Pharmacodynamics I and II

Pharmacodynamics Overview

• Pharmacodynamics explores how drugs interact with biological systems through receptor engagement.
• Drug effects are mediated by receptors on target cells, altering cellular activities and organ function.

Receptors

• Defined as cellular macromolecules that interact with drugs to trigger biochemical events.
• Types of ligands that act on receptors: neurotransmitters, ions, hormones, immunoglobulins, lipoproteins, carbohydrates, and exogenous drugs.

Affinity and Intrinsic Activity

• KD indicates the concentration of ligand at which 50% of receptors are occupied; a lower KD signifies higher affinity.
• Efficacy measures the ability of a drug to produce an effect after binding to a receptor.

Receptor-Mediated Signal Transduction

• Includes a sequence: reception, activation of effectors, transduction, cellular response, signal amplification, and feedback regulation.
• The physiological processes are controlled by receptors, regulated by endogenous molecules.

Types of Agonists and Antagonists

• Full agonists elicit maximum response and have 100% intrinsic activity.
• Partial agonists bind fully but produce only partial effects.
• Antagonists block receptor activation without producing significant intrinsic activity.

Dose-Response Relationships

• The response to drug doses typically follows a non-linear relationship; low doses yield incremental responses which diminish at higher doses.
• Graded dose-response curves depict varying effects with increasing doses, while quantal curves show the drug's effect across a population.

Dose-Response Curves

• Arithmetic scale is less effective for large dose differences; it obscures changes in high concentrations.
• Logarithmic scale allows clearer visualization of drug effects and facilitates easier comparison across drugs.

Concepts of Efficacy and Potency

• Efficacy defines the maximum achievable effect of a drug, while potency measures the required dose for a specific effect.
• ED50 defines the effective dose for 50% of the population; EC50 indicates the concentration for half of the maximal response.

Types of Antagonism

• Competitive antagonism occurs when an antagonist competes with an agonist for binding, shifting the agonist’s curve to the right.
• Non-competitive antagonism results from irreversible binding or slow dissociation, depressing maximum response while shifting the curve rightward.

Therapeutic Index

• Therapeutic Index (TI) is the safety ratio of median lethal dose (LD50) to median effective dose (ED50).
• A higher TI indicates a safer drug with a larger margin before toxicity occurs.

Regulation of Receptors

• Receptors undergo adaptation through desensitization (reduced response despite continued stimulation) and can be upregulated (increased receptor number) or downregulated (decreased receptor number).
• Covalent modifications and association with regulatory proteins also influence receptor activity.

Drug Interactions

• Synergism occurs when the combined effect of two drugs is greater than the sum of their individual effects.
• Additive effects represent the straightforward sum of effects from two drugs.
• Potentiation refers to a scenario where one drug enhances the effect of another, even if it does not elicit a response by itself.