6Tb: NSAIDs

Mechanism of Action

  • NSAIDs function by inhibiting the synthesis of prostaglandins and leukotrienes in the arachidonic acid pathway through cyclooxygenase (COX) inhibition.

    • No effect on other inflammatory mediators.

    • Effective in reducing signs and pain related to inflammation.

    • Generally safer than corticosteroids, but can be ineffective without corticosteroid therapy.

Types of Cyclooxygenase Enzymes

  • COX-1:

    • Found in most tissues, involved in housekeeping functions.

  • COX-2:

    • Induced in inflammatory cells and blood vessels.

    • The anti-inflammatory effects of NSAIDs are primarily related to COX-2 inhibition.

    • COX-2 selective agents have reduced gastrointestinal side effects.

Selectivity and Potency

  • Different NSAIDs have different levels of COX-2 selectivity and potency, affecting their therapeutic effects.

    • NSAIDs Ordered by COX-2 Selectivity:

    • Rofecoxib, Celecoxib (higher efficacy, reduced side effects)

    • Diclofenac, Sulindac, Piroxicam, Ibuprofen, Naproxen, Aspirin, Indomethacin

Major Actions of NSAIDs

  • All NSAIDs possess three major therapeutic actions:

    1. Anti-inflammatory: Reduces redness and swelling.

    2. Analgesic: Alleviates pain.

    3. Anti-pyretic: Lowers fever.

Oral NSAIDs

  • NSAIDs are among the most widely used drugs globally, with over 50 available on the market.

    • Commonly used NSAIDs include Aspirin, Paracetamol, Indomethacin, and Ibuprofen.

  • Indications for use:

    • Headaches, menstrual pain, sprains, colds, flu, arthritis, and other chronic pain conditions.

  • side effects: GI problems

Side Effects

  • Common side effects include:

    • Nausea, vomiting, and gastric damage.

    • Protective agents, such as synthetic prostaglandin (PGE1) analogs, can be used to guard against gastric mucosa damage.

  • Other adverse effects:

    • Reversible renal insufficiency, nephropathy (caution in kidney disease), skin reactions, liver disorders.

COX-2 Inhibitors and Associated Risks

  • Newer NSAIDs like Valdecoxib and Rofecoxib were developed to avoid gastrointestinal issues; however, they have shown increased risks of vascular events (e.g., myocardial infarction, stroke).

  • Potential mechanism: Inhibition of COX-2 leads to decreased prostacyclin production, resulting in prothrombus conditions and elevated blood pressure.

Ocular Use of NSAIDs

  • NSAIDs have both analgesic and anti-inflammatory effects in ocular conditions:

    • Control of corneal surface pain & photophobia

    • Corneal abrasions, recurrent corneal erosions, bullous keratopathy

    • Pain after refractive surgery

    • Prophylaxis (cataract surgery, cystoid macular oedema, inflammation)

    • Mild inflammatory conditions (episcleritis)

    • Allergies, treat itch

  • Topical NSAIDs are prescribed for conditions such as:

    • Ketorolac (Acular): allergic conjunctivitis, inflammation in cataract surgery

    • Diclofenac (Voltaren): miosis, cataract surgery inflammation

    • Nepafenac (Ilevro): inhibition of post-op inflammation, episcleritis, allergic conjunctivitis

Specific Drugs and Their Uses

  1. Ketorolac (Acular): S4

    • Action: Topical NSAID, prostaglandin D2 inhibitor

    • Other Uses: Effective relief of itching in seasonal allergic conjunctivitis (SAC); no effect on hyperemia.

    • Contraindications/Cautions: Aspirin/NSAID sensitivity, peptic ulcers, pregnancy, lactation.

    • Adverse Effects: Significant stinging/burning upon instillation; an uncomfortable burning sensation in approximately 40% of patients; may delay wound healing.

    • Packaging: 0.5%, 10 ml.

    • Dosage: Up to 4 times per day for 2-4 weeks; questionable efficacy noted.

    • Note: No oral form available due to risks of gastrointestinal bleeding, severe allergic reactions, and fluid retention.

  1. Diclofenac (Voltaren):

    • Action: Topical NSAID, potent cyclooxygenase inhibitor, analgesic properties

    • Use: Corticosteroid sparing agent, episcleritis, postoperative inflammation and pain, allergic conjunctivitis, cystoid macular oedema

    • Contraindications/Cautions: Aspirin/NSAID sensitivity, peptic ulcers, pregnancy, lactation

    • Adverse Effects: Delayed wound healing

    • Packaging: 0.1%, 10 ml

    • Dosage: One drop 3-5 times per day.

  2. Nepafenac (Ilevro):

    • Action: Topical NSAID, potent cyclooxygenase inhibitor, analgesic properties

    • Use: Corticosteroid sparing agent, episcleritis, postoperative inflammation and pain, allergic conjunctivitis, cystoid macular oedema

    • Contraindications/Cautions: Aspirin/NSAID sensitivity, peptic ulcers, pregnancy, lactation

    • Adverse Effects: Delayed wound healing, punctate keratitis

    • Packaging: 0.1%, 10 ml

    • Dosage: One drop 3-5 times per day.

Topical NSAID Adverse effects

  • delayed epithelial growth

  • impaired wound healing

  • epithelial toxicity