Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 13 NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND CHONDROPROTECTIVE AGENTS
be N-acetyl-p-benzoquinoneimine). This metabolite is
normally conjugated with glutathione but when hepatic
glutathione is depleted the metabolite binds covalently
to amino acid residues of protein in the liver, resulting
in centrilobular hepatic necrosis.
Glucuronidation is the major metabolic pathway in
most species but cats have a low concentration of glucuronyl
transferase, which catalyzes the final step, so
metabolism via this pathway is insignificant. Sulfation
is the major metabolic pathway in the cat but it is capacity
limited – as the dose is increased, a greater percentage
of the drug is oxidized.
Therapy of toxicosis
Treatment of paracetamol toxicity involves supportive
therapy (intravenous fluids, typed blood transfusion if
required) as well as more specific therapy.
N-acetylcysteine (140 mg/kg PO followed by 70 mg/
kg PO every 6 h) is efficacious in the treatment of
paracetamol toxicity in humans and dogs if given within
a few hours following drug administration. In cats,
paracetamol is slowly eliminated so N-acetylcysteine
should be given if clinical signs are present regardless of
the time elapsed since drug administration.
There are several mechanisms by which N-
acetylcysteine is thought to act. It is rapidly hydrolyzed
to cysteine and therefore can provide a substrate for
glutathione in erythrocytes and the liver. It has also been
shown to react directly with the reactive metabolite of
paracetamol to form an acetylcysteine conjugate. It has
also been shown to increase sulfate conjugation.
Other glutathione and sulfate precursors such as
methionine (70 mg/kg q.8 h) have also been used successfully.
The use of ascorbate to reduce methemoglobin
has been recommended but has been shown not to be
effective in dogs and has not been evaluated in cats.
It has been suggested that cimetidine may be useful
for treatment of paracetamol toxicity as it is a potent
inhibitor of cytochrome P450-mediated drug metabolism.
In rats it is as efficacious as N-acetylcysteine in
protecting against paracetamol-induced hepatic necrosis.
However, its use in cats has not been evaluated and
the potential benefit may be less in this species because
hepatocellular damage is not as extensive as in other
species.
Piroxicam
(Feldene ® )
Clinical applications
Piroxicam is not approved for use in dogs. It has been
used in the management of canine transitional cell carcinoma
of the bladder. It is believed that its antitumor
effect is by inhibition of COX-2, although piroxicam
has not been shown to have cytotoxic activity in vitro.
A small number of dogs (approximately 20%) may
achieve partial or complete remission with piroxicam
therapy. It has been reported that combination therapy
with cisplatin (50–60 mg/m 2 intravenously, once every
21 d) increases the partial or complete remission rate to
as high as 70%. It is also reported to be useful in the
symptomatic relief of stranguria associated with cystitis,
urethritis or transitional cell carcinomas. Because of its
side effects, piroxicam is not recommended for musculoskeletal
pain as there are other more effective and
safer NSAIDs available.
Formulations and dose rates
Piroxicam is available in tablet form.
DOGS
• 0.3 mg/kg PO q.24 h
Mechanism of action – additional information
Piroxicam is a member of the oxicam class of
NSAIDs.
Adverse effects
● The incidence of gastrointestinal and renal side
effects in dogs treated with piroxicam is relatively
high.
● The synthetic prostaglandin E analog misoprostol
may be administered concurrently to reduce the likelihood
of gastric ulceration occurring.
CHONDROPROTECTIVE AGENTS FOR
SMALL ANIMAL PRACTICE
The use of chondroprotective agents in veterinary medicine
started with equine medicine. Application in dogs
followed but there is currently little use in cats. Therapeutic
approaches may be divided into at least three
broad categories:
● component building blocks necessary for cartilage
function and regeneration, such as polysulfated glycosaminoglycans
(PSGAGs)
● boundary lubricants to reduce joint trauma and
improve joint motion, such as hyaluronan (HA)
● nutraceutical supplements to supply essential nutrients
to joint function, such as chondroitin sulfate and
glucosamine.
PSGAGs and other polysulfated polysaccharides are
similar to the glycosaminoglycans present in articular
cartilage. These agents are synthetic heparinoids and
have affinity for proteoglycans and noncollagenous proteins
in cartilage. Studies have documented a stimula-
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