Respiratory Pharmacology: Inflammation, NSAIDs, and Histamine

Introduction to Respiratory Pharmacology

  • Module 4 overview: Inflammation, NSAIDs, Histamine, Asthma, COPD, Cough, Case-based discussions.
  • Learning Objectives: Understand inflammation in respiratory diseases, NSAID pharmacodynamics/pharmacokinetics, histamine's role, and prepare for respiratory pharmacology study.

Clinical Relevance

  • Inflammation's role in asthma, COPD, allergic rhinitis.
  • Case: Asthma patient with nasal polyps experiencing shortness of breath after ibuprofen.

NSAIDs

  • Nonsteroidal anti-inflammatory drugs inhibit prostaglandin (PGs) synthesis.
  • Eicosanoids: PGs, thromboxanes (platelet activation), leukotrienes (vasodilation, chemotaxis).
  • Derived from arachidonic acid (AA), act as local hormones (autacoids).

Eicosanoid Synthesis

  • Membrane phospholipids are converted by Phospholipase A2 into Arachidonic acid.
  • Arachidonic acid is converted by Cyclooxygenases into PGG2, then PGH2.
  • PGH2 is the precursor for: Thromboxanes, Prostacyclin, and Prostaglandins.

COX Enzymes

  • COX (cyclooxygenase) is involved in prostanoid synthesis (PGs, prostacyclin, thromboxanes).
  • Two isoforms: COX-1 (constitutively active, homeostatic functions like gastric acid suppression) and COX-2 (induced by inflammation).
  • NSAIDs inhibit COX enzymes, reducing PGs, prostacyclin, and thromboxane synthesis.

NSAIDs and Inflammation

  • PGs and prostacyclin promote blood flow and leukocyte infiltration.
  • With leukotrienes, they increase vascular permeability, leading to edema and inflammation.
  • Peripheral inflammation: increased COX-2 expression in the spinal cord's dorsal horn.
  • NSAIDs alleviate pain in inflammatory disorders.
  • Therapeutic effect varies based on COX-2 vs COX-1 selectivity.

Types of NSAIDs

  • NSAIDs: antipyretic, analgesic, and anti-inflammatory.
  • Examples: Aspirin, Celecoxib, Diclofenac, Ibuprofen.
  • Other analgesics: Acetaminophen.

NSAIDs - Group Work

  • Aspirin: Irreversible COX-1/COX-2 inhibitor; used for pain, fever, antiplatelet effects; side effects include GI ulcers and Reye’s syndrome.
  • Non-selective NSAIDs (e.g., ibuprofen, diclofenac): Reversible COX-1/COX-2 inhibitors; used for pain, inflammation, fever; side effects include GI, renal, and CV risks.
  • COX-2 Selective Inhibitors (e.g., celecoxib): Selective COX-2 inhibitor; used for osteoarthritis, RA, and pain; less GI risk but increased CV risk.
  • Acetaminophen: Weak COX inhibitor, mostly central; used for fever and mild pain; risk of hepatotoxicity in overdose.

Inflammation Overview

  • Inflammation in asthma/COPD: increased inflammatory cells, edema, dilated blood vessels, excessive mucus.
  • Smooth muscle contraction leads to bronchospasm and hypertrophy (in asthma).

Recap

  • Patient case: 32-year-old woman with asthma and nasal polyps experiencing symptoms after taking ibuprofen.