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Padayachee, Vaneshree. "Awareness regarding non-steroidal anti-inflammatory drug-related side effects in Johannesburg, South Africa." University of Western Cape, 2021. http://hdl.handle.net/11394/8370.
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>Magister Scientiae - MScNon-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most commonly used medications globally, as they are highly effective and easily accessible. The NSAIDs are indicated for mild to moderate pain management. The increasing incidence of NSAID related side effects and hospitalisations has raised a concern about these medications’ safety. The prevalence of these side effects has drastic consequences to a challenged South Africanpublic healthcare system. The implications of not treating severe, potentially preventable upper gastrointestinal complications attributed to NSAIDs’ consumption continue to be a significant problem that healthcare professionals (HCP) face.
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Sigthorsson, Gudmundur. "Studies into the pathogenic mechanism of NSAID-enteropathy." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272070.
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Barton, Garry Richard. "Economic aspects of NSAID (non-steroidal anti-inflammatory drug) provision : use, benefits and optimal decisions." Thesis, University of Nottingham, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444633.
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Sasane, Rahul Madhukar. "Assessment of the effectiveness of a non-steroidal anti-inflammatory drug (NSAID) algorithm in an integrated healthcare system /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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Morales, Daniel. "Quantifying the risk of beta-blockers and non-steroidal anti-inflammatory drugs in asthma." Thesis, University of Dundee, 2014. https://discovery.dundee.ac.uk/en/studentTheses/56ca8828-73f6-47cc-b919-6e3e78e11a7b.
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Beta-blockers and non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided in asthma over risk of bronchospasm which may vary according to drug selectivity and duration of administration. This thesis attempts to quantify the risk of beta-blocker and NSAID exposure in asthma by synthesising clinical trial evidence and conducting observational studies using linked electronic medical records. As part of this thesis, three systematic reviews of clinical trials were conducted evaluating: the prevalence of aspirin-exacerbated respiratory disease (AERD); risk of selective NSAIDs/COX-2 inhibitors in people with AERD; and risk of acute beta-blocker exposure in people with asthma. Electronic primary care data from the Clinical Practice Research Datalink (CPRD) was used to define a cohort of people with active asthma, measure the prevalence of beta-blocker and NSAID prescribing, and perform a series of nested case control studies evaluating asthma death, asthma hospitalisation and primary care asthma exacerbations (PCAE). A self-controlled case-series was performed for PCAE as well. Based upon work in this thesis, the prevalence of AERD in people with asthma was around 9%. Selective NSAIDs triggered respiratory symptoms in 8% of people with AERD whilst no significant changes in lung function or symptoms occurred with COX-2 inhibitors. Acute non-selective beta-blocker exposure caused a significant mean fall in FEV1 of 10%, a significant increase in respiratory symptoms in around 1 in 13 and a non-significant increase in falls in FEV1 of ≥20% in around 1 in 9. Acute selective beta-blocker exposure caused a significant mean fall in FEV1 of 7%, significant falls in FEV1 of ≥20% in around 1 in 8 and a non-significant increase in respiratory symptoms in around 1 in 33. The prevalence of selective beta-blocker prescribing in asthma rose by around 200% over the 12 year period whilst the prevalence of non-selective beta-blocker prescribing rose by around 90%. Changing trends in NSAID prescribing occurred over the 12 year period with COX-2 inhibitors now rarely prescribed. Using the nested case control design, both incident and high-dose non-selective beta-blocker exposure was associated with significantly increased risk of asthma morbidity (hospitalisation and PCAE). In contrast, no significant increased risk of asthma morbidity occurred with any type of selective beta-blocker exposure. Consistent findings were seen for PCAE using the self-controlled case series. No significantly increased risk was seen with different oral NSAIDs apart from weak evidence of an association between asthma death and non-selective NSAID exposure which is unlikely to be causal. Significant numbers of people with asthma are prescribed beta-blockers and NSAIDs. Evidence from clinical trials and observational studies demonstrate that non-selective beta-blockers significantly increase asthma morbidity with risk appearing to vary according to dose and duration of administration. Although selective beta-blockers have the potential to cause significant changes in lung function, no significant increase in asthma morbidity was observed in observational studies. Although around 9% of asthmatics may be susceptible to NSAIDs, no strong evidence was found to suggest that the current practice of NSAID prescribing increases asthma morbidity. At the same time, COX-2 inhibitors are infrequently prescribed despite apparently being well tolerated by people with AERD.
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Rafi, Shegufta Susan. "Studies on the pathogenesis of NSAID-induced damage to the gastrointestinal tract with special reference to the mitochondria." Thesis, King's College London (University of London), 1998. https://kclpure.kcl.ac.uk/portal/en/theses/studies-on-the-pathogenesis-of-nsaidinduced-damage-to-the-gastrointestinal-tract-with-special-reference-to-the-mitochondria(10f8f528-5777-4452-9706-359076c35bca).html.
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Jacob, Molly. "Mechanism of non-steroidal anti-inflammatory drug induced damage in the small bowel." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313890.
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Buckley, Trevor R. "Does Non-Steroidal Anti-Inflammatory Drug (NSAID) Use Affect Dementia Progression and Survival Rates in Alzheimer's Disease? The Cache County Study." DigitalCommons@USU, 2011. https://digitalcommons.usu.edu/etd/990.
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Alzheimer's disease (AD) has multiple factors that contribute to the disease process. Among these is a state of chronic inflammation that is endured by the brain during the aging process. The use of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the amount of neuroinflammation sustained by the brain, and greater levels of NSAID use have been demonstrated to be associated with decreased probability of developing AD. This study looked at whether greater rates of NSAID use were also associated with decreased rates of cognitive and funtional decline and survival in a population-based sample of persons with AD.
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Pangburn, Heather Ann. "Effects of the non-steroidal anti-inflammatory drug (NSAID) sulindac on epidermal growth factor receptor (EGFR) expression and signaling in colorectal cancer /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Toxicology) -- University of Colorado Denver, 2007.Typescript. Includes bibliographical references (leaves 156-176). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Harmzen, Magdalena Adriana. "Overview of the prescribing patterns of non-steroidal anti-inflammatory drugs : 2004-2006 / Magdalena Adriana Harmzen." Thesis, North-West University, 2008. http://hdl.handle.net/10394/3719.
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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for systemic control of acute and chronic pain and inflammation (Lin et ah, 2000:1129), but usage problems and side-effects that occur during the post-marketing phase of these drugs are well documented (Thiefin & Beaugerie, 2005:287). Following the demonstration of the value of anti-inflammatory therapy in diseases like rheumatoid arthritis (Boardman & Dudley Hart, 1967:268), new NSAIDs appeared on the market (Dieppe et al., 2004:867), and the indications steadily broadened from inflammatory diseases to almost any painful condition. Studies have indicated that NSAID-associated serious upper gastro-intestinal (GI) adverse events result in 103 000 hospitalisations (Bombardier, 2002:4) and 165 000 deaths per year in the United States.
A study in South Africa in 2002 indicated that NSAID utilisation contributed considerably to the total cost of all medicine items from a medicine claim database in the private health care sector (Joubert, 2002:260).
The objective of this study was to determine the prevalence and cost of non-steroid anti-inflammatory drugs in a section of the private health care sector, and specifically to determine the prevalence, usage and cost of Coxib (Specific cyclo-oxygenase-2 inhibitor) medicine items before and after the withdrawal of Vioxx® from the market in September 2004 (Merck, 2004).
Data from two medicine claim databases for the years 2004, 2005 and 2006 (medicine claim database I) and the years 2005 and 2006 (medicine claim database M), were analysed by means of a retrospective drug utilisation review (DUR) study. The usage of Coxib medicine items was determined, and compared for the periods before and after the withdrawal of Vioxx® in September 2004.
It was found that between 9 and 10.5 per cent of prescriptions dispensed through both medicine claim database I and medicine claim database M during the study period were NSAID prescriptions. NSAID medicine items on medicine claim database I represented between 3.9 % (R25 942 986) and 2.9 % (R8 073 034) of the total cost of all medicine items claimed from 2004 to 2006. NSAIDs represented 3.1 % (R58 290 412) and 2.8 % (R57 752 267) of the cost of all medicine items claimed through medicine claim database M during 2005 and 2006 respectively, indicating similar trends in the two medicine claim databases.
The prevalence of Coxibs on medicine claim database I decreased from almost 20 % (47 938) in 2004 to 8.4 % (13 276) in 2005, but showed an increase again to 10.9 % (12 355) in 2006. The prevalence of both cyclo-oxygenase (COX) inhibitors, and Coxibs demonstrated a change during 1 September 2004 to 31 December 2004 when COX-inhibitors showed an increase in use, while Coxibs showed and almost equal but opposite trend with a decrease in use. This could possibly be related to perceptions of providers and public with regard to Coxibs and their related safety after the withdrawal of Vioxx® on 30 September 2004 (Merck, 2004) and other Coxibs such as Bextra® (FDA, 2005) in 2005 in USA.
It is concluded that most patients who were using Coxibs before the withdrawal of Vioxx®, substituted Coxibs for COX-inhibitors, that are known for their possible gastro-intestinal side-effects.
Recommendations for future research regarding NSAID use were also made, and included an investigation of the usage of Coxibs in different age groups, as well as the combination of NSAIDs with gastro-protective medicines in long-term use.Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.
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Chennamaneni, Snigdha. "FROM NON-STEROIDAL ANTI-INFLAMMATORY DRUG (NSIAD) INDOMETHACIN TO ANTI-CANCER AGENTS: DESIGN, SYNTHESIS, BIOLOGICAL EVALUATION AND MECHANISM INVESTIGATION." Cleveland State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1421084668.
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Swenson, Victor, and Mattias Ekberg. "Usage of Non-steroidal anti-inflammatory drugs in a sample of New Zealanders with osteoarthritis : A cross-sectional study." Thesis, Umeå universitet, Avdelningen för fysioterapi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-171613.
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Introduction Oral Non-steroidal anti-inflammatory drugs (NSAID) is an analgesia and is commonly used by people with osteoarthritis (OA). Oral NSAID is currently recommended as the second level of treatment for OA, and could be considered if physical activity, topical NSAID or paracetamol do not supply sufficient pain relief. Aim To investigate how frequently oral NSAID is used in a sample of New Zealanders with OA and also to investigate the exposure to heightened risk of adverse events while using oral NSAID. Method A cross-sectional survey was conducted to collect information about the use of oral NSAID by people with self-reported OA. The survey included 75 participants who were over the age of 45 with an average age of 70.6 years. Results While having OA, 57,3% of the sample reported oral NSAID use. The results also show that 52% of the participants with cardiovascular (CV), gastrointestinal (GI) or renal comorbidities used oral NSAID, and 17,3% of them also combined that NSAID with medication for their comorbidity. Concerning the heightened risks of adverse events, 21% of the participants did acquire the analgesia over the counter (OTC), and 76,6% stated that they were over the age of 65. Conclusion A majority of the participants in the study with self-reported OA take NSAID as an analgesia. Also, the study shows that NSAID is commonly used among participants with co-morbidity, which is similar to figures presented in previous studies in the area. However, the small sample size limits its generalizability to a larger population.Introduktion Orala icke-steroida antiinflammatoriska läkemedel (NSAID) är en grupp smärtstillande mediciner som är vanligt använt av personer mer artros. Orala NSAID-preparat rekommenderas idag som en andrahandsbehandling och kan övervägas om fysisk aktivitet, topikala NSAID-preparat eller paracetamol inte ger tillräcklig smärtlindrande effekt. Syfte Att undersöka hur vanligt användandet av orala NSAID-preparat är i ett stickprov av personer med artros i Nya Zeeland samt att undersöka exponering av orala NSAID-preparat i subgrupper med ökad risk för biverkningar vid användande av orala NSAID-preparat. Metod En tvärsnittsstudie genomfördes för att samla in information kring användning av orala NSAID-preparat av personer med självrapporterad artros. Studiepopulationen bestod av 75 personer över 45 års ålder med en medelålder på 70,6 år. Resultat 57,3% av deltagarna använder orala NSAID-preparat som behandling för sin självrapporterad artros. Gällande subgrupper med ökad risk för biverkning av NSAID användning visar studien att 52% av deltagare med kardiovaskulära, gastrointestinala eller njurpåverkade sjukdomar använder orala NSAID-preparat och av dessa kombinerar 17,3% NSAID-preparaten med medicin för sin samsjuklighet. Av deltagarna som uppgav att de använder orala NSAID-preparat erhåller 21% av dessa NSAID-preparaten receptfritt över disk. Av deltagare som var 65 år eller äldre uppgav 76,6% att de använder orala NSAID-preparat för behandling av artros. Slutsats En majoritet av deltagarna med självrapporterad artros tar orala NSAID-preparat i smärtstillande syfte för sin artros. Studien visar också att NSAID ofta används bland deltagare med samsjuklighet, vilket motsvarar presenterade siffror från tidigare studier inom området. Den lilla stickprovsstorleken begränsar emellertid studiens generaliserbahet gentemot en större population.
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Lomas, Amy. "The renal effects of nonsteroidal anti-inflammatory drugs (NSAIDS) in dogs with chronic kidney disease (CKD)." Thesis, Kansas State University, 2013. http://hdl.handle.net/2097/20475.
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Master of ScienceDepartment of Clinical Sciences
Gregory F. Grauer
Prostaglandins play many important roles in the kidney including regulation of renal blood flow, glomerular filtration, renin release, and sodium excretion. Upon activation of the renin angiotensin aldosterone system (RAAS), prostaglandin upregulation becomes critical to offset the vasoconstrictive effects of norephinephrine, angiotensin II, and vasopressin. Nonsteroidal anti-inflammatory drugs (NSAIDs) produce both their beneficial and detrimental effects through inhibition of the cyclooxygenase enzyme and subsequent interference with prostaglandin production. Healthy canine kidneys express both COX-1 and COX-2, although basal COX-2 expression in dogs is significantly higher than in other species. Nonsteroidal anti-inflammatory drugs that spare COX-1 have exhibited less gastrointestinal toxicity, but no NSAID has been proven safe for the kidney. The kidney is the organ with the second highest reports of adverse drug events, which is usually manifested as functional changes. However, structural changes including renal papillary necrosis, can occasionally be observed. Dogs with chronic kidney disease could be expected to be at increased risk for NSAID-related adverse drug effects. As nephrons and renal reserve are lost in chronic kidney disease, the canine kidney becomes more dependent on COX-2 for production of prostaglandins. Inasmuch as the prevalence of both CKD and OA increases with age, it is expected that many dogs being treated with NSAIDs for OA will have loss of renal reserve and/or early stage CKD. If administration of an NSAID is required for long term treatment of osteoarthritis, frequent monitoring of blood pressure and renal parameters, as well as hepatic enzymes are recommended.
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Elliott, Christopher S. "The Chemoprevention of Lung Cancer Using Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)." The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1041537546.
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Connolly, Christopher Kevin. "The effects of the preferential COX-2 inhibitor, Meloxicam and motion on fracture healing." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343095.
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Glover, Janine Avril. "Non steroidal anti-inflammatory drugs (NSAIDs) and neoplasms in women : trends, risk and progression." Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.601620.
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Non steroidal anti -inflammatory drugs (NSAIDs) inhibit the cyclooxygenase enzymes (COX-l and COX-2) and are commonly used to treat pain and inflammation. Recent evidence suggests that COX- 2 inhibition may beneficially influence a range of molecular processes involved in carcinogenesis. This thesis investigated the role of NSAlDs in risk or progression of breast and cervical neoplasms. A systematic review showed high prevalence of COX-2 expression in pre-malignant and invasive breast cancer, indicating involvement of COX-2 in early stage breast cancer carcinogenesis and suggesting that NSAIDs may have the potential to prevent breast cancer development. A study of trends in the diagnosis of carcinoma in situ (CIS) of the breast (pre-invasive disease) in the United Kingdom and Republic of Ireland showed substantial increases in diagnosis rates in both countries indicating an increasing opportunity to prevent invasive breast cancer through the use of chemopreventive agents such as NSAIDs. A study of post-diagnostic NSAID exposure among breast cancer patients, undertaken within the General Practice Research Database (GPRD), showed that NSAID use was associated with an increased risk of breast cancer death and all-cause mortality. These findings may be confounded by indication for use, i.e. patients with more extensive cancer may use NSAIDs for symptom control and also have a poorer prognosis. There was no evidence that use of NSAIDs prevented breast cancer progression. COX-2 has been shown to be over expressed in cervical intraepithelial neoplasia (eIN) and NSAIDs may protect against this premalignant state. The association between NSAID exposure and risk of eIN III was explored. also within the GPRD, but no association was observed. The studies undertaken within this thesis did not provide evidence for a beneficial effect of NSAIDs on neoplasia development or progression but as these drugs are frequently used, and generally well tolerated, further research in this area is warranted.
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Lobb, Ian Thomas. "The role of nucleolar stress in the anti-tumour activity of non-steroidal anti-inflammatory drugs (NSAIDs)." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17878.
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Overwhelming evidence indicates that aspirin (ASA) and related non-steroidal anti-inflammatory drugs (NSAIDs) have anti-tumour activity against colorectal cancer (CRC). Although the underlying mechanisms have yet to be fully elucidated, the host laboratory have shown that nucleolar sequestration of the NF-κB component RelA is critical. In the course of these studies, it was noted that alongside effects on the NF- κB pathway, ASA has a profound effect on nucleoli, including a dramatic increase in nucleolar size. These data were particularly interesting as, in addition to its role in ribosome biogenesis, the nucleolus is known to act as a stress sensor and play a key role in the regulation of cell growth and apoptosis. Indeed, this organelle has been identified as a potential target for anti-tumour agents. However, how stress causes changes to nucleolar function, and how these are translated into changes in cell phenotype, remain unclear. Therefore, the aim of my thesis was to fully characterise ASA effects on nucleoli and to determine whether these effects contribute to the anti-tumour activity of this agent. I found that ASA induced an atypical form of nucleolar stress that was associated with enlargement of the organelle, relocalisation of nucleolar markers to the periphery, depletion of the critical component of the Pol I transcription factor complex, TIF-IA, and inhibition of rRNA transcription. These effects were independent of the p38 and JNK2 MAP kinase pathways. However, they were mimicked by inhibition of CDK4, which had previously been shown to lie upstream of ASA effects on the NF-κB pathway. These data describe a novel mechanism by which ASA, and CDK4 inhibition, may inhibit the growth of colon cancer cells. In addition to this candidate approach, I used Stable Isotope Labelling by Amino acids in Cell culture (SILAC) based quantitative proteomics to obtain a global overview of ASA effects on nucleoli of colon cancer cells. Firstly, a protocol was successfully developed to isolate pure nucleoli from SW480 CRC cell lines. This protocol was then applied to SILAC labelled cells treated with ASA for three time-points (0, 6, 10 h). In collaboration with R.T Hay and M. Tatham (University of Dundee), proteomic analysis was then carried out by tandem-mass spectrometry. These data confirmed that ASA has a significant effect on the nucleolar proteome. They also revealed that ASA induces a distinct type of nucleolar stress that is associated with the accumulation of chaperones, translational regulators and members of the ubiquitin-proteasome system (UPS) in this organelle. These data were reminiscent of studies previously published on the effect of proteasome inhibition on nucleoli. I therefore used SILAC-based proteomics to compare ASA effects on nucleoli to those induced by the proteasome inhibitor, MG132. I found that similar sub-groups of proteins accumulate in nucleoli in response to both agents and that ASA induced proteotoxic stress in a similar manner to MG132. Fluorescence correlation spectroscopy in collaboration with R. Duncan and K. Martin (Heriot-Watt University) demonstrated the relative reduction in mobility of nucleolar DsRed-RelA, indicating that, similar to MG132, ASA induces formation of nucleolar aggresomes. Mechanistic studies suggested that blocking ASA-mediated proteotoxic stress blocked the apoptotic effects of the agent. Taken together, these data define a distinct type of nucleolar stress that may be involved in the cells response to proteotoxic stress and be required for the anti-tumour activity of ASA.
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Quattrocchi, Cinzia. "Nitric oxide donating non steroidal anti-inflammatory drugs (NO-NSAIDs) for the treatment of cancer." Doctoral thesis, Università di Catania, 2014. http://hdl.handle.net/10761/1631.
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Nitric oxide donating non steroidal anti-inflammatory drugs (NO-NSAIDs) represent an emerging class of compounds with chemopreventive, chemotherapeutic, chemio-, radio- and immunosensitizing properties against a variety of cancers. These compounds consist of a conventional NSAID to which an NO-releasing moiety ONO2 has been covalently attached. The aim of our study was to evaluate the anticancer potential of the novel NO-NSAID naproxcinod, since it is the only NO-NSAID that, differently from other compounds belonging to the same class, has so far demonstrated a clear safe profile in humans and has not been extensively studied yet as a potential novel anticancer therapeutic. We show here that Naproxcinod is particular effective in both androgen-dependent and androgen-independent prostate cancer cells and colon cancer cells. We have further validated the results obtained in vitro in murine xenograft models. The data show a strong antitumoral effect of Naproxcinod in all of the models tested. However, Naproxcinod was not able to significantly decrease the metastatic potential of the CT26CL25 colon cancer cells to the lungs. In conclusion, these data provide strong support for the design of phase II trials based on the administration of Naproxcinod to cancer patients in association to conventional therapies or to prevent disease recurrence.
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Davis, Brian Robert. "Non-Steroidal Anti-Inflammatory Drug Use in Collegiate Athletes." PDXScholar, 2015. https://pdxscholar.library.pdx.edu/open_access_etds/2477.
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Non-steroidal anti-inflammatory drugs (NSAID) are a class of medications used in the treatment of pain, inflammation, and illness. These medications are common, affordable, and easy to access. For these reasons, NSAIDs are commonly used by athletes of all backgrounds for treating injuries and as ergogenic aids. However, despite these behaviors, NSAIDs have well-documented side effects and the efficacious nature of these medications has been brought into question. Despite this, many athletes continue to use these medications frequently and indiscriminately. It is not known why athletes use these medications in light of their questionable effectiveness and cited adverse effects. Therefore, this study was designed to (1) further investigate the prevalence of NSAID use in collegiate-level athletes, (2) investigate attitudes and behaviors toward the use of NSAIDs cross-tabulated by sport, gender, and competition level, and (3) investigate athletes' general knowledge of NSAIDs.
Subjects for this study included 79 student-athletes (44 male; 25 female) attending Portland State University (PSU). The majority of the athletes started taking NSAIDs before high school (72% of the males and 64% of the females). Thirty-three percent of males and 32% of females reported that they had been taking NSAIDs within the past week. High in-season use of NSAIDs was reported by 52% of the male athletes and 48% of the female athletes, whereas off-season use was reported by 21% and 12% of the males and females, respectively. Cited reasons for NSAID use both in-season and off-season were relief of pain due to injury, prevention, recovery, soreness, and tightness. In total, 83% of males and 76% of females reported obtaining NSAIDs primarily through means other than health-care professionals. With regard to dosage, athletes reported taking NSAIDs based on product directions, instructions of an athletic trainer or perceived pain levels. An overwhelming majority of athletes (83% male; 76% female) were not aware of any side-effects from taking NSAIDs
In summary, this study revealed a pattern of high NSAID use in athletes competing in-season compared to a high prevalence of low NSAID use in athletes off-season. It also revealed a high prevalence of non-prescription NSAID use. Additionally, there was a high prevalence of self-purchasing of NSAIDs, combined with self-medication and a long history of NSAID use. This study also revealed a general lack of knowledge about NSAIDs.
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Foxon, Graham Ronald. "An investigation of the neuropharmacological and behavioural effects of fenamate and other NSAIDs." Thesis, Durham University, 2001. http://etheses.dur.ac.uk/3990/.
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Recent evidence has indicated that NSAIDs might have direct effects on CNS tissue in addition to their classical inhibitory action on COX enzymes. This thesis addresses this hypothesis using electrophysiological and behavioural techniques. The effects of fenamate and other NSAIDs on native neuronal GABA(_A), 5-HT(_3), nicotinic ACh, P2x and strychinine-sensitive glycine receptors, expressed on isolated vagus or optic nerves, was investigated using an extra-cellular recording technique. The fenamate NSAID, mefenamic acid (MFA) potentiated GABA (10µM)- evoked responses in the vagus nerve. Application of MFA also resulted in non-competitive inhibition of 5-HT-and a,βMeATP- evoked responses. Non-competitive like inhibition was also observed with flufenamic acid on DMPP- and a,βMeATP- evoked responses and with meclofenamic acid on GABA- evoked responses. Non-fenamate NSAIDs, including aspirin, did not significantly modulate the GABA(_A), 5-HT(_3), nicotinic ACh, P2x or glycine receptors. The cognitive and behavioural effects of fenamates and other NASIDs were then investigated. MFA (5-20mg/kg) caused a significant dose- and time-dependent enhancement in the non-spatial object discrimination working memory task when compared to saline controls. The enhancement observed with MFA was greater than that of the cognitive enhancer piracetam. This enhancement was not due to a change in non-mnemonic processes such as arousal, anxiety or locomotion. MFA also enhanced rats' performance in the spatial object location working memory task. The fenamate NSAID, meclofenamic acid (20mg/kg) mimicked the effect of MFA, but the non-fenamate NSAIDs aspirin and ibuprofen, did not enhance object discrimination indicating that these cognitive effects are not via inhibition of COX. The GABA(_A) receptor modulators diazepam, bicuculline and loreclezole, did not replicate the effect of MFA on object discrimination, suggesting that its effects do not depend entirely on the GABAa receptor. Scopolamine (0.25-lmg/kg) significantly impaired object discrimination in a dose-dependent manner. This action could be fully reversed by co-treatment with MFA (20mg/kg).In the T-maze task, MFA (20mg/kg) decreased the number of arm entry errors and days taken to reach criterion. The number of arm entry errors made when a 5-minute intra-trial interval was introduced was also significantly reduced by MFA compared with saline treated animals. In the radial maze, MFA (20mg/kg) did not decrease the number of never baited arm entries to reach criterion. However MFA did significantly reduce the number of re-entry errors to baited arms, compared to controls, when an intra-trial delay (10-30 sees) was introduced. These results support the hypothesis that MFA enhances spatial working memory and that these effects are not task-specific. Overall, the data in this thesis show that fenamate NSAIDs can directly modulate native neuronal ligand-gated ion channels and that MFA can enhance working memory in normal and scopolamine-impaired rats. These results suggest additional pharmacological potential for certain fenamate NSAIDs.
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Gregg, Catherine Nicola. "Structure-activity studies in non-steroidal anti-inflammatory drugs." Thesis, Liverpool John Moores University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238686.
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Fredriksson, Sundbom Marcus. "Characterisation of anandamide uptake in resting and activated murine cells." Thesis, Umeå universitet, Farmakologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100031.
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Modifying the metabolism of the body’s own endocannabinoids is a novel approach for analgesia. Two key catabolic enzymes are fatty acid amide hydrolase (FAAH) and inflammation-inducible cyclooxygenase 2 (COX-2). The cellular uptake of the key endocannabinoid anandamide (AEA) has been found to be regulated by its FAAH-catalysed intracellular degradation, but COX-2 has not been investigated in this respect. We aimed to find out whether or not COX-2 in an in vitro inflammation setting would be able to gate AEA uptake. To achieve this, C6 cells and Raw 264.7 cells were stimulated with LPS/INF-γ and lysates then analyzed by immunoblot in order to verify COX-2 expression. AEA cellular uptake was quantified using a radioassay with [3H]-AEA. It was found that COX-2 was not inducible in C6 cells using the LPS/INF-γ conditions studied, while it was inducible in Raw 264.7 cells. AEA uptake in the COX-2-induced Raw 264.7 cells was not reduced by inhibitors of this enzyme. FAAH appeared to be down-regulated in the stimulated Raw 264.7 cells, and this was reflected in an overall lower AEA uptake. Our interpretation of the data points to FAAH as gating AEA uptake. Additional experiments are required to validate our findings by verifying significance.
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Gordon, Leonard A. "THE NON-STEROIDAL ANTI-INFLAMMATORY DRUGS-MYOCARDIAL INFARCTION ASSOCIATION: AN INVESTIGATION OF KENTUCKY MEDICAID PRESCRIPTION CLAIMS." UKnowledge, 2015. http://uknowledge.uky.edu/epb_etds/8.
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Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications globally. There are generally two types: selective (COX-2) and traditional NSAIDs (COX-1). They are primarily used for the treatment of pain. They gained attention after a study about their basic mechanisms highlighted their toxicity.
Several studies have reported an association between NSAIDs and risk of myocardial infarction (MI). However, the direction of the relationship is not conclusive. Further studies are needed to ascertain the direction of this relationship and evaluate the present situation with available drugs. Due to the seriousness of cardiovascular diseases as one of the leading cause of death, continuous monitoring of the NSAIDs-MI association is needed.
The purpose of this dissertation was to investigate the association between NSAIDs and MI in a younger (30-64 years) Kentucky Medicaid population with a 12 year window of data. The three specific aims were: (1) to understand the characteristics of the Kentucky Medicaid population with respect to NSAID use: (2) to evaluate the NSAID-MI relationship with a 12 year follow-up in a young heavily-burdened population for cardiovascular diseases: and (3) to investigate the MI risk of meloxicam, celecoxib and naproxen compared to no exposure.
A retrospective study was conducted employing data from January 1st 2000 and December 31st 2012. The data comprised demographic, prescription and medical files. Within this cohort, a nested case control study was conducted. Cases of MI were matched to four controls on race and gender.
The results suggested that exposure to COX 2 presented an increased adjusted risk for MI (1.138(0.983, 1.318)). However, this risk was significantly increased for COX-2 only users compared to COX-1 only users (1.221 (1.03, 1.485)) and 30-40 year olds (1.600 (1.082, 2.367)).
Meloxicam, celecoxib and naproxen compared to no exposure showed meloxicam presented a non-significant different risk for MI (1.26 (0.98, 1.63)) and celecoxib presented a significantly increased risk for MI (1.52 (1.26, 1.82)).
This study considered pattern of use in determining continuous usage by looking at both continuous and sporadic users of NSAIDs and also considered patient switching patterns between classes of NSAIDs.
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Omile, Clement Ibe. "Analysis and pharmacokinetics of non-steroidal anti-inflammatory drug combinations in man." Thesis, University of Strathclyde, 1988. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=21283.
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High Performance Liquid Chromatographic methods for quantifying 11 commonly used non-steroidal antiinflammatory drugs in serum were developed. Rapid, specific and sensitive adaptations of the methods were achieved by extraction with chloroform : acetonitrile 3:2 or diethylether : n-hexane 1:1 , giving recoveries of 85-98 %. The methods were used to study the in-vivo kinetic properties of aspirin in healthy volunteers when aspirin (652mg) was taken alone (I), with paracetamol (l000mg) (II) or with indomethacin (l00mg) (III) The salicylate absorption rate for I was 0.75 ± 0.03 hr⁻¹ (mean ± S.E.M) but for II the absorption rate was 0.99 ± 0.03 hr⁻¹; for III the absorption rate was 1.14 ± 0.05 hr⁻¹.These constants for II and III were different (p = 0.05) from that for I but not from each other. Statistically significant differences were not found between other pharmacokinetic parameters viz: (mean ± S. E. M. ) I II II Distribution Volume ( L ) 8.60 ± 0.79 : 7.97 ± 0.57 : 7.27 ± 0.45 : Rate (hrp-1s) blood to tissue 0.07 ± 0.02 : 0.11 ± 0.02 : 0.23 ± 0.03 : Tissue to blood 0.15 ± 0.01 : 0.20 ± 0.02 : 0.23 ± 0.03 : Elimination rate (hr⁻¹) Pseudodistribution ( body) 0.08 ± 0.01 : 0.08 ± 0.01 : 0.09 ± 0.01 : Central compartment (plasma) 0.12 ± 0.01 : 0.13 ± 0.02 : 0.13 ± 0.01 Relating the findings to changes in electropotential differences across the gastric mucosa it is apparent that a reduced gastric mucosal distribution of aspirin with an increased intestinal mucosal transport of aspirin when combined with paracetamol or indomethacin confer protective effect on the gastric mucosa.
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Dunagan, Fiona M. "Non-steroidal anti-inflammatory drugs : pharmacokinetics and clinical response in rheumatoid arthritis." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236497.
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Mezzelani, Marica. "Ecotoxicological potential of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in marine organisms: bioavailability, biomarkers and natural occurrence in Mytilus galloprovincialis." Doctoral thesis, Università Politecnica delle Marche, 2016. http://hdl.handle.net/11566/243116.
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I residui dei composti farmaceutici presenti in ambiente rappresentano una problematica emergente dato che le informazioni riguardo la loro presenza, distribuzione e potenziale ecotossicologico sono molto limitate, specialmente per le aree costiere. In questa tesi è stata valutata la sensibilità del mitilo Mediterraneo Mytilus galloprovincialis nei confronti di diversi farmaci anti infiammatori non steroidei (FANS), applicando un approccio integrato che ha previsto sia attività di laboratorio che indagini di campo. In condizioni di laboratorio i mitili sono stati esposti a diverse concentrazioni ambientalmente realistiche (25, 2.5 e 0.5 μg/L) di acetaminofene AMP, diclofenac DIC, ibuprofene IBU, ketoprofene KET e nimesulide NIM, per diversi tempi di esposizione (da 14 a 60 giorni). Il potenziale ecotossicologico dei FANS è stato valutato combinando le analisi chimiche del bioaccumulo dei farmaci con un approccio multi-biomarker, basato sullo studio di un ampio numero di risposte subcellulari che rappresentano dei segnali di allerta precoce di alterazione cellulare e di tossicità. Per alcune condizioni sperimentali, le alterazioni funzionali misurate a livello cellulare sono state integrate con modificazioni trascrittomiche a livello molecolare attraverso la tecnica di microarray a DNA. I risultati ottenuti hanno dimostrato che i mitili sono in grado di bioaccumulare DIC, IBU e NIM non seguendo, tuttavia, una cinetica dose dipendente, mentre AMP e KET non sono mai stati misurati indipendentemente dalla dose e dal tempo di esposizione. Ciononostante, tutte le molecole testate e tutte le condizioni sperimentali hanno determinato l’insorgenza di alterazioni a carico dei parametri immunitari, modulazione del metabolismo lipidico e danno genotossico. Le analisi trascrittomiche hanno rivelato modificazioni a carico degli organismi esposti alle dosi più basse, sia nel breve (KET e NIM) che nel lungo termine (KET). I risultati ottenuti a livello molecolare supportano le alterazioni misurate a livello cellulare e suggeriscono che il meccanismo di azione dei FANS negli invertebrati risulta essere molto simile a quello ampiamente documentato nei mammiferi. Le indagini a lungo termine hanno permesso di comprendere che l’effetto dei FANS si mantiene costantemente per 60 giorni. Le indagini in campo hanno rivelato, per la prima volta, la presenza di DIC, IBU e NIM nei mitili naturali campionati in primavera e in estate da tipiche aree turistiche del Mare Adriatico centrale. Complessivamente tutti i risultati hanno dimostrato che il M. galloprovincialis è una buona specie sentinella per i FANS, e il reale pericolo ecotossicologico dei farmaci nel Mediterraneo.Pharmaceuticals represent a major environmental concern since the knowledge on their occurrence, distribution and ecotoxicological potential is still limited particularly in coastal areas. In this thesis the sensitivity of the Mediterranean mussels Mytilus galloprovincialis toward different Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) was assessed, applying an integrated approach which combined laboratory studies with field investigation. In laboratory conditions mussels were exposed to different environmental realistic concentrations (25, 2.5 and 0.5 μg/L) of acetaminophen AMP, diclofenac DIC, ibuprofen IBU, ketoprofen KET and nimesulide NIM, for different periods (from 14 to 60 days). The ecotoxicological potential of NSAIDs was evaluated combining chemical analyses on pharmaceuticals bioaccumulation with a multi-biomarker approach, based on a wide array of molecular and subcellular responses reflecting early warning signals of biological disturbance, modulation of specific cellular pathways, onset of various typologies of cellular damages and toxicity. For some experimental condition, functional alteration at cellular level were further integrated with transcriptomic changes at molecular level using DNA microarray. Obtained results demonstrated that mussels are able to bioconcentrate DIC, IBU and NIM without dose dependent response, while AMP and KET are never detected independently from the doses and the exposure period. Nonetheless, for all tested NSAIDs and in all experimental conditions, measurement of a large panel of ecotoxicological biomarkers highlighted impairment of immunological parameters, modulation of lipid metabolism and genotoxic effects. The analyses on transcriptomic profile highlighted changes at molecular level for organisms exposed to lower doses, both in short (for KET and NIM) and long-term condition (for KET). Molecular results supported changes obtained at cellular level and suggest similar mechanisms of action of NSAIDs in mammals and vertebrates. Long-term responses allowed to determine that the effects of anti-inflammatory pharmaceuticals were constantly maintained over 60 days. Field studies provided the first evidence on the occurrence of DIC, IBU and NIM in tissues of wild mussels sampled during summer and spring periods from typical, touristic areas of Central Adriatic Sea. Overall results demonstrated M. galloprovincialis as a good sentinel species toward anti inflammatory pharmaceuticals and the actual ecotoxicological hazard of pharmaceuticals in the Mediterranean.
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Persson, Per-Erik. "Heterotopic Ossification : Clinical and Experimental Studies on Risk Factors, Etiology and Inhibition by Non-steroidal Anti-inflammatory Drugs." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3908.
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Normington, Charmaine. "Genotoxic effects of NSAIDs and hydrocortisone in bulk and nano forms in lymphocytes from patients with haematological cancers." Thesis, University of Bradford, 2017. http://hdl.handle.net/10454/17440.
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Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.
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Davies, Gareth Robert. "Intestinal injury due to non-steroid anti-inflammatory drugs : studies of its measurement, pathogenesis, treatment, and relationship to disease activity of inflammatory arthropathies." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285154.
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Sade, Asli. "Interaction Of The Non Steroidal Anti-inflammatory Drug Celecoxib With Pure And Cholesterol-containing Model Membranes." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/3/12610749/index.pdf.
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The interactions of the non steroidal anti-inflammatory drug celecoxib with pure and cholesterol containing distearoyl phosphatidylcholine multilamellar vesicles were studied using Fourier transform infrared spectroscopy, differential scanning calorimetry and turbidity technique at 440 nm.
The results reveal that celecoxib exerts opposing effects on membrane order in a concentration dependent manner while cholesterol disorders and orders the membrane in the gel and liquid crystalline phase, respectively. Ternary mixtures of DSPC/Cholesterol/celecoxib behave similar to cholesterol with a small effect of celecoxib. While celecoxib decreases fluidity of the DSPC membranes, cholesterol shows an opposite effect, and in ternary mixtures, a dominant effect of cholesterol is observed. Celecoxib induces opposite effects on the hydration status of the carbonyl groups in the binary system whereascholesterol induces hydrogen bonding around this group. An evidence of phase separation has also been observed for all three systems (DSPC/celecoxib, DSPC/Chol, and DSPC/Chol/celecoxib). In addition, a possible location of celecoxib in the interfacial region of the membrane has been proposed. Finally, penetration of celecoxib into the hydrophobic core of the ternary system at high cholesterol concentrations and formation of a new phase has also been suggested. Thus, depending on the concentration used, celecoxib induces significant changes in the biophysical properties of membranes that may aid in understanding its mechanism of action. Furthermore, highly complex interactions take place in ternary membrane systems and further investigations are needed to explore them in detail.
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Tesak, Jennifer Lynn. "STUDY OF CLICK CHEMISTRY: WORKING TOWARDS ‘CLICKING’ A NON-STEROIDAL ANTI-INFLAMMATORY TO AN APOPTOSIS INHIBITOR Q-VD-OPH." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1335402166.
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Duz, Marco. "Biochemical and epidemiological investigations of non-steroidal anti-inflammatory drug usage and related side effects in equids." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7581/.
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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in equine veterinary practice. These drugs exert their effect by inhibiting cyclooxygenase (COX) enzymes, which control prostaglandin production, a major regulator of tissue perfusion. Two isoforms of COX enzymes exist: COX-1 is physiologically present in tissues, while COX-2 is up-regulated during inflammation and has been indicated as responsible for the negative effects of an inflammatory response. Evidence suggests that NSAIDs that inhibit only COX-2, preserving the physiological function of COX-1 might have a safer profile. Studies that evaluate the effect of NSAIDs on COX enzymes are all performed under experimental conditions and none uses actual clinical patients. The biochemical investigations in this work focus on describing the effect on COX enzymes activity of flunixin meglumine and phenylbutazone, two non-selective COX inhibitors and firocoxib, a COX-2 selective inhibitor, in clinical patients undergoing elective surgery. A separate epidemiological investigation was aimed at describing the impact that the findings of biochemical data have on a large population of equids. Electronic medical records (EMRs) from 454,153 equids were obtained from practices in the United Kingdom, United States of America and Canada. Information on prevalence and indications for NSAIDs use was extracted from the EMRs via a text mining technique, improved from the literature and described and validated within this Thesis. Further the prevalence of a clinical sign compatible with NSAID toxicity, such as diarrhoea, is reported along with analysis evaluating NSAID administration in light of concurrent administration of other drugs and comorbidities. This work confirms findings from experimental settings that NSAIDs firocoxib is COX-2 selective and that flunixin meglumine and phenylbutazone are non-selective COX inhibitors and therefore their administration carries a greater risk of toxicity. However the impact of this finding needs to be interpreted with caution as epidemiological data suggest that the prevalence of toxicity is in fact small and the use of these drugs at the labelled dose is quite safe.
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Dao, Tuan. "A randomised clinical trial on the effectiveness of topical non-steroidal anti inflammatory drug for painful temporomandibular disorders." Thesis, Faculty of Dentistry, 2008. http://hdl.handle.net/2123/4051.
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Gunter, Bryan R., Kristen A. Butler, Rick L. Wallace, Steven M. Smith, and Sam Harirforoosh. "NSAIDs-Induced Cardio- and Cerebro-Vascular Adverse Events: a Meta-analysis." Digital Commons @ East Tennessee State University, 2017. https://doi.org/10.1111/jcpt.12484.
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What is known and objective: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular (CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 (COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk.
Methods: We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib.
Results and discussion: Incidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs (OR: 1·811, 95% CI: 1·379-2·378), placebo (OR: 1·655: 95% CI: 1·029-2·661), nsNSAIDs (OR: 2·155, 95% CI: 1·146-4·053), and COXIBs (OR: 1·800, 95% CI: 1·217-2·662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0·583, 95% CI: 0·396-0·857) and (OR: 0·609, 95% CI: 0·375-0·989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [(OR: 1·488, 95% CI: 1·027-2·155) and (OR: 1·933, 95% CI: 1·052-3·549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [(OR: 0·603, 95% CI: 0·410-0·887), (OR: 0·517, 95% CI: 0·287-0·929), and (OR: 0·509, 95% CI: 0·280-0·925), respectively]. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs [(OR: 1·612, 95% CI: 1·313-1·981), (OR: 1·572, 95% CI: 1·123-2·201) and (OR: 1·838, 95% CI: 1·323-2·554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [(OR: 0·805, 95% CI: 0·658-0·986) and (OR: 0·557, 95% CI: 0.404-0.767), respectively]. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data.
What is new and conclusion: This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group.
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Vejarano, Maria Eugenia. "Effect of a non-steroidal, anti-inflammatory drug (Indocin) on selected parameters of muscular function following concentric and eccentric work." Thesis, Virginia Tech, 1985. http://hdl.handle.net/10919/45648.
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Evidence from various studies indicates that eccentric contractions produce more post-exercise changes in muscular function than do concentric contractions. Delayed muscular soreness, the pain and tenderness present 1 or 2 days after exercise, is negatively correlated with muscular performance and occurs particularly after eccentric work. The action of an analgesic, anti-inflammatory drug (Indocin) on muscular soreness indicates it may be effective in accelerating recovery of muscle function after eccentric work.
In the study reported herein the effects of Indocin on muscular performance, as evaluated on the Cybex II isokinetic dynamometer, following prolonged concentric and eccentric work, were evaluated in 48 subjects who were randomly assigned to one of four drug groups. Subjects performed a 30 minute step test during which one limb led the stepping movement throughout (concentric contractions) and the contralateral limb trailed throughout (eccentric contractions). The muscular performance parameters of peak torque (PT), torque acceleration energy (TAE) and average power (AVP), evaluated at slow and high velocities, andthe range of motion (ROM) at the knee joint were assessed prior to the step test and at five intervals thereafter. A nonâ significant decrease in PT and TAE at the contraction speed of 60 deg/sec were present in the eccentric limbs, greater reductions evidenced in the placebo group. Non-significant changes occured in the concentric limbs, Non-significant changes in ROM and in muscular function parameters evaluated at 250 deg/sec were observed.
Master of Science
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Saunders, Fiona R. "An investigation of non-steroidal anti-inflammatory drug mediated modulation of the polyamine pathway in an in vitro model of colorectal cancer." Thesis, University of Aberdeen, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=53328.
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Our hypothesis is that the polyamine biosynthetic pathway, a pathway essential in many cellular functions, is modulated by NSAIDs and that this is, at least in part, how NSAID chemoprevention is mediated. An in vitro model of colorectal cancer was used: two cell lines one of which is COX positive and one COX negative to determine the effects of a range of selective and non-selective NSAIDs on various reactions within the polyamine pathway. NSAIDs are cytotoxic to colorectal cancer cells regardless of their COX expression. NSAID-mediated inhibition of cell growth is accompanied by inhibition of ODC activity, partial depletion of polyamine concentrations and up-regulation of polyamine catabolism. In order to investigate the importance of polyamine metabolism, a specific polyamine inhibitor α-difluoromethylornithine (DFMO) was used in combination with the NSAIDs. DFMO per se is not toxic to cells and it does not enhance NSAID mediated toxicity. DFMO in combination with the NSAIDs did cause increased catabolic activity and more sustained polyamine depletion than either alone, however no additional decrease in ODC activity was observed. This suggests that NSAID toxicity is not enhanced by DFMO in this in vitro model. Analysis of the mode of death indicated that the NSAIDs caused apoptotic cell death, confirmed through biochemical and morphological studies and that the NSAIDs affected gene expression of key enzymes in the polyamine biosynthetic pathway. Our findings suggest that modulation of the polyamine pathway by NSAIDs is at least part of the mechanism of action involved in cancer chemoprevention. Therefore modulation of the polyamine pathway may be useful for design of new chemopreventative drugs.
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Bhala, Neeraj. "Coxibs and traditional NSAIDs : systematic overviews of the randomised evidence for the effects of traditional non-steroidal anti-inflammatory drugs and selective inhibitors of cyclo-oxygenase-2 on vascular and upper gastrointestinal outcomes." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:2b6d8279-bce1-44bd-84c5-7658723786b2.
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Background: Comparative assessments of the vascular and upper gastrointestinal risks of different regimens of non-steroidal anti-inflammatory drugs (NSAIDs) are required. Methods: Meta-analyses were conducted, using individual participant data where possible, of placebo-controlled trials of a selective cyclo-oxygenase [COX]-2 inhibitor ('coxib') or traditional NSAID, or randomised trials of a coxib versus traditional NSAIDs. A prespecified subdivision of traditional NSAID regimens of those with antiplatelet activity (mainly naproxen) and those without (mainly diclofenac) was made. Primary outcomes were major vascular events (MVEs; nonfatal myocardial infarction, nonfatal stroke or vascular death) and upper gastrointestinal complications (UGICs; perforation, obstruction or bleed). Findings: Searches identified 788 trials: 200 comparisons of a coxib vs placebo (88,604 participants, mean follow-up 0.60 years), 206 comparisons of a traditional NSAID vs placebo (43,482 participants, 0.46 years) and 149 comparisons of a coxib vs traditional NSAID (137,466 participants, mean follow-up 0.95 years). Compared to placebo, allocation to a coxib increased the risk of MVEs (rate ratio 1.38, 95% CI 1.14-1.66), vascular mortality (1.58, 1.11-2.24) and UGICs (1.81, 1.17-2.81). Overall, in the population studied, coxibs were associated with three additional major vascular events (one fatal) and two (rarely fatal) upper gastrointestinal complications per 1000 person-years exposure. There was no evidence of heterogeneity by duration of follow-up, coxib type, dose (other than for celecoxib), or patient characteristics, for the primary outcomes. The risk of MVEs for traditional NSAIDs without antiplatelet activity (mostly diclofenac 75mg bd or ibuprofen 800mg tds) were comparable to coxibs (1.40, 1.15-1.72); but the risk of UGICs (1.98, 1.39-2.84) was significantly greater. For traditional NSAIDs with antiplatelet activity (mostly naproxen 500mg bd) there were no significant excess of MVEs (0.84, 0.66-1.08), but UGICs were substantially increased (4.06, 2.85-5.78). Both coxibs and traditional NSAIDs increased risk of hospitalisation for heart failure by about two-fold. Interpretation: The vascular and upper gastrointestinal risks of coxibs and high-dose tNSAID regimens can be predicted, allowing the choice of analgesia to be tailored for particular patients.
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Schaefer, Jeffrey Paul. "The relationship between non-steroidal anti-inflammatory drug prescription and the prescription of cardiovascular medications and prevalence of cardiovascular diseases among senior Albertans." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0016/MQ48039.pdf.
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Schmitt, Michael Ronald. "The relationship among health literacy, physician and pharmacist counseling, written medicine information and non-steroidal anti-inflammatory drug risk awareness in older adults." Oklahoma City : [s.n.], 2009.
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Svobodová, Dagmar. "Chirální analýza residuí léčiv v odpadních vodách." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2011. http://www.nusl.cz/ntk/nusl-216766.
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The theoretical part shortly describes chirality with focus on chiral pharmaceuticals. The processes of their absorption, distribution, metabolism and elimination in human body are discussed. These points are very important to understand possible fate of chiral drugs in the environment as there is only little data concerning their environmental behaviour. The occurrence and enantioselective toxicity of chiral drugs is also discussed here. One of the chapters describes non-steroidal anti-inflammatory drugs, as they are analyzed in the wastewater in the experimental part, and their occurrence in the environment. The experimental part describes optimization of the enantioselective HPLC method using Chiralpak AD as column for ibuprofen and ketoprofen. Reproducible separation of enantiomers wasn’t achieved for naproxen. Optimized methods were then applied for analysis of samples from municipal wastewater treatment plant in Brno-Modřice.
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Rigato, Hamilton Modesto 1977. "Determinação do perfil farmacocinético de anti-inflamatórios não hormonais aplicados à clinica." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311495.
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Orientador: Ney Carter do Carmo BorgesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Objetivo: O presente trabalho teve por objetivo avaliar o perfil farmacocinético do diclofenaco de colestiramina (cápsula de 140mg) e de duas apresentações farmacêuticas (comprimidos 100mg e suspensão oral 50mg/mL) de nimesulide realizado em voluntários sadios de ambos os sexos e relacioná-los aos desfechos clínicos em enzimas do painel hepático e da contagem de plaquetas. Materiais e métodos: Os estudos foram do tipo aberto, aleatório, cruzado, em dois períodos. As amostras de sangue foram analisadas em cromatografia líquida de alta eficiência acoplada, a um detector de ultravioleta (UV) para o primeiro fármaco, e a um espectrômetro de massa (EM/EM) para outro. Os valores séricos do painel hepático e contagem de plaquetas foram comparados pré e pós-medicação. Resultados: As razões geométricas e respectivos 90% do IC para a cápsula de diclofenado de colestiramina/Flotac® 140 mg foram 100.22% (84.99 - 118.19%) para a CMAX e 90,53% (82.86-98.91%) para a ASCULTIMO. Os valores para o comprimido de Nimesulide/Nisulid® 100mg foram 85.96% (77.54 - 95.30%) para a CMAX e 93.91% (84.42 - 104.46%) para a ASCULTIMO, e a formulação de suspensão oral de Nimesulide/Nisulid® 50mg/mL obteve 100.1% (91.05 - 110.15%) para CMAX e 107.7% (99.74 - 116.39%) para ASCULTIMO. Quanto ao desfecho clínico foi observada elevação significante no parâmetro de ALT para o diclofenaco de colestiramina e na formulação comprimido de nimesulide. A formulação de suspensão oral teve elevação significante para o parâmetro de ALP. Não foi observada diminuição na contagem de plaquetas. Conclusão: Considerando que 90% dos intervalos de confiança das razões de CMAX e ASCULTIMO, se encontram dentro de 80-125% do intervalo proposto pelo FDA e aceita pela ANVISA, concluiu-se que a formulação de cápsula de diclofenaco de colestiramina (140mg) e a formulação de suspensão oral (50mg/mL) de nimesulide são bioequivalentes em relação à taxa e extensão de absorção e que a formulação comprimido de nimesulide (100mg) não é bioequivalente ao Nisulid® com relação a taxa de absorção. Clinicamente os medicamentos se mostraram seguros mesmo apresentando alterações estatisticamente significantes nos parâmetros clínicos avaliados
Abstract: Objective: The present work aims to evaluation the pharmacokinetic profile of the diclofenac-cholestyramine (140mg capsule) and two pharmaceuticals formulations (100mg tablets and 50mg/m oral suspension) of nimesulide in healthy adult subjects related with clinic outcomes in the hepatic enzymes panel and platelet count. Method: The studies were open, randomized, simple crossover balanced with two periods. The blood samples were analyzed by high performance liquid chromatography coupled to ultraviolet detection in diclofenac formulations. For nimesulide a mass espectrometer was performed (MS/MS). Seric enzymes from liver panels and whole blood platelet count was compared with pre and post single dose treatment. Results: The geometric mean and 90% confidence intervals (CI) for the diclofenac-cholestyramine/Flotac® ratio were 100.22% (84.99 - 118.19%) for CMAX and 90,53% (82.86-98.91%) for AUCLAST. The geometric mean and 90% confidence intervals (CI) for the Nimesulide/Nisulid® 100mg tablet were 85.96% (77.54 - 95.30%) for CMAX and 93.91% (84.42 - 104.46%) for AUCLAST, and for the oral suspension 50mg/mL were 100.1% (91.05 - 110.15%) for CMAX and 107.7% (99.74 - 116.39%) for AUCLAST. For the hepatic enzyme panel was observed significant rise in the ALT for diclofenac-cholestyramine and nimesulide tablet. The oral suspension was significant rise in the ALP parameter (p<0.05). No platelet count decrease was observed. Conclusion: Since the 90% CI for CMAX and AUCLAST ratios were all inside the 80-125% interval proposed by the US Food and Drug Administration and accepted by ANVISA, it is concluded that the diclofenac-cholestyramine 140mg capsule and the nimesulide oral suspension formulation 50mg/mL are bioequivalent in regard to both extent and rate of absorption. The nimesulide 100mg tablet is not bioequivalent to Nisulid® 100mg tablet with respect to the rate of absorption. Clinically all the evaluated pharmaceuticals are safety despide the significant changes in the hepatic enzymes panel observed
Doutorado
Ciencias Basicas
Doutor em Clínica Médica
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Farney, Jaymelynn Kay. "Effects of inflammation on the transition dairy cow." Diss., Kansas State University, 2012. http://hdl.handle.net/2097/14180.
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Doctor of PhilosophyDepartment of Animal Sciences
Barry Bradford
The transition into lactation is a period of primary concern to dairy producers because of the tremendous incidence of health disorders observed during this time. Two common disorders that lead to decreases in production and retention within the herd include fatty liver disorder (FL) and ketosis. These two disorders have been commonly associated with negative energy balance, yet recently it has been hypothesized that inflammation is a contributor to the etiology of these disorders. Three individual projects were completed for this dissertation, all involving inflammation. The role of endogenous inflammation was determined by administration of sodium salicylate (SS) to cows for 7 d after parturition, and metabolites and production responses were evaluated. Overall it appears that SS induced hypoglycemic conditions and increased triglyceride accumulation in the liver (while administered), increased lipid mobilization and ketones (2 weeks after administration ended), and increased whole lactation milk production in older cows. A sensitive, specific sandwich ELISA for bovine tumor necrosis factor-[alpha] was developed, which provided the ability to measure “normal” circulating levels of this cytokine. The final study involved inducing inflammation by daily injections of the TNF[alpha] to the early lactation dairy cow. In this model, cows receiving TNF[alpha] had a reduction in dry matter intake, water intake, and decreases in milk production and milk components. Overall, it appears that inflammation is involved in the normal biology of the transition dairy cow and disrupting this can lead to interesting negative effects and some improvements of production; however, when inflammation is much greater it can lead to negative production effects.
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Lopes, Carlize. "Toxicidade renal e hepática da tepoxalina em cães submetidos à hipotensão com isofluorano." Universidade Federal de Santa Maria, 2011. http://repositorio.ufsm.br/handle/1/10094.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoThis study aimed to evaluate the possible renal and hepatic toxicities, acute and subacute, of the administration of tepoxalin in dogs submitted to hypotension with isoflurane. A total of 12 dogs were used, which received 10 mg kg-1 of tepoxalin PO two hours before induction of hypotension (T) or were only submitted to hypotension with isoflurane (C). For the subacute study, animals in T were treated with tepoxalin during 5 days, following the hypotensive procedure. The dogs were submitted to hypotension (MAP= 50-60mmHg) for isoflurane in a circular circuit valve, with adjusted FR for the ETCO2 remained between 35-45mmHg. ToC was maintained between 37 and 38oC. HR, SAP, MAP, DAP, CVP, ETCO2 and ETIso were evaluated at 0, 10 and every 10 min up to 60min of hipotension. pH, PaO2, PaCO2, SaO2, HCO3-, BD, Na+, K+, Ca2+ and bleeding time evaluations were carried out before hypotension and at 30 and 60min of hipotension. For renal and hepatic evaluation, serum levels of U, Cr, ALT, alkaline phosphatase, GGT and urinary levels of GGT, Cr and GGT:Cr ratio were determined at 12h, 24h and seven days after the procedure. During the anesthetic procedure, only CVP presented elevation in relation to 0min in both groups at 50 and 60min of evaluation. In blood gas and electrolyte measurement, only Na+ presented levels below to basal at 60min in T, and this same group showed increased values at all intervals, in comparison between groups. Moreover, bleeding time was shown to be more elevated at 30min of evaluation in animals in T, when compared to the ones in C. The variables corresponding to creatinine depuration, GGT:Cr ratio and UV remained stable during the evaluations; however, urinary GGT levels presented increased values in animals in C when compared to T, at 60min of evaluation. At this same interval, urinary Cr values were elevated in T. Serum levels of ALT, alkaline phosphatase, U and Cr presented minor alterations, remaining within reference values; however, GGT presented increased values at 60min of evaluation, when compared to 0min. On the seventh day of evaluation, a reduction in leukocyte number was observed in animals in T, when compared to C. Side effects were not observed in both groups. The prior administration of tepoxalin in healthy dogs submitted to hypotension did not cause significant effects upon renal and hepatic functions. Moreover, daily administrations during five days, following the anesthetic procedure, did not alter the functions of the organs mentioned. Therefore, tepoxalin showed to be a safe NSAID to be used in healthy dogs, submitted to hypotension during anesthesia with isoflurane.
Objetivou-se avaliar as possíveis toxicidades renal e hepática, aguda e subaguda, da administração de tepoxalina em cães submetidos à hipotensão com isofluorano. Foram utilizados 12 cães, os quais receberam 10mg kg-1 de tepoxalina VO duas horas antes da indução da hipotensão (T) ou somente foram submetidos à hipotensão com isofluorano (C). Para o estudo subagudo, os animais do T foram tratados com tepoxalina, durante cinco dias, seguidos ao procedimento hipotensor. Os cães foram submetidos à hipotensão (PAM = 50-60mmHg) por isofluorano em circuito circular valvular, com FR ajustada para que o ETCO2 permanecesse entre 35-45mmHg. A TºC foi mantida entre 37 e 38ºC. Avaliaram-se FC, PAS, PAM, PAD, PVC, ETCO2, e ETIso em 0, 10 e a cada 10min até 60min da hipotensão. As avaliações de pH, PaO2, PaCO2, SaO2, HCO3-, DB, Na+, K+ e Ca2+ e tempo de sangramento foram realizadas antes da hipotensão e aos 30 e 60min da hipotensão. Para a avaliação renal e hepática foram determinados os níveis séricos de U, Cr, ALT, FA, GGT e os níveis urinários de GGT, Cr e a proporção GGT:Cr em 12h, 24h e sete dias após o procedimento. Durante o procedimento anestésico somente a PVC apresentou elevação em relação aos 0min, em ambos os grupos aos 50 e 60min de avaliação. Na mensuração dos gases sanguíneos e eletrólitos, apenas o Na+ demonstrou níveis menores que o basal aos 60min no T, e este mesmo grupo apresentou valores aumentados em todos os momentos, na comparação entre os grupos. Ainda, o tempo de sangramento foi maior aos 30min de avaliação, nos animais do T, quando comparado aos do C. As variáveis correspondentes à depuração da creatinina, razão GGT:Cr e DU permaneceram estáveis durante as avaliações, porém, os níveis de GGT urinária apresentaram valores aumentados nos animais do C, quando comparados ao T, aos 60min de avaliação. Nesse mesmo momento, os valores de Cr urinária estavam aumentados dentro do T. Os níveis séricos de ALT, FA, U e Cr apresentaram poucas alterações, permanecendo dentro dos limites de referência, porém, a GGT apresentou valores aumentados aos 60min de avaliação, comparando-se com 0min. No sétimo dia de avaliação, observou-se redução do número de leucócitos nos animais do T, quando comparados aos do C. Não foram observados efeitos colaterais em ambos os grupos. A administração prévia de tepoxalina em cães hígidos submetidos à hipotensão, não ocasionou efeitos significativos sobre as funções renal e hepática dos mesmos. Da mesma forma, administrações diárias durante cinco dias, seguidas ao procedimento anestésico, não alteraram as funções dos referidos órgãos. Portanto, a tepoxalina demonstrou ser um AINE seguro para utilização em cães hígidos, submetidos à hipotensão durante anestesia com isofluorano.
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Freitas, Gabrielle Coelho. "Efeito da tepoxalina sobre as funções renal e hepática em Gatos submetidos à hipotensão com isofluorano." Universidade Federal de Santa Maria, 2012. http://repositorio.ufsm.br/handle/1/4079.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe aim of this study was to evaluate acute and subacute renal and hepatic toxicity of the oral administration of tepoxalin in cats submitted to hypotension with isoflurane. Eighteen adult male mongrel cats were used in this study, weighing between 3 and 5 kg and clinically healthy. The animals were divided into three groups, which were anesthetized and submitted to hypotension with isoflurane (CON), or which, in addition, tepoxalin was administered two hours prior to the hypotension procedure (PRE) or after the hypotension procedure (POS). The animals from groups PRE and POS also received the same doses of tepoxalin every 24 hours, during the five days following the procedure. In order to achieve a condition of moderate hypotension, animals were induced and maintained with isoflurane in variable concentration, for maintenance of mean arterial pressure (MAP) between 45 and 60 mmHg, during 60 minutes. Complete blood count and serum concentrations of alanine aminotransferase (ALT), alkaline phosphatase (FA) and urea (U) were evaluated at baseline and 24 hours, 48 hours and 7 days after hypotension. Serum concentration of creatinine (Cr), fractional excretion of sodium (FENa) and urinary concentrations of Cr, gamma-glutamyl transferase (GGT), proteinuria and albuminuria were evaluated at baseline and 24 hours, 48 hours and 7 days after hypotension. The model chosen was efficient in maintaining the proposed condition of hypotension. No physiological changes were observed in complete blood count, serum biochemistry profile (ALT, FA, U and Cr), FENa and urinary GGT. An increase in urine protein-creatinine ratio was observed in CON and PRE at 24 and 48 hours after hypotension. Urine albumin-creatinine ratio showed increase in CON at 24 hours and maintained elevated values with regard to the other groups until 7 days after hypotension. The authors conclude that administration of tepoxalin does not cause changes in hepatic parameters, urea, creatinine, fractional excretion of sodium and urinary GGT in cats submitted to anesthetic hypotension. However, there is a risk of mild renal injury by administering the drug prior to the hypotensive procedure.
Este estudo objetivou avaliar a toxicidade renal e hepática, aguda e subaguda, da administração oral da tepoxalina em gatos submetidos à hipotensão com isofluorano. Foram utilizados 18 gatos, machos, adultos, sem raça definida, com peso entre 3 e 5 kg e comprovadamente hígidos. Os animais foram alocados em três grupos, os quais foram anestesiados e submetidos à hipotensão com isofluorano (CON), ou que ainda receberam tepoxalina duas horas antes do procedimento de hipotensão (PRÉ) ou após a recuperação anestésica do procedimento de hipotensão (PÓS). Os animais dos grupos PRÉ e PÓS também receberam as mesmas doses de tepoxalina a cada 24 horas, durante cinco dias pós procedimento. Para a caracterização de um quadro de hipotensão moderada, os animais foram induzidos e mantidos anestesiados com isofluorano em vaporização variável, para a manutenção da pressão arterial média (PAM) entre 45 e 60 mmHg durante 60 minutos. Foram avaliados hemograma e concentrações séricas de alanina amino-transferase (ALT), fosfatase alcalina (FA) e ureia (U) no período basal e 24 horas, 48 horas e 7 dias após a hipotensão. A concentração sérica de creatinina (Cr), a fração de excreção de sódio (FENa) e as concentrações urinárias de Cr, gama-glutamiltransferase (GGT), proteínas totais e albumina foram avaliadas no momento basal e 24 horas, 48 horas e 7 dias após a hipotensão. O modelo escolhido foi eficiente na manutenção do quadro de hipotensão proposto. Não foram observadas alterações fisiológicas no hemograma, bioquímica sérica (ALT, FA, U e Cr), FENa e na GGT urinária. Observou-se elevação estatística na razão proteína-creatinina na urina no CON e no PRÉ em relação ao PÓS às 24 e às 48 horas de avaliação. A razão albumina-creatinina na urina apresentou elevação estatística no CON em relação aos demais à partir das 24 horas de avaliação, mantendo essa elevação até os 7 dias de avaliação. Concluiuse que a administração de tepoxalina não causou alterações de parâmetros hepáticos, ureia, creatinina, FENa e GGT urinária em gatos submetidos à hipotensão anestésica, entretanto há o risco de ocorrência de injúria renal discreta devido à proteinúria observada no grupo em que a tepoxalina foi administrada antes do procedimento hipotensor.
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Bée, Lais Regina. "INTERAÇÕES POTENCIAIS ENTRE AINES PRESCRITOS EM ENDODONTIA E MEDICAMENTOS EM USO PELOS PACIENTES ODONTOLÓGICOS." Universidade Federal de Santa Maria, 2015. http://repositorio.ufsm.br/handle/1/6170.
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The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in Endodontics and when associated with some risk factors, such as concomitant use of other drugs, may develop undesirable and possibly serious effects. This cross-sectional study evaluated, through data collecting on dental records, potential interactions among the most commonly prescribed NSAIDs and medications used by patients treated in the Integrated Clinical Dentistry of UFSM, from 2007 to 2011. The data were processed on the EpiData and the statistical analysis was performed with SPSS Software. For analysis of interactions between drugs two tertiary bibliographic source were used: the book Drug Interaction Facts and computerized tool Drugdex in the Micromedex. Potential drug interactions with NSAIDs occurred with 20.2% of the drugs related by patients. The most common consequences in this context were gastrointestinal bleeding, decrease antihypertensive effect and renal failure. In relation to gravity and documentation of interaction, there was a higher frequency of the important gravity and well-documented in the issue of pharmacological interaction. Hence, special attention must be given to the elderly and other patients using several drugs at the same time alongside with educational initiatives focused on a more safe prescription method should be taught in educational institutions.Os anti-inflamatórios não esteroides (AINEs) são fármacos amplamente utilizados em Endodontia e, quando associadas a alguns fatores de risco, como uso concomitante de outros medicamentos, podem desenvolver efeitos indesejados e possivelmente graves. Esse estudo transversal avaliou, por meio de uma coleta de dados nos prontuários odontológicos, as potenciais interações entre os AINEs mais comumente prescritos e os medicamentos em uso pelos pacientes atendidos nas Clínicas Integradas do Curso de Odontologia da UFSM, no período de 2007 a 2011. Os dados foram codificados no Programa EpiData e a análise estatística foi realizada com o Software SPSS. Para análise das interações entre os fármacos foram utilizadas duas fontes bibliográficas terciárias: o livro Drug Interaction Facts e a ferramenta informatizada Drugdex do Micromedex. As potenciais interações medicamentosas com AINEs ocorreram em 20,2% dos medicamentos relatados pelos pacientes. As consequências mais frequentes nesse contexto foram sangramento gastrointestinal, diminuição do efeito anti-hipertensivo e insuficiência renal. Em relação à gravidade e a documentação da interação, observou-se maior frequência de gravidade importante e bem documentada no quesito interação farmacológica. Então, atenção especial deve ser dada a pacientes idosos e outros pacientes que utilizem diversos medicamentos de forma paralela e iniciativas educacionais focadas em um método de prescrição mais seguro devem ser lecionadas em instituições de ensino.
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Maijó, Ferré Irene. "Preconcentration strategies in capillary electrophoresis for the determination of pharmaceutical and personal care products." Doctoral thesis, Universitat Rovira i Virgili, 2012. http://hdl.handle.net/10803/84043.
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L'objectiu principal d'aquestaTesi Doctoral és el desenvolupament de diferents estratègies per disminuir els límits de detecció de l’electroforesicapil•lar per a la determinació de compostos farmacèutics i els productes de cura personal. Aquestes estratègies es basen en les tècniques de preconcentració electroforètiques i cromatogràfiques, i l'ús de l’espectrometria de masses com a sistema de detecció. Com a tècniques de preconcentració electroforètiques s'han estudiat les tècniques de samplestacking i sweeping, i com a tècnica de preconcentració cromatogràficas’ha avaluat l'acoblament en línia entre l'extracció en fase sòlida i l'electroforesicapil•lar (In-line SPE-CE). Entre elsPPCPs, aquesta tesi doctoral es centra específicament en els antiinflamatoris no esteroïdals(AINE), els parabens i els filtres ultraviolats.
Un altre dels objectius d'aquestaTesi Doctoral és estudiarl’aplicabilitat de les metodologies desenvolupades per a l'anàlisi de mostres ambientals per determinar PPCP.The main objective of this Doctoral Thesis is the development of different strategies to decrease the detection limits of capillary electrophoresis for the determination of pharmaceutical and personal care products. These strategies are based on electrophoretic and chromatographic preconcentration techniques, and the use of mass spectrometry as a detection system. The electrophoretic preconcentration techniques studied included sample stacking techniques and sweeping while the chromatographic preconcentration technique evaluated was in-line coupling between solid phase extraction and capillary electrophoresis. With respect to PPCPs, this Doctoral Thesis focuses specifically on non-steroidal anti-inflammatory drugs (NSAIDs), parabens and UV-filters. Another objective of this Doctoral Thesis is to study the suitability of the developed methodologies for the determination of PPCPs in environmental samples.
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Tomazoni, Shaiane da Silva. "Efeitos da laserterapia de baixa potência, anti-inflamatório não-esteroidal tópico e atividade física no tratamento de osteoartrite induzida por papaína." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/42/42136/tde-05102015-200655/.
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Introdução: A osteoartrite (OA) é uma doença que comumente afeta os seres humanos, sendo caracterizada como um processo degenerativo que abrange as articulações. A OA afeta a cartilagem articular, osso subcondral, ligamentos, cápsula articular, membrana sinovial e músculos periarticulares. O tratamento para esta desordem se baseia em terapia farmacológica, não farmacológica e cirúrgica, isoladamente ou em combinação, a fim de maximizar os efeitos benéficos e minimizar os efeitos indesejáveis. O presente estudo tem como objetivo avaliar e comparar os efeitos isolados e combinados da terapia farmacológica com anti-inflamatório não-esteroidal (AINE) de uso tópico, aos efeitos da atividade física, e por fim, aos efeitos da laserterapia de baixa potência (LBP), em um modelo experimental de OA. Materiais e Métodos: A OA foi induzida por injeção de papaína intra-articular no joelho direito de ratos Wistar machos. Após 21 dias os animais começaram a ser tratados com AINE de aplicação tópica e/ou com atividade física (natação) e/ou LBP. Os tratamentos foram realizados 03 vezes por semana, durante 08 semanas, perfazendo um total de 24 sessões de terapia. Foram realizadas análises bioquímicas e morfológicas da articulação do joelho, compreendendo análise histológica, contagem total de células, atividade de mieloperoxidase (MPO), RT-PCR (COX-1, COX-2, IL-1β, IL-6, IL-10, TNF-α, MMP-3 e MMP-13), análise de citocinas pelo método de ELISA (TNF-α, IL-1β, IL-6 e IL-10), PGE2 e por fim, a análise de Western-Blot (COX-1 e COX-2). Resultados, discussão e conclusão: Os resultados do presente estudo indicam que o tratamento com laserterapia de baixa potência é o mais eficiente em diminuir os danos à articulação e modular o processo inflamatório induzido pela injeção de papaína na articulação do joelho de ratos.Introduction: Osteoarthritis (OA) is a disease that commonly affects humans and it is characterized as a degenerative process that reachs joints. OA affects the articular cartilage, subchondral bone, ligaments, joint capsule, synovial membrane and periarticular muscles. The treatment for this disorder is based on pharmacological therapy, non-pharmacological therapy and surgery, alone or in combination, in order to maximize the beneficial effects and minimize side effects. This research project aims to evaluate and compare the isolated and combined effects of pharmacological therapy with non-steroidal anti-inflammatory drug (NSAID) of topical use, to effects of physical activity and finally to effects of low-level laser therapy (LLLT) in an experimental model of osteoarthritis. Materials and Methods: OA was induced by intra-articular injection of papain in the right knee of male Wistar rats. After 21 days animals started to be treated with topical NSAID and/or physical activity (swimming) and/or LBP. Treatments was performed 3 times per week for 8 weeks, a total of 24 therapy sessions. It was performed morphological and biochemical analysis of the knee joint, including histology, counting of total cells, activity of myeloperoxidase (MPO), RT-PCR (COX-1, COX-2, IL-1β, IL-6, IL-10, TNF-α, MMP-3 and MMP-13) cytokines analysis by ELISA (TNF-α, IL-1β, IL-6 and IL-10), PGE2, and finally Western- Blot analysis (COX-1 and COX-2). Results, discussion and conclusion: The results of this project indicate that treatment with low-level laser therapy is more efficient in order to decrease damage in joint and to modulate inflammatory process induced by papain injection in rats knee join.
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Hoxha, M. "THE POTENTIAL THERAPEUTIC ROLE OF MONTELUKAST AND NEW HYBRID AGENTS, TXA2 ANTAGONIST-COX-2 INHIBITORS IN CARDIOVASCULAR EVENTS." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/347148.
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The main target of my PhD research project was to explore new alternatives to reduce the cardiovascular (CV) risk targeting the arachidonic acid metabolites. Hence, I have been part of two different projects, one studying multitarget compounds with balanced COXIB and TP receptor antagonist properties, and the other evaluating the potential role of a leukotriene (LT) antagonist drug such as montelukast in improving the CV outcome.
In reference to the first project, new multitarget compounds were synthesized at the University of Turin, by substituting the carboxylic function of Lumiracoxib. This strategy led to several new compounds, of which we have analyzed the platelet aggregation, total inositol phosphate production, COX-1 and COX-2 inhibitory activity. Out of all the studied compounds compound 18, the terazole derivative as well as compound 20 were the most active, with a decent balanced activity as COXIB and TP antagonist . Whereas, compound 32, displaying a functional group of terutroban did not accomplish our expectation to be a more potent TP antagonist with respect to compounds 7,18,20. Our main goal is to obtain new molecules with higher TP antagonist properties but at the same time retaining the COXIB activity. It is important to highlight that the therapeutic effect of these new compounds depend on the balance of two pharmacological profiles. The results we obtained demostrate that it is possible to have new chemical entities with higher TP antagonist potencies, and better balanced COX-2 selectivity. This approach will provide further benefits for patients with chronic pain taking a COXIB, and in patients with higher CV risk, like diabetics and hopefully can lead to a new generation of safer non steroidal antiinflammatory drugs.
The second project of my PhD was focused on a LT antagonist drug such as montelukast, which is a pharmacological alternative for patients suffering asthma, allergic rhinites and urticaria. We performed a retrospective study including patients exposed or not to montelukast for a total of eight hundred asthmatic patients to assess the potential role of montelukast in primary and secondary prevention of major CV events as ischemic stroke (IS) or myocardial infarction (MI). Each of the two subjects sample was further classified in patients with or without MI or IS based on their diagnosis according to the International Classification of Diseases (ICD). The myocardial infarction event rate was almost 6 fold higher in asthmatic patients not taking montelukast and 9 fold higher for ischemic stroke events. Drug used in these patients were also monitored in order to exclude potential confounders of the results. Overall, our results suggest a reduction of CV events by montelukast, including both MI and IS eventhough the study should be expanded to a larger number of subjects. Given their association with the inflammatory onset and amplification, LTs synthesis inhibitors or LT receptor antagonists such as montelukast could be consider as potential approach for CV diseases.
The results obtained during this three years of PhD cycle have shown that new innovative strategies targeting arachidonic acid metabolites can be implied to improve the CV outcome. There is still an unmet need for an anti-inflammatory treatment to reduce the CV risk, and these strategies can lead to new pharmacological approaches.
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Vašíčková, Petra. "Stanovení reziduí léčiv pomocí separačních metod." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2010. http://www.nusl.cz/ntk/nusl-216632.
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Nonsteroidal anti-inflammatory substances became a very frequently used and constantly evolved group of the drugs, particularly in a human medicine. The risk of their penetration into the environment, especially to the water environment, is rising during the recent years. The diploma thesis is focused on a selection of appropriate separation method and optimization of analytical procedure for the identification and determination of the non-steroidal anti-inflammatory drugs in sewage and surface waters. Salicylic acid, ketoprofen, diclofenac and ibuprofen were chosen from the wide range of NSAIDs as the most widespread agents of this drugs group in the medical practice. The method was optimized and elaborated using the model water samples. This method was used for determination of the analytes contained in the real water samples. Waste water samples were taken from the large-scale wastewater treatment plant in Brno-Modřice and surface water samples were taken from the Highlands river Křetínka. Solid phase extraction (SPE) was used for the real samples treatment and preconcentration, the determination was performed using the high performance liquid chromatography with mass spectroscopy method (LC-MS).
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Misumi, Denise Shimbo. "Validação do Teste de ativação de basófilos no diagnóstico de reações de hipersensibilidade a anti-inflamatórios não esteroidais." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-24062013-152145/.
Full textAbstract:
Introdução: Atualmente, o diagnóstico das reações de hipersensibilidade a anti-inflamatórios não esteroidais (AINEs) baseia-se na história relatada pelo paciente e, em determinados casos, é realizado o Teste de Provocação. Todavia, este teste pode expor os pacientes a riscos graves, inclusive anafilaxia. Em busca de ferramenta mais segura, tem-se estudado o Teste de Ativação de Basófilos (BAT). Trata-se de um teste in vitro, no qual é possível testar diversos estímulos em uma única amostra de sangue, avaliando a ativação dos basófilos (indicativo de reação de hipersensibilidade), através do aumento da expressão de moléculas na superfície desses leucócitos, como o CD63. Objetivo: Padronizar e validar o BAT para ácido acetilsalicílico (AAS), diclofenaco, dipirona e paracetamol em pacientes com hipersensibilidade a AINEs. Metodologia: Participaram 20 (testados com os quatro AINEs) + 33 (testados somente com AAS) pacientes atendidos no Serviço de Imunologia Clínica e Alergia do HCFMUSP, que apresentaram manifestações cutâneas em até 24 horas após exposição a um ou múltiplos AINEs, bem como 13 (quatro AINEs) + 26 (AAS) controles. A técnica consistiu em incubar sangue total com os AINEs já mencionados e, depois, marcar as amostras com anticorpos monoclonais (CD45, anti-IgE e CD63) para posterior leitura por citometria de fluxo. Os resultados obtidos foram comparados com as histórias clínicas e os testes de provocação oral, quando realizados. Resultados: Utilizando os critérios de positividade do BAT empregados na literatura (isto é, porcentagem de CD45+IgE+highCD63+ e índice de estimulação), a sensibilidade e a especificidade variaram de acordo com o AINE: para ácido acetilsalicílico foram 75,0% e 16,7%, respectivamente, diclofenaco, 100% e 0%, dipirona, 23,5% e 66,7%, paracetamol, 40,0% e 42,9%. Após a realização de curvas dose-resposta e tempo-resposta somente com AAS, foi encontrado novo critério de positividade: média de intensidade de fluorescência (MFI) menor do que 6575 representava BAT positivo; com isso, os valores de sensibilidade e especificidade foram: 84,4% e 34,6%, respectivamente. O BAT foi mais sensível em pacientes cuja última reação ocorreu há menos de um ano da data de execução do BAT (93,7%). Conclusão: Devido aos baixos valores de sensibilidade e/ou especificidade, não foi possível padronizar e, por conseguinte, validar o BAT para ácido acetilsalicílico, diclofenaco, dipirona e paracetamol.Introduction: Currently, the diagnosis of nonsteroidal antiinflammatory drugs (NSAIDs) hypersensivitity is based on patients´ clinical history and drug provocation tests, which are done in selected cases. Nevertheless, this test may expose patients to severe risks, including anaphylaxis. Looking for a safer tool, Basophil Activation Test (BAT) for allergy diagnosis has been studied in the last years. It is an in vitro method where a wide variety of stimuli can be tested, incubating them with the patient\'s blood sample, and observing basophil activation (indication of hypersensitivity) through upregulation of CD63 (or other basophil activation markers) on this leucocyte\'s membrane. Objective: To standardize and validate BAT stimulated with acetylsalicylic acid (ASA), diclophenac, dipyrone and paracetamol in NSAID hypersensitive patients. Methods: Patients which reported immediate reactions (less than 24 hours) after exposure to one or multiple NSAIDs, with cutaneous symptoms were enrolled from Clinical Immunology and Allergy outpatient clinic from HC-FMUSP. BAT with the four NSAIDs was tested on 20 patients and 13 controls and BAT with ASA only, on 33 patients and 26 controls. BAT consisted of incubating whole blood with NSAIDs, then triple-labeled with monoclonal antibodies (CD45, anti-IgE, CD63) for analysis by flow cytometry. BAT results were compared to clinical history and oral provocation tests, when available. Results: According to literature\'s positivity criteria (percentage of CD45+IgE+highCD63+ and stimulation index), sensitivity and specificity varied according to the NSAID tested: for ASA was 75.0% and 16.7% respectively, diclophenac, 100.0% and 0.0%, dipyrone, 23.5% and 66.7%, paracetamol, 40.0% and 42.9%. A new positivity criterion was possible to be defined after further dose-response and time-response curves only for ASA: Mean Fluorescence Intensity lower than 6575 (positive BAT). Accordingly, new sensitivity and specificity for BAT in ASA hypersensitivity were 84,4% and 34,6%. Patients that presented the last reaction in the last year were more likely to present a positive BAT (93.7%). Conclusion: Due to low values for sensitivity and/or specificity, it was not possible to standardize and validate BAT for ASA, diclophenac, dipyrone and paracetamol.