Adequan - possibly an answer
for dogs with joint damage
GENERAL Information: Adequan Canine polysulfated glycosaminoglycan (PSGAG) is the only product in use today proven to control both the symptoms and to alter the underlying degenerative disease process of canine arthritis. Adequan Canine is a member of a new class of drugs termed disease-modifying osteoarthritis drugs (DMOAD). It is the first therapy proven to control the pain and inflammation of canine arthritis while breaking the destructive cycle of osteoarthritis by inhibiting or blocking cartilage and synovial enzyme destruction to the cartilage matrix.
Previous and other medical options (nonsteroidal anti-inflammatory drugs and corticosteroids) only served to relieve the pain and inflammation of arthritis without slowing down or stopping the continued joint degeneration caused by the disease process.
Canine arthritis: More than eight million dogs per year suffer arthritis damage in their joints. This damage often starts with an injury to the joint cartilage that covers the bone. An injury can occur any time a dog jumps, runs or otherwise stresses its joints. Injury also may be the result of joints fitting too loosely with altered movement and weight-bearing of the joint cartilage and underlying bone. Upon damage to cartilage in the joint of a dog, typical inflammation with associated pain, heat and redness does not occur due to absence of nerves and blood vessels; the animal thus does not recognise that there has been injury and due to further activity additional damage may result. Meanwhile the damaged tissues have triggered the release of tissue messengers/mediators to activate enzymes to eliminate damaged tissues and to attempt repair.
Excesses of this response due to repeated damage and to the animal's body's limited ability to balance the processes leads to further damage and spread of the action to impact the lubricating ability of the joint fluid, to enzymatic breakdown of the joint cartilage and to remodelling of the underlying bone.
Joint function is thus further compromised. It is only when the reactions impact the sensory nerves of the joint capsule, its lining or the underlying bone that pain is detected - a time when significant damage may already have occurred.
How Adequan Canine works
Once in the joint, Adequan limits joint damage and facilitates the return of joint function in a number of different ways, much more than just by the alleviation of pain and inflammation alone. It stimulates the synovial lining of the joint cavity while at the same time suppressing inflammation of the lining. The synovial lubricant (HA) is enhanced and the damaging products of inflammation in the synovial fluid are reduced; the quality of the synovial fluid, which supplies nutrients for the articular cartilage is thus improved. At the same time, Adequan blocks the excesses of the degrading enzymes affecting both the lubricant of the joint fluid and components of the joint cartilage. Additionally, Adequan conserves and promotes the production of key substances of the cartilage.
Adequan Canine polysulfated glycosaminoglycan (PSGAG) is available by prescription only from a licensed veterinarian and is administered through intramuscular injection. Studies have demonstrated that Adequan Canine reaches major synovial joints within two hours after injection. An initial eight-dose series is recommended, administering two milligrams per pound of the dog's weight twice a week for four weeks.
Effectiveness - In clinical trials involving a number of different arthritic conditions, Adequan Canine was proven to provide significant improvement in more than 70percent of the arthritic limbs. Adequan Canine for the treatment of signs associated with osteoarthritis in the dog has been evaluated in a radiolabelled study of the drug's distribution in canine serum, synovial joint fluid and articular cartilage and in controlled field trials.
Many factors - such as breed, age and obesity - predispose a dog to a variety of joint problems that can lead to osteoarthritis. Though large breeds typically come to mind when questions of arthritis crop up, small dogs are not exempt. Typically in large or giant breed dogs, the following conditions may cause arthritis: Canine Hip Dysplasia is a progressive disease that begins as laxity in the hip joints and moves on to joint instability and osteoarthritis. Osteochondroisis appears when bone does not form properly. Usually found in dogs four to 12 months old, it typically appears in the shoulder and leads to arthritis.
A fragmented cornonoid process or united anconeal process, both affecting a dog's elbow, also lead to arthritis.
The following conditions can occur in dogs of any age or breed, but appear to favour small and toy breeds:
Ruptured cruciate ligament - is commonly seen in overweight, middle-aged, small breed dogs. If not corrected, instability in the joints may lead to osteoarthritis.
Patella luxation - dislocation of the kneecap - may be congenital or the result of joint trauma. Uncorrected it also can lead to arthritis.
Legg-Perthes' disease - attacks the head of the thigh-bone and can bring on arthritis.
Affecting dogs of all sizes and breeds:
lntra-articular fractures, joint luxations and synovitis usually occur as a result of a traumatic injury such as an auto accident or fall and can lead to arthritis.
Spondylosis is caused by excessive movement in the vertebral joints. Long-term wear-and-tear of joints commonly seen in older dogs, contributes to the development of canine osteoarthritis.
What you may not know about Adequan Canine (polysulfated glycosaminoglycan): Recent focus groups of veterinarians indicates that certain aspects of degenerative joint disease (DJD), osteoarthritis and treatment with Adequan Canine require clarification: Adequan Canine is indicated for use in the medical management of non-infectious degenerative disease or traumatic arthritis of any synovial joint, including DJD associated with old age, hip dysplasia and joint injury. Adequan Canine is the only treatment for canine DJD with the ability to treat the underlying disease process as well as the clinical signs of osteoarthritis. No other treatment does both.
An impact injury has caused a loose joint, possible synovial fluid loss, and breakdown of the cartilage at the impact site.
After the initial eight-injection series, many cases need no further treatment. Simply alleviating the pain of DJD without attacking the disease may not be in the best interests of the patient because doing so can encourage (without attacking the disease) the animal to use the affected joint, which may lead to further damage. Because the DJD process in dogs starts within the cartilage itself, it is often advanced when the first signs of discomfort appear; therefore, it is better to start canine patients on Adequan Canine as soon as they show even the earliest clinical signs of disease. Although modified significantly, PSGAG is chemically similar to the glycosaminoglycans that are part of the normal articular cartilage matrix, with added sulfate to enhance its action.
Degenerative joint disease - Also known as osteoarthritis, degenerative joint disease is a progressive (though often intermittent) disorder of synovial joints that systematically damages the joints with impairment of function and mobility in approximately 15-20 percent of all dogs.
Geriatric osteoarthritis - A degenerative condition in one or more joints potentiated by ageing.
Hip dysplasia - A developmental deformity of the ball-and-socket hip joint leading to abnormal mobility (increased laxity) of the joint and osteoarthritis.
Inflammation - Inflammation is a normal body response to any injury in which the body attempts to dilute, localize, destroy and remove a threatening agent and overcome any damage created. Agents that cause inflammation include physical injury, chemicals, infective agents (viruses, bacteria), allergies (dust, pollen), and foreign particles and tissues.
Osteochondritis dissecans (OCD) - The result of improper bone development just beneath the cartilage, causing articular cartilage separation and leading to secondary osteoarthritis.
Ruptured cruciate ligament(s) - A tear of one or both of the internal ligaments that stabilise movement back and forth of the femur on the head of the tibia with increased joint laxity and secondary arthritis.
Spondylitis - An arthritic condition in one or more joints of the spinal column.
Synovial joint - A Synovial joint is a structure that joins two or more bones together to form a movable articulation.
Traumatic joint injury - Joint injury due to a trauma, such as failing or impact with a blunt object.
The active ingredient in Adequan Canine is polysulfated glycosaminoglycan (PSGAG). Polysulfated glycosaminoglycan is a semi-synthetic glycosaminoglycan prepared by extracting glycosaminoglycans (GAGS) from bovine tracheal cartilage. GAGs are polysaccharides composed of repeating disaccharide units. The GAG present in PSGAG is principally chondroitin sulphate containing three to four sulphate esters per disaccharide unit. The molecular weight for PSGAG used in the manufacture of Adequan is 3000 to 15000 daltons. Each ml of Adequan Canine contains 100 mg of PSGAG, 0.9percent vlv benzyl alcohol as a preservative and water for injection q.s. to 1 ml. Sodium hydroxide and/or hydrochloric acid added to adjust pH.
The specific mechanism of action of Adequan in canine joints is not known. PSGAG is characterised as a "disease modifying osteoarthritis drug". Experiments conducted in vitro have shown PSGAG to inhibit certain catabolic enzymes which have increased activity in inflamed joints, and to enhance the activity of some anabolic enzymes. For example, PSGAG has been shown to significantly inhibit serine proteinases. Serine proteinases have been demonstrated to play a role in the interleukin-1 mediated degradation of cartilage proteoglycans and collagen. PSGAG is reported to be an inhibitor of prostaglandin E2 (PGE2) synthesis. PGE2 has been shown to increase the loss of proteoglycan from cartilage. PSGAG has been reported to inhibit some catabolic enzymes such as elastase, stromelysin, metalloproteases, cathepsin B1, and hyaluronidases, which degrade collagen, proteoglycans, and hyaluronic acid in degenerative joint disease. Anabolic effects studied include the ability to stimulate the synthesis of protein, collagen, proteoglycans, and hyaluronic acid in various cells and tissues in vitro.
Cultured human and rabbit chondrocytes have shown increased synthesis of proteoglycan and hyaluronic acid in the presence of PSGAG. Absorption, distribution, metabolism and excretion of PSGAG following intramuscular injection have been studied in several species, including rats, rabbits, humans, horses and dogs.
Studies in rabbits showed maximum blood concentrations of PSCAC following IM injection were reached between 20 and 40 minutes following injection and that the drug was distributed to all tissues studied, including articular cartilage, synovial fluid, adrenals, thyroid, peritoneal fluid, lungs, eyes, spinal cord, kidneys, brain, liver, spleen, bone marrow, skin, and heart. Following intramuscular injection of PSGAG in humans, the drug was found to be bound to serum proteins. PSGAG binds to both albumin and chi-globulins and beta-globulins and the extent of the binding is suggested to be 30 to 40 percent. Therefore, the drug may be present in both bound and free form in the bloodstream. Because of its relatively low molecular weight, the synovial membrane is not a significant barrier to distribution of PSGAG from the bloodstream to the synovial fluid. Distribution from the synovial fluid to the cartilage takes place by diffusion. In the articular cartilage the drug is deposited into the cartilage matrix.
Serum and synovial fluid distribution curves of PSGAG have been studied in dogs and appear similar to those found in humans and rabbits. In rabbits, metabolism of PSGAG is reported to take place in the liver, spleen, and bone marrow. Metabolism may also occur in the kidneys. PSGAG administered intramuscularly and not protein bound or bound to other tissues is excreted primarily via the kidneys, with a small proportion excreted in the faeces.
Toxicological studies have revealed no significant toxic effects for Adequan Canine at the recommended dose. In a subacute toxicity study, 32 adult dogs (four males and four females per treatment group) received either 0.9percent saline solution or PSGAG at a dose of 5 mg, 15 mg or 50 mg per kg of body weight (approximately 2.3, 6.8, or 22.7 mg/lb), via intramuscular injection twice weekly for 13 weeks. PSGAG doses represent approximately 1X, 3X, and 10X the recommended dosage of 2mg/lb, and more than three times the recommended four-week duration of treatment. During week 12, one dog in the 50 mg/kg dosage group developed a large haematoma at the injection site which necessitated euthanasia. No other mortalities occurred during treatment.
Efficacy of Adequan Canine was demonstrated in two studies. A laboratory study using radiolabelled PSGAG established distribution of PSGAG into canine serum and synovial fluid following a single intramuscular injection of 2 mg/lb. A clinical field trial was conducted in dogs diagnosed with radiographically-confirmed traumatic and/or degenerative joint disease of one or two joints. Joints evaluated included hips, stifles, shoulders, hocks and elbows. Fifty-one dogs were randomly assigned to receive either Adequan Canine at 2 mg/lb of body weight or 0.9percent saline. Both treatments were administered by intramuscular injection twice weekly for four weeks. Investigators administering treatment and evaluating the dogs were unaware of the treatment assignment. At the end of the treatment period, dogs treated with Adequan Canine showed a statistically significant improvement in range of motion and total orthopaedic score over placebo treated control dogs.
Indication for use
Adequan Canine polysulfated glycosaminoglycan (PSGAG) is FDA-approved for the control of signs associated with non-infectious degenerative and/or traumatic arthritis of canine synovial joints. Canine arthritis results from such conditions (or predisposition to such conditions) as hip dysplasia, ruptured cruciate ligament(s), OCD, spondylitis and traumatic joint injury. Adequan Canine is recommended for intramuscular injection for the control of signs associated with non-infectious degenerative and/or traumatic arthritis of canine synovial joints.
Adequan Canine polysulfated glycosaminoglycan (PSGAG) should not be used in dogs that are hyper-sensitive to PSGAG. It should be used only with caution in dogs with renal or hepatic impairment. Possible side effects (pain at injection site, vomiting, diarrhoea, depression and abnormal bleeding) are mild, transient and self-limiting. PSGAG is a synthetic heparinoid; do not use in dogs with known or suspected bleeding disorders.
Information on this product supplied by Luitpold Pharmaceuticals Inc. More information on their website at www.luitpold.com