Pharmacodynamics Overview

Pharmacodynamics Overview

• Pharmacodynamics examines how drugs affect the body, encompassing the pharmacological actions and mechanisms of both therapeutic and toxic effects.
• Explores dose-response phenomena that illustrate the relationship between drug dosage and biological response.

Mechanisms of Drug Action

• Enzyme Inhibition: Certain drugs inhibit enzyme activity, affecting metabolic processes. Examples include:

  • ACE inhibitors and NSAIDs in patients
  • Penicillins and sulfonamides in microbes
  • 5-Fluorouracil (5-FU) and Mercaptopurine (6-MP) in cancer cells

• Ion Channel Modulation: Local anesthetics block sodium (Na+) channels, while calcium channel blockers (e.g., Verapamil) inhibit L-type calcium channels in the heart and blood vessels.

• Interference with Metabolic Pathways: Drugs like 6-MP compete with endogenous purine bases, disrupting DNA synthesis and cell division. Sulfonamides inhibit folic acid synthesis in bacteria by competing with PABA.

Drug-Receptor Interaction

• Receptors are specific cellular macromolecules that interact with ligands (e.g., drugs, hormones) to evoke biological responses, often described by the "Key and Lock Theory".

• Types of Ligands:

  • Agonists: Stimulate receptors mimicking endogenous ligands (e.g., adrenaline on adrenergic receptors).
  • Antagonists: Block receptor activation, possessing affinity but no intrinsic activity (e.g., Prazosin, Propranolol).

Types of Antagonism

• Pharmacological Antagonism: Can be competitive (reversible binding) or non-competitive (irreversible or allosteric).
• Chemical Antagonism: Involves rendering another drug inactive (e.g., Protamine with Heparin).
• Physiological Antagonism: Different receptors initiating opposite physiological effects (e.g., epinephrine countering histamine).

Dose-Response Relationships

• Drug effect magnitude correlates with drug concentration at receptor sites, depicted as graded response curves.
• EC50: Concentration causing 50% of maximum response, used to assess drug potency; lower EC50 indicates higher potency.
• Efficacy: Reflects a drug's ability to produce a desired physiological response, reliant on the number of drug-receptor complexes formed.

Tolerance and Dependence

• Tolerance: Decreased response to a drug after repeated use, often requiring higher doses for the same effect.
• Dependence: Refers to the body's reliance on a drug, leading to withdrawal symptoms upon cessation; can be psychological (e.g., tobacco) or physical (e.g., morphine).

Drug-Drug Interactions

• Additive Effect: Combined effect of drugs equals the sum of each drug's effect (1 + 1 = 2).
• Synergism: Combined use leads to a greater effect than the sum of individual effects (1 + 1 > 2).
• Potentiation: An inactive drug enhances the effect of an active drug (0 + 1 > 1).