Lecture #107: Pharmacology: Pharmacodynamics Part 1: Terminology and Introduction to Drug-receptor Interactions and the Dose-Response Relationship

What is Pharmacodynamics?

The Study of drug effects and mechanism of action; what the drug does to the body

What is Pharmacokinetics?

The Study of drug movement in the body; what the body does to the drug

What is a Drug?

A substance that produces a biological effect by interacting with the body

What is a Receptor?

Specific biological molecule that a drug binds to produce an effect

What is the Law of Mass Action?

Drug receptor binding is reversible and proportional to drug concentration

What is the Structure activity relationship?

The Relationship between chemical structure and biological activity

What are the Physicochemical properties affecting drug action?

Size, shape, chirality, charge, lipid solubility

What is an Agonist?

Binds and activates a receptor to produce a physiological response

What is a Full agonist?

Produces maximal receptor response

What is a Partial agonist?

Binds receptor but cannot produce maximal response even at high dose

What is an Antagonist?

Binds receptor but does not activate it; blocks receptor

What is a Competitive antagonist?

Competes with agonist at same receptor site; reversible by increasing agonist dose

What is a Noncompetitive antagonist?

Binds allosteric or irreversible site; cannot be overcome by increasing agonist dose

What is an Allosteric activator?

Increases receptor activity by binding to a non-primary site

What is an Allosteric inhibitor?

Decreases receptor activity by binding to a non-primary site

What is an Inverse agonist?

Reduces constitutive receptor activity by stabilizing inactive form

What is Constitutive receptor activity?

Receptor produces baseline activity without agonist present

What is Intrinsic activity?

Ability of a drug to activate a receptor after binding

Define Efficacy (Emax):

The maximum response a drug can produce

Define Potency (EC50):

The Drug concentration needed to reach 50% of maximal effect

Define Affinity:

The Strength of drug receptor binding

Define Kd:

The Drug concentration that binds 50% of receptors; lower Kd = higher affinity

Define EC50:

The Drug concentration producing 50% maximal effect

What is the Graded dose response curve?

It Shows the magnitude of response vs dose

What is the Log dose response curve?

A Sigmoid curve; easier to compare potency and efficacy

What are Spare receptors?

It is when the Maximal effect occurs without full receptor occupancy

What is the Mechanisms of spare receptors?

Long signaling cascades or excess receptor number compared to effectors

What is the Therapeutic index?

LD50 / ED50; measure of drug safety margin

What is the Therapeutic window?

Range between effective and toxic doses

What is Receptor down regulation?

Decreased receptor number due to chronic agonist exposure; leads to tolerance

What is Receptor up regulation?

Increased receptor number due to chronic antagonist exposure; leads to supersensitivity

What is Tachyphylaxis?

A Rapid decrease in drug response after repeated doses

What is Tolerance?

A Gradual decrease in drug effect requiring higher doses

What is a Chemical antagonist?

It Inactivates another drug by chemical reaction (example: protamine and heparin)

What is a Physiologic antagonist?

It Opposes another drug by acting on different receptors or pathways

What is the Duration of drug effect influenced by?

Receptor binding duration, second messenger persistence, receptor turnover, desensitization