Doctor of veterinary sciences, associate professor, Nametov A.M.
Graduate master. Zhumabayev A.K.
A.BaitursynovKostanaiStateUnversity
Therapeutic
effects of nonsteroidal anti-inflammatory drugs in veterinary medicine
In recent years, joint diseases in dogs have considerably spread in Kazakhstan.
The reasons may vary: mechanical, physical,
chemical, many biological factors (specific and nonspecific agents of
microbial, viral,
fungal nature), metabolic disorders, feeding and maintenance of animals,
genetic predisposition, and finally allergic effects arising under the
influence of these reasons and because
of autoimmunization of
organism by products
of inflammation [1,2]. This explains the wide interest of veterinarians to
methods of diagnosis, treatment and prevention of this disease.
According to the sources, it is known that
diseases of joints and limbs of animals are up to 35 % of all non-communicable
diseases, among dogs - 10-15%. The degree of incidence of joint diseases
increases with age, thus 90% of all cases occur in dogs older than 5 years or
more, 40 % - over 5 years. Almost half of the cases of arthritis occurs in large
breeds especially in German shepherds, Rottweilers, Labradors, etc. [3, 4].
Joint pathologies prevention, treatment
and rehabilitation of dogs with joints injuries are one of the urgent problems
in veterinary medicine. Duration and character of diseases, their prevalence,
dysfunction of joints - all these set the problem of searching for modern
approaches to elaborate methods for joints correction through the use of new
generation drugs.
The most common medicine used in clinical
practice for the treatment of animals with diseases of joints, are nonsteroidal
anti-inflammatory drugs (NSAIDs) [5]. The frequency of use is explained by hard
replaceability for many diseases involving inflammation, pain and fever. These
drugs are widely used, especially in inflammatory and degenerative diseases of
joints and spine bone (osteoarthritis, ostheoarthrosis, synovitis, etc.), but
in recent years the field of application of non-steroidal anti-inflammatory
drugs has expanded significantly, they are used for autoimmune diseases in dogs
[6] Many of them are also used for anesthesia, for example during a surgical
treatment.
Therapeutic and toxic effects of NSAIDs
are mainly due to the inhibition of the key enzyme of paths of slowing down the
synthesis of arachidonic acid (AA). When cellular membranes are damaged, AA
goes into the cytoplasm where it serves as a substrate for several enzymes
including cyclooxygenase involved in the formation of prostaglandins.
Prostaglandins are the main
"actors" in the genesis of pain, inflammation and fever, as they:
- are mediators of the local inflammatory
reaction, cause local vasodilation, edema, exudation, leukocyte migration
(mainly PgE2 and PgI2);
- sensitize receptors to the pain
mediators (histamine and bradykinin) and mechanism, reducing pain threshold;
- increase the sensitivity of the
hypothalamic thermoregulatory centers to endogenous pyrogens [7].
NSAIDs block the production of
prostaglandins by inhibiting the cyclooxygenase activity, which exist in two
isoforms: COX -1 and COX -2. Prostaglandins synthesized with COX -1
(constitutive) are in many tissues and involved in the homeostatic processes
(maintaining blood circulation in kidneys, protection of gastric mucosa, etc.).
Prostaglandins synthesized with a COX -2 (induced) are in tissues in low
concentrations. They are formed in response to injury and responsible for
initiating and maintaining many parameters of inflammatory process. Trying to
strengthen anti-inflammatory effects and reduce side effects, NSAIDs have been
developed that selectively inhibit COX -2. Since the integrity of gastric
mucosa greatly depends on COX-1, the use of NSAIDs with a selective effect on
COX-2 reduces chances of side effects from gastrointestinal tract.
The most active NSAIDs against COX -1 are
Indomethacin, aspirin and piroxicam, more selective for COX -2 are nimesulide,
meloxicam, nabumetone and etodolac. The selectivity index has been calculated
(ratio of inhibition TSOG-1/TSOG-2) for some drugs. For instance, meloxicam -
0.33, diclofenac - 2.2, tenoxicam - 15, piroxicam – 33, Indomethacin - 107 [8,
9].
Nonsteroidal anti-inflammatory drugs of
coxibs, celecoxib and rofecoxib have appeared recently on the market of
veterinary drugs, they are distinct in relatively high efficiency and minimum
side effects.
In this regard, the aim of our study was
the use of medical NSAID parecoxib in dogs with osteo-articular pathology
system.
According to the data analysis of the
incidence of dogs in Kostanai region for the last five years (2009-2013),
osteo-articular pathology of dogs (osteoarthritis, synovitis) is on average 30
% of all non-communicable diseases. For their treatment in clinics of Kostanai
diclofenac sodium, voltaren, hexenal, thiopental sodium, rumafen, ketamine and
other drugs are used.
Parecoxib registered on Ukrainian
pharmaceutical market under the trade name Dinastat, is water-soluble prodrug.
It is hydrolyzed in the liver and converted to valdecoxib the concentration of
which increases rapidly in blood plasma during the first hour after giving the
drug, being kept at a high level for 7-24 hours depending on the dose [10].
Dose-dependent effect of parecoxib and its
effective long duration with a comparable analgesic effect were demonstrated in
the clinical trials on dogs with osteoarthritis and synovitis, in which
parecoxib was used in a dose of 2 mg/kg body weight intramuscularly for 7-12
days. During and after the treatment they examined general physiological signs
including blood pressure, heart rate, respiratory rate, body temperature and
blood hematological levels: number of red blood cells, white blood cells,
hemoglobin, erythrocyte sedimentation rate and leucogram.
The results obtained show the therapeutic efficiency
of parecoxib, relief of pain, reducing inflammation, improving joint mobility,
increasing the activity level of dogs and prevention of further degeneration of
articular cartilage. The improvement was also observed in general analysis of
blood.
Taking into consideration a better safety profile
[4.], at comparable therapeutic and analgesic effect parecoxib - a selective
inhibitor of COX-2 is preferred.
The research on the use of new medical anesthetic
drugs in veterinary medicine should not be considered as an alternative, but as
an obligatory supplement to regulated schemes of diagnostics and therapy [10].
References:
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modeling / M.F. Landoni, P. Lees // Equine Vet. Journal. 1995. - Vol. 27. - P.
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Baker, C.S.
Cyclooxygenase 2 is widely expressed in atherosclerotic lesions affecting
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