scholarly journals Computer search for molecular mechanisms of ulcerogenic action of nonsteroidal antiinflammatory drugs

2014 ◽  
Vol 60 (1) ◽  
pp. 7-16 ◽  
Author(s):  
S.M. Ivanov ◽  
A.A. Lagunin ◽  
A.V. Zakharov ◽  
D.A. Filimonov ◽  
V.V. Poroikov
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Structural Formula ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Mechanisms Of Action ◽  
Computer Search ◽  
Peptic Ulcers ◽  
Antiinflammatory Drugs ◽  
Material Resources ◽  
Data Signal

“Peptic ulcers” is the most frequent side effect of non-steroidal anti-inflammatory drugs (NSAIDs). Experimental data indicate that pathogenesis of peptic ulcers cannot be explained only by the inhibition of cyclooxygenases. The knowledge about other molecular mechanisms of action of drugs related with development of peptic ulcers could be useful for design of new safe NSAIDs. However, considerable time and material resources are needed for corresponding experimental research. For simplification of experimental search, we have developed an approach for in silico identification of probable molecular mechanisms of action of drugs related with its side effects. We have created the set of NSAIDs containing 85 substances with data about structures and side effects. The computer program PASS (Prediction of Activity Spectra for Substances) predicting more than 3000 molecular mechanisms of action based on structural formula of substances was used to estimate unknown molecular mechanisms of action for these set of NSAIDs. Statistically significant relationships between predicted molecular mechanisms of action and development of peptic ulcers have been established. We have discovered twenty-six molecular mechanisms of action (two known previously and twenty-four new) which probably related with development of peptic ulcers. By analyzing of Gene Ontology data, signal and metabolic pathways, publications in Medline, we formulated hypotheses about the role of ten molecular mechanisms of action in pathogenesis of peptic ulcer.

Aspirin Synergistically Potentiates Isoflurane Minimum Alveolar Concentration Reduction Produced by Morphine in the Rat 

1998 ◽  
Vol 89 (6) ◽  
pp. 1489-1494 ◽  
Author(s):  
Ignacio A. Gomez de Segura ◽  
Ana B. Criado ◽  
Martin Santos ◽  
Francisco J. Tendillo
Keyword(s):  
Side Effects ◽  
Minimum Alveolar Concentration ◽  
Synergistic Effects ◽  
Objective Measure ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Before And After ◽  
Male Wistar Rats ◽  
Clinically Significant ◽  
Analgesic Potency

Background The combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. This synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. The aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. The reduction in minimum alveolar concentration of isoflurane (MAC(ISO)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination. Methods Thirty-seven male Wistar rats were anesthetized with isoflurane in oxygen, and the MAC(ISO) was determined before and after the intravenous administration of aspirin and morphine. Rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). The MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The duration of MAC(ISO) reduction was recorded. Results Aspirin did not have an effect on MAC(ISO), (average, 1.35+/-0.1%), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of MAC(ISO) reduction. Actual MAC(ISO+drug) data were as follows: 1 mg/kg morphine, 1.17+/-0.14%; 3 mg/kg morphine, 0.98+/-0.15%; 1 mg/kg morphine plus aspirin, 0.90+/-0.04%; 10 mg/kg morphine, 0.63+/-0.13%; and 3 mg/kg morphine plus aspirin, 0.64+/-0.06%. Conclusions The synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.

scholarly journals Colonic Side Effects of Nonsteroidal Antiinflammatory Drugs

1999 ◽  
Vol 38 (3) ◽  
pp. 219-220 ◽  
Author(s):  
Norihiro KAMINAGA ◽  
Adolfo PARRA-BLANCO ◽  
Rikiya FUJITA
Keyword(s):  
Side Effects ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs

scholarly journals Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-κB and NFAT transcriptional pathways

2015 ◽  
Vol 113 (2) ◽  
pp. 434-439 ◽  
Author(s):  
Nicholas S. Kirkby ◽  
Melissa V. Chan ◽  
Anne K. Zaiss ◽  
Eliana Garcia-Vaz ◽  
Jing Jiao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Side Effects ◽  
Constitutive Expression ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Cyclooxygenase 2 ◽  
Antiinflammatory Drugs ◽  
Activated T Cells ◽  
Nfat Activation ◽  
Cox 2 ◽  
Specific Tissue

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system.

Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis.

1994 ◽  
Vol 12 (12) ◽  
pp. 2756-2765 ◽  
Author(s):  
E Eisenberg ◽  
C S Berkey ◽  
D B Carr ◽  
F Mosteller ◽  
T C Chalmers
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Cancer Pain ◽  
Multiple Dose ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Efficacy And Safety ◽  
Antiinflammatory Drugs ◽  
Pain Scores ◽  
Multiple Doses ◽  
Dose Effects

PURPOSE To assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs). PATIENTS AND METHODS Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients. RESULTS Single-dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low- and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered. CONCLUSION These findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid analgesic alone) is warranted. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain.

scholarly journals Adverse Effects of Nonsteroidal Antiinflammatory Drugs: An Update of Gastrointestinal, Cardiovascular and Renal Complications

2014 ◽  
Vol 16 (5) ◽  
pp. 821 ◽  
Author(s):  
Sam Harirforoosh ◽  
Waheed Asghar ◽  
Fakhreddin Jamali
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Gi Tract ◽  
Antiinflammatory Drugs ◽  
Controlled Release Formulations ◽  
Gi Toxicity ◽  
Inflammatory Drugs ◽  
Cox 2

Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients. Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme. NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition. However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations. In addition, previously unpublished data stored in the sponsor’s files, question the GI sparing properties of rofecoxib, a COXIB that has been withdrawn due to cardiovascular (CV) side effects. Presently, the major side effects of NSAIDs are the GI complications, renal disturbances and CV events. There is a tendency to believe that all NSAIDs are associated with renal and CV side effects, a belief that is not supported by solid evidence. Indeed, lower but still therapeutics doses of some NSAIDs may be cardioprotective. In this review, we briefly discuss the GI toxicity of the NSAIDs and assess their renal and CV adverse effects in more detail. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Plants and Natural Compounds with Antidiabetic Action

2012 ◽  
Vol 40 (1) ◽  
pp. 314 ◽  
Author(s):  
Cristina COMAN ◽  
Olivia Dumitrita RUGINA ◽  
Carmen SOCACIU
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Side Effects ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Antidiabetic Therapy ◽  
Synthetic Drugs ◽  
Antidiabetic Effects

Diabetes has become the most common metabolic disease worldwide. In particular, type 2 diabetes is the most commonly encountered type of diabetes, which is characterised by the inability of the organism to respond to normal levels of circulating insulin, also called insulin resistance. Current antidiabetic therapy is based on synthetic drugs that very often have side effects. For this reason, there is a continuous need to develop new and better pharmaceuticals as alternatives for the management and treatment of the disease. Natural hypoglycaemic compounds may be attractive alternatives to synthetic drugs or reinforcements to currently used treatments. Their huge advantage is that they can be ingested in everyday diet. Recently, more attention is being paid to the study of natural products as potential antidiabetics. This mini review of the current literature is structured into three main sections focused on: (a) plant extracts, (b) plant biomolecules, and (c) other natural molecules that have been used for their antidiabetic effects. Potential molecular mechanisms of action are also discussed.

Peptic Ulcer Diseases

2015 ◽  
Author(s):  
Edward A Lew
Keyword(s):  
Peptic Ulcer ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Ulcer Formation ◽  
Peptic Ulcers ◽  
Antiinflammatory Drugs ◽  
Gastrointestinal Series ◽  
X Ray ◽  
Ulcer Disease ◽  
Chest X Ray ◽  
H Pylori

The etiology of peptic ulcers is generally related to impaired mucosal defenses in the presence of aggressive factors (e.g., gastric acid and pepsin). Major risk factors include infection with Helicobacter pylori and the use of nonsteroidal antiinflammatory drugs; high rates of acid secretion can also predispose to ulcer formation. The prevalence of peptic ulcers in Western countries has declined since the 1950s, a phenomenon that is likely due to a corresponding decrease in H. pylori infections among the general population. This review summarizes the epidemiology, etiology, diagnosis, and treatment of peptic ulcers. Figures show the etiopathogenesis of peptic ulcers, the approach to a patient who has new and undiagnosed ulcerlike symptoms, and images of a gastrointestinal series in which double contrast (barium and air) was used, as well as an upright chest x-ray of a patient with an acute abdomen caused by a perforated duodenal ulcer. Tables list the differential diagnosis of peptic ulcer disease and commonly used regimens to eradicate H. pylori. This review contains 3 highly rendered figures, 2 tables, and 35 references.

Recent Development on Anti-Obesity Compounds and their Mechanisms of Action: A Review

2020 ◽  
Vol 27 (21) ◽  
pp. 3577-3597 ◽  
Author(s):  
Yixing Qiu ◽  
Huanghe Yu ◽  
Rong Zeng ◽  
Shiyin Guo ◽  
Muhammad Daniyal ◽  
...  
Keyword(s):  
Weight Loss ◽  
Natural Products ◽  
Heart Disease ◽  
Side Effects ◽  
Small Molecules ◽  
Human Health ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
The Novel ◽  
Great Progress

Obesity, associated with a series of complications such as diabetes, hypertension, and heart disease, is a great threat to human health and leads to increased morbidity and mortality. Despite the presence of anti-obesity agents on the market, the application of these drugs is limited because of their typical side effects. More effective and safe weight-loss drugs are being pursued by many researchers, correspondingly, growing small molecules and natural products with anti-obesity effects have been identified and the molecular mechanisms underlying the action of the novel and known compounds have at least partially been revealed. Therefore, the field does witness great progress year by year. In this review, we intend to provide a comprehensive and updated view on the known and novel compounds which possess anti-obesity effects and further classify them according to the molecular mechanisms of their actions in regulating the major anti-obesity pathways.

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