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