Inflammation

Chapter 6: Drugs for Treating Inflammation

Introduction to Inflammation

  • Definition of Inflammation: A normal physiological process that is triggered by tissue injury.

    • Purpose: To facilitate the repair of damaged tissues.

    • Characteristics of Inflammation:

    • Redness (Rubor)

    • Swelling (Tumor)

    • Heat (Calor)

    • Pain (Dolor)

  • Inflammation involves the release of chemical mediators, activation of various cells, and the involvement of plasma protein systems.

Cellular Injury and Chemical Mediators

  • Process of Cellular Injury:

    1. Tissue Damage: May result from various factors including invasions by pathogens.

    • Pathogen entry triggers release of chemokines from surrounding tissues.

    1. Chemokines activate basophils and mast cells (types of leukocytes), leading to the release of:

    • Histamine: Increases blood flow and vascular permeability.

    • Prostaglandins: Contribute to vasodilation and direct blood flow to the injury site.

    1. These mediators help bring essential resources like phagocytes to the injury area to combat pathogens.

  • Key Chemical Mediators:

    • Histamine (from mast cells):

    • Increases capillary blood flow.

    • Increases vascular permeability.

    • Arachidonic Acid Metabolites:

    • Leukotrienes: Involved in bronchoconstriction and increased mucus secretion.

    • Prostaglandins: Induce inflammation, mediate pain response, and have normal physiological functions.

Plasma Protein Systems

  • Clotting System:

    • Responsible for the formation of blood clots upon injury.

  • Kinin System:

    • Produces Bradykinin, which causes vasodilation and increases vascular permeability.

  • Complement System:

    • Initiates inflammation, promotes chemotaxis, destroys microorganisms, and increases vascular permeability.

Arachidonic Acid Pathways

  • Membrane Bound Arachidonic Acid:

    • Enzymatic pathways involving Phospholipase A2 lead to the production of:

    • Prostaglandins

    • Thromboxanes

    • Leukotrienes (via Lipoxygenase - LOX)

    • Prostacyclin

  • COX Pathway (Cyclooxygenases)

    • COX-1: Found in most tissues and involves normal physiological functions such as protecting gastric mucosa and maintaining renal blood flow.

    • COX-2: Inducible in inflammatory processes and is involved in increased pain and inflammation.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

  • Categories:

    • Non-selective NSAIDs: Inhibit both COX-1 and COX-2

    • Examples: Aspirin, Ibuprofen, Naproxen, Indomethacin.

    • Selective NSAIDs: Specifically inhibit COX-2

    • Example: Celecoxib (Celebrex).

  • Mechanism: NSAIDs inhibit the cyclooxygenase enzymes, decreasing the formation of arachidonic acid metabolites (particularly prostaglandins), leading to anti-inflammatory effects.

  • Therapeutic Uses:

    • Anti-inflammatory, analgesic, and antipyretic effects.

    • Specific to aspirin: Irreversible inhibition of COX-1 leading to reduced platelet aggregation, thus utilized for cardiovascular protection.

  • Usage Considerations:

    • Despite benefits, effectiveness may vary among patients.

    • Combination therapy (NSAIDs with non-pharmacologic methods) may enhance outcomes.

  • Pharmacokinetics of NSAIDs:

    • Rapid oral absorption; can be administered with food to minimize gastrointestinal upset.

    • Extensive distribution, including crossing the CNS and passing into breast milk.

    • High protein binding; metabolized and excreted via urine.

  • Dosing Examples:

    • Aspirin: 650-975 mg, 4 times/day (OTC)

    • Ibuprofen: 400-800 mg, 3-4 times/day (OTC)

    • Naproxen Sodium: 275-550 mg, twice/day (OTC)

    • Indomethacin: 50 mg, 2-4 times/day (Prescription)

    • Celecoxib: 100-200 mg, 1-2 times/day (Prescription)

Adverse Effects of NSAIDs

  • Common Adverse Effects:

    • Gastrointestinal Effects: Ranging from mild irritation to severe outcomes like ulcers and perforation, primarily due to inhibition of COX-1, which protects gastric mucosa.

    • Cardiovascular Risks: Increased incidence of heart attacks and strokes correlated with selective COX-2 inhibitors.

    • Hypersensitivity Reactions: Varying from mild (urticaria) to severe (bronchospasm).

    • Renal Toxicity: Impaired kidney function due to decreased renal blood flow from reduced prostaglandins.

Corticosteroids

  • Overview: Endogenous corticosteroids produced by the adrenal cortex, primarily glucocorticoids (e.g., cortisol) and mineralocorticoids (e.g., aldosterone).

  • Potency Comparison:

    • Hydrocortisone: Equal anti-inflammatory and sodium retention.

    • Dexamethasone: 25X more potent anti-inflammatory, no sodium retention.

    • Prednisone: 4X more potent anti-inflammatory with equal sodium retention.

  • Adverse Effects:

    • Suppresses HPA axis, leading to various adverse effects like hypertension, increased blood glucose, osteoporosis, and risk of infection.

  • Therapeutic Uses:

    • Inflammatory conditions (e.g., asthma, rheumatoid arthritis), suppression of organ transplant rejection, and replacement therapy for adrenal insufficiency.

Gout

  • Characteristics: Pain and swelling in distal joints; caused by elevated uric acid levels.

  • Symptoms: Severe, acute attacks with varying intervals; risk factors include age, gender, and genetic predispositions.

  • Dietary Triggers: Foods rich in purines like organ meats and alcohol exacerbate conditions.

  • Treatment Options:

    • Acute Attacks: Indomethacin, colchicine.

    • Preventative: Allopurinol (uric acid synthesis inhibitor), probenecid, sulfinpyrazone.

Role of the Athletic Trainer

  • Evaluation of patient history with NSAIDs: weigh risks versus benefits.

  • Educate on taking NSAIDs with food to mitigate GI discomfort and avoid potential kidney impairment.

  • Monitor for any signs of adverse reactions, especially in sensitive populations like children and pregnant women.

These comprehensive notes cover all significant concepts from the transcript on inflammation and its pharmacologic treatments, providing detailed explanations, examples, and guidance on the use of various medications and their implications for athletes. They serve as a robust study guide for understanding pharmacology within athletic training context.