Lesson 02: Pharmacodynamics

Pharmacodynamics Overview

• Pharmacodynamics defines the relationship between drug concentration and physiological responses in the body.
• It involves the mechanisms of drug action within living tissues, focusing on how drugs interact with receptors.

Mechanism of Drug Action

• Drugs bind to specific receptors, activating cell signaling pathways, leading to physiological responses.

Therapeutic Index (TI)

• TI is a ratio estimating a drug's safety margin, calculated as TI = LD50/ED50.
• ED50: Effective dose in 50% of a population.
• LD50: Lethal dose in 50% of a population.
• A lower TI indicates a narrow safety margin, requiring close monitoring; a high TI indicates a wider margin and lower toxicity risk.

Therapeutic Range

• Refers to the concentration between minimum effective plasma concentration and minimum toxic concentration.
• Example:
  • Carbamazepine therapeutic range: 6-12 mcg/ml; toxic >12-15 mcg/ml.
  • Phenytoin therapeutic range: 10-20 mcg/ml; toxic >30 mcg/ml.

Dose-Response Relationship

• The dose-response relationship measures the effects of varying drug dosages on response.
• Onset of Action: Time to reach minimum effective concentration after administration.
• Peak Action: Maximum plasma concentration of the drug.
• Duration of Action: Length of time the drug produces a pharmacologic effect.

Graded Dose-Response Relationship

• Potency refers to the amount of drug needed for a therapeutic effect; more potent drugs act at lower doses.
• Efficacy is the maximum response produced by a drug.
• The relative importance of potency vs. efficacy in pharmacotherapy varies by situation.

Drug Mechanisms

• Drugs can function in several ways:
  • Replace or supplement missing chemicals.
  • Increase certain cellular activities.
  • Inhibit or slow down cellular activities.
  • Interfere with foreign cell functions (e.g., chemotherapy).

Receptor Theory

• Drugs exert effects by binding to specific receptors which may initiate or block physiological responses.
• Drug activity is reliant on the affinity for specific receptors.

Receptor Families

• Kinase-linked Receptors: Cell surface receptors activating intracellular enzymes upon binding.
• Ligand-gated Ion Channels: Receptors that open channels for ion flow, mainly sodium and calcium.
• G Protein-Coupled Receptors:
  • Involves interaction with G proteins and downstream effectors, either enzymes or ion channels.
• Nuclear Receptors: Located in the nucleus, modulating gene expression and producing extended responses.

Types of Drug-Receptor Interactions

• Agonists: Drugs that activate receptors to produce a response (e.g., bethanechol).
• Antagonists: Drugs that block receptor activation without producing a response.