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Antirheumatics. Treatment of RA. Antirheumatics Nonsteroidal antiinflammatory drugs (NSAID) Slowly acting drugs (DMARD) Glucocorticoids Biologic treatment monoclonal antibodies inhibitors of IL-1, TNF (infliximab, adalimumab). Acidic NSA.
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Treatment of RA • Antirheumatics • Nonsteroidal antiinflammatory drugs (NSAID) • Slowly acting drugs (DMARD) • Glucocorticoids • Biologic treatment monoclonal antibodies inhibitors of IL-1, TNF (infliximab, adalimumab)
Acidic NSA Derivates ofEnolicAcids Pyrazolons Oxicams phenylbutazone azapropazone piroxicam meloxicam izooxicam Derivates ofCarboxylicAcids salicylic acid acetoacetatic acid antranilinic acid propionic acid ASA diflunizal aloxipyrin indomethacin sulindac diclofenak tolphenamic acid mefenamic acid ibuprofen ketoprofen naproxen Neutral NSA Alkanons Sulfonamides Coxibs nabumetone nimesulid celecoxib rofecoxib valdecoxib Nonsteroidal antiinflammatory drugs (NSAID)
Properties Cyklooxygenase 1 Cyklooxygenase 2 Localisation cytoplasmatic in ER perinuclear Regulation constitutional inducable / constitutional Presence intissues GIT mucosa, renal parenchyma, endothelium, Tr Mf, Mo, CNS, kidneys, uterus, seminiferous Predicted function Integrity of stomach mucosa, kidney perfusion, Tr function Patogenesis of inflammation andgenesis of pain
NSAID Ratio COX 1 / COX 2 Aspirin (ASA) 166 Indomethacin 80 Flurbiprofen 10 Ketoprofen 5,1 Piroxikam 3,3 Ibuprofen 0,9 Naproxen 0,6 Diclofenak 0,5 Meloxicam 0,37 Nimesulid 0,19 Rofecoxib 0,013
Selective inhibitors of COX-1 ASA (doseto 300 mg daily) Nonselective inhibitors of COX-1 and also COX-2 ASA (more than 500 mg/day), ibuprofen, diclofenac, indomethacin Preferential and selective inhibitors of COX-2 Etodolac, nimesulid, meloxicam, celecoxib
NSAID Risk ofGIT bleeding Ibuprofen 2,1 Naproxen 3,1 Diclofenac 3,4 Ketoprofen 5,4 ASA 7,2 Indomethacin 14,4
DMARDs Chloroquine Hydroxichloroquine Sulfasalazine Methotrexate Leflunomid Penicillamine Azathioprine Ciclosporin Infliximab Etanercept Adalimumab
Glucocorticoids Short-acting metylprednisolone Intermediate –acting triamcinolone Long-acting dexametazone
Rapid acting drugs (SYRADOA) Analgetic drugs – paracetamol, metamizol Nonsteroidal antiinflammatory drugs (NSAID) Weak opioids – tramadol Topic transdermal treatment NSAID (diclofenac, ketoprofen) Iritanciá (capsaicin, menthol) Steroid antiflogistic drugs (corticoids) intraarticular(triamcinolone, betametazone) Slowly acting drugs (SYSADOA) Qaulified as chondroprotectives Disease modifying drugs (DMOAD) Glucosaminsulphate Chondroitinsulphate Hyaluronic acid Treatment of OA
Chondroprotective Agents Characteristics ofChondroprotective Agents Chondroprotective Agents Characteristics ofChondroprotective Agents Glucosamine Glucosamine Stimulate chondrocyte and synoviocyte metabolism Stimulate chondrocyte and synoviocyte metabolism Chondroitin sulfate Chondroitin sulfate Inhibit degradative enzymes Inhibit degradative enzymes Chondroitin sulfate Chondroitin sulfate Prevent fibrin thrombi in periarticular tissues Prevent fibrin thrombi in periarticular tissues Chondroprotectives • Drugs improving nutrition of joint cartilage