Nonsteroidal anti-inflammatory drugs as potential ecto-nucleotide phosphodiesterase inhibitors

Phosphodiesterases (PDE) are group of enzymes which catalyze the hydrolysis of cAMP and cGMP. Since these cyclic phosphate moieties worked as intracellular second messengers in numerous physiological processes, their inhibition can affect normal physiology of living system. NSAIDs are among the frequently prescribed medications, because of their efficacy as analgesic, antipyretic and anti-inflammatory agents. They are known to block cyclooxygenase pathway. In limited data NSAIDs has been shown anti-tumor potential, and phosphodiesterase inhibition has assumed to be one of the mechanism. To date no further evaluation being done. Further, NSAIDs are classified as cyclooxygenase inhibitors and phosphodiesterase inhibition can imprint its side effects. This study first time investigates the effects of NSAIDs on phosphodiesterase 1 inhibition. The activity against snake venom phosphodiesterase 1 was assayed on a microtitre plate reader spectrophotometer. Selective COX-2 inhibitor, celecoxib, exhibited a potent PDE1 inhibitory activity, at therapeutic doses, with an IC50 value of 29.4 µM. The findings of our study are indicative of new pharmacological actions of cyclooxygenase inhibitors. This article presents the PDE inhibitory properties as a new effects of already existing drugs. These additional effects could be potentially helpful for researchers to assess other physiological and pathological states.

Respondiendo a la interrogante: ¿el metamizol es o no un antiinflamatorio no esteroideo? / Answering the question: is metamizole a non-steroidal anti-inflammatory or not?

Resumen: El objetivo de este artículo es determinar la importancia del metamizol como analgésico en México, al conocer la frecuencia de su uso y los mecanismos de acción y así clasificar adecuadamente al medicamento dentro de la farmacopea de analgésicos. Pocos fármacos generan discusión sobre su filiación, pero el metamizol, desde que salió al mercado en 1922 hasta el día de hoy, se mantiene sin definirse claramente. Comúnmente cuando se busca una clasificación de los antiinflamatorios no esteroideos (AINE), se clasifica al metamizol dentro de los mismos como derivados de la pirazolona. Se debe comenzar entonces con los aspectos farmacológicos para relacionar las semejanzas y diferencias con otros AINEs y poder sacar conclusiones adecuadas. Aun así, el medicamento es de los más utilizados por los médicos en los hospitales de segundo y tercer nivel (82%), aunque la mayoría no sabe en realidad cuál es su mecanismo de acción (91%), por ello, la importancia de conocer el mecanismo de acción de este fármaco.

Abstract: The aim of this article is to know the importance of metamizol as analgesic in Mexico, knowing the frequency of their use and the mechanisms of action and to adequately classify the drug in the pharmacopoeia of painkillers. Few drugs generate discussion about their parentage but metamizol from that hits the market in 1922 until today, it has no clearly defined. Commonly when NSAIDs rated seeks to metamizol is classified within the same as pyrazolone derivatives. We then start with the pharmacological aspects and later to know the similarities and differences with other NSAIDs and can draw appropriate conclusions. Even so, the medicine is one of the most used by physicians in second and third level hospitals (82%), although most do not really know what their mechanism of action is (91%), so the importance of knowing the mechanism of action of this drug.

Continuation of low-dose aspirin combined with rabeprazole on healing of peptic ulcer bleeding / 中国基层医药

Objective To investigate the effect of low-dose aspirin combined with rabeprazole on the healing of peptic ulcer after hemostasis with aspirin-related peptic ulcer bleeding,and to explore the independent factors associated with ulcer healing failure.Methods A total of 138 patients with acute upper gastrointestinal hemorrhage in the Department of Gastroenterology of the Second Affiliated Hospital of Fujian Medical University from June 2016 to June 2018 were enrolled.The clinical data of 138 patients with upper gastrointestinal ulcer bleeding caused by aspirin were analyzed.The patients were randomly divided into two groups.Aspirin group (n =68) received aspirin 100 mg/d plus rabeprazole 80 mg/d,while the placebo group (n =70) received rabeprazole 80 mg/d plus placebo.The patients were treated for 8 weeks.Subjects with H.pylori infection were treated with standard quadruple therapy.Follow-up endoscopy was performed at the end of 8 weeks.The primary endpoint was the healing of peptic ulcers.Results The ulcer healing rate was 79.4％ (54/68) in the aspirin group and 84.3％ (59/70) in the placebo group.There was no statistically significant difference between the two groups (x2 =0.552,P ＞ 0.05).There were 5 cases of ulcer bleeding in aspirin group and placebo group.The rehaemorrhage rate was 7.4％ (5/68) and 7.1％ (5/70),respectively.There was no statistically significant difference between the two groups(x2 =0.002,P ＞ 0.05).Among the factors affecting the healing of aspirin-associated peptic ulcer,the healing rate was significantly associated with steroid use during treatment (x2 =6.135,P =0.041) and smoking status (x2 =5.616,P =0.018).Other factors,including age,hypertension,diabetes,alcohol history,history of previous ulcer bleeding,initial Helicobacter pylori status,and ulcer location did not affect ulcer healing.Conclusion After aspirin-associated peptic ulcer bleeding,continued low-dose aspirin plus rabeprazole did not affect the healing of peptic ulcers,and the use of steroids and smoking status are independent risk factors for ulcer healing.

Effect of premedication with aceclofenac and ibuprofen on the success rate of two different local anesthetic agents in irreversible pulpitis cases of maxillary posterior teeth (a prospective randomized double-blind clinical trial)

A double blind, randomized controlled clinical trial was done to investigate the effect of analgesics aceclofenac and ibuprofen in reducing pre-operative pain following local anesthesia with lidocaine and articaine. One hundred and twenty patients with irreversible pulpitis of the maxillary premolars and first molar region were randomly divided into 2 groups with group 1, 2% lidocaine with 1:200000 epinephrine and group 2, 4% articaine with 1:100000 epinephrine. The two groups were again subdivided into 3 subgroups in which patients were given identical capsules containing ibuprofen 600 mg, aceclofenac 100 mg, placebo (vitamin tablets), half an hour before the administration of buccal infiltration anesthesia. Patients indicated their pain scores on a Heft Parker Visual analog scale (VAS). Infiltration anaesthesia was given under sterile condition.1 min after the injection, electric Imrana Tasneem, B.R. Bharat, Murari Uday Kumar, Srirekha A. Effect of premedication with aceclofenac and ibuprofen on the success rate of two different local anesthetic agents in irreversible pulpitis cases of maxillary posterior teeth (a prospective randomized double-blind clinical trial). IAIM, 2019; 6(5): 40-45. Page 41 pulp test and cold test were done and testing was repeated after every 2 minutes for a total of 10 minutes. Premedication with ibuprofen (600 mg) and aceclofenac (100 mg) resulted in statistically significant increase in onset of action for both the anesthetic agents. There was no significant difference in the time of onset of anesthesia between the two local anesthetic solution (chi-square test/ One way ANOVA).

Prescription pattern of analgesics in orthopedics outpatient department at a tertiary care hospital.

Background: Analgesics are the most common class of drugs prescribed for various conditions in the orthopedics outpatient department (OPD). This study is performed for a better understanding of analgesics prescribing pattern in orthopedics and to correlate the use of selective cyclooxygenase-2 (COX-2) inhibitors, conventional non-steroidal anti-infl ammatory drugs (NSAIDs), and opioid analgesics in practice in the present scenario. Methods: The prescriptions from the OPD of Orthopedics at Dr. B. R. Ambedkar Medical College was reviewed between June 2013 and November 2013, entered in a pre-designed proforma. Pain was quantifi ed using numeric rating scale. The type of analgesics administered, whether monotherapy or combined therapy and the duration of therapy, was analyzed to obtain an overview of the current prescribing pattern. Results: A total of 300 prescriptions were analyzed. 800 drugs were prescribed with an average of 2.6 drugs per prescription. Of these, 62.3% were NSAIDs, 15.4% were opioid analgesics and 22.3% were gastroprotective agents. 61% of the NSAIDs were prescribed as monotherapy and 39% were prescribed as fi xed drug combination (FDC). The ratio of selective to non-selective NSAIDs is 1.3:1. Conclusions: The results of the present study show frequent use of selective COX-2 inhibitors, although non-selective NSAIDs topped the list of various selective NSAIDs, non-selective NSAIDs, and opioid analgesics. This suggests that gastrointestinal safety was an important concern while prescribing these drugs. Many FDCs were found to be irrational.

Tratamiento acupuntural y medicamentoso en el alivio de la cervicalgia / Drug and acupuncture therapies in neck pain relieving

INTRODUCCIÓN: el dolor cervical es considerado como uno de los síntomas más relevantes del de espalda, con una incidencia del 10 % de la población adulta, lo cual influye en la calidad de vida de las personas. OBJETIVO: comparar la eficacia de la acupuntura y del tratamiento medicamentoso para el alivio de la cervicalgia no traumática. MÉTODOS: estudio comparativo, abierto y aleatorizado en 100 pacientes de ambos sexos mayores de 18 años, seleccionados aleatoriamente en el municipio Marianao. Se conformaron dos grupos de 50 pacientes cada uno; al grupo A se le aplicó tratamiento con acupuntura y al grupo B terapia con analgésicos y antiinflamatorios no esteroideos. La evaluación comparativa de los resultados se realizó por la prueba de Mc Gill modificada, al quinto día y al final del tratamiento. Para el análisis y el procesamiento de los datos se utilizó la prueba de chi cuadrado. RESULTADOS: no hubo diferencias significativas para el alivio del dolor a favor de alguno de los tratamientos aplicados, aunque los pacientes tratados con acupuntura refirieron la mejora del dolor cervical, además de un menor tiempo de tratamiento. CONCLUSIÓN: ambos tratamientos son igualmente eficaces para el alivio de la cervicalgia, pero el acupuntural deviene en una terapia electiva a considerar por la rapidez en el alivio del dolor.

INTRODUCTION: the high incidence of cervical pain at the consultations of health areas has motivated this study, which was carried out during year in patients with neck pain diagnosis. 10 % of the population suffers cervical pain in a specific moment of their lives; it represents an important factor for their professional lives. OBJECTIVE: to compare the acupuncture efficacy and the medical treatment for relieving non-traumatic neck pain. METHODS: a comparative, open and randomized study was conducted in 100 patients of both sexes older than 18 years. They were randomly selected in Marianao municipality. Two groups of 50 patients each were formed; group A had acupuncture treatment and group B therapy had analgesics and nonsteroidal antiinflammatory drugs. The result comparative evaluation was performed by Mc Gill modified test, on the fifth day and at the end of treatment. For data processing and analyzing, chi square test was used. RESULTS: there was no significant difference for pain relief in any of the treatments applied, although patients treated with acupuncture reported improvement neck pain, and a shorter treatment time. CONCLUSIONS: both treatments are equally effective for neck pain relief, but acupuncture therapy is an option to consider due to fast pain relief.

Ciprofloxacin induced fixed drug eruption.

Fixed drug eruption (FDE) is a clinical entity occurring in the same site or sites each time the drug is administered. Acute lesions appear as sharply marginated erythematous plaques, which are usually found on lips, genitalia, abdomen, and legs. The eruptions usually occur within hours of administration of the offending agent and resolves spontaneously without scarring after few weeks of onset. Most common drugs causing FDE are sulfonamides, tetracyclines, salicylates, barbiturates, doxycycline, fluconazole, clarithromycin, etc. Ciprofloxacin, a widely used fluoroquinolone antimicrobial, induces cutaneous adverse drug reactions (ADRs) in about 1-2% of treated patients. Urticaria, angioedema, maculopapular exanthems, and photosensitivity are the most frequently documented cutaneous adverse reactions. In this case report, the patient soon after taking ciprofloxacin tablets, developed itching in the lips, palms and in scrotal region. On continuing the treatment, the next day he developed fluid filled lesions over palm, knuckle, and hyperpigmentation. He gives a history of severe itching and rashes in scrotal region. He gives a history of similar complaints in the previous month after taking ciprofloxacin medication. There was no history of intake of any other medication. On examination, bullous lesions and pustules in finger webs, hyperpigmentation on knuckles, and scrotal erosions were seen. In the present case report, the patient presented with FDE immediately after oral administration of ciprofloxacin and got completely cured after stopping the drug and taking adequate treatment. According to the Naranjo’s ADR probability scale (score=8), this ADR is categorized as a “probable” reaction to the drug.

El dolor: los opioides: los anti-inflamatorios no esteroideos y los canabinoides / Pain: opioids: nonsteroidal antiinflammatory drugs and cannabinoids

Aquí exponemos un modelo que explica por qué, en el sistema nervioso central, los anti-inflamatorios no esteroideos, para ejercer su acción analgésica, deben interactuar con los opioides endógenos y los canabinoides endógenos. La sustancia gris del acueducto de Silvio es una estructura clave del llamado "sistema descendente de control nociceptivo". La activación de este sistema disminuye el flujo de mensajes nociceptivos hacia la corteza cerebral y, por lo tanto, el dolor. En la sustancia gris el ácido araquidónico es el elemento donde los opioides endógenos, los analgésicos opioides y los no-opioides (anti-inflamatorios no esteroideos) convergen para inducir analgesia. Las enzimas degradantes de los endocanabinoides son el punto donde estos y los analgésicos no-opioides convergen para inducir analgesia. Parece ventajoso el hecho de que los analgésicos que se compran libremente en la farmacia pueden aprovechar para su acción los mecanismos endógenos que todos nosotros poseemos

Here we present a model that explains why, in the central nervous system, the nonsteroidal antiinflammatory drugs, in order to induce analgesia, must interact with the endogenous opioids and the endocannabinoids. The periaqueductal gray matter is a key structure in the socalled "descending pain control system". Activations of this system diminishes the flow of nociceptive signals towards the cerebral cortex and, therefore, pain perception. In the periaqueductal gray matter, arachidonic acid is the elements where endogenous opioids analgesics and nonopioid analgesics converge to induce analgasia. The endocannabinoid metabolizing enzyme are the point at which endocannabinoids and nonsteroidal antinflammatory drugs converge to induce analgesia. There seems to be some advantage in that analgesics that can be bought over the counter can use for their action some endogenous mechanisms that we all possess

The role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis:a meta analysis / 中国综合临床

Objective To evaluate the efficacy of NSAIDs in the prevention and alleviation of postERCP pancreatitis and to provide theoretical basis for clinical practice and enhance the improvement of clinical studies on post-ERCP pancreatitis medication.Methods We performed extensive literature search from computerized databases MEDLINE(Jan.1966-Jan.2011),EMBASE(Jan.1966-Jan.2011) and the Cochrane Central Register of Controlled Trials(Issue 1,2011) using the key wordsendoscopic retrograde cholangiopancreatography or ERCP, NSAIDs or nonsteroidal anti-inflammatory drugs, pancreatitis,indomethacin anddiclofenac.The following primary outcomes were assessed:(1) Incidence of PEP;(2)Mortality of PEP;(3) Adverse events.Pooled odds ratio and 95％ confidence interval were computed using Revman version 4.3.2 from Cochrane.org web.Results Five multinational RCTs were included in our metaanalysis.There were in total 1119 patients involved in this meta-analysis,including 561 individuals in the treatment group and 558 participants in the placebo group.Among the patients in the treatment group,265 were treated by diclofenac and 296 were treated by indomethacin.The placebo group had same duration and dose of treatment with the treatment group.The prevalence of post-ERCP pancreatitis was significantly lower in the treatment group than in the placebo group(6.60％ vs.13.26％ ; OR =0.45 ; P ＜ 0.001).The pooled odds ratio for NSAIDs with mild PEP was 0.48(95 ％ CI:0.31-0.76 ; P =0.002) and the pooled odds ratio for NSAIDs with moderate to severe PEP was 0.44(P =0.08).Conclusion Based on the findings from the present systematic review of 5 RCTs,NSAIDs are effective and well tolerated in the prevention of PEP.

Gastropatía reactiva: Frecuencia en biopsias endoscópicas evaluadas en la Universidad Nacional de Colombia / Reactive gastropathy: Frequency in endoscopic biopsies evaluated at the Universidad Nacional de Colombia

La gastropatía reactiva (GR) es producida principalmente por antiinflamatorios no esteroideos (AINEs) y reflujo biliar; puede presentarse aisladamente o coexistir con otros tipos de gastritis crónica (GC). Se revisaron 5.079 informes de estudios histopatológicos de biopsias gástricas de 4.254 pacientes, 825 en seguimiento con 2 a 7 estudios. La GR correspondió a 12,8% de los diagnósticos, las GC no atrófica (GCNA) y atrófica multifocal (GCAMF) correspondieron a 63,4% y 27,3% respectivamente. La infección por Helicobacter pylori se presentó en 61,6% de casos con GCNA, 51,5% con GCAMF, 18,5% con GR (p < 0.0001); en casos con coexistencia de GR+GCNA fue 43,9% y de 40,7% para GCAMF+GR. En pacientes en seguimiento aumentaron los diagnósticos de GR: 2 estudios con 22,2%, 3 estudios con 26,7% y 4-7 estudios con 28,8%; los hallazgos histológicos de GR en estos casos posiblemente son residuales, luego de la desaparición de los infiltrados inflamatorios por el tratamiento.

Reactive gastropathy (RG) is primarily produced by non-steroid antiinflammatory drugs (NSAIDs) and bile reflux. It can occur alone or coexist with other types of chronic gastritis (CG). 5,079 histopathological reports of gastric biopsies from 4,254 patients were reviewed: 825 of them had 2 to 7 follow-up studies. 12.8% of these patients were diagnosed with GR while 63.4% were diagnosed with chronic non-atrophic gastritis (CNAG) and 27.3% were diagnosed with chronic multifocal atrophic gastritis (CMAG). Helicobacter pylori infections were found in 61.6% of the cases with CNAG, 51.5% with CMAG, and in 18.5% of cases with GR only (p <0.0001). Among patients suffering from both RG and CNAG 43.9% had H. pylori infections. 40.7% of those suffering from both CMAG and RG were infected with H. pylori. During monitoring of patients RG diagnoses increased to 22.2% in the second study, 26.7% in the third study, and 28.8% in the fourth through seventh studies. Histological findings of RG in these cases are probably residual following disappearance of inflammatory infiltrates due to treatment.

Actividad antiinflamatoria de productos naturales / Anti-inflammatory activity of natural products

Some natural products have been reported effects on the production of proinflammatory cytokines (IL-1b, IL-6, IL-8, GM-CSF and TNF-), enzyme mediators (MMP-3, MMP-13, iNOS and COX-2) and their catabolites (NO and PGE2). These activities have been associated with inactivation of NF-B by preventing IkBphosphorylation and degradation, or regulation of AP-1 transcription factors, which may be the mechanistic basis for the anti-inflammatory effects of some compounds. This article tries to review the behavior of various medicinal plants or isolated compounds, whose antiinflammatory action is known by previous trials carried in a number of in vivo and in vitro experimental inflammatory models.

Se ha reportado que algunos productos naturales presentan efectos sobre la expresión de: citoquinas proinflamatorias (IL-1b, IL-6, IL-8, GM-CSF and TNF-), enzimas mediadoras (MMP-3, MMP-13, iNOS y COX-2) y catabolitos (NO y PGE2). Esta actividad ha sido asociada con: la inactivación del NF-B, por la prevención de la fosforilación- degradación de IkBo la regulación ciertos factores de trascripción, entre otros, lo cual constituye el mecanismo de acción de tales compuestos. En este trabajo se da una visión general de la química y los diferentes modelos in vivo e in vitro de evaluación del proceso inflamatorio de compuestos de origen natural.

Cancer Pain Management-Nonopoid Analgesics

Cancer pain patients have various diagnosis, stage of disease, response to pain, and treatments and individualized treatment methods are thus needed. Use of Nonopioid analgesics is the first step treatment (according to WHO ladder) for mild to moderate pain, and may be useful for second or third step treatments when combined with weak or strong opioids to reduce side effects of opioids and to create synergy between the two drugs. Acetaminophen and nonsteroidal antiinflammatory drugs(NSAIDs) are also nonopioid analgesics. NSAIDs have a ceiling effect, along with antipyretic, analgesic and antiinflammatory effects, while not producing physical and psychological dependence. Adverse effects of NSAIDs include gastrointestinal hemorrhage, coagulopathy, and deterioration of renal function.

Empleo de antiinflamatorios no esteroideos (AINEs) como coadyuvante en el tratamiento de la enfermedad periodontal

Estudios previos han indicado que las drogas antiinflamatorias no esteroideas (AINEs) actúan en la modificación de la respuesta inflamatoria por parte del huésped. El propósito del presente trabajo es presentar una revisión bibliográfica relacionada con el empleo de los AINEs y su efectividad comprobada sobre la enfermedad periodontal. Se desarrollarán diversos aspectos dentro de los cuales se mencionarán la etiología y patogenia de la enfermedad periodontal, características de los AINEs, su clasificación, farmacocinética, farmacodinamia (haciendo énfasis en el mecanismo como antiinflamatorio), uso terapéutico, así como diferentes estudios experimentales sobre el uso de los mismos en animales y en pacientes con enfermedad periodontal.

This review presents information about nonsteroidal antiinflammatory drugs their clinical efficacy in the periodontal disease, doing emphasis on the indications, pharmaceutical preparations, classification and adverse effects which they can produce on the basis of scientific knowledge. This report describes the use of nonsteroidal antiinflammatory drugs as an adjunct to scaling and root planning in periodontal disease.

Survey on the clinical use of nonsteroidal antiinflammatory drugs in China / 中华消化杂志

Objective To acknowledge the present status of clinical use of nonsteroidal antiinflammatory drugs(NSAIDs) in China. Methods Five hundred and seventy-five valid questionnaires were collected from 50 hospitals in different areas of China including Shanghai, Beijing, Tianjin, Shenyang and Guangzhou. Results 54.7% of doctors used cyclooxygenase-2 (COX-2) selective inhibitors. The ratio of the doctors prescribing loxoprofen, diclofenac, meloxicam were 22.6%, 23.3%, 14.60%, respectively. The ratio of the doctors who prescribe uncoated routine-dose aspirin, uncoated low-dose aspirin, enteric-coated routine-dose aspirin, enteric-coated low-dose aspirin and others were 17.0%, 14.7%, 36.8%, 28.5% and 3.0%, respectively. The ratio of doctors who only "some-times" prescribed co-medicine to prevent gastrointestinal damages when they prescribed aspirin, conventional NSAID and COX-2 selective inhibitors were 41.10%, 40.70% and 45.1%, respectively, while the most commomly used co-medicine were H2 receptor antagonist (H2 RA) and proton pump inhibitor respectively. 37.1% of doctors examined H. pylori infection status, and 76.3% of doctors would eradicate H. pylori if positive. Conclusions The most commonly used conventional NSAID is diclofe-nac. The most commonly used formulation of aspirin is enteric-coated aspirin. Most doctors only "sometimes" prescribe co-medicine together with aspirin, conventional NSAID and COX-2 selective inhibitors to prevent gastrointestinal damages, and the most commonly used co-medicine is acid inhibitor. Only a few doctors examine H. pylori infection prior to the administration of NSAID.

Effect of aspirin and celecoxib on proliferation of breast cancer cell line MCF-7 / 吉林大学学报(医学版)

Objective To discuss and compare the anti-tumor effects of aspirin and celecoxib on breast cancer cell MCF-7 through investigating the effects of aspirin,celecoxib,and combined with anastrozole respectively on the growth of human breast cancer cell MCF-7.Methods The human breast cancer cell MCF-7 were treated with 2.5,5.0,and 10.0 mmol?L-1 aspirin and 30,60,and 120 ?mol?L-1 celecoxib for 24,48,and 72 h respectively,the MCF-7 without treatment with drug was used as negative control group,the MCF-7 treated by ADM was used as positive control group,the inhibitory effect was detected by MTT assay.Besides,the MCF-7 cells were treated by anastrozole(0.5 and 1.0 ?mol?L-1),anastrozole(0.5 and 1.0 ?mol?L-1)combined with aspirin(2.5,5.0,and 10.0 mmol?L-1)or celecoxib(30,60,and 120 ?mol?L-1)for 48 h,respectively,the inhibitory rate was detected by MTT assay.Results ① The inhibitory rate of the MCF-7 cell line treated with aspirin was reduced compared with controls,which was in time-dependent and dose-dependent manner(P

Nonsurgical Treatment of Osteoarthritis

Osteoarthritis (OA) is the most common cause of localized or generalized joint pain in adults. OA is a condition that represents a complex of interactive degradative and reparative processes in the cartilage and bone with secondary inflammatory changes, particularly in the synovium. Although there is no known cure for OA, the treatment designed for the individual patients can reduce pain, maintain joint mobility, and limit the functional impairment. Guidelines for the treatment of OA include patient education and physical and occupational therapy. Weight loss has been shown to slow the progression of disease and to relieve symptoms in obese patients with OA of the knee. While low-impact exercise is beneficial, the adverse effects of high-impact and high-intensity activitiesy on the aggravation of OA have been documented. Most drug therapies with drugs are targeted to specific symptomsatic response. It is certainly worthwhile to initiate a trial of acetaminophen, known to be beneficial in OA patients with mild to moderate pain, on the basis of the risk-to-benefit ratio and cost. However, previous studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a better efficacy. The COX-2-specific inhibitors appear to be better tolerated, with a lower incidence of GI side effects, than comparator nonselective NSAIDs. However, the potential cardiovascular thrombotic events of these medications are considerable in the patients with hypertension or coronary artery disease. Although a number of agents are on the horizon, including glucosamine, chondroitin, diacerein, S-Adenosyl-LMethionine, and hyaluronan, no agent has been shown to have a disease-modifying OA drug (DMOAD) effect at this time.

Comparison of Clinical Efficacy between Nonsteroidal Anti-inflammatory Drugs and Acetaminophen in Knee Osteoarthritis according to Ultrasonographic Findings / 대한류마티스학회지

OBJECTIVE: To compare the clinical efficacy between nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen in knee osteoarthritis according to ultrasonographic findings. METHODS: We administered 12 mg of NSAIDs (lornoxicam) plus misoprostol 300microgram or 1,950 mg of acetaminophen in 40 randomly selected patients who fulfilled the ACR criteria for knee osteoarthritis. The effectiveness of these drugs on osteoarthritis was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. In addition, we performed ultrasonography of the knee joints and assessed length of capsular distension, length of medial and lateral osteophyte, amount of joint effusion, and the presence of synovial proliferation. RESULTS: There were significant correlations between WOMAC score and length of capsular distension and length of medial/lateral osteophyte. At 6 weeks, both lornoxicam and acetaminophen-treated patients had significant lower levels of WOMAC score compared to the entry into the trial (p or =0.7 cm) or severe medial osteophyte (length of osteophytes > or =0.4 cm) showed better responses to lornoxicam than to acetaminophen in terms of the reduction of WOMAC score (p=0.008 for severe capsular distension, p=0.03 for severe medial osteophyte). However, in the subgroup with mild forms of capsular distension (<0.7 cm) or medial osteophytes (<0.4 cm), no difference was found in the reduction of WOMAC score 6 weeks after treatment with lornoxicam versus acetaminophen. CONCLUSIONS: Patients with osteoarthritis of the knee had significantly greater improvements in pain score over 6 weeks with lornoxicam than with acetaminophen, particularly in patients with severe forms of capsular distension and medial osteophyte on joint ultrasonography. Ultrasonography could be an useful tool to determine the usage of NSAIDs versus acetaminophen in knee osteoarthritis patients.

Efficacy of Topical NSAIDs and Anesthetic Drug in Reducing Post-PRK Pain: Comparative Study

To evaluate the efficacy and safety of topical NSAIDs and topical anesthetics on post-PRK pain control, we performed a prospective, randomized, paralle group, placebe-controlled study of 105 consecutive eyes having excimer laser PRK, that were divided into 7 pain management groups. The groups were arranged in order, Group 1: Suprofen(Profenal), Group 2: Diclofenac I(Naclof), Group 3: Diclofenac II (Decrol), Group 4: diluted proparacaine, Group 5: Diclofenac I(Naclof)+diluted proparacaine, Group 6: Fluorometholone, Group 7(conrol): Tears Naturale. Results were evaluated by several types of questionnaires and pain score was recorded using visual analogue scale. Corneal epithelial defect area was measured on post-operative day 1, 2, 3, 4 and 1 week. Diclofenac-treated groups showed the best analgesic effect and the least discomfort at instillation. Diclofenac, used with diluted proparacaine, had some additive effect on pain control, but not statistically significant. Full epithelial closure occurred in all eyes within 4 days without any clinically significant complications. Topical diclofenac and combinatin with diluted proparacaine can be used in post-PRK pain management effectively and safely.

A Case of Segmental Ischemic Colitis Associated with Nonsteroidal Antiinflammatory Drugs / 대한류마티스학회지

Acute colonic ischemia is the most common form of gastrointestinal ischemia. The majority of cases of non-occlusive ischemic colitis are associated with severe congestive heart failure with low cardiac output, or disease states resulting in dehydration, or the splanchnic vasoconstrictive effect of some dedications. Reactive splanchnic vasoconstriction is responsible for nonocclusive ischemic colitis. The authors report a case of 37-year-old man, who had a history of 8-year gout and no evidence of heart disease or severe dehydration and developed segmental ischemic colitis during nonsteroidal antinflammatory drug treatment, which ultimitely progressed to transmural infacrction, therby undergone extended right hemicolectomy

The antiinflammatory effects of an adenosine / 中国药理学通报

Adenosine is an endogenous purine uncleoside released by cells as part of the normal metablic mechinary. During inflammation, massive ATP degradation increases the local adenosine concentration to the micromolar range, at the range, adenosine extert potent antiinflammatory rale. In vivo or in vitro experiments, the addition exogenious adenosine, its analogues and inhibition of its degradation attenuate injury of animal models of inflammation. Antiinflammatory mechinasms involve in;(1)Adenosine inhibites neutrophil function in vitro, including chemotaxiz, adhesion, phogocytosis, and oxygen radical generation. (2) Decrease the expression of collagenase, and reduce the amount of collagenase. (3)Blocking neutrophil adhesion to the endothelium mediated by L-selectin and ftrEategrin. (4)inhibition activated humanmonocytes and macrophage secreting cytokins. (5) Adenosine enhances IL-10 secretion by human monocytes. (6)inhibition of immune response and so on. Relation with nonsteroidal antiinflammatory drugs (NSALDs) includes:(1)MTX and SASP inhibit the activity of 5-aminoimidazole-4-carboxam-ide ribonucleotide (AICAR) transformylase resulting in increased local adenosine concentraton. (2) Azathioprine and its potential metabolite inhibits adenosine kinase, diminish AMP formation by adenosine. In conclusion, the existance of a novel class of antiinflammatory agents, affects adenosine metabolism and may be a useful antiinflammatory drug as well.