Antiinflammatory Antirheumatic Antigout Drugs NSAIDs Large and chemically

Antiinflammatory Antirheumatic Antigout Drugs

NSAIDs • Large and chemically diverse group of drugs with the following properties: – – Analgesic Antiinflammatory Antipyretic Antirheumatic • Mechanism of Action: – Activation of the arachidonic acid pathway causes: • • Pain Headache Fever Inflammation

NSAIDs Mechanism of Action • Analgesic: relieves pain – treatment of headaches – mild to moderate pain – inflammation • Block the chemical activity of either or both COX enzymes (prostaglandin [PG] pathway) and lipoxygenase (LT pathway) • Result: limits the undesirable inflammatory effect of PGs Antipyretic: reduce fever • Inhibit prostaglandin E 2 within the area of the brain that controls temperature

Chemical Categories of NSAIDs Seven structurally related groups • Acetic acids • Carboxylic acids (salicylates) – Acetylated and nonacetylated • • • Propionic acids COX-2 inhibitors Fenamic acids Napthylalkanones (nonacidic) Oxicams

NSAIDs Acetic Acids • diclofenac sodium (Voltaren) • diclofenac potassium (Cataflam) • indomethacin (Indocin) • sulindac (Clinoril) • tolmetin (Tolectin)

NSAIDs Carboxylic Acids Acetylated • aspirin (ASA), choline salicylate (Arthropan) • diflunisal (Dolobid) Nonacetylated • ketorolac (Toradol) • salsalate (Salsitab) • sodium salicylate

NSAIDs Salicylates • Salicylates (Aspirin) also have antiplatelet activity – Inhibit platelet aggregation • More potent effect on platelet aggregation and thermal regulatory center in the brain – Analgesic – Antipyretic – Antiinflammatory • Antithrombotic effect: used in the treatment of MI and other thromboembolic disorders

NSAIDs Salicylate Toxicity • Adults: tinnitus and hearing loss, others • Children: hyperventilation and CNS effects • Effects arise when serum levels exceed 40 to 60 mg/d. L • Metabolic acidosis and respiratory alkalosis may be present

NSAIDs Propionic Acids • • • fenoprofen (Nalfon) flurbiprofen (Ansaid) ibuprofen (Motrin, Advil) ketoprofen (Orudis KT) naproxen (Naprosyn, Aleve) oxaprozin (Daypro)

NSAIDs COX-2 Inhibitor celecoxib (Celebrex) – Little effect on platelet function – Cause fewer GI adverse effects – May pose CV risks- monitored closely by FDA – Severe skin reactions – toxic epidermal necrolysis

NSAIDs Other Drugs Oxicams • meloxicam (Mobic) • piroxicam (Feldene) Fenamic acids • meclofenamate • mefenamic acid (Ponstel) Napthylalkanones (Nonacidic) • nabumetone (Relafen)

NSAIDs Indications • • • • Analgesia (mild to moderate) Antigout effects Antiinflammatory effects Antipyretic effects Relief of vascular headache Platelet inhibition (aspirin) Relief of mild to moderate pain Acute gout Various bone, joint, and muscle pain Osteoarthritis Rheumatoid arthritis Juvenile rheumatoid arthritis Dysmenorrhea Fever Many other conditions

NSAIDs Interactions Serious interactions can occur when given with: • • • Anticoagulants Aspirin Corticosteroids and other ulcerogenic drugs Protein bound drugs Others

NSAIDs Adverse Effects Gastrointestinal • Dyspepsia, heartburn, epigastric distress, nausea – GI bleeding* – Mucosal lesions* (erosions or ulcerations) Renal • Reductions in creatinine clearance • Acute tubular necrosis with renal failure Cardiovascular • Noncardiogenic pulmonary edema *misoprostol (Cytotec) can be used to reduce these dangerous effects

Antigout Drugs • Gout: condition that results from inappropriate uric acid metabolism – Underexcretion of uric acid – Overproduction of uric acid • Uric acid crystals are deposited in tissues and joints, resulting in pain

Antigout Drugs allopurinol (Zyloprim) – Used to reduce production of uric acid colchicine – Reduces inflammatory response to the deposits of urate crystals in joint tissue probenecid (Benemid), sulfinpyrazone (Anturane) – Increase excretion of uric acid in the urine

Antirheumatoid Arthritis Drugs • • • Also known as disease-modifying antirheumatic drugs (DMARDs) Slow onset of action—several weeks May take 3 to 6 months to see full effects Can have much more toxic adverse effects than the NSAIDs Anti-inflammatory, antiarthritic, immunomodulating effects Drugs: Auranofin (Ridaura) Aurothioglucose (Solganal) gold sodium thiomalate (Aurolate) - weekly injection Leflunomide (Arava)

NSAIDs Nursing Implications • Before beginning therapy, assess for conditions that may be contraindications to therapy, especially: – GI lesions or peptic ulcer disease – Bleeding disorders • Assess also for conditions that require cautious use • Perform lab studies as indicated (cardiac, renal, and liver function studies, CBC, platelet count) • Perform a medication history to assess for potential drug interactions • Several serious drug interactions exist

Nursing Implications Patient Education • Salicylates are NOT to be given to children under age 18 because of the risk of Reye’s syndrome • Administer with food, milk, or an antacid to avoid GI upset • Therapeutic effects may not be seen for 3 to 4 weeks • Various adverse effects of NSAIDs, and to notify their physician if these effects become severe or if bleeding or GI pain occurs • Watch closely for the occurrence of any unusual bleeding – stool, urine, bruising, sclera, skin and mucous membranes • Enteric-coated tablets should not be crushed or chewed

Nursing Implications • Monitor for therapeutic effects, which vary according to the condition being treated – Decrease in swelling, pain, stiffness, and tenderness of a joint or muscle area