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      Pre-emptive 8 mg dexamethasone and 120 mg etoricoxib for pain prevention after periodontal surgery: A randomised controlled clinical trial

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          Abstract

          Several anti-inflammatory drugs have been used to reduce pain and discomfort after periodontal surgeries. This study evaluates the efficacy of using etoricoxib and dexamethasone for pain prevention after open-flap debridement surgery. In this study, 60 patients who were undergoing open flap debridment surgery were randomly assigned to receive a single dose preoperative medication 1 hour prior to surgery. The patients were divided into three groups. In Group 1, 20 patients were given placebo drug orally. In Group 2, 20 patients were given 8 mg Dexamethasone orally and in Group 3, 20 patients were given 120 mg Etoricoxib orally. Patients were instructed to complete a pain diary hourly for the first 8 hours after each surgery and three times a day on the following 3 days. The four point verbal rating scale (VRS 4) and Numerical rate scale were used to assess discomfort. Post-operative Assessment of Pain and Discomfort showed that persistent discomfort and pain were found to be more in the placebo group compared to dexamethasone and etoricoxib group. The adoption of a preemptive medication protocol using either etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries.

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          Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.

          Glucocorticoids have pleiotropic effects that are used to treat diverse diseases such as asthma, rheumatoid arthritis, systemic lupus erythematosus and acute kidney transplant rejection. The most commonly used systemic glucocorticoids are hydrocortisone, prednisolone, methylprednisolone and dexamethasone. These glucocorticoids have good oral bioavailability and are eliminated mainly by hepatic metabolism and renal excretion of the metabolites. Plasma concentrations follow a biexponential pattern. Two-compartment models are used after intravenous administration, but one-compartment models are sufficient after oral administration.The effects of glucocorticoids are mediated by genomic and possibly nongenomic mechanisms. Genomic mechanisms include activation of the cytosolic glucocorticoid receptor that leads to activation or repression of protein synthesis, including cytokines, chemokines, inflammatory enzymes and adhesion molecules. Thus, inflammation and immune response mechanisms may be modified. Nongenomic mechanisms might play an additional role in glucocorticoid pulse therapy. Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics. Pharmacokinetic parameters such as the elimination half-life, and pharmacodynamic parameters such as the concentration producing the half-maximal effect, determine the duration and intensity of glucocorticoid effects. The special contribution of either of these can be distinguished with pharmacokinetic/pharmacodynamic analysis. We performed simulations with a pharmacokinetic/pharmacodynamic model using T helper cell counts and endogenous cortisol as biomarkers for the effects of methylprednisolone. These simulations suggest that the clinical efficacy of low-dose glucocorticoid regimens might be increased with twice-daily glucocorticoid administration.
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            Annexin 1: more than an anti-phospholipase protein.

            Annexin 1 (ANXA1) is the first characterized member of the annexin family of proteins able to bind (i.e. to annex) to cellular membranes in a calcium-dependent manner. ANXA1 may be induced by glucocorticoids in inflammatory cells and shares with these drugs many anti-inflammatory effects. Originally described as a phospholipase A2 (PLA2)-inhibitory protein, ANXA1 can affect many components of the inflammatory reaction besides the metabolism of arachidonic acid. Recent data have shown that ANXA1 may specifically target cytosolic PLA2 by both direct enzyme inhibition and suppression of cytokine-induced activation of the enzyme. ANXA1 inhibits the expression and/or activity of other inflammatory enzymes like inducible nitric oxide synthase (iNOS) in macrophages and inducible cyclooxygenase (COX-2) in activated microglia. The inhibition of iNOS expression may be caused by the stimulation of IL-10 release induced by ANXA1 in macrophages. Like glucocorticoids, ANXA1 exerts profound inhibitory effects on both neutrophil and monocyte migration in inflammation. Several mechanisms may contribute to the protein effect on cell migration, namely the activation of receptors like the formyl peptide receptor (FPR) and the lipoxin A4 receptor (ALXR), the shedding of L-selectin, the binding to alpha4beta1 integrin and carboxylated N-glycans. Furthermore, again mimicking the action of glucocorticoids, ANXA1 promotes inflammatory cell apoptosis associated with transient rise in intracellular calcium and caspase-3 activation. Finally, ANXA1 has been recently identified as one of the 'eat-me' signals on apoptotic cells to be recognised and ingested by phagocytes. Thus, ANXA1 may contribute to the anti-inflammatory signalling that allows safe post-apoptotic clearance of dead cells.
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              Dexamethasone reduces pain and swelling following extraction of third molar teeth.

              Extraction of multiple third molar teeth can cause significant postoperative pain, swelling and trismus, which may result in delayed hospital discharge. We have examined the effect of a single prophylactic dose of oral dexamethasone 8 mg on these complications, in a randomised double-blind study of 50 adult patients. The number of extractions performed and the operative approach were standardised. Dexamethasone resulted in a significant reduction in pain 4 h postoperatively, and eliminated the need for opioid analgesia in the postoperative period. The incidence of severe swelling was also reduced significantly, but there was no effect on trismus. Postoperative nausea and vomiting were significantly lower in the dexamethasone group. We conclude that the use of prophylactic oral dexamethasone is useful in reducing postoperative analgesia requirements in this group of patients, and may facilitate surgery performed on a day case basis.
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                Author and article information

                Journal
                J Indian Soc Periodontol
                J Indian Soc Periodontol
                JISP
                Journal of Indian Society of Periodontology
                Medknow Publications & Media Pvt Ltd (India )
                0972-124X
                0975-1580
                Jul-Aug 2015
                : 19
                : 4
                : 474-476
                Affiliations
                [1] Department of Periodontics, M. S. Ramaiah Dental College and Hospital, Bengaluru, Karnataka, India
                Author notes
                Address for correspondence: Dr. Kranti Konuganti, Department of Periodontics, M. S. Ramaiah Dental College and Hospital, MSR Nagar, MSRIT Post, Bengaluru - 560 054, Karnataka, India. E-mail: drkrantireddy@ 123456gmail.com
                Article
                JISP-19-474
                10.4103/0972-124X.153475
                4555812
                26392703
                e30035b8-fd0c-4781-b4d0-775ee889ff02
                Copyright: © Journal of Indian Society of Periodontology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 February 2014
                : 02 February 2015
                Categories
                Short Communication

                Dentistry
                analgesia,dexamethasone,etoricoxib,pain
                Dentistry
                analgesia, dexamethasone, etoricoxib, pain

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