Comparison of Ketorolac Tromethamine with Other Injectable Nonsteroidal Anti-Inflammatory Drugs for Pain-on-Injection and Muscle Damage in the Rat

1994 ◽  
Vol 13 (2) ◽  
pp. 111-117 ◽  
Author(s):  
Gary J. Chellman ◽  
Lance O. Lollini ◽  
Albert E. Dorr ◽  
Linval R. DePass

The local tolerance of ketorolac tromethamine (Toradol®, Syntex) was compared with that of four other injectable nonsteroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium, piroxicam, ketoprofen, and metamizol magnesium) in the rat paw-lick/muscle irritation assay as described previously,1 All drugs were tested at concentrations approved for clinical use. After subplantar (footpad) injection, ketorolac produced virtually no pain-on-injection as assessed by the number of paw-lick/lift responses during a 15 min observation period. The other NSAIDs produced slight to moderate paw-lick/lift responses. Redness and swelling at the injection site were less severe for ketorolac than for the other NSAIDs, After intramuscular (i.m.) injection, all of the. NSAIDs produced some degree of muscle damage, as assessed histopathologically 24 h after injection. The lesions, consisting primarily of muscle degeneration, were less severe for ketorolac than for the other NSAIDs. Ketorolac and metamizol produced the smallest elevations in serum creatine kinase, as measured 2 h after i.m. dosing, not significantly different from isotonic saline. Overall, ketorolac was better tolerated in the assay than the other injectable NSAIDs, thereby suggesting the possibility of improved local tolerance on clinical use.

1994 ◽  
Vol 22 (2) ◽  
pp. 100-106 ◽  
Author(s):  
G Hasçelik ◽  
B ŞLener ◽  
Z Hasçelik

The effects of piroxicam, tenoxicam, diclofenac sodium, acetylsalicylic acid and tiaprofenic acid on the chemotaxis and random migration of human polymorphonuclear leukocytes were investigated, using zymosan-activated serum as chemo-attractant, with a modified Boyden chamber technique. All five compounds significantly reduced chemotaxis. The random migration of polymorphonuclear leukocytes was inhibited by piroxicam, diclofenac sodium and tiaprofenic acid but not by tenoxicam or acetylsalicylic acid. The inhibitory effect of these non-steroidal anti-inflammatory drugs on polymorphonuclear leukocyte chemotaxis and on random migration was generally dose-dependent. The results suggest that the drugs studied may have a direct effect on polymorphonuclear leukocyte chemotaxis and that this activity may contribute to their anti-inflammatory properties.


2021 ◽  
Vol 49 (06) ◽  
pp. 407-413
Author(s):  
Julia Lieser ◽  
Claudia Schwedes ◽  
Maria Walter ◽  
Judith Langenstein ◽  
Andreas Moritz ◽  
...  

Abstract Objective To investigate oxidative erythrocyte damage in dogs treated with different non-steroidal anti-inflammatory drugs. Material and methods Case-controlled prospective observational study using blood obtained from dogs presenting for lameness examinations or standard surgical procedures to a private referral clinic. Sampling was performed from April 2018 to July 2019. Groups comprised dogs receiving either metamizole (dipyrone) (22 dogs), carprofen (20 dogs) or meloxicam (20 dogs) for a minimum of 10 days. Dogs with gastrointestinal hemorrhage were excluded from the study. A complete hematological, as well as a basic biochemical profile were performed in every dog. Pappenheim stained blood smears were evaluated for eccentrocytes and brilliant cresyl blue stained smears for Heinz bodies. EDTA blood was frozen at –80°C immediately after sampling for measurement of superoxide dismutase and gluthathione peroxidase activity at an external laboratory. Hemoglobin concentration, superoxide dismutase and gluthathione peroxidase activities, reticulocyte count, eccentrocyte and Heinz body numbers were determined prospectively as key parameters for further statistical assessment with Kruskal-Wallis test and Dunn’s multiple comparisons test. Results Dogs receiving metamizole showed a significant increase in eccentrocyte (median 14.5/500 cells vs. 0/500 cells in the other groups, p < 0.0001) and reticulocyte number (median 191.4 × 109/l vs. 31.6–37.9 × 109/l, p < 0.0001) and a significant decrease in hemoglobin concentration (median 8.4 mmol/l vs. 10.1–10.5 mmol/l, p < 0.0003). No significant difference in superoxide dismutase and gluthathione peroxidase activities was observed between dogs receiving metamizole and the other groups. Heinz bodies were not found in any of the dogs. Conclusion Treatment with metamizole for 10 or more days resulted in decreased hemoglobin concentration, eccentrocytosis and reticulocytosis in dogs in this study. This might be a sign of increased oxidative damage caused by this drug. Clinical significance Prolonged metamizole therapy should be evaluated critically in patients already affected by severe illness or underlying anaemia.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Mirghani HO

Background: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a serious disease. The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of PEP is conflicting. Objectives: This review aimed to assess the preventive role of NSAIDs in PEP with special emphasis on the dose and route of administration. Methods: We searched PubMed and Google Scholar for relevant observational studies published in English during the period from January 2010 to January 2020. The terms post-ERCP pancreatitis, diclofenac sodium, indomethacin, NSAIDs, dose, route of administration were used. Results: Of the 179 identified, 19 full texts were screened and included in the review. Ten studies were from Europe, seven from Asia and two were published in the USA, the studies showed that NSAIDs were effective in preventing PEP when used rectally or intramuscularly, higher doses are more efficacious and the combination with stents was not superior, careful patients selection is needed in particular regarding the body mass index. Conclusion: NSAIDs were effective in PEP prevention; however, the evidence is weak due to the observational nature and the different methods used in the included studies. Randomized controlled studies are needed to solve the issue.


2006 ◽  
Vol 6 ◽  
pp. 1048-1065 ◽  
Author(s):  
Thea Morris ◽  
Melanie Stables ◽  
Derek W. Gilroy

Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has both anti-inflammatory as well as cardio-protective properties. The cardio-protective properties arise form its judicious inhibition of platelet-derived thromboxane A2over prostacyclin, while its anti-inflammatory effects of aspirin stem from its well-established inhibition of prostaglandin (PG) synthesis within inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion of inhibiting PG biosynthesis as a common anti-inflammatory strategy based on the erroneous premise that all eicosanoids are generally detrimental to inflammation. However, our fascination with aspirin has shown a more affable side to lipid mediators based on our increasing interest in the endogenous control of acute inflammation and in factors that mediate its resolution. Epi-lipoxins (epi-LXs), for instance, are produced from aspirin’s acetylation of inducible cyclooxygenase 2 (COX-2) and together with Resolvins represent an increasingly important family of immuno-regulatory and potentially cardio-protective lipid mediators. Aspirin is beginning to teach us what nature knew all along – that not all lipid mediators are bad. It seems that while some eicosanoids are pathogenic in a variety of diseases, others are unarguable protective. In this review we will re-count aspirin’s colorful history, discuss its traditional mode of action and the controversies associated therewith, as well as highlight some of the new pathways in inflammation and the cardiovascular systems that aspirin has recently revealed.


2006 ◽  
Vol 43 (3) ◽  
pp. 233-237 ◽  
Author(s):  
Afonso Luiz Villa ◽  
Ceneviva Reginaldo ◽  
Fernanda Viaro ◽  
Fernando Ramalho ◽  
Antonio Dorival Campos ◽  
...  

BACKGROUND: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent. AIM: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment. METHODS: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration. RESULTS: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared to each other. CONCLUSION: Isosorbide dinitrate has a cytoprotective activity on the gastric mucosa of rats submitted to ketoprofen action.


2017 ◽  
pp. 80-83
Author(s):  
Mykola Shevchuk ◽  
Viktor Bekar ◽  
Oksana Kharysh

The death incident case caused by the continuous uncontrolled consuming of the non-steroidal anti-inflammatory drugs (diclofenac sodium) that resulted in developing of side effects of the organism - medication allergy and cardiovascular disorders is given.


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