Doctor of veterinary sciences, associate professor, Nametov A.M.,

Candidate of veterinary sciences, associate professor, Baikenov М.Т.,

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:

1. Lazutina R.R., Moscow "Use of nonsteroidal anti-inflammatory drugs in treatment of dogs with aseptic synovitis of knee" Dissertation.2004.-P.146

2. Shukhov, L.S. Analgesia in Russia: Problems /L.S. Shukhov//Clinical Pharmacology and Therapeutics 1999. - № 8 (6). - P.10-18.

3. Landoni, M.F. Comparison of the anti-inflammatory action of flunixin and ketoprofen in horses applying PK/PD modeling / M.F. Landoni, P. Lees // Equine Vet. Journal. 1995. - Vol. 27. - P. 247-256.

4. McCormack, K. Toward defining the analgesic role of NSAID in the management of acute soft tissue injuries / K. McCormack, K. Brune // Clinical Journal of Sports Medicine. -1993.-V.3.-P.106-117.

5. Burleigh, M.E. Cyclooxygenase —2 promotes early atherosclerotic lesion formation in LDL receptor deficiency mice / M.E. Burleigh, V.R. Babaev, J.A. Oates, et al. // Circulation. 2002. -V. 105. - P. 816-1823.

6. Nassonov E.L. Perspectivess of the new NSAID nimesulide/E.L.Nassonov//Klin, pharmocol. and therapy. 1999. - № 8. - P.65-69.

7. Barskova, V.G. Use of nimesil in gouty arthritis/V.G. Barskova, I.A. Yakunin, V.A. Nassonova //Ter.arhiv. 2003. - № 5. -P.60-64.

8. Proceedings of the meetings of the National Congress of Anesthesiologists V (2008) Professor Frederic Camus (Department of Anesthesiology, Flemish University, Brussels, Belgium)

9. Baker, C.S. Cyclooxygenase 2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalized with inducible nitric oxide synthase and nitrotyrosine particularly macrophages /

10. Mario Giorgiа, Tae-Won Kim, Alessandro Saba, Mohammad-Reza Rouinid, Hyoin Yun, Helen Owenf «Detection and quantification of cimicoxib, a novel COX-2 inhibitor, in canine plasma by HPLC with spectrofluorimetric detection: Development and validation of a new methodology», Thomson Reuters ELSEVIER, «Pharma-ceutical and Bio-medical Analysis» №83 2013y. p.28-33.