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NSAID Ster Update This is the question you should be able to answer at the conclusion is… Leo Semes, OD, FAAO UAB Optometry How will this information help me when I see my next patient? OptoWest Newport Beach California Optometric Association 2016 2 Contact Allergy / Dermas Treatment with Contact Allergy / Dermas Treatment with Oral Steroids Oral Steroids 78 AA/F with suspected Alphagan allergy Prednisone 5 mg PO qid X 7 d – good results ♦ Topical hydrocortisone (1%) failed ♦ Final diagnosis: nickel allergy Oral Steroids – Side Effects 60 mg oral prednisone (35 D) Skin effects Thinning and bruising may occur during OD application with dose-response effect Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta- analysis. Arch Int Med 1999 159(9): 941-55. Elevated BP PSC cataract OS Elevated IOP (?) Tham CCY, et al. Am J Ophthalmol 2004;137:198–201. 1 10 mg oral prednisone (28 D) (same 9 yo f) Prostaglandins Ubiquitous OD Initiate and modulate cell & tissue responses Platelet aggregation Renin release INFLAMMATION Synthesized on demand OS Not stored Short half-life Tham CCY, et al. Am J Ophthalmol 2004;137:198–201. 8 Mechanism of NSAID Action A video is worth a thousand words http://www.youtube.com/watch?v=8v1H2N-9Hf4 Inhibition of Prostaglandin synthesis* Arachadonic acid pathway Leukotriene arm (steroids) Cycloxygenase I and II (COX-II) / NSAIDS * Mechanisms may overlap 14 15 NSAID Inhibition of Prostaglandin synthesis* General Features (Oral) Cycloxygenase I and II (COX-II) COX-I Metabolized rapidly (30 min to 2 hrs) inhibit thromboxane production & Generally rapid effect [anti-inflammatory, thus platelet aggregation pain relief, fever reduction] (leads to blood thinning) Peak plasma levels: 4-6 hrs following Selective COX-II isoenzymes, (do NOT interfere with dosing platelet aggregation) may adversely affect hemostatic balance & Metabolized in the kidneys favor thrombosis but may be less disruptive to mucosal membranes * Mechanisms may overlap 16 17 2 Oral NSAID Properes NSAID Actions (the 3 As) Anti-inflammatory Act to reduce inflammation Anti-pyretic (requires higher dosage than for analgesia) Analgesic Widely used for arthritis pain management (chronic) Also offer analgesia 1.4 million regular users (USA) Mechanism of action is inhibition of COX-1 and COX-2 enzymes Most are anti-pyretic Aspirin is the prototype 18 19 Precautions/Warnings Every silver lining has a cloud … Precautions/Warnings Elderly: renal clearance is reduced; resulting in GI Toxicity w/ chronic TX higher plasma levels Ulceration Renally impaired: same scenario Bleeding; can also aggravate pre-existing disorders [⇓ pl. clearance] (diverticulosis) Hepatically impaired: no significant difference Perforation from above 2 examples* (cyclooxygenase is Prevalence: needed for renal blood flow) 1- 2% (3-6 mo); 2- 4% @ 1 yr *Use minimum dosage [⇑ unbound %] may be asymptomatic 20 21 Continuum of NSAID-related upper GI injury Precautions/Warnings Peripheral edema (2% prevalence) Caution: fluid retention hypertension heart failure L May interfere with ß-blockers & ACE inhibitors 22 23 3 Precautions/Warnings Precautions/Warnings Stevens-Johnson syndrome Hypersensitivity reactions Caution: asthma → rashes and urticaria photosensitivity Stevens-Johnson syndrome… X 12 years 24 25 Drug interactions - Precautions/Warnings ophthalmic Drug interactions Brimonidine (Alphagan) Aspirin (⇑ unbound %) May be ineffective with the concomitant Warfarin (may ⇓ platelet formation) administration of indomethacin (25 mg. QID) Gingko biloba !!! Antacids (no interference, ex., Pepcid) Diuretics (reduced K+, Cl-excretion) Not so for latanaprost (Xalatan) Digoxin Sponsel WE, et al. Am J Ophthalmol. 2002; 133: 11-18. 26 27 Precautions/Warnings Indications for Oral NSAIDs Miscellaneous Mild to Moderate Pain Pregnancy: Generally Category B; Rheumatoid Arthritis Lodine, Motrin, Vioxx, Voltaren [C] OsteoArthritis Not recommended during lactation/ Ankylosing Spondylitis nursing Tendinits NEAS for pediatric use (< 6 months) Primary Dysmenorrhea (600 mg, qid) (Ibuprofen arginate: Castelo-Branco C,Casals G,Haya J. Efficacy and Safety of Ibuprofen Arginine in the Treatment of Primary Dysmenorrhoea. Clin Drug Invest 24(7):385-393, 2004.) 28 29 4 Oral NSAIDS (O-T-C) – Ibuprofen [“Escape,” or “rescue” drugs] Oral NSAIDS (O-T-C) - Ibuprofen Motrin, Advil, Nuprin - 200 mg. Standard dosage: 400 mg q 4-6 h ♦ DOSAGE (Rx): 2 tabs (400 mg) q Pediatric dosing: 10 mg/Kg q6-8 h (up to 40 mg / Kg / D; ages 6 mo. to 12 yrs.) 4-6 h (management of adult pain) Also available as suspension (100mg/5ml) Ophthalmic application in Children's Elixsure IB keratitis, uveitis, eg. Chewable tabs 50, 100 mg Capsules 100 mg 31 32 Oral NSAIDS (O-T-C) - Ketoprofen Ketoprofen (12.5, 25, 50 mg) Orudis 12.5 mg. 12.5-25 mg may be faster than ibuprofen 200 mg Sunshine A, Olson NZ, Marrero I, Tirado S. Onset and duration of analgesia for low-dose ketoprofen in the treatment of postoperative dental pain Clin Pharmacol. 1998 Dec;38(12): 1155-64. ♦ DOSAGE: 4 caps / tabs (50 mg.) q 4-6 h But similar onset compared to ibuprofen ♦ Orudis (Ketoprofen) Capsules and Extended-release liquigel 200mg Olson NZ, Otero AM, Marrero I, Tirado S, Cooper S, Doyle G, Jayawardena S, Sunshine A. Capsules (approved 08/13/03) Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain. Clin Pharmacol. 2001 Nov; 41(11):1238-47. Ketoprofen: analgesic, anti-pyretic, anti- 25 -50mg may be a superior analgesic to inflammatory ketorolac 10 or 20 mg Olmedo MV, Galvez R, Vallecillo M. Double-blind parallel comparison of multiple doses of ketorolac, ketoprofen and placebo administered orally to patients with postoperative dental pain. Pain. 2001 Feb 1;90(1-2):135-41. 33 34 NSAIDS as alternatives to narcotic analgesics Oral NSAIDS (O-T-C) - Naproxen may offer superior analgesia to natural Naprosyn 220 mg. and synthetic narcotics in a variety of ♦ DOSAGE: 1-2 tabs (220-440 mg.) q 4-6 h situations [for analgesic effect; lower dosage than for anti- Malan TP Jr, Gordon S, Hubbard R, Snabes M. The cyclooxygenase-2-specific inflammatory effect] inhibitor parecoxib sodium is as effective as 12 mg of morphine administered intramuscularly for treating pain after gynecologic laparotomy surgery. Anesth Analg. 2005 Feb;100(2):454-60. Anaprox, Aleve 220 mg. Lovell SJ, Taira T, Rodriguez E, Wackett A, Gulla J, Singer AJ. Comparison of valdecoxib and an oxycodone-acetaminophen combination for acute ♦ DOSAGE: 2 tabs (440 mg.) initially, musculoskeletal pain in the emergency department: a randomized controlled trial. Acad Emerg Med. 2004 Dec;11(12):1278-82. then 1 tab q 4-6 h [for analgesic effect] Brill S, Plaza M. Non-narcotic adjuvants may improve the duration and quality of analgesia after knee arthroscopy: a brief review. Can J Anaesth. 2004 Dec;51(10): 975-8. 35 36 5 Relative risk of UGI bleeding w/ NSAID Semes’ Anti-inflammatory Siege administration 600 mg Ibuprofen AM 440 mg Naprosyn mid-AM 600 mg Ibuprofen PM 440 mg Naprosyn qhs 37 38 Oral NSAIDS (By prescription) – Oral “NSAID” (O-T-C) – Acetaminophen Ketoprofen Acetaminophen 325 mg. (Tylenol) Oruvail 100, 150, 200 mg Caps Orudis 25, 50, 75 mg Caps requires 500 – 1000 mg to reach analgesic dosage; and higher for anti-inflammatory ♦ DOSAGE: effect ♦ Oruvail (sustained release) 200 mg qD ♦ Orudis 50-75 mg qid/tid [respectively] May have more rapid onset than ibuprofen ♦ Maximum 200 / 300 mg / day Sunshine A, Olson NZ, Marrero I, Tirado S. Onset and duration of analgesia for low-dose ketoprofen in the treatment of postoperative dental pain Clin Pharmacol. 1998 Dec;38(12): 1155-64. Ketoprofen: The three A’s Metabolized in the liver! DOSAGE: q 4-6 h 39 40 Oral NSAIDS (Rx) – Etodolac Oral NSAIDS (Rx) – Naproxen Lodine 200, 300 mg Caps; 400, 500 mg Tabs Naprelan 412.5, 550 mg. (equivalent to 375/500 mg) DOSAGE: DOSAGE: 1000 mg q D, then 500 - 1000 mg q D ♦ for analgesia 200 - 400 mg q 6-8 h ♦ (higher for OA, RA; anti-inflammatory effect) Has been shown in 3 studies to reduce the risk of ♦ Maximum 1000 - 1200 mg / day acute myocardial infarction (AMI) probably by blocking platelet aggregation; advantage over Lodine XL COX-II’s ♦ 400-100 mg / day • The three A’s • The three A’s Solomon DA, et al. Arch Int med 2002; 162: 1099-1104. Watson DJ et al. Arch Int med 2002; 162: 1105-1110. Rahme E, et al. Arch Int med 2002; 162: 1111-1115. 41 42 6 NSAIDS and AMD NSAIDS and AMD, too 2334 participants in the BMES 551 VA patients w/AMD diagnosis (ICD-9) 5-year FU 5500 controls NSAID and steroid use was measured @ baseline Patients with a prescription filled for Anti- Results: 2.0% late, 4.9% early AMD but inflammatory meds were 81% less likely to have a disgnosis of AMD no association with NSAID/ Steroid use Swanson MW, McGwin G Jr. Anti-inflammatory drug use and age-related macular degeneration. Optom Vis Sci. 2008 Oct;85(10):947-50. Wang JJ, et al. Ophthalmic Epidemiol 2003; 10: 37-47. 43 44 NSAIDS and AMD, III Oral NSAIDS (Rx) – Diclofenac Conclusion: In patients with neovascular AMD Voltaren 25, 50, 75 mg Caps. manifesting persistent exudation despite monthly ♦ DOSAGE: intravitreal antivascular endothelial growth factor ♦ Voltaren 50-100 mg initially; 50 mg q 8 h anti-VEGF therapy, we could not detect a beneficial ♦ Maximum 200 mg / day effect of adding topical bromfenac (0.09%) twice daily over 2 months. The three A’s (n = 22 eyes with persistent submacular fluid) Zweifel SA, et al. Retrospective review of the efficacy of topical bromfenac (0.09%) as an adjunctive therapy for patients with neovascular age-related macular degeneration. RETINA 29:1527–1531, 2009 45 46 Oral NSAIDS (Rx) – Others Oral NSAIDS (Rx) – Others Tramadol (Ultram) 100 mg.
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