Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

APPROVED CHONDROPROTECTIVE DRUGS FOR SMALL ANIMAL PRACTICE
tory role in the production of HA and glycosaminoglycan
synthesis. It is believed that long-term use of these agents
helps cartilage regeneration and/or repair. Additionally,
activity has been attributed to PSGAGs for the inhibition
of cartilage degradative enzymes and even as an
anti-inflammtory with inhibition of PGE 2 . Initial formulations
were for intra-articular administration. However,
at least in horses, there was occasional joint infection
associated with treatment. Subsequently, intramuscular
and oral formulations have been developed that apparently
still give good joint penetration of the active ingredients.
Potential adverse events, in addition to the
iatrogenic infection described above, primarily include
hemorrhage. Since these agents are heparinoids, they
can interfere with normal clotting activity. Elevations in
activated partial thromboplastin time, prothrombin
time and activated clotting time have been reported.
Clinically these effects may manifest as hemarthrosis,
local hematoma and thrombocytopenia.
Boundary lubricants have been used primarily in
equine medicine. Most of the products available vary
based on molecular weight of the HA and any additional
cross-linking or polymerization between HA
chains. HA itself is a component of both synovial fluid
and cartilage. In synovial fluid, its viscoelastic properties
confer boundary lubrication. In cartilage, HA may not
be the primary lubricant but may be involved in what
is called boosted lubrication. In this case, as the opposing
cartilage surfaces come together, water is driven into
the cartilage and a concentrated pool of HA remains.
Additionally, HA has been shown to have antiinflammatory
properties, particularly in terms of
inhibiting chemotaxis of leukocytes. HA products for
horses are available for intra-articular or intravenous
administration.
Nutraceutical supplements are defined variously
around the world. One definition, from Health Canada,
is ‘a product isolated or purified from foods and generally
sold in medicinal forms not usually associated with
food and demonstrated to have a physiological benefit
or provide protection against chronic disease’. Nutraceuticals
are not generally regulated as drugs, but rather
as foodstuffs or nutritional supplements. As such, most
nutraceuticals have not undergone the safety and efficacy
testing, nor the manufacturing rigor, required of
pharmaceuticals. In the area of joint disease, the most
commonly used nutraceuticals include chondroitin
sulfate and glucosamine, generally in association with
ascorbic acid (vitamin C) and manganese. Additionally,
some preparations include special fatty acids, such as
omega-3, coenzyme Q10 (ubiquinone), various other
antioxidants and various other free radical-scavenging
agents. These products may be available as powders, in
gelatin capsules, as liquids or in pet foods. Because these
products are less regulated and there literally are hundreds
of offerings, it is important to purchase them from
reputable companies that guarantee their content and
have study data to support their use.
The most extensively studied nutraceuticals in small
animal practice are chondroitin sulfate and glucosamine.
Chondroitin sulfate is a normal component of cartilage
and is part of the proteoglycan molecule. In joint disease,
proteoglycans and their synthesis are diminished. Chondroitin
sulfate is believed to stimulate production of
glycosaminoglycans and cartilage matrix production.
The mechanism of action for glucosamine is not fully
determined, although it is believed to influence synthesis
of HA and glycosaminoglycans. Glucosamine appears
to be synergistic with chondroitin sulfate and the combination
of the two may also inhibit proteolytic enzymes
to further retard joint damage. These effects are slow
acting and may take 4–6 weeks of supplementation for
improvement to be seen.
APPROVED CHONDROPROTECTIVE DRUGS
FOR SMALL ANIMAL PRACTICE
Pentosan polysulfate
(Cartrophen Vet ® , Elmiron ® )
Clinical applications
Pentosan polysulfate is approved for use in dogs in
Europe and Australasia. It is indicated for the treatment
of primary and secondary osteoarthritis. Clinical efficacy
has been demonstrated in dogs with chronic osteoarthritis.
Anecdotal reports suggest that pentosan has
value in assisting healing after surgical procedures such
as cranial cruciate repair and luxating patella fixation.
Pentosan has also been used in the management of
refractory cases of feline lower urinary tract disease or
recurrent urinary tract infection in dogs.
Formulations and dose rates
Available in injectable (SC) or oral formulations. Intra-articular administration
has been shown to predispose to the development of septic
arthritis.
CATS AND DOGS
• 3 mg/kg PO or SC once weekly for four treatments
Mechanism of action
Pentosan polysulfate is a polysulfated polysaccharide
drug that acts as a chondroprotective agent. It can:
● retard the degradation of articular cartilage in osteoarthritis
through inhibition of many enzymes that are
implicated in the degradation of cartilage
● in some circumstances have a positive effect on chondrocyte
metabolism, which may encourage repair of
articular cartilage
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