsic activity (IA) of this agonist is equal to 1.

Partial agonist

[CLASSES OF LIGANDS]

The intrinsic activity (IA) of this agonist is less than 1 but greater than 0.

Inverse agonist

[CLASSES OF LIGANDS]

The intrinsic activity (IA) of this agonist is less than 0.

Partial agonist

[CLASSES OF LIGANDS]

This ligand has a mixed agonist and antagonist effect.

Partial agonist

[CLASSES OF LIGANDS]

This ligand acts as an AGONIST when given ALONE but becomes ANTAGONIST when combined with a full agonist.

● Nalbuphine

● Buprenorphine

● Butorphanol

📌 Many opioids with -bup in their names act as partial agonists

[CLASSES OF LIGANDS]

Example of PARTIAL agonist

Reduced analgesia

📌 Nalbuphine (partial agonist) will act as an antagonist in the presence of morphine (full agonist)

[CLASSES OF LIGANDS]

What will happen if nalbuphine is given together with morphine?

Antagonist

[CLASSES OF LIGANDS]

This ligand possesses affinity only.

● Mechanism of action

● Duration of action

● Surmountability

[CLASSES OF LIGANDS]

Classification of antagonism:

● Functional antagonism

● Receptor antagonism

● Chemical antagonism

[CLASSIFICATION OF ANTAGONISM]

Classification of antagonism based on mechanism of action:

Functional antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

This is also known as PHYSIOLOGIC antagonism.

Physiologic antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

Functional antagonism is also known as __________ antagonism.

Functional antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

This happens when two ligands act on DIFFERENT target, producing OPPOSITE effects.

Functional antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

Example of this antagonism is norepinephrine + acetylcholine.

● Norepinephrine activates beta-1 receptors = tachycardia

● Acetylcholine activates muscarinic (M2) receptors = bradycardia

Norepinephrine + Acetylcholine

● Norepinephrine activates beta-1 receptors = tachycardia

● Acetylcholine activates muscarinic (M2) receptors = bradycardia

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

Example of functional antagonism:

Receptor antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

This antagonism is also known as PHARMACOLOGIC antagonism.

Pharmacologic antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

Receptor antagonism is also known as ___________ antagonism.

Receptor antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

This happens when two ligands act on SAME target, producing OPPOSITE effects.

Receptor antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

Example of this antagonism is norepinephrine + propranolol

● Norepinephrine activates beta-1 receptor = tachycardia

● Propranolol inhibits beta-1 receptor = bradycardia

Norepinephrine + Propranolol

● Norepinephrine activates beta-1 receptor = tachycardia

● Propranolol inhibits beta-1 receptor = bradycardia

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

Example of RECEPTOR antagonism:

Chemical antagonism

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

This antagonism includes NEUTRALIZATION and CHELATION.

● Neutralization

● Chelation

[CLASSIFICATION OF ANTAGONISM - MECHANISM OF ACTION]

Examples of CHEMICAL antagonism:

● Reversible

● Irreversible

[CLASSIFICATION OF ANTAGONISM]

Classification of antagonism based on duration of action:

Reversible

[CLASSIFICATION OF ANTAGONISM - DURATION OF ACTION]

This is a FAST, NON-COVALENT interaction that occurs within 24 hours.

Reversible

[CLASSIFICATION OF ANTAGONISM - DURATION OF ACTION]

This interaction is SAFER.

Irreversible

[CLASSIFICATION OF ANTAGONISM - DURATION OF ACTION]

This is a SLOW, COVALENT interaction that occurs within days to weeks.

Irreversible

[CLASSIFICATION OF ANTAGONISM - DURATION OF ACTION]

This interaction is TOXIC.

● Competitive

● Noncompetitive

[CLASSIFICATION OF ANTAGONISM]

Classification of antagonism based on surmountability:

Competitive

[CLASSIFICATION OF ANTAGONISM - SURMOUNTABILITY]

This antagonism is SURMOUNTABLE, meaning the effect can be overcome by INCREASING the dose of the agonist.

Competitive

[CLASSIFICATION OF ANTAGONISM - SURMOUNTABILITY]

This antagonism is REVERSIBLE and SAFE.

Noncompetitive

[CLASSIFICATION OF ANTAGONISM - SURMOUNTABILITY]

This antagonism is NON-SURMOUNTABLE, meaning the effect CANNOT be overcome even by increasing the dose of the agonist.

Noncompetitive

[CLASSIFICATION OF ANTAGONISM - SURMOUNTABILITY]

This antagonism is IRREVERSIBLE and TOXIC.