Salicylates: Interactions 10/14/2009. Salicylates DRUGS USED IN THE MANAGEMENT OF MUSCULOSKELETAL DISORDERS. Chapters 17, 18, 34 & Pages 577 &

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1 DRUGS USED IN THE MANAGEMENT OF MUSCULOSKELETAL DISORDERS Chapters 17, 18, 34 & Pages 577 & Salicylates aspirin Have analgesic, antipyretic, and anti-inflammatory effects. Inhibits the production of prostaglandins Adverse Reactions: GI upset, heartburn, N/V, anorexia, GI bleeding Salicylism Salicylates: Interactions Interactant drug Anticoagulant NSAIDs Activated charcoal Antacids Carbonic anhydrase inhibitors Effect of interaction Increased risk for bleeding Increased serum levels of the NSAID Decreased absorption of the salicylates Decreased effects of the salicylates Increased risk for salicylism 1

2 Nonsalicylates Acetaminophen Drug of choice for children with fever and flu-like symptoms Analgesic, antipyretic Not an anti-inflammatory, does not inhibit platelet aggregation Toxicity liver failure Nonsalicylates: Interactions Interactant drug Barbiturates Hydantoins Isoniazid and rifampin Loop diuretics Effect of interaction Increased possibility of toxicity and decreased effect of acetaminophen Increased possibility of toxicity and decreased effect of acetaminophen Increased possibility of toxicity and decreased effect of acetaminophen Decreased effectiveness of the diuretic NSAIDs COX 1 Inhibitors Ibuprofen and naproxen Inhibit COX -1 and COX -2 Cox 2 Inhibitors Celebrex (celecoxib) Relieve pain and inflammation with less GI adverse reactions 2

3 NSAIDs: Interactions Anticoagulants: Increased risk of bleeding Lithium: Increased effectiveness of and possible toxicity of lithium Cyclosporine: Increased effectiveness of the cyclosporine Hydantoins: Increased effectiveness of the anticonvulsant NSAIDs: Interactions Diuretics: Decreased effectiveness of the diuretic Antihypertensive drugs: Decreased effectiveness of antihypertensive drug Acetaminophen in long-term use: Increased risk of renal impairment 3

4 NSAIDS Major effect: reduce acute inflammation thereby decreasing pain and improving function Alone they do notchange the course of the disease of RA or prevent joint destruction. NSAIDS No one NSAID better than others Trial period few weeks to 1 month Dosage Low dose used in mild inflammation, with the elderly, or if patient at increased risk of toxicity. Higher dose required to decrease inflammation in RA and other forms of inflammatory arthritis. 4

5 NSAIDS Can impair renal function Salt retention Edema High blood pressure Disease-modifying Anti-rheumatic Drugs (DMARDS) Shown to alter disease course and improve radiographic outcomes. Produce immunosuppression which decreases body s autoimmune response Adverse reactions: nausea, stomatitis, alopecia Methotrexate Plaquenil DMARDS Tumor Necrosis Factor Inhibitors T-Cell Costimulatory Blocking Agents Intramuscular Gold Other Immunomodulatory and Cytotoxic agents 5

6 Methotrexate First line DMARD agent Rapid onset of action (4-6 weeks) Trial 3-6 months Relatively low cost Effective in reducing S/S of RA as well as slowing or halting radiographic damage. Can be safely combined with nearly every other DMARD Methotrexate Adverse Reactions: nausea, vomiting, anorexia, severe bone marrow depression, nephrotox, blurred vision, decreased platelet count, leukopenia, stomatitis, alopecia. Plaquenil (hyrdoxychloroquine) Antimalaril drug Limited ability to prevent joint damage on their own Methotrexate Usual time to effect: 2-4 months Toxicities: related to vision 6

7 Tumor Necrosis Factor (TNF) Inhibitors Enbrel (etanercept ) Humira (adalimumba ) Remicade (infliximab) Tumor Necrosis Factor (TNF) Inhibitors TNF found in large quantities in RA joints TNF Inhibitors first FDA approved biological response modifiers Decrease S/S of RA, slow or halt radiographic damage, & improve function and quality of life Tumor Necrosis Factor (TNF) Inhibitors Cost and insurance reimbursement limit availability Increased risk of infection Parenteral Administration Time to effect 7

8 T-Cell Costimulatory Blocking Agents Orencia (abatacept ) Interferes with the interactions between antigen-presenting calls and T lymphocytes Administered monthly Time to effect 3 months Adverse effects Gold Compounds Used to treat active juvenile and adult rheumatoid arthritis Act to decrease synovial inflammation and retard cartilage and bone destruction Adverse Reactions dermatitis, stomatitis, pruritus, chrysiasis, photosensitivity, thrombocytopenia OA Hyalrunic Acid injections Injected into the joint Supplement a natural substance that gives joint fluid its viscosity 8

9 Glucosamine & Chondroitin May halt or slow cartilage breakdown in OA. Glucosamine an amino acid sugar that helps in forming and repairing cartilage Chondroitin major component of cartilage, major component in the production of new cartilage. Glucosamine Liquid form recommended Do not take if Allergic to shellfish Diabetic Pregnant Dosage Chondroitin mg per day Relief within 2 weeks Mild side effects N & V, diarrhea or constipation, indigestion, stomach pain. 9

10 Prednisone Corticosteroids Given PO, IM, IV, or injected directly into the joint Synthetic hormones with antiinflammatory action Suppresses inflammation and modifies the immune response Corticosteroids Useful early as temporary adjunctive therapy Useful as chronic adjunctive therapy Adverse effects: weight gain, cushingoid appearance, increased B/P, increased Blood Sugar, increased risk of cataracts, associated with accelerated osteoporosis. Glucocorticoid Used to treat: collagen diseases (Lupus erythematosus), Rheumatic disorders Adverse reactions: Display 50 2, page577 10

11 Disease-modifying Anti-rheumatic Drugs (DMARDS) Interactant Effect of interaction drug Sulfa antibiotics Increased risk of methotrexate toxicity Aspirin and NSAIDs Increased risk of methotrexate toxicity Bisphosphonates Used to treat osteoporosis, Paget s disease, postoperative hip replacement Act to inhibit normal and abnormal bone resorption, increasing bone density Adverse Reactions nausea, diarrhea, increased or recurrent bone pain, headache, dyspepsia, acid regurgitation, dysphagia, abdominal pain Bisphosphonates Interactant drug Calcium supplements or antacids, with magnesium and aluminum Aspirin Effect of interaction Decreased effectiveness of bisphosphonates Increased risk of GI bleeding Theophylline Increased risk of theophylline toxicity 11

12 Gout Form of arthritis in which uric acid accumulates in increased amounts in the blood and is often deposited in the joints Uric Acid Inhibitors Allopurinol Colchicine Probenecid 12

13 Allopurinol Allopurinol (Zyloprim) Acts to reduce uric acid production Adverse Reactions skin rash, nausea, vomiting, diarrhea, abdominal pain, hematologic changes, Stevens Johnson syndrome. Allopurinol : Interactions Interactant drug Ampicillin Effect of interaction Increased risk of rash Theophylline Increased risk of theophylline toxicity Aluminum-based antacids Decreased effectiveness of allopurinol Colchine Used to treat acute gout attack Exact mechanism of action is unknown But decreases inflammation Has no effect on uric acid metabolism Adverse Reactions nausea, vomiting, diarrhea, abdominal pain, bone marrow depression. 13

14 Probenecid Benemid (probenecid) Increases excretion of uric acid Adverse Reactions: headache, GI symptoms, urinary frequency Interactions: Probenecid Interactant drug Penicillins, cephalosporins, acyclovir, rifampin, and the sulfonamides Barbiturates and benzodiazepines NSAIDs Salicylates Effect of interaction Increased serum level of anti-infective Increased serum level of sedative Increased serum level of NSAIDs Decreased effectiveness of probenecid 14

15 Skeletal Muscle Relaxants Used to treat various acute painful musculoskeletal conditions Examples carisoprodol (Soma), baclofen (Lioresal), cyclobenazprine (Flexeril), diazepam (Valium), orphenadrine citrate (Banflex, Flexojet, Flexon, Norflex) Adverse Reactions Drowsiness (most common) Diazepam sedation, sleepiness, lethargy, constipation or diarrhea, bradycardia or tachycardia Skeletal Muscle Relaxants: Interactions Interactant drug CNS depressants, such as alcohol, antihistamines, opiates, and sedatives Cyclobenzaprine with MAOIs Orphenadrine with haloperidol Tizanidine with antihypertensives Effect of interaction Increased CNS depressant effect Risk for high fever and convulsions Increased psychosis Increased risk of hypotension 15

16 The End 16

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