Lecture 8 Rheumatologic Disorders Osteoarthritis University of Nizwa College of Pharmacy and Nursing School of Pharmacy PHARMACOTHERAPY II PHCY 410 Lecture 8 Rheumatologic Disorders Osteoarthritis Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

Course Outcomes Upon completion of this lecture the students will be able to Describe etiology, clinical manifestations and diagnosis of osteoarthritis. Develop skills for monitoring drug therapy and patient education in patients with osteoarthritis. Explain drug related problems and develop pharmaceutical care plan in patients with osteoarthritis.

Osteoarthritis (OA) is a common, slowly progressive disorder affecting primarily the weight-bearing diarthrodial joints of the peripheral and axial skeleton. It is characterized by progressive deterioration and loss of articular cartilage, resulting in osteophyte formation, pain, limitation of motion, deformity, and progressive disability. It is a complex disease involving cartilage and bone and result from an imbalance in erosive(destructive) and repairing process.

PATHOPHYSIOLOGY Primary (idiopathic) OA, the most common type, has no known cause. Secondary OA is associated with a known cause such as rheumatoid arthritis or another inflammatory arthritis, trauma, metabolic or endocrine disorders, and congenital factors. Begins with damage to articular cartilage through injury, excess joint loading from obesity, or joint instability or injury that causes abnormal loading. Damage to cartilage increases the metabolic activity of chondrocytes, leading to increased synthesis of matrix constituents with cartilage swelling.

Increased synthesis of matrix metalloproteinases (MMPs) causes collagen destruction to occur, with a net loss of cartilage. Chondrocytes contribute to collagen loss by secreting MMPs in response to inflammatory mediators present in OA (interleukin-1 and tumor necrosis factor-α). Substantial loss of cartilage causes joint space narrowing and leads to painful, deformed joints. Predisposing factors includes age, race, genetics, gender(OA knee common in females), obesity, physical and occupational factors, joint trauma.

CLINICAL PRESENTATION Localized deep, aching pain associated with the affected joint. In addition to pain, limitation of motion, stiffness, crepitus, and deformities may occur. Patients with lower extremity involvement may report a sense of weakness or instability. Upon arising, joint stiffness typically lasts less than 30 minutes and resolves with motion. The presence of a warm, red, and tender joint may suggest an inflammatory synovitis.

DIAGNOSIS Patient history, clinical examination of the affected joint(s), radiologic findings, and laboratory testing. Criteria for the classification of OA based on American College of Rheumatology (ACR). Criteria include presence of pain, bony changes on examination, a normal erythrocyte sedimentation rate (ESR), and radiographs showing characteristic osteophytes or joint space narrowing. The rheumatoid factor test is negative. Analysis of the synovial fluid reveals fluid with high viscosity with a mild leukocytosis (less than 2,000 white blood cells/mm3) predominantly mononuclear cells.

TREATMENT NONPHARMACOLOGIC THERAPY Educate the patient about the extent of the disease. Dietary counseling. Structured weight-loss program for overweight OA patients. Physical therapy—with heat or cold treatments and an exercise program. Assistive and orthotic devices such as canes, walkers. Surgical procedures (e.g., osteotomy, partial or total arthroplasty, joint fusion) are indicated for patients with functional disability.

NONPHARMACOLOGIC THERAPY Drug therapy in OA is targeted at relief of pain. For mild or moderate pain, topical analgesics or acetaminophen can be used. If these measures fail or if there is inflammation, nonsteroidal antiinflammatory drugs (NSAIDs) may be useful. Appropriate nondrug therapies should be continued when drug therapy is initiated. Acetaminophen first-line drug therapy for pain management of OA. The dose is 325 to 650 mg every 4 to 6 hours on a scheduled basis (maximum dose 4 g/day; maximum 2 g/day if chronic alcohol intake or underlying liver disease). It should be used with caution in patients with liver disease and those who chronically abuse alcohol.

Nonsteroidal Antiinflammatory Drugs It is prescribed for patients after treatment with acetaminophen proves ineffective, or patients with inflammatory OA. Analgesic effects begin within 1 to 2 hours, antiinflammatory benefits may require 2 to 3 weeks of continuous therapy. If the first NSAID fails, another agent in the same or another chemical class can be tried until an effective drug is found. Combining two NSAIDs increases adverse effects. Cyclooxygenase-2 (COX-2) selective inhibitors (e.g., celecoxib) demonstrate analgesic benefits.

COX-2 selective inhibition reduce NSAID induced gastropathy (e. g COX-2 selective inhibition reduce NSAID induced gastropathy (e.g., ulcers, bleeding, perforation). Due to concerns about adverse cardiovascular events (e.g., myocardial infarction, stroke) it is given in selected patients who are at high risk for NSAID-related GI effects and low risk for cardiovascular toxicity. NSAIDs also cause kidney diseases, hepatitis, hypersensitivity reactions, rash, and CNS complaints of drowsiness, dizziness, headaches, depression, confusion, and tinnitus.

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, β- blockers, and diuretics. Topical Therapies Capsaicin, an extract of red peppers causes release and depletion of substance P from nerve fibers, providing pain relief in OA when applied topically over affected joints. Topical diclofenac is safe and effective treatment for OA pain.

Glucosamine and Chondroitin They are dietary supplements that were shown to stimulate proteoglycan synthesis from articular cartilage. Glucosamine adverse effects are mild and include GI gas, bloating, and cramps; should not be used in patients with shellfish allergies. The most common adverse effect of chondroitin is nausea. Corticosteroids Systemic corticosteroid therapy is not recommended in OA. Intraarticular corticosteroid injections can provide relief, particularly when a joint effusion is present. Therapy is generally limited to three or four injections per year because of potential systemic effects.

Hyaluronate Injections High-molecular-weight hyaluronic acid is a constituent of normal cartilage that provides lubrication with motion and shock absorbency during rapid movements. Hyaluronic acid injections temporarily and modestly increase synovial fluid viscosity and were reported to decrease pain. The intra articular hyaluronic acid preparations available for treating pain associated with OA are sodium hyaluronate, hylan polymers and hyaluronan. Injections are well tolerated, but causes acute joint swelling and local skin reactions (e.g., rash, ecchymoses, or pruritus)

Opioid Analgesics Low-dose opioid analgesics (e.g., oxycodone) may be useful for patients who experience no relief with acetaminophen, NSAIDs, intraarticular injections, or topical therapy. Tramadol It may also be effective as add-on therapy in patients taking concomitant NSAIDs or COX-2 selective inhibitors. Tramadol should be initiated at a lower dose (100 mg/day in divided doses) and may be titrated as needed. Opioid-like adverse effects such as nausea, vomiting, dizziness, constipation, headache, and somnolence are common.