Lege Artis Medicinae

[PHARMACEUTICAL PREVENTION OF THE UPPER GASTROINTESTINAL SIDE-EFFECTS OF NSAID THERAPY]

HERSZÉNYI László, TULASSAY Zsolt

NOVEMBER 30, 2004

Lege Artis Medicinae - 2005;15(01 klsz)

[Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation in patients with rheumatoid arthritis and osteoarthritis. However, they are also associated with a significant risk of gastrointestinal events with clinical and economic consequences. It is mandatory to rationalise the use of different NSAID treatment strategies in patients with varying degrees of gastrointestinal and cardiovascular risk. In patients for those aged <65 years with no previous gastrointestinal event and not concurrently on aspirin (low risk patients), the use of an NSAID should be considered as appropriate. For patients with a previous gastrointestinal event (high risk patients) or who concurrently received aspirin, an NSAID alone should be rated as inappropriate and either a coxib or selective cyclooxygenase-2 inhibitor, or an NSAID + proton pump inhibitor combination is considered as appropriate. Finally, for patients aged >65 years with a previous gastrointestinal event and on aspirin (patients with very high risk) a coxib in conjunction with a proton pump inhibitor is considered to be the best therapeutic strategy.]

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[Changes to Gastroenterology Specialist Training Following Hungary’s Accession to the European Union]

LONOVICS János

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[FROM ASPIRIN TO COXIBS - JANUS-FACE OF THE NONSTEROIDAL ANTI-INFLAMMATORY THERAPY]

NEMESÁNSZKY Elemér

[Since the introduction of aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) proved to be the most commonly used drugs in the world. One of the major factors limiting their use is gastrointestinal toxicity. It has long been recognised that NSAID use is associated with serious, sometimes life-threatening adverse effects, like gastrointestinal ulcers, bleeding and perforation. Recent studies have indicated that the combination of NSAID and aspirin significantly increases the risk of complications. Aspirin is like a two-edged sword, balancing cardiovascular prevention with the risk of gastrointestinal side effects. Past history of ulcer carries the highest individual risk and other contributing factors include age, concurrent anticoagulation, cortocisteroid therapy, as well as high-dose or multipleforms of NSAID use. The mechanism of action of NSAID is to inhibit prostaglandin production through cyclooxygenase (COX). The inhibition of COX-2 isoenzyme reduces inflammatory-mediated prostaglandins, while the inhibition of COX-1 reduces the level of prostaglandins needed for normal protecting mechanism of the gastric mucosa. Non-selective NSAID has impact on both COX-enzymes, while selective COX-2-inhibitors (such as coxibs) exert their effects without affecting mucosal defence significantly. It is important to note that the risk of complications can not be reduced to zero by any therapeutic approach. The most appropriate treatment modality is to administer PPI co-therapy for the sake of gastro-protection, especially in high-risk cases. Histamine-2-receptor antagonists are not effective in reducing ulcer and complication in that particular group of patients. It has turned out that the inhibition of the synthesis of COX-2 by rofecoxib increases the risk of developing thromboembolic events and myocardial infaction. This has led to the withdrawal of Vioxx from the market on 30. 09. 2004. Studies conducted in recents years shed new light on numerous beneficial effects of NSAID other than alleviate pain, cure inflammatory processes and diminish higher temperature. The incidence of colon polyps and adenomas as well as cancers is reduced among people who are on maintanance NSAID therapy. The process of stone formation in the biliary tract is also reduced in patients who are on NSAID treatment. Development of Alzheimer's disease seems to be hindered, however, this finding can not yet be considered as evidence based.]

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[Gastrointestinal Protective Efficacy of Esomeprazole Comparative Studies in the International Literature]

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[NOVEL ASPECTS OF COX-2 SELECTIVE NON-STEROIDAL ANTI-INFLAMMATORY DRUG THERAPY]

MŰZES Györgyi

[The cyclooxygenase (COX) metabolic pathway and prostaglandin production appear to play a causal role in the promotion and progression of human cancers. Recently COX-2 has received a great deal of interest since it is frequently overexpressed in a wide spectrum of cancers and precancerous lesions. Furthermore, elevated production of prostanoids (particularly PGE2) via COX-2 is associated with several pro-carcinogenic effects including increased proliferation, apoptosis resistance, tumor neoangiogenesis and invasiveness, host immunosuppression, and altered xenobiotic metabolism. Inhibitors of COX-1 and COX-2 (aspirin and most other nonsteroidal anti-inflammatory drugs) and of COX-2 alone (e.g. coxibs) have shown cancer preventive efficacy in epidemiological studies, experimental studies and in human clinical trials. Due to their improved side effect profile, COX-2 selective inhibitors appear to hold substantial promise for long-term administration in the setting of cancer prevention. Emerging data suggest that these agents may have potential in cancer treatment as well. In addition recent results indicate that COX-2 enzyme is also overexpressed in inflammatory processes of the central nervous system, e.g. in Alzheimer’s disease, so its suppression could offer a possible new therapeutic strategy even in the prevention and treatment of Alzheimer’s disease.]

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[GASTROINTESTINAL COMPLICATIONS OF LOW-DOSE ASPIRIN TREATMENT]

RÁCZ István

[Since its synthesis more than 100 years ago aspirin has become one of the most successful drug. Low-dose, long-term aspirin therapy reduces the risk of myocardial infarction, the frequency of cerebral stroke and also reduces the mortality of peripheral arterial diseases and systemic embolisms. With aspirin therapy becoming more and more widespread current knowledge is also getting more concerned about the gastrointestinal risks and beneficial effects. Aspirin therapy causes gastrointestinal damages by the inhibition of endogenous prostaglandin synthesis. The ion trapping effect and the injury of mucosal barrier as well as the inhibition of platelet aggregation are also responsible for gastrointestinal damages. According to epidemiological studies lowdose aspirin treatment increases the risk of acute upper gastrointestinal bleeding by 1.5-2.0 fold. However, endoscopic studies indicate that gastroduodenal ulcers may develop even in 10 percent of cases on long term aspirin treatment, most frequently in a symptom-free form. Older age as well as Helicobacter pylori infection increase the risk of aspirin induced ulcers. Beside Helicobacter pylori eradication therapy, preventive proton-pump-inhibitor treatment and the widespread of new non-toxic aspirin derivates may decrease the risk of gastrointestinal complications. Capsule endoscopy also seems to be a promising diagnostic tool for detecting aspirin induced small bowel erosions and ulcers. Long-term aspirin treatment increases the risk of acute bleeding from large bowel diverticulas especially with non-steroidal anti-inflammatory drug co-therapy present. Long-term, low-dose aspirin treatment is a promising method for the chemoprevention of colorectal cancers.]

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[TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE]

PAPP János

[In the acidic type of gastroesophageal reflux disease treatment is based on the use of proton pump inhibitors. Efficiency of the treatment is primarily assessed by the changes in symptoms. A long-term, continuous drug use is invariably necessary. In typical cases an increased dose or combination therapy is rarely required, however, in the presence of extraesophageal symptoms, the use of higher doses has been found to be beneficial. The minimum efficient drug amount is usually determined by gradually decreasing the dose. Surgery is mainly recommended for young patients, but it is indispensable in the management of complications or in volume reflux. Endoscopic antireflux therapy is still considered a clinical trial. Treatment of Barrett’s oesophagus by drugs or antireflux surgery does not decrease the incidence of Barrett’s cancer - the mostly recommended approach is endoscopic ablation.]

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[GASTROINTESTINAL COMPLICATIONS OF LOW-DOSE ASPIRIN TREATMENT]

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[NSAID-ASSOCIATED GASTROPATHY: RECENT ASPECTS OF PREVENTION]

HERSZÉNYI László

[Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide. Gastroduodenal ulcers are found at endoscopy in 15 to 30% of patients who use NSAIDs regularly. The annual incidence of severe upper gastrointestinal complications such as bleeding or perforation is 1.0 to 1.5%. From a cost-benefit perspective, prevention strategies should consider both gastrointestinal, and recently, cardiovascular risk factors. No prophylaxis is necessary with low gastrointestinal risk. There are currently four possible strategies to reduce the risk of adverse gastrointestinal effects: 1. the use of selective COX-2 inhibitors or coxibs rather than traditional NSAIDs; 2. cotherapy, primarily with proton pump inhibitors, to ensure protection to gastric mucous membrane; 3. co-therapy with a coxib and a proton pump inhibitor in patients with very high risk (eg., history of bleeding); 4. eradication of Helicobacter pylori infection in patients with a history of ulcer. The use of coxibs decrease the risk of gastrointestinal damage by roughly 50%. In the presence of gastrointestinal risk factors or for patients on aspirin also treated with an NSAID or a coxib, protection with a proton pump inhibitor is recommended. Proton pump inhibitor therapy is also useful for the prevention and treatment of NSAID-induced dyspepsia. The beneficial effects of proton pump inhibitors cannot solely be explained by their profound antisecretory action. Therefore, several acid secretion- independent mechanisms of action have been proposed.]

Lege Artis Medicinae

[THE INFLUENCE OF GASTROESOPHAGEAL REFLUX DISEASE AND ITS TREATMENT ON ASTHMATIC COUGH]

BÖCSKEI Csaba, VICZIÁN Magdolna, BÖCSKEI Renáta, HORVÁTH Ildikó

[INTRODUCTION - Gastroesophageal reflux is known to cause chronic cough and it is also implicated in worsening of asthma. We conducted a prospective study to examine the clinical significance of gastroesophageal reflux disease in asthmatic patients with chronic cough, to analyse the temporal relationship between reflux events and coughing and to assess the effect of esomeprazole treatment on respiratory symptoms and lung function in these patients. PATIENTS AND METHODS - 126 asthmatic patients with chronic dry cough were studied. Diagnosis of gastroesophageal reflux disease was based on typical symptoms and the effectiveness of therapeutic test or on pH monitoring, while control group consisted of the patients without gastroesophageal reflux (negative pH results). The study group patients received the proton pump inhibitor esomeprazole (40 mg/day for three months) and standard treatment for asthma was continued. During the study pulmonary function tests (forced expiratory volume in one second and peak expiratory flow) were evaluated four times and the reflux symptom scores as well, using a questionnaire. RESULTS - The results of pH monitoring showed that 64% of cough episodes were related to acid reflux and in 91% of reflux events preceded coughing. Esomeprazole treatment (40 mg/day for three months) not only diminished gastroesophageal reflux symptoms but also improved asthma outcome measures. Baseline pulmonary function values increased significantly together with a decrease in symptom scores and the use of rescue medication. In most patients included in the extended part of the study for another three months, the dose of inhaled steroids could be reduced with sustained therapy against gastroesophageal reflux. CONCLUSION - Our data shows that reflux events preceded coughing in most cases and that treatment of gastroesophageal reflux disease caused an improvement in different outcome measures of asthma suggest that gastroesophageal reflux disease worsens asthma and its treatment is of clinical importance in the effective management of these patients.]

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[THE EFFECTS AND SIDE-EFFECTS OF COXIBS IN THE RHEUMATOLOGICAL PRACTICE]

GÉHER Pál

[The author reviews the various tools of pain control in rheumatic disorders, with special attention to the pharmacological modalities, focusing on the use of cyclo-oxygenase inhibitors (coxibs). The new pain control drugs have different side-effect profiles, and even though these are more favourable than those of the traditional drugs, not all of them meet the strict safety requirements. The new drugs that are available in Hungary have a lower gastrointestinal side effect risk than the traditional nonsteroidal anti-inflammatory drugs, still with comparable effectiveness. The non-steroidal antiinflammatory drugs - including the selective cyclo-oxygenase inhibitors - increase the risk of cardiovascular disease, though to varying extent. When choosing a drug to control pain and inflammation in the diseases of the locomotor system, the physician should balance between the effectiveness and the most common side effects (gastrointestinal, cardiovascular).]