Ryan S Mills Pharm.D Candidate WVU School of Pharmacy
<ul><li>Generally, a non-inflammatory disorder of the joints whereby deterioration and changes to the articular cartilage ...
<ul><li>Affects men and women equally </li></ul><ul><li>Approx. 21 million Americans affected </li></ul><ul><li>Prevalence...
<ul><li>Not entirely understood </li></ul><ul><li>Combination of mechanical, cellular, and biochemical mechanisms. </li></...
<ul><li>Cartilage is composed of water, collage, and proteoglycans. </li></ul><ul><li>Chondrocytes affect production of co...
<ul><li>Osteoarthritic cartilage </li></ul><ul><ul><li>age related changes in the matrix and  decrease in chondrocyte func...
<ul><li>Primary symptom-deep, localized ache relieved by rest and aggravated by activity </li></ul><ul><li>Most often seen...
<ul><li>Symptoms </li></ul><ul><ul><li>Joint pain </li></ul></ul><ul><ul><li>Morning stiffness lasting LESS THAN 30 minute...
<ul><li>Nonpharmacological therapy for everyone </li></ul><ul><li>Pharmacological treatment for symptomatic patients. </li...
<ul><li>Patient education </li></ul><ul><li>Self-management programs </li></ul><ul><li>Social support </li></ul><ul><li>We...
<ul><li>Regular and moderate physical activity is beneficial in decreasing fatigue, strengthening muscles and bones, incre...
<ul><li>Washing and waxing car </li></ul><ul><li>Volleyball </li></ul><ul><li>Touch football </li></ul><ul><li>Gardening <...
<ul><li>Quadricep weakness is common among patients with knee OA </li></ul><ul><li>Originally thought to be caused by disu...
<ul><li>Diet can help manage OA </li></ul><ul><li>Vitamin C and other antioxidants reduce the risk of OA and its progressi...
<ul><li>Used for symptomatic patients </li></ul><ul><li>Depends on joint(s) involved </li></ul><ul><li>APAP up to 1 g QID ...
<ul><li>“ High Dose” NSAID </li></ul><ul><li>Selective COX-2 Inhibitors </li></ul><ul><ul><li>Celecoxib </li></ul></ul><ul...
<ul><li>20-30% of all hospitalizations due to peptic ulcer disease in patient >65 years old was attributable to NSAIDs </l...
<ul><li>Age > 65 years </li></ul><ul><li>History of PUD or GI bleed </li></ul><ul><li>Concomitant use of glucocorticoids o...
<ul><li>Enzyme that converts arachidonic acid to prostaglandins </li></ul><ul><li>Prostaglandins have important signaling ...
<ul><li>Cox-1  (constitutive) </li></ul><ul><ul><li>Mucous secretions </li></ul></ul><ul><ul><li>Renal function </li></ul>...
<ul><li>The chief advantages of COX-2 inhibitors over traditional NSAIDs include a decreased capacity to induce gastroduod...
<ul><li>Large trial of > 8000 patients compared rofecoxib to naproxen </li></ul><ul><li>50% cumulative reduction in rates ...
<ul><li>Compared celecoxib to diclofenac and/or ibuprofen </li></ul><ul><li>Recruited high risk patients </li></ul><ul><li...
<ul><li>COX-2 inhibitors may cause renal toxicity </li></ul><ul><ul><li>Caution must be used in patients with hypertension...
<ul><li>A retrospective study was performed at a large VA hospital </li></ul><ul><li>Compared celecoxib to rofecoxib </li>...
<ul><li>You, et al concluded that COX-2 inhibitors appeared to be least costly alternatives in patients with medium-to-hig...
<ul><li>Tramadol </li></ul><ul><ul><li>Centrally acting oral analgesic  </li></ul></ul><ul><ul><li>Synthetic opioid agonis...
<ul><li>COX-2 effects on the kidneys require further study </li></ul><ul><li>Study showed that 50 mg of rofecoxib did not ...
<ul><li>Recognize symptoms of GI bleed and perforation </li></ul><ul><li>Review patient profile </li></ul><ul><li>Counsel ...
<ul><li>Selective COX-2 inhibitors have a role in patients with OA </li></ul><ul><li>Patient selection is key </li></ul><u...
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Managing Osteoarthritis

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Managing Osteoarthritis

  1. 1. Ryan S Mills Pharm.D Candidate WVU School of Pharmacy
  2. 2. <ul><li>Generally, a non-inflammatory disorder of the joints whereby deterioration and changes to the articular cartilage result in formation of new bone on the joint surface. </li></ul><ul><li>There is an imbalance between cartilage synthesis and degradation which may cause inflammation. </li></ul><ul><li>Most common joint disease </li></ul><ul><li>Leading cause of disability </li></ul>
  3. 3. <ul><li>Affects men and women equally </li></ul><ul><li>Approx. 21 million Americans affected </li></ul><ul><li>Prevalence increases with age </li></ul><ul><li>Approximately 70% of people over the age of 70 are known to have osteoarthritis (OA). </li></ul>
  4. 4. <ul><li>Not entirely understood </li></ul><ul><li>Combination of mechanical, cellular, and biochemical mechanisms. </li></ul><ul><li>Net result is degeneration of the joint cartilage </li></ul>
  5. 5. <ul><li>Cartilage is composed of water, collage, and proteoglycans. </li></ul><ul><li>Chondrocytes affect production of collagen and proteoglycans </li></ul><ul><li>Collagen (type II) provides tensile strength and maintains tissue volume </li></ul><ul><li>Proteoglycans provide “stuffing”, give cartilage resilience and load-bearing properties. It also helps to retain and maintain the water content of cartilage. </li></ul>
  6. 6. <ul><li>Osteoarthritic cartilage </li></ul><ul><ul><li>age related changes in the matrix and decrease in chondrocyte function </li></ul></ul><ul><ul><li>leads to osteophytes and subchondral cysts formation </li></ul></ul><ul><ul><li>inflammatory process caused by macrophages </li></ul></ul><ul><ul><li>studies suggest the presence of T-cells to explain chronic inflammation </li></ul></ul>
  7. 7. <ul><li>Primary symptom-deep, localized ache relieved by rest and aggravated by activity </li></ul><ul><li>Most often seen in middle to old age individuals </li></ul><ul><li>Joints most often affected: knee, hip, hand, spine, feet. (weight bearing joints) </li></ul><ul><li>Radiographic findings can usually confirm the presence of OA, although non-specific. </li></ul><ul><li>Bone demineralization is NOT a radiographic feature of OA. (Feature of Rheumatoid Arthritis) </li></ul>
  8. 8. <ul><li>Symptoms </li></ul><ul><ul><li>Joint pain </li></ul></ul><ul><ul><li>Morning stiffness lasting LESS THAN 30 minutes </li></ul></ul><ul><ul><li>Joint instability or buckling </li></ul></ul><ul><ul><li>Loss of function </li></ul></ul><ul><li>Signs </li></ul><ul><ul><li>Bony enlargement of affected joints </li></ul></ul><ul><ul><li>Limitation in range of motion (ROM) </li></ul></ul><ul><ul><li>Crepitus </li></ul></ul><ul><ul><li>Pain with motion </li></ul></ul><ul><ul><li>Malignant and/or joint deformity </li></ul></ul>
  9. 9. <ul><li>Nonpharmacological therapy for everyone </li></ul><ul><li>Pharmacological treatment for symptomatic patients. </li></ul><ul><li>The American College or Rheumatology has published guidelines for therapy </li></ul>
  10. 10. <ul><li>Patient education </li></ul><ul><li>Self-management programs </li></ul><ul><li>Social support </li></ul><ul><li>Weight loss </li></ul><ul><li>Aerobic exercise </li></ul><ul><li>ROM exercises </li></ul><ul><li>Muscle strengthening exercises </li></ul><ul><li>Assistive devices </li></ul><ul><li>Patellar taping </li></ul><ul><li>Appropriate footwear </li></ul><ul><li>Lateral-wedged insoles </li></ul><ul><li>Bracing </li></ul><ul><li>Occupational therapy </li></ul><ul><li>Joint protection </li></ul>
  11. 11. <ul><li>Regular and moderate physical activity is beneficial in decreasing fatigue, strengthening muscles and bones, increasing flexibility and stamina, and improving overall well-being </li></ul><ul><li>NIH advises the amount and form of exercise should depend on joints involved, amount of inflammation, the stability of the joints, and whether a joint replacement procedure has been performed </li></ul>
  12. 12. <ul><li>Washing and waxing car </li></ul><ul><li>Volleyball </li></ul><ul><li>Touch football </li></ul><ul><li>Gardening </li></ul><ul><li>Basketball </li></ul><ul><li>Dancing </li></ul><ul><li>Raking leaves </li></ul><ul><li>Walking </li></ul><ul><li>Running </li></ul><ul><li>Swimming </li></ul><ul><li>Water aerobics </li></ul><ul><li>Pushing a stroller </li></ul><ul><li>Washing windows </li></ul><ul><li>Stair walking </li></ul><ul><li>and many others </li></ul>
  13. 13. <ul><li>Quadricep weakness is common among patients with knee OA </li></ul><ul><li>Originally thought to be caused by disuse atrophy </li></ul><ul><li>New studies show weakness in patients that do not have knee pain </li></ul><ul><li>Quadricep weakness may be a risk factor for knee OA </li></ul><ul><li>Exercise can be beneficial </li></ul>
  14. 14. <ul><li>Diet can help manage OA </li></ul><ul><li>Vitamin C and other antioxidants reduce the risk of OA and its progression </li></ul><ul><li>Folic acid, found in oranges and other citrus fruits, is believed to alleviate some symptoms associated with OA </li></ul>
  15. 15. <ul><li>Used for symptomatic patients </li></ul><ul><li>Depends on joint(s) involved </li></ul><ul><li>APAP up to 1 g QID OR “low dose” NSAIDs are the initial treatment of choice </li></ul><ul><li>Should be dosed on schedule, NOT PRN </li></ul>
  16. 16. <ul><li>“ High Dose” NSAID </li></ul><ul><li>Selective COX-2 Inhibitors </li></ul><ul><ul><li>Celecoxib </li></ul></ul><ul><ul><li>Rofecoxib </li></ul></ul><ul><ul><li>Valdecoxib </li></ul></ul><ul><li>Selection based upon patient risk factors for GI distress, renal toxicity, comorbidities, concomitant drug therapy, adverse effects, and cost of treatment </li></ul>
  17. 17. <ul><li>20-30% of all hospitalizations due to peptic ulcer disease in patient >65 years old was attributable to NSAIDs </li></ul>
  18. 18. <ul><li>Age > 65 years </li></ul><ul><li>History of PUD or GI bleed </li></ul><ul><li>Concomitant use of glucocorticoids or anticoagulants </li></ul><ul><li>Presence of comorbid medical conditions </li></ul><ul><li>Smoking </li></ul><ul><li>Alcohol consumption </li></ul>
  19. 19. <ul><li>Enzyme that converts arachidonic acid to prostaglandins </li></ul><ul><li>Prostaglandins have important signaling and “housekeeping” function in platelets, GI tract, lungs, and kidneys </li></ul><ul><li>There are two isoforms of the enzyme </li></ul><ul><ul><li>COX-1 </li></ul></ul><ul><ul><li>COX-2 </li></ul></ul>
  20. 20. <ul><li>Cox-1 (constitutive) </li></ul><ul><ul><li>Mucous secretions </li></ul></ul><ul><ul><li>Renal function </li></ul></ul><ul><ul><li>Erythema </li></ul></ul><ul><ul><li>Increase clot formation (thrombaxane) </li></ul></ul><ul><ul><li>Decrease clot formation (prostacyclin) </li></ul></ul><ul><li>Cox-2 (inducible) </li></ul><ul><ul><li>Peripheral and central sensitization (pain) </li></ul></ul><ul><ul><li>Edema formation </li></ul></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Decreases clot formation (prostacyclin) </li></ul></ul><ul><ul><li>Role in tissue repair </li></ul></ul>
  21. 21. <ul><li>The chief advantages of COX-2 inhibitors over traditional NSAIDs include a decreased capacity to induce gastroduodenal damage and a lack of antiplatelet activity </li></ul><ul><li>Several studies have been published comparing the various specific COX-2 inhibitors with placebo and other non-selective NSAIDs </li></ul>
  22. 22. <ul><li>Large trial of > 8000 patients compared rofecoxib to naproxen </li></ul><ul><li>50% cumulative reduction in rates of GI bleed, perforation, and obstruction in the rofecoxib group </li></ul><ul><li>Increased risk of CV thromboembolic events (heart attack, angina, PVE) in the rofecoxib group </li></ul><ul><li>However, other studies have shown similar rates of adverse events in both study groups </li></ul>
  23. 23. <ul><li>Compared celecoxib to diclofenac and/or ibuprofen </li></ul><ul><li>Recruited high risk patients </li></ul><ul><li>Study failed at assembling all of the criteria from patients meeting the goals </li></ul><ul><li>However, celecoxib caused a statistically significant reduction in symptomatic ulcers </li></ul>
  24. 24. <ul><li>COX-2 inhibitors may cause renal toxicity </li></ul><ul><ul><li>Caution must be used in patients with hypertension and CHF </li></ul></ul><ul><ul><li>NOT recommended in advanced renal disease </li></ul></ul><ul><li>Celecoxib is contraindicated in patients allergic to sulfonamides </li></ul><ul><li>NOT studied in inflammatory bowel disease (IBD) </li></ul>
  25. 25. <ul><li>A retrospective study was performed at a large VA hospital </li></ul><ul><li>Compared celecoxib to rofecoxib </li></ul><ul><li>Primary endpoints were: </li></ul><ul><ul><li>Drug strength </li></ul></ul><ul><ul><li>Quantity dispensed </li></ul></ul><ul><ul><li>Days supply for the prescription </li></ul></ul><ul><li>Evaluators concluded that rofecoxib would produce an annual savings of 2.1 million dollars in 2000 </li></ul>
  26. 26. <ul><li>You, et al concluded that COX-2 inhibitors appeared to be least costly alternatives in patients with medium-to-high risk of GI toxicity </li></ul><ul><li>COX-2 inhibitors may reduce associated expenses of medical and/or surgical treatment due to long-term NSAID use </li></ul>
  27. 27. <ul><li>Tramadol </li></ul><ul><ul><li>Centrally acting oral analgesic </li></ul></ul><ul><ul><li>Synthetic opioid agonist that inhibits the reuptake of norepinephrine and seratonin </li></ul></ul><ul><ul><li>Approved for use in patients contraindicated for COX-2 inhibitors </li></ul></ul><ul><ul><li>Useful as adjunctive therapy </li></ul></ul><ul><ul><li>SE: common and include nausea, constipation, and drowsiness </li></ul></ul>
  28. 28. <ul><li>COX-2 effects on the kidneys require further study </li></ul><ul><li>Study showed that 50 mg of rofecoxib did not increase the incidence of hypertension or pedal edema in RA patients </li></ul><ul><li>More studies comparing the efficacy of COX-2 inhibitors to nonselective NSAIDs </li></ul>
  29. 29. <ul><li>Recognize symptoms of GI bleed and perforation </li></ul><ul><li>Review patient profile </li></ul><ul><li>Counsel on short and long-term effects of the drugs </li></ul><ul><li>Encourage patient adherence </li></ul><ul><li>Remind patients to consult you or MD about any new meds they may take </li></ul><ul><li>Take meds as prescribed </li></ul><ul><li>Maintain up-to-date profile on all patients </li></ul>
  30. 30. <ul><li>Selective COX-2 inhibitors have a role in patients with OA </li></ul><ul><li>Patient selection is key </li></ul><ul><li>Be aware of contraindications and side effects </li></ul><ul><li>Encourage the proper use of these agents </li></ul><ul><li>Counsel patients appropriately </li></ul>
  31. 31. Questions?
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