Pharmacology: Types of Agonists

Types of Agonists

• Full agonist: high affinity and maximum efficacy
• Partial agonist: high affinity but submaximal efficacy
• Inverse agonist: stabilizes receptors in an inactive conformation, producing an effect opposite to that of an agonist

Competitive Antagonists

• Bind to the same binding site as the agonist
• Resemble the agonist chemically
• Right shift of the dose-response curve
• Surmountable antagonism by increasing the agonist dose
• Response depends on the concentration of both the agonist and antagonist
• Examples: Ach – Atropine, Morphine - Naloxone

Non-competitive Antagonists

• Bind to a different binding site than the agonist
• Do not resemble the agonist chemically
• Flattening/downward shift of the dose-response curve
• Unsurmountable antagonism
• Maximum response depends on the concentration of the antagonist
• Examples: Diazepam - Bicuculline

Therapeutic Index

• Calculated as TD50/ED50
• Helps compare the safety of two drugs

Receptor Regulation

• Receptor occupancy: the more receptors occupied, the greater the pharmacodynamic response
• Spare receptors: not all receptors need to be occupied for a maximal response
• Receptor up-regulation: chronic exposure to an antagonist leads to an increased number of receptors
• Receptor down-regulation: chronic exposure to an agonist leads to a decreased number of receptors

Efficacy

• Ability of a drug to provoke a response after binding
• Maximum effect produced by a drug after combining with the receptor
• Drugs with greater efficacy are more therapeutically useful

Potency

• Amount of drug required to produce a desired effect
• Lower the dose, higher is the potency

Dose-Response Curve

• Determines the relationship between the dose administered and the extent of response produced

Ligands

• Agonists: produce a response by binding to receptors
• Antagonists: no response, used to block receptor sites

Receptors

• Regulatory macromolecular component of the cell (usually proteins; can be nucleic acids also)
• Interacts with a drug (ligand) to produce a response
• Usually present on the surface or inside the cell
• Help determine qualitative differences in drug responses and quantitative relationships between the drug concentration and various effects

Classification of Receptors

• G-protein coupled receptors
• Enzyme-linked receptors
• Intracellular receptors
• Ion channels