Nonsteroidal Anti-inflammatory

1. See Also
   1. Acetaminophen
   2. Pediatric Analgesics
   3. Narcotic Analgesics
2. Mechanism
   1. Blocks Cyclooxygenase (COX)
   2. COX Enzyme converts arachidonic acid to PGG2
   3. COX1 Enzyme
      1. Location
         1. Gastric mucosa and intestinal mucosa
         2. Platelets
         3. Renal
         4. Vascular endothelium
      2. Inhibition Effects
         1. Predisposes to gastric or intestinal ulcers
         2. Predisposes to bleeding (anti-platelet adhesion)
         3. No anti-inflammatory effect
         4. Renal effects
            1. Fluid retention
            2. Decreased Glomerular Filtration Rate (GFR)
   4. COX2 Enzyme
      1. Location
         1. Brain
         2. Renal (ascending tubule, macula densa)
         3. Adenoma (colon)
         4. Cytokine-induced (inflammation related)
      2. Inhibition Effects
         1. Anti-inflammatory action
         2. Analgesic action
         3. Predisposes to renal injury in hypovolemia
         4. Decreased malignant potential of Colonic Polyps
         5. May have benefit in Alzheimer's Disease
3. Precautions
   1. Peptic ulcer risk, nephrotoxicity, and cardiovascular risk are FDA black box warnings
4. Adverse Effects
   1. NSAID Gastrointestinal Adverse Effects
   2. NSAID Renal Adverse Effects
   3. Bleeding risk
      1. Reversible inhibition of platelet aggregation
      2. Associated with standard NSAIDs (esp. Naprosyn)
      3. COX2 Inhibitors have minimal effect on bleeding
      4. Avoid in patients with Thrombocytopenia and other platelet disorders
      5. Stop Aspirin 7-10 days before procedures
      6. Stop NSAIDS five half-lives prior to the procedure
         1. Stop Ibuprofen 2 days before the procedure
         2. Stop Naprosyn 2-3 days before the procedure
         3. Stop piroxicam (Feldene) 10 days before the procedure
   4. Headache
   5. CNS effects (esp. Indomethacin)
   6. May delay healing in Tendinopathy
   7. Interferes with Aspirin anti-platelet effects (risk of cardiovascular and cerebrovascular events)
      1. Avoid NSAIDs in patients with vascular disease
      2. Diclofenac may least effect platelet activity
      3. Naprosyn (Naproxen) may be associated with less cardiovascular risk
      4. Take Aspirin 2 hours before or 8 hours post-Ibuprofen
      5. Take Aspirin 36 hours after last Naproxen
      6. Steinhubl (2005) Am College Card 45:1302
   8. Hypertension
      1. On average NSAIDs increase Blood Pressure 5 mmHg
      2. Blood Pressure increase is more common with Diabetes Mellitus, Congestive Heart Failure, or Kidney or liver disease
      3. Associated with daily use (intermittent use is unlikely to have an effect)
      4. Calcium Channel Blockers are less affected by NSAID induced Blood Pressure increases
5. Monitoring: Protocol for NSAID use in elderly
   1. Monitor Blood Pressure
   2. Labs: Obtain at baseline and q3-12 months
      1. Complete Blood Count (CBC)
      2. Creatinine
      3. Liver Function Tests
   3. Review of Systems for NSAID adverse effects
      1. Nausea or Vomiting
      2. Dark stools or bloody stools
      3. Dyspepsia
      4. Cognitive changes
   4. References
      1. Lipsky (2000) J Rheumatol 27:1338
6. Preparations: Non-Narcotic alternatives to NSAIDs
   1. Acetaminophen (Tylenol)
   2. Non-acetylated Salicylate
   3. Low dose Prednisone (Rheumatoid Arthritis)
   4. Single joint local Corticosteroid Injection
7. Preparations: COX2 Selective NSAID
   1. Celecoxib (Celebrex) 200 mg PO qd-bid
   2. Rofecoxib (Vioxx) is no longer available in the United States due to cardiovascular risks
8. Preparations: Acetic acids
   1. Partially COX2 selective (less GI adverse effects)
      1. Etodolac (Lodine) 200-400 mg PO bid-tid
         1. Etodolac 400 mg superior to Aspirin 650 mg
      2. Etodolac XL (Lodine XL) 400-1200 mg qd
      3. Nabumetone (Relafen) 1000 mg PO qd-bid
   2. Indoles
      1. Indomethacin 25-50 mg PO/PR tid
      2. Sulindac (Clinoril) 150-200 mg PO bid
      3. Tolmetin sodium (Tolectin) 200-600 mg PO tid
   3. Pyrrolo-pyrroles: Parenteral NSAID
      1. Ketorolac tromethamine (Toradol)
         1. Ketorolac 30 mg IV or 60 mg IM
9. Preparations: Salicylates
   1. Acetylsalicylic acid (Aspirin) 500-1000 mg q4-6 hours
   2. Trisalicylate (Trilisate) 1000-1500 mg q8-12 hours
   3. Diflunisal (Dolobid) 500 mg q8-12 hours
      1. Superior and longer acting than Aspirin 650 mg
      2. Superior and longer acting than Acetaminophen 650 mg
   4. Salsalate (Disalcid)
   5. Sodium Salicylate (Uracil 5)
   6. Sodium thiosalicylate (Tusal)
10. Preparations: Propionic Acids
    1. Ibuprofen (Motrin)
       1. Ibuprofen 400 mg comparable to Tylenol #3
    2. Naproxen (Naprosyn) 500 mg q12 hours
       1. Naproxen 500 mg superior to Aspirin 650
    3. Naproxen Sodium (Anaprox) 550 mg q12 hours
       1. Naproxen Sodium 550 mg superior to Aspirin 650
    4. Flurbiprofen (Ansaid) 200-300 mg/day divided bid-qid
    5. Fenoprofen (Nalfon) 200 mg q4-6 hours
       1. Similar to Aspirin
       2. Avoid in renal insufficiency
    6. Ketoprofen (Orudis) 25-75 mg q6-8 hours
       1. Ketoprofen 25 mg comparable to Ibuprofen 400 mg
       2. Ketoprofen 50 mg more potent than Tylenol #3
    7. Oxaprozin (Daypro) 1200 mg qd
11. Preparations: Oxicams
    1. General
       1. Long half life (once a day dosing)
    2. Meloxicam (Mobic) 7.5 to 15 mg orall daily
    3. Piroxicam (Feldene) 20 mg qd
12. Preparations: Fenamate
    1. Anthranilic Acid
       1. Meclofenamate (Meclomen) 50-100 mg PO q4-6 hours
          1. Comparable to Aspirin
    2. Acetic Acid
       1. Diclofenac (Voltaren, Arthrotec)
          1. Oral:
             1. Diclofenac 50 mg PO q8 hours (Comparable to Aspirin)
             2. Arthrotec (50 mg Diclofenac with 200 mcg Misoprostel)
          2. Topical
             1. Diclofenac Gel
             2. Flector Patch (applied to most painful area every 12 hours)
13. References
    1. (2000) Tarascon Pocket Pharmacopoeia
    2. Wolfe (1999) N Engl J Med 340:1888
    3. (2000) Med Lett Drugs Ther 42(1085):73-8