Pharmacology for Pharmacy Technicians, 4th Edition PDF

Pharmacology for Pharmacy Technicians, 4th Ed by Kathy Moscou PhD RPh MPH and Karen Snipe CPhT AS BA MEd  Chapter 13 Treatment of Gout, Osteoarthritis, and Rheumatoid Arthritis  Lesson 13.1 Treatment of Gout, Osteoarthritis,...

Pharmacology for Pharmacy Technicians, 4th Ed by Kathy Moscou PhD RPh MPH and Karen Snipe CPhT AS BA MEd  Chapter 13 Treatment of Gout, Osteoarthritis, and Rheumatoid Arthritis  Lesson 13.1 Treatment of Gout, Osteoarthritis, and Rheumatoid Arthritis 1. Learn the terminology associated with drugs used in the treatment of gout, osteoarthritis, and rheumatoid arthritis. 2. Describe the signs and symptoms of gout, osteoarthritis, and rheumatoid arthritis. 3. List and classify medications used in the treatment of gout, osteoarthritis, and rheumatoid arthritis. 4. Describe the mechanism of action for each class of drugs used in the treatment of gout, osteoarthritis, and rheumatoid arthritis. 5. Identify warning labels and precautionary messages associated with medications used in the treatment of gout, osteoarthritis, and rheumatoid arthritis.  Key Terms Autoimmune Arthritis Autoantibody Gout disease Rheumatoid Rheumatoid Hyperuricemia Synovium Arthritis Factor Tumor Urates Uricosuric necrosis factor Copyright © 2019 by Elsevier, Inc. All rights reserved. 4 Poll question 1 Copyright © 2019 by Elsevier, Inc. All rights reserved. 5  Overview ⬤ Hyperuricemia: Urate levels build up in the blood serum ⬤ Urates: Product of metabolism of purines Medical Conditions Associated with Hyperuricemia ⬤ Gout ⬤ Cardiovascular disease ⬤ Chronic kidney disease ⬤ Hyperlipidemia ⬤ Insulin resistance ⬤ Obesity  Pathophysiology of Gout (1 of 3) ⬤ Urate crystals deposited in joints ⬤ Crystals produce inflammation and pain Tophi: Lumps under skin around joints and at rim of ear  Pathophysiology of Gout (2 of 3) ⬤ Flare-ups produced by foods high in purine ⬤ Affected joints: Big toe Foot Ankle Knee Wrist Finger Elbow  Pathophysiology of Gout (3 of 3) ⬤ Sharp, needlelike pain ⬤ Possibly no symptoms ⬤ Resolves spontaneously in 7 to 10 days Poll question 2 Copyright © 2019 by Elsevier, Inc. All rights reserved. 11 Poll question 2 Copyright © 2019 by Elsevier, Inc. All rights reserved. 12  Drugs Used to Treat Gout ⬤ Analgesics ⬤ Antiinflammatories ⬤ Uricosurics ⬤ Inhibitors of uric acid synthesis  Antiinflammatory Drugs Used in the Treatment of Gout ⬤ Colchicine ⬤ NSAIDS: indomethacin ⬤ Glucocorticosteroids: Oral prednisone Glucocorticosteroid injections  Uricosurics Used in the Treatment of Gout ⬤ Probenecid ⬤ Probenecid + colchine  Inhibitors of Uric Acid Synthesis ⬤ Xanthine oxidase inhibitors: Block final enzymatic step in synthesis of uric acid Allopurinol: Absorbed and eliminated easily For hyperuricemia caused by gout, malignancy, or other drugs Febuxostat: More selective that allopurinol For chronic hyperuricemia and gout  Drugs Used to Treat Gout: MOA (1 of 2) ⬤ Colchicine: Penetrates inflammatory cells Inhibits ability to respond to site of irritation Inhibits histamine release and blocks cell division  Drugs Used to Treat Gout: MOA (2 of 2) ⬤ Recombinant urate oxidase enzymes: Metabolize uric acid to water-soluble benign purine metabolic allantoin Pegloticase: Chronic gout Rasburicase: Hyperuricemia induced by chemotherapy ⬤ Uricosurics Increase clearance of uric acid Inhibit reabsorption of uric acid in renal tubules Promote elimination of urates  Nonpharmacological Therapy ⬤ Weight loss ⬤ A diet low in purines has been recommended to prevent gout attacks. ⬤ Rest and application of ice packs for acute attacks  Warning Labels ⬤ Antiinflammatories: Avoid alcohol Take with lots of water ⬤ Uricosurics: Take with food Take with lots of water Avoid aspirin  Osteoarthritis ⬤ Inflammation of the fluid that surrounds the joint (synovial fluid) contributes to the pain associated with osteoarthritis Symptoms Risk factors Joint pain Previous joint injury or surgery, Stiffness obesity, Swelling, increasing age, Crepitus (creaking joints). muscle weakness, Pain may occur after activity or at occupations that involve excessive rest. joint use.  Osteoarthritis ⬤ Pain Control Acetaminophen Aspirin Nonsteroidal anti-inflammatory drugs (NSAIDs) Poll question 3 Copyright © 2019 by Elsevier, Inc. All rights reserved. 23  Rheumatoid Arthritis (1 of 2) ⬤ Inflammation of the lining of the joints: Pain, joint damage, and disability Elevated levels of rheumatoid factor ⬤ Other symptoms: Fatigue, weakness, flulike symptoms, nodules under skin, muscle pain, decreased appetite, depression, and dry mouth  Rheumatoid Arthritis (2 of 2) ⬤ Phase 1: Synovial membrane inflamed Swelling, pain, stiffness ⬤ Phase 2: Rapid cell growth causes synovium to thicken ⬤ Phase 3: Inflamed cells in synovium release enzymes Enzymes digest bone and cartilage  Treatment of Rheumatoid Arthritis ⬤ Suppress inflammation and reduce swelling and pain: Glucocorticosteroids NSAIDs Salicylates ⬤ Slow progression of disease: DMARDs Biological response modifiers  Tumor Necrosis Factor-α Inhibitors (1 of 2) ⬤ Genetically engineered drugs ⬤ Block inflammatory process triggered by high concentrations of TNF ⬤ Prevent cell lysis ⬤ Prevent release of substances that cause inflammation ⬤ Monoclonal antibodies ⬤ Fusion protein (etanercept)  Tumor Necrosis Factor-α Inhibitors (2 of 2) ⬤ Can produce allergic reaction and anaphylactic shock ⬤ Opportunistic infections: tuberculosis and fungal infections ⬤ Can cause onset of MS ⬤ Associated with development of secondary cancers  Antiinflammatories and Analgesics (1 of 3) ⬤ Glucocorticosteroids: Reduce flare-ups and treat pain Restore effectiveness of blood–brain barrier to screen out harmful antibodies May be prescribed for other conditions Eliminated in urine  Antiinflammatories and Analgesics (2 of 3) ⬤ Glucocorticosteroids: Inhibit synthesis of proinflammatory substances and antibodies responsible for attacking healthy cells Decrease accumulation of leukocytes and T cells Interfere with binding of antibodies to receptor sites on cell surfaces Decrease synthesis of proinflammatory substances, such as prostaglandins, leukotrienes, cytokines, arachidonic acid, and macrophages  Antiinflammatories and Analgesics (3 of 3) ⬤ Adverse reactions and precautions for glucocorticosteroids: CNS: insomnia and euphoria Cardiovascular: edema and hypertension Endocrine system: hyperglycemia, leading to diabetes GI: increased risk of infection and ulceration ⬤ Also: nausea, weight gain, osteoporosis, acne, cataracts, and poor wound healing  Antiinflammatories and Analgesics: Look-Alike/Sound-Alike Drugs ⬤ Hydrocortisone, cortisone, and hydrocodone ⬤ Medrol and Mebaral ⬤ Methylprednisolone and medroxyprogesterone ⬤ Prednisone, prednisolone, Pramosone, and primidone  Nonsteroidal Antiinflammatory Drugs (1 of 2) ⬤ Inhibit synthesis and release of prostaglandin ⬤ Block activity of the enzyme cyclooxygenase (COX-1 and COX-2)  Nonsteroidal Antiinflammatory Drugs (2 of 2) ⬤ Black box warning: Cardiovascular toxicity Gastrointestinal ulceration  Disease-Modifying Antirheumatic Drugs (DMARDs) ⬤ Immunosuppressives ⬤ TNF inhibitors ⬤ Interleukin antagonists ⬤ Antimalarials ⬤ Leflunomide ⬤ Gold salts ⬤ Penicillamine ⬤ Sulfasalazine  NSAID’s and DMARD’s: Look-Alike/Sound-Alike Drugs ⬤ Celebrex, Celexa, and Cerebyx ⬤ Naprosyn, Naprelan, and Niaspan ⬤ Anaprox and Avapro  Immunosuppressives (1 of 3) ⬤ Azathioprine: Blocks purine synthesis and causes DNA damage Suppresses immune system responses mediated by T cells ⬤ Cyclophosphamide: Interferes with DNA synthesis and cell replication Inhibits B-cell antibody production and T-cell activity Suppresses cytokine and immunoglobulin production Suppresses antigen-induced response to T cells  Immunosuppressives (2 of 3) ⬤ Cyclosporine: Selectively interferes with T-cell proliferation and interleukin production ⬤ Methotrexate: Inhibits formation of folates needed for purine synthesis Decreases cytokine and immunoglobulin production and COX-2 activity ⬤ Mitoxantrone: Interferes with DNA repair and RNA synthesis  Immunosuppressives (3 of 3) ⬤ Cyclosporine solution for injection: Do not refrigerate Protect from light Dilute and use immediately; stable for 6 hours in plastic IV bag or 24 hours in glass Poll Question 4 Copyright © 2019 by Elsevier, Inc. All rights reserved. 40  Antimalarials ⬤ Accumulate in cell structures ⬤ Raise pH and interfere with immune response ⬤ Exact mechanism not known ⬤ Hydroxychloroquine  Look-Alike/Sound-Alike Drugs ⬤ Cyclosporine, cycloserine, and cyclophosphamide ⬤ Gengraf and Prograf ⬤ Neural and Nizoral  Additional DMARDs ⬤ Leflunomide: blocks replication of lymphocytes by interfering with pyrimidine synthesis ⬤ Sulfasalazine: slows progression of rheumatoid arthritis ⬤ Gold compounds: decrease release of antibodies and inhibit action of collagenase ⬤ Penicillamine: inhibits T-cell function and blocks collagen cross- linking  Additional DMARDs: Adverse Effects ⬤ Leflunomide: box warning for liver toxicity; fetal toxicity, nausea, diarrhea, rash, hair loss, and liver dysfunction ⬤ Sulfasalazine: GI upset, photosensitivity, allergy, crystalluria, impaired folic acid absorption, and damage to white blood cells ⬤ Gold compounds: itching, rash, metallic taste, sore mouth, photosensitivity, cytopenias, interstitial pneumonia, and proteinuria ⬤ Penicillamine: rash, GI upset, nephrotoxicity  Biological Response Modifiers ⬤ Inhibit or modify immune response ⬤ Inhibit release of cells that body believes are harmful and invasive ⬤ Inhibit release of substances that produce inflammation ⬤ Interfere with the activity of immune system mediators such as cytokines, leukocytes, B cells, and T cells Questions?