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