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Managing arthritic dogs and cats (Proceedings)
Osteoarthritis (OA) is a chronic, non-infectious, progressive disorder of any synovial joint.
Osteoarthritis (OA) is a chronic, non-infectious, progressive disorder of any synovial joint. OA is characterized by deterioration of the articular cartilage, synovitis, with secondary bony changes. Osteoarthritis is classified as being primary or secondary in nature. Primary arthritis (age-related) results from abnormalities within the cartilage (abnormal quality) and is considered an intrinsic problem with the cartilage homeostasis associated with aging. In this form of OA, normal joint forces impact abnormal cartilage. The affected cartilage has limited ability to regenerate and maintain itself in the face of the cumulative effects of ongoing trauma and/or inflammation. Primary osteoarthritis has a slow progressive course, generally involves one or more joints, and is most common in geriatric patients.
Secondary arthritis is a more common cause of clinical lameness in the younger dog. It is the consequence of some external event or force affecting the articular cartilage adversely. In this form there are abnormal forces affecting normal cartilage. Examples would include overt trauma, joint incongruity (instability), and joint malalignment. Secondary arthritis can be seen in any age animal and usually involves a single joint. In order to prevent, halt or minimize the degeneration process, the underlying joint incongruity must be eliminated.
The pathophysiology of primary arthritis involves a series of steps that eventually becomes a progressive self-perpetuating process. The mediators of the inflammation, pain, and joint destruction include prostaglandins, cytokines, leukotriens, and kinnins. The variation in clinical response of the each pharmacological agent used in treating OA reflects the specific effect on each of these specific inflammatory mediators or pathways. Articular cartilage is a very complex and dynamic structure. The cartilage matrix is composed of proteogycan macromolecules (hyaluronic acid and GAGs), type 1 collagen, and 80% water. The matrix is synthesized and maintained primarily by the chondrocytes. In primary arthritis, there is a shift in the cartilage homeostasis towards catabolism. Initially there is decreased production of proteogycan by the chondrocytes, a loss of chondroitin sulfates and water from the matrix. The resultant articular cartilage is less elastic with less shock absorption. Any minor trauma produces cartilage fissures and chondrocytes damage. Surface cracks produce "flaking" exposing the collagen fibers to wear and tear. Some cracks extend into the deeper layers and bone produce fibrillation. Degrading enzymes are released which further break down cartilage matrix and collagen. These enzymes include serines, collagenase, cathepsins, metalloproteinase's, hyaluronidases, stromelysins, plus the cartilage breakdown products, initiate a mild synovitis The resulting inflamed synovial membrane releases primary inflammatory mediators IL 1, IL 6, tissue necrosis factor, proteases, and prostaglandins that further increasing cartilage destruction and inhibiting new matrix production. The further decreased resiliency of the cartilage results in sclerosis of the subchondral bone and osteophyte development in the periarticular margins in advanced cases.
The clinical signs of osteoarthritis are similar regardless of whether the disorder is primary or secondary. The onset is often insidious but progressive. Early in the course of the disease, the animal may sporadically be reluctant to perform previous tasks or activities, i.e., jumping into the car. In the next stage, a lameness or stiffness occurs following periods of excess activity or overexertion. These signs often disappear after several days of rest. As the degeneration progresses, the stiffness and lameness may be most pronounced following periods of rest. The pet typically "warms out" of the signs with activity. Any cold or damp weather will increase the severity and duration of the symptoms. Continuous stiffness, lameness and chronic pain typify the final stage producing an irritable, reclusive and restless pet. In a recent study, 90% cats > 12 years had radiographic evidence of osteoarthritis (Hardie, E., JAVMA 2002). The most common location in cats was the spine followed by the elbow and the hip. Common feline symptoms include grooming difficulties, inappropriate eliminations, less jumping, aggressive when handled, and lameness.
There is no cure for arthritis, only control. The goals in the treatment should be to alleviate patient discomfort, minimize further degenerative changes, and to restore the affected joints to as near normal and pain-free as function possible. The management of arthritis involves the following strategies and should be tailored to best meet the patient and clients needs; 1. Client education on the progressive nature of the disease is critical; 2. Set realistic outcome goals (expectations); 3. Adequate rest periods; 4. Sensible exercise program; 5. Weight assessment and reduction if necessary; 6.Analgesics and anti-inflammatory therapy for rapid results; and/or 6. Chondroprotective agents; 7.Anti-oxidant nutritional therapy (dietary); 8. Complementary therapies, i.e. message therapy, physical therapy, acupuncture, chiropractic, etc.
When choosing between NSAIDs and Chondroprotective agents we initially select the NSAIDS because NSAIDS have a more consistent, predictable and faster response our client expects. In addition NSAIDS have more research backing the products and generally the product quality control is much better. Unfortunately there are potentially serious side effects that must be communicated and assessed. Conversely the chondroprotective are less reliable in there effect, slower to work, but are much less toxic. NSAIDS have a variable combination of anti-inflammatory, antipyretic, and analgesic effects. The variation in clinical response of the each pharmacological NSAID agent used in treating arthritis reflects the specific effect on various mediators of the inflammation via selective inhibition of pyrogens, COX1, COX2, and pain mediators. While all NSAIDS have some common toxicity, each has unique pharmacological and dosing advantages and should never be considered identical or interchangeable. In fact when switching NSAIDs, I always recommend a "WASH OUT" period of at least 7 days. Managing feline osteoarthritis involves the judicious use of chondroprotective agents, steroids and/or a non-approved long term NSAIDs such as metacam.
NSAIDS toxicity ranks at the very top of the geriatric adverse drug reaction list. Primarily this is because of their wide spread usage and potential life threatening side effects. Adverse Drug Events (toxicity) are usually associated with over dosages, misuse by owners, combined therapy with steroids, failure to "wash-out" a NSAID before switching to another one, concomitant disease, and the lack of pharmaco-vigilance on the veterinarians part. During washout period, tramadol at 2-5mg/kg q12h can be safely used in dogs. It stimulates the opiate, adrenergic, and serotonin receptors. This pain reliever is compatible with all the COX inhibiting NSAIDS drugs but NOT with serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors such as Anipryl. The induced enzyme Cyclooxygenase 1 (COX1) is responsible for maintaining the gastrointestinal mucosa health, renal and hepatic blood flow. Nonselective inhibition of COX1 can result in gastrointestinal damage, decreased renal blood flow and/or hepatopathies. The resultant toxicity(s) includes gastro-duodenal hemorrhage, gastro-duodenal ulcerations, bleeding dyscrasias, and analgesic nephropathy/hepatopathies. Most toxicity associated with the administration of NSAIDS results from Prostaglandin E inhibition by blocking the COX1. This is often dose-related adverse drug event. Prostaglandin E is gastric cyto-protective by inhibiting gastric acid secretion, maintaining mucosa blood flow, stimulating epithelial cell renewal /restitution, increasing gastric bicarbonate and mucus secretion. Cyto-protective strategies are aimed at eliminating or reducing the possible side effects with prolonged NASAID administration. Using more selective COX2 inhibitors (COX1 sparing), accurate dosing, administering NSAIDs with a meal, the use of concomitant antacids, the use of H2 receptor blockers can all aid in prevent most of the untoward side effects of nonsteroidal anti-inflammatory medication. Misoprostal, a synthetic PGE1 replacement, was first advocated to combat the side effects of NSAIDS. The dosage is 2-5 ug/kg PO TID and is contraindicated in pregnancy.
Glucocorticoids are very effective at decreasing the inflammation associated with arthritis however they should only be used in those advanced cases that are unresponsive to NSAIDS since steroids hasten the cartilage degeneration via chondromalacia. PU/PD, GI bleeding and ulceration are common adverse reactions which are amplified when used concomitantly with NSAIDs.
Chondroprotective Agents: Chondroprotective agents are a group of compounds that directly benefit and/or support the cartilage matrix. As a group, these compounds act to decrease the breakdown of articular cartilage and/or provide the building blocks to up regulate cartilage synthesis. Some actually decrease inflammation and increase beneficial synovial fluid secretion. Therefore chondroprotective agents may not only relieve some symptoms but they may also decrease the degenerative process thereby may actually "reverse" the degeneration. Although chondroprotective agents are not considered analgesics, recent studies indicate they may have a direct anti-inflammatory effect on the synovial membrane. Principle components of chondroprotective agents include one or
more of the following; PSGAG's, glucosamine, and chondroitin sulfate. Unfortunately clinical failures with chondroprotective therapies are common and could be attributed to minimal cartilage remaining (bone to bone), unresponsive inflammation, time /dose dependant responses, and the lack of analgesia. The low daily dosage of chondroprotective in some diets, there efficacy in treating arthritis is questionable. While more expensive, the injectable PSGAG's give a faster and longer lasting response than the oral forms. Although more expensive, the combination of NSAIDs plus chondroprotective is attractive to many owners, especially if the chondroprotective agent decreases the NSAID dosage and frequency of usage.
Of recent interest is the use of nutrition as part of an overall arthritis management strategy. Dietary glucosamine (IAMS senior) and/or dietary n-3 fatty acids, especially DHA and EPA, can reduce production of the pro-inflammatory factors and result in clinical improvement is some arthritic patients (Purina L, Hills j/d, and IAMS).
A wide variety of other drugs have been used in the management of DJD in small animals including Vitamin C, crysotherapy (gold injections), free radical scavengers orgotein (Palosein), MSN, and hyaluronate sodium. In most cases the exact mechanisms of action is poorly understood and little scientific data exists to determine any efficacy.
Complementary therapies continue to gain favor among the veterinary community and pet owning public in managing arthritis. At Kansas State University we have a faculty member Board Certified in acupuncture, chiropractic, and holistic medicine that I common refer patients to for complimentary therapy when western medicine has failed, is too toxic, or the owner wants to take another approach.