1. Nonsteroidal Anti-inflammatory Drugs, Disease-Modifying Antirheumatic Drugs, Nonopioid Analgesics, & Drugs Used in Gout Florencia D. Munsayac, MD, MBA, RMT

3. Some of the mediators of acute inflammation & their effects - +++ - Leukotrienes + +++ +++ Prostaglandins +++ - +++ Bradykinin - - +/- Serotonin - - ++ Histamine Pain Chemotaxis Vascular Permeability Vasodilation Mediators

4. Some of the Mediators of Chronic Inflammation Fibroblast chemotaxis, proliferation Macrophages, endothelial cells, fibroblasts, platelets PDGF Many Macrophages, endothelial cells, T lymphocytes Interferons PG production Macrophages TNF-alpha Macrophage & granulocyte activation T lymphocytes, endothelial cells, fibroblast GM-CSF Lymphocyte activation, PG production Macrophages, T lymphocytes Interleukins-1, -2, and -3 Primary Effects Sources Mediators

23. COX-2 Selective inhibitors Inc BP, MI, inc transaminases MI, CVA/HTN, CHF, Stevens-Johnson syndrome Slightly less ulcerogenic dyspepsia Side Effects 40% decreased in elderly kidney Affected by hepatic impairment Excretion liver CYP2C9 Metabolism 1-3 hrs Peak Plasma concentration high Protein binding 24 hrs 8-11 hours 20% 20-26% 11 hrs Half-life Rapid & well absorbed 15 minutes (IV, IM) 1-2 hours Slowly absorb 83% 20-30% (affected by food) Absorption Lumiracoxib Parecoxib Valdecoxib/ Rofecoxib Meloxicam Etoricoxib Celecoxib Drugs

24. Non-selective COX inhibitors (Heteroacyl/Phenylacetic acid derivative) Somnolence, dizziness, HA, dyspepsia, nausea pain at injection site GI distress, Occult GI bleeding, Gastric ulceration,  amino-transferases Side effects Urine (90%) Biliary (30%) & urine (65%) Excretion CYP3A4 & CYP2C9 Metabolism 80% 80% 30-70% Bioavailability 30-50 min. Peak Plasma Concentration 99% 99% 99% Protein-binding 4-6 hours 7 hours 1-2 hours Half-life Rapid (oral, IM), IV, oral rinse, topical Rapid, well absorbed rapid Absorption Ketorolac Etodolac Diclofenac Drugs

26. Non-selective COX inhibitors (Propionic acid derivative) Probenecid Drug Interactions GIT & CNS (30%) GI irritation & bleeding Interstitial nephritis, GI irritation, tinnitus, rash pruritus Side effects urine urine Excretion CYP2C8 & CYP2C9 Extensive hepatic Extensive hepatic Metabolism 1-2 hours 1-2 hours 2 hours Peak Plasma Concentration 99% 99% 99% Protein-binding 1-3 hours 1-2 hours 0.5-4 hours 2-4 hours Half-life Well absorbed Rapid, incomplete Absorption Ketoprofen Ibuprofen Flurbiprofen Fenoprofen Drugs

27. Non-selective COX inhibitors (Propionic acid derivative) UGIB, allergic pneumonitis, leukocytoclastic vasculitis, pseudoporphyria Side effects Excretion CYP2C9, less in CYP1A2 & CYP2C8 Metabolism Bioavailability Peak Plasma Concentration high Protein-binding 50-60 hours 10-16 hours 1-2 hours, 2-4 hours (elderly) 12 hours Half-life Absorption Oxaprozin Caprofen Tiaprofen Naproxen Drugs

29. Non-selective COX inhibitors (Para-chlorobenzoic acid derivative or indole) Furosemide, thiazide, beta blockers, ACEI, probenecid Drug interaction GIT, CNS, hematologic, renal, allergic reactions GIT, CNS, hematologic, psychosis w/ hallucination Side effects Urine, bile, feces Urine, bile, feces Excretion First pass hepatic, sulfide, active metabolite Liver Metabolism 1 hour, t1/2: 7 hours 2 hours Peak concentration 90% absorption Rapid & almost complete Absorption Sulindac Indomethacin Drugs

32. Non-selective COX inhibitors (Pyrazolone derivative) aplastic anemia, agranulocytosis Toxicities 12-16 hours Half-life Structurally related to phenylbutazone Withdrawn from the market Properties Azapropazone Phenylbutazone Drugs

52. Biologics that bind & neutralize TNF Opportunistic infections, leukopenia, vasculitis, lupus Upper RTI, nausea, headache, sinusitis, rash & cough with MTX Injection site reactions, activation of latent pulmonary tuberculosis Side Effects 10-20 days 8-12 days Half-life 40mg every other week SC 3 or 10mg/kg at 0, 2 & 6 weeks I V infusion 25mg SC b.i.d. Route of Administration 72 hour Peak Serum Concentration Adalimumab Infliximab Etanercept Drugs

53. Biologics increased risk of infection, hypersensitivity reactions related to transfusion reaction injection site reaction Side Effects 13-16 days, May or may not be combined with MTX, but not with anti-TNF May be combined with MTX Not recommended to combined with anti-TNF Half-life/Drug interaction I V infusion, 3 initial dose (day 0, week 2, week 4), then followed by monthly infusion 2 I V infusions 2 weeks apart Route/Dose Inhibits the activation of T cells by inhibiting the binding to CD28 and CD80/86 A chimeric monoclonal antibody that targets CD20 B lymphoctyes A recombinant IL-1 receptor antagonist that competitively blocks the binding of IL-1 β & IL-1  MOA Abatacept Rituximab Anakinra Drugs

70. Thank You & God Bless...