Canine Arthritis Medication Options

Canine Arthritis Medications are often used as part of the therapy to combat the two major problems associated with osteoarthritis are pain and loss of joint function. Therefore the main aims of therapy are to improve joint function and to reduce pain.

The goals of treatment, in order of importance are:
• Reduction of pain associated with the disease
• Improve function of the affected joint(s)
• Prevent or slow continued degradation of the affected joint(s)
• Encourage repair of the diseased joint where possible

There are three options with the treatment of osteoarthritis; conservative therapy, medical treatment or surgical treatment.

Conservative Therapy

Surgical Treatment

Medical Treatment

Non Steroidal Anti-Inflammatory Drugs (NSAIDs)

Carprofen belongs to the Carbazole class, and is a propionic acid-derived NSAID

Carprofen (Rimadyl) was the first drug to be specifically approved for the treatment of OA in dogs. It works as a canine arthritis medication by improving limb function. Limb function is measured by both subjective and objective gait analysis in clinical trials of dogs with osteoarthritis.Carprofen has anti-inflammatory (reduces swelling), analgesic (reduces pain) and antipyretic (reduces fever/temperature) activity.

The way that carprofen works, or its “Mode of Action”, is not fully understood; however inhibition of prostaglandin synthesis plays a role. Prostaglandins are chemical substances released by the body which cause swelling and pain. Prostaglandins also have a role in protecting the inner lining of the intestines. This is why when NSAIDs are taken for too long and prostaglandin is inhibited, patients can get gastro-intestinal ulceration.

The recommended dose of Rimadyl in dogs is 2.2mg/kg bid (twice per day) or 4.4mg/kg sid (once per day)

Rimadyl (carprofen) causes minimal gastrointestinal damage, less than when compared to the gastrointestinal toxicity that aspirin may cause.

At therapeutic levels Rimadyl does not have a negative impact on cartilage metabolism.

The average half life of Rimadyl (carprofen) is approx 8hrs (range 4.5-9.8hrs).

Carprofen is eliminated primarily by biotransformation in the liver, followed by rapid excretion in the urine and faeces (70-80%).

Carprofen is considered a very safe drug in dogs. Dogs receiving 1, 3 and even up to 5 times the recommended dosage for 42 days in clinical studies did not develop any clinically significant adverse effects.

Adverse effects can include vomiting, diarrhoea, lethargy, increased appetite, and decreased appetite.

Metacam is one of the most popular canine arthritis medications used by vets in the UK. It is a non-steroidal anti-inflammatory drug (NSAID) and works by relieving pain and inflammation associated with arthritis. Therefore, it plays an important role in improving quality of life for dogs with arthritis.

Metacam consistently demonstrates higher activity against COX-2 than COX-1, which is good in terms of the safety of a drug. The gastrointestinal tract safety profile appears superior to piroxicam and approaching that of carprofen (rimadyl).

Phenylbutazone is another canine arthritis medication that falls into the nonsteroidal anti-inflammatory drug (NSAID)group. It is effective in treating fever, pain, and inflammation in the body. However, because of an unique risk of bone marrow suppression (causing dangerously low white blood counts), phenylbutazone is generally reserved only for short-term use in selected patients.can cause:
o Bleeding dyscrasias
o Hepatopathy
o Nephropathy
o May also cause irreversible bone marrow suppression
Is capable of displacing other highly protein-bound drugs – causing adverse drug reaction.

Aspirin has been used for many years due to its ready availability and its cheap cost. Dose for anti-inflammatory effect is higher than for antipyretic (reducing fever) or analgesic (pain killing) effect.

Experimental studies suggest that the effective dose for dogs is 25mg/kg tid (three times per day) – to maintain salicylate levels in the range defined as therapeutic for humans. This dose frequently results in GI toxicity, again, this is due to the reduced levels of prostaglandins from its use.

A positive clinical response is frequently obtained from a dose of 10-20mg/kg tid, although this is anecdotal!

Aspirin at 16.5mg/kg bid (twice per day) caused significant gastroduodenal bleeding (compared with carprofen and etodolac).
o Dog dose = 10-40mg/kg tid (three times per day)

Adverse effects are more pronounced in older patients. This is a feature common to all NSAIDs..

Aspirin has a Narrow safety margin.

Another canine arthritis medication is ketoprofen, which is a propionic acid derived NSAID, similar to Carprophen. It is a strong inhibitor of COX, bradykinin, and may inhibit some lipoxygenases (LOX) and therefore prevent leukotrienes.

The safety profile of Ketoprofen in dogs is still largely unknown. It is possibly poorly tolerated. Some studies have shown a high incidence of endoscopic haemorrhage (5/6 dogs).

Piroxicam undergoes extensive entero-hepatic recycling, which accounts for its long half life (37-40hrs). It has a low safety margin in dogs. Piroxicam can cause gastrointestinal ulceration and haemorrhage. Concurrent use of misoprostol is recommended for patients receiving piroxicam.

Paracetamol is a para-aminophenol derivative. Paracetamol is only effective as an analgesic (pain killer) and antipyretic (to reduce fever). It is NOT effective as an anti-inflammatory.

Recommended dose = 15mg/kg tid in dogs.

Adverse effects include:
o Cyanosis (lack of oxygen)
o Dose-dependent hepatic necrosis (liver damage)
o Renal dysfunction (Kidney damage)
o Respiratory depression (decreased breathing/oxygen intake)
o GI intolerance (stomach upsets)
o Heinz-body formation (a condition which affects the red blood cells)
o Methaemoglobinaemia
o Anaemia
o Haemoglobinuria
o Icterus (jaundice)

PARACETAMOL SHOULD NEVER BE USED IN CATS. Cats lack the enzyme glucouronosyltransferase and the use of paracetamol will cause Red Blood Cell lysis (death) and hepatic necrosis (liver damage) Therefore the use of paracetamol in cats is strictly contraindicated.

Human over-the-counter NSAIDs demonstrate different pharmacokinetics in dogs compared to humans which makes them unsafe for use in dogs. They should never be used as a canine arthritis medication.

IBUPROFEN (NEUROFEN) AND NAPROXEN (NAPROSYN) SHOULD NOT BE USED IN DOGS UNDER ANY CIRCUMSTANCES .

The reason for this is that dogs seem to have a predisposition toward enterohepatic recirculation, which considerably increases serum half life. When the half life of a drug is significantly increased multiple doses can quickly lead to overdose and internal organ damage.

Gastrointestinal Protectants

Cimetidine works as a canine arthritis medication by blocking secretion of acid from the stomach. It is used to treat and prevent ulcers, to treat gastroesophageal reflux disorder (GERD), and to treat conditions associated with excessive acid secretion. In humans, cimetidine is often used to relieve heartburn and acid indigestion.

In dogs it does not appear effective in decreasing the tendency of GI ulceration potentially caused by the long term use of NSAIDs.

Misoprostol is a synthetic prostaglandin. Prostaglandins are substances naturally found in the stomach as well as in other organs of the human body. In the stomach, prostaglandins are believed to protect the inner stomach lining from the ulcer producing effects of acid, aspirin, and other nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used in the treatment of arthritis and other inflammatory conditions. Scientists now believe that aspirin and NSAIDs produce stomach ulceration mostly by inhibiting the production of prostaglandins in the stomach. Misoprostol (Cytotec) has been shown to be effective in decreasing GI hemorrhage when given to dogs treated with NSAIDs.

Corticosteroids

Effects:
• Corticosteroids reduce the synovitis associated with experimental models of canine joint disease – most of which include transection of the Cranial Cruciate Ligament. It is thought that decreasing the severity of synovitis may improve cartilage nutrition by enabling return of normal synovial fluid properties such as high viscosity. It may also improve fluid exchange within the joint.
• When used in low-doses, corticosteroids may reduce enzymatic activity in osteoarthritic cartilage.
• Corticosteroids can slow the progression of bone remodelling in models of osteoarthritis.
• Long-term use of corticosteroids as a canine arthritis medication, and for other treatment purposes, is likely to have systemic side-effects.
• Corticosteroids inhibit proinflammatory cytokine production by synoviocytes and enhance the synthesis and release of tissue inhibitors of metalloproteinase.

Key point: Controversy surrounds the intra-articular use of corticosteroids because of their detrimental effects on articular cartilage.

Key point: Corticosteroids inhibit proteoglycan and collagen synthesis, inducing changes in the biochemical composition and morphology of articular cartilage.

Polysulfated Glycosaminoglycans (Chondroitin Sulfate)

Due to their high negative charge, they bind to connective tissue and degradative enzymes.

Evidence has shown incorporation of polysulfated glycosaminoglycans into the articular cartilage and menisci after intra-articular injection, and the local concentration in cartilage should be high enough to inhibit proteinase activity, which has a protective effect on the cartilage. This means PSGAG's can be effective as a canine arthritis medication.

Key point: Polysulfated glycosaminoglycans are generally accepted to have a protective effect on cartilage homeostasis.

Hyaluronan (Synvisc)

Justification: Because the viscosity of synovial fluid in osteoarthritic joints is often decreased, increasing the viscosity with injections of hyaluronan may be beneficial.

Hyaluronan exerts its beneficial effect by:
• Anti-inflammatory action
• Interference with O2-derived free radicals
• Interference with chemotaxis of inflammatory cells
• Inhibition of degradative enzymes produced by inflammatory cells
• Increased production of hyaluronan by fibroblasts and synoviocytes

Nearly all information about hyaluronan is derived from experimental animal models. Conflicting information about the value of hyaluronan administration subsequently exists with respect to influence on pathological change.Clinical trials in horses and humans suggest that Hyaluronic Acid is beneficial for the relief of pain, although it is recognized that many clinical trials are subject to design criticism, and therefore results must be interpreted with caution.

Key point: On the basis of available information, it is reasonable to conclude that Hyaluronic Acid is a potential therapy for canine osteoarthritis.

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