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Aspirin ulcer: Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment

Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment

J Multidiscip Healthc. 2014; 7: 137–146.

Byron Cryer

1University of Texas Southwestern Medical School, Dallas, TX, USA

Kenneth W Mahaffey

2Department of Medicine, Stanford University, Stanford, CA, USA

1University of Texas Southwestern Medical School, Dallas, TX, USA

2Department of Medicine, Stanford University, Stanford, CA, USA

Correspondence: Byron Cryer, University of Texas Southwestern Medical School, 5223 Harry Hines Blvd, Dallas, TX 75390-8504, USA, Tel +1 214 648 2590, Email [email protected] © 2014 Cryer and Mahaffey. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) LicenseThe full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.This article has been cited by other articles in PMC.

Abstract

Peptic ulcer disease is a major cause of morbidity and mortality in the US with more than six million diagnoses annually. Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI) bleeding and are often a clinical concern due to the widespread use of aspirin and nonsteroidal anti-inflammatory drugs, both of which have been shown to induce ulcer formation. The finding that Helicobacter pylori infection (independent of aspirin use) is associated with the development of ulcers led to a more thorough understanding of the causes and pathogenesis of ulcers and an improvement in therapeutic options. However, many patients infected with H. pylori are asymptomatic and remain undiagnosed. Complicating matters is a current lack of understanding of the association between aspirin use and asymptomatic ulcer formation. Low-dose aspirin prescriptions have increased, particularly for cardioprotection. Unfortunately, the GI side effects associated with aspirin therapy continue to be a major complication in both symptomatic and asymptomatic patients. These safety concerns should be important considerations in the decision to use aspirin and warrant further education. The medical community needs to continue to improve awareness of aspirin-induced GI bleeding to better equip physicians and improve care for patients requiring aspirin therapy.

Keywords: low-dose aspirin, cardioprotection, ulcers, Helicobacter pylori, gastrointestinal bleeding, cardiovascular disease

Introduction

Peptic ulcer disease (PUD) has evolved as a major cause of morbidity and mortality throughout the 20th and 21st centuries,1 with more than six million people affected each year in the US alone.2 Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI) bleeding3 and remain an important clinical problem due to the increasingly widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are known to induce ulcers.1 The most common ulcers associated with PUD arise in the stomach, duodenum, and jejunum, with gastric ulcers presenting most frequently ().2 Although ulcers are widely diagnosed and recognized, asymptomatic ulcers remain a pressing problem and may lead to long-term damage to the GI tract. While the risk of symptomatic ulcers with aspirin is well defined, the association between aspirin and asymptomatic ulcer formation remains less clear.

Hospitalizations based on ulcer type from 1998–2005.

Note: Data from Feinstein et al.2

The general understanding of ulcer formation greatly changed with the discovery of Helicobacter pylori in 1982. Since the discovery of H. pylori, the causes and pathogenesis of ulcers are better understood and the treatment protocols have evolved. The belief that ulcers develop due to an acid-driven mechanism was transformed to an understanding that H. pylori and aspirin are both important contributors to ulcer development. Now ulcer treatment efforts should focus on H. pylori eradication by antibiotics1 and reduction of aspirin’s contribution to ulcer pathogenesis. Strikingly, more than 50% of the population worldwide has chronic H. pylori infection, and an estimated 5%–10% of these persons will develop symptomatic ulcers.1 Although infection with H. pylori is commonly associated with PUD, many of those infected are asymptomatic and, therefore, remain undiagnosed.4 Undiagnosed peptic ulcer perforation is recognized as a cause of severe complications, such as perforations, and can result in death.5,6 Although symptomatic ulcers may be masked or delayed in some high-risk patients by using appropriate GI protection therapy, any delay in making the correct diagnosis may result in increased risk of complications and mortality. Among patients with symptomatic ulcers, nearly 30% of associated upper GI events result in hospitalization or death,7–9 and the total direct and indirect costs for PUD have been reported to be approximately $3.4 billion.10 Thus, evaluation of patients with ulcers for H. pylori infection is an important step in reducing the progression of uncomplicated ulcers to ulcers with complications.

H. pylori infection and NSAID (including aspirin) use are independently associated with adverse GI effects ranging from mild dyspepsia to serious GI bleeding, and may additively increase the risk of PUD.11 Other causes of PUD exist, but are much less common ().12 Aspirin is a common cause of ulcers, even in patients not infected with H. pylori.13 With administration of daily low-dose aspirin (LDA), GI mucosal damage14–16 occurs in approximately 40%–50% of patients; increased risk of GI bleeding17 is also observed. These risks typically peak closer to the beginning of therapy and increase with patient age.17,18 History of GI bleeding is important to consider, as 15% of patients who have bleeding from ulcers report recurrent bleeding within 1 year.19 As such, physicians should be cognizant of the potential for their patients to develop asymptomatic ulcers throughout the course of aspirin administration during cardiovascular disease therapy. In rare cases, patients who are negative for H. pylori and who have no history of aspirin use can develop ulcers.1 Due to the additive nature of these factors, all patients presenting with an ulcer, regardless of whether they are taking aspirin, should be tested for H. pylori infection to determine the best treatment plan.11

Table 1

General classifications of peptic ulcers

Aspirin use H. pylori infection


Yes No
Yes H. pylori and aspirin-positive Aspirin-induced
No H. pylori-positive Other rare causes
– Acid hyper-secretion (eg, Zollinger-Ellison syndrome)
– Tumors
– Crohn’s disease
– Viral infections
– Idiopathic ulcers

For some patients, the clinical consequences beyond GI bleeding may be severe. Patients who continue to exhibit persistent symptoms of PUD should be referred for upper endoscopy. While GI bleeding is a common indication for surgery, the development of complications from PUD, unresponsiveness to therapy or a need for multiple rounds of medical therapy for ulcers, and high-risk factors (eg, history of PUD, dependence upon steroid or NSAID therapy) may increase the need for surgery. Surgical options for these patients include gastroduodenotomy and oversewing of the blood vessel, and excision of the ulcer with vagotomy and drainage/partial gastrectomy in bleeding gastric ulcers.20 If endoscopy is unsuccessful (ie, bleeding continues) or patients are not candidates for surgical intervention, angiography is an option.21

Aspirin-induced ulcers

Aspirin is among the most widely used medications in the US22 and is administered for an extensive variety of indications. Further, it is readily available over the counter.23 Aspirin originated as a medication to treat pain and inflammation, but due to its antiplatelet properties, it has evolved into a drug commonly used to prevent cardiovascular disease. Standard doses of aspirin ranging from 500 to 1,000 mg daily are mostly prescribed for inflammatory conditions and pain relief, whereas doses between 75 and 325 mg daily are usually prescribed as antiplatelet therapy for primary and secondary prevention of cardiovascular and cerebrovascular events.24,25 While the LDA for cardiovascular disease refers to doses <300 mg or <162 mg, it will be categorized as ≤325 mg for the purpose of this review.

All antithrombotic agents increase bleeding; aspirin, in particular, significantly increases the risk of major bleeding by about 60%.26 LDA is associated with intracranial or major extracranial events27 as well as prolonged bleeding;24 however, some of the most common side effects from aspirin are related to the upper GI tract. These range from mild conditions, such as dyspepsia, to more severe side effects, such as PUD and severe GI bleeding.24 Chronic aspirin consumption is associated with lower GI bleeding in more than 50% of aspirin users, indicating that GI injury is not only limited to the upper GI tract.28 Overall, aspirin has emerged as one of the most prominent causes of peptic ulcer bleeding in developed countries over the last 2 decades,29 and is associated with a 2- to 4-fold increased risk of upper GI bleeding and ulcers.30

Aspirin and H. pylori induce ulcers by different mechanisms, and the combination of the two can greatly increase the risk of ulceration ().31 Theoretically, aspirin and H. pylori may interact in many ways to influence ulcer formation, yet H. pylori infection is not required for aspirin-associated ulcers to develop.12 Specifically, GI damage attributable to aspirin use is typically caused by a combination of epithelial and microvascular effects with little or no inflammation, while H. pylori ulcers are usually associated with diffuse inflammatory cell infiltration.12 LDA causes GI mucosal and systemic effects from prostaglandin depletion via inhibition of cyclooxygenase-1,30,32,33 but the relative contributions of local versus systemic effects of aspirin-related GI injury remain to be fully elucidated.34 Prostaglandins play a pivotal role in protecting gastric mucosal integrity via increasing local blood flow and promoting synthesis and secretion of mucus and bicarbonate. In the absence of normal prostaglandin synthesis, the gastric environment becomes more vulnerable to exogenous (eg, smoking) or endogenous factors (H. pylori, acid, pepsin, bile salts) and, consequently, more prone to develop peptic ulcer and bleeding complications.35 The acidic environment causes aspirin to remain nonionized, forcing it to accumulate in gastric mucosal cells, which alters the permeability of the cell and causes ulceration.30 Within only minutes of aspirin administration, topical gastric mucosa effects can be visualized by endoscopy.36 Additionally, LDA promotes GI bleeding via its antiplatelet effect.30

Model of peptic ulcer formation. In the stomach, both Helicobacter pylori and aspirin are able to induce gastric ulcer formation. Proton pump inhibitors act to reduce gastric acid production, thereby reducing ulceration in the stomach lining.

Abbreviations: ASA, aspirin; H+, hydrogen; PPI, proton pump inhibitor; H. pylori, Helicobacter pylori.

Major risk factors for upper GI events associated with aspirin use include a history of peptic ulcer or bleeding ulcer,37–42 concomitant use of other NSAIDs or antithrombotics,38,40,43–46 and H. pylori infection ().39,47–49 Other factors that may increase the risk of peptic ulcers are smoking, excessive alcohol consumption, drug use, and emotional stress. These factors are considered to be environmental, as they contribute to ulcer formation by increasing gastric acid secretion, ultimately resulting in a weakened mucosal barrier.1 Among the risk factors for LDA-associated ulcer bleeding, H. pylori infection is one of the few that are treatable and curable.29 Combination therapy of aspirin with other anti-platelet or anticoagulant therapy is increasingly common and includes dual antiplatelet therapy in patients treated with coronary stents or after acute coronary syndrome,50,51 in patients with cardiovascular disease who are on anticoagulant therapy for atrial fibrillation,52 or other indications. Dual antiplatelet therapy has clearly been shown to increase bleeding risk.53 Meta-analyses and randomized clinical trials have demonstrated that, while effective in management of cardiovascular disease,54 dual therapy can increase the risk of major bleeding events.55–58

Table 2

Risk factors for aspirin-induced ulcers

Aspirin-relateda
 High aspirin dose
 Concomitant use with
  – Other NSAIDs
  – Corticosteroids
  – Anticoagulants
   • Ticagrelor
   • Prasugrel
   • Clopidogrel
 Triple antithrombotic therapy (aspirin, clopidogrel, and warfarin)
Patient-related
Helicobacter pylori infection
 History of peptic ulcer disease or GI bleeding
 Older age
 Presence of severe comorbidities

Patients who require triple therapy (dual antiplatelet therapy and anticoagulant therapy) face unique clinical challenges and an increased risk of bleeding.59 Many studies have demonstrated a higher risk for bleeding,60–64 with the number of minor and major bleeds reported to be as high as 27.5%.63–66 As a result of these findings, the most critical element when determining the duration of triple therapy appears to be the risk of bleeding.67 US Food and Drug Administration approval of several new oral anticoagulants (dabigatran, apixaban, and rivaroxaban), as well as the ease of use of these agents, may eventually increase the use of anticoagulant therapy compared with current practice patterns with warfarin. It is clear that intracranial hemorrhage is reduced significantly with these agents compared with warfarin. GI side effects and bleeding events may be increased compared with warfarin.68,69 Further work is needed to better understand these observations and strategies to minimize patient risk.

Ulcer diagnosis

Several symptoms are associated with the diagnosis of ulcers, including epigastric pain, fullness, bloating, premature satiety, weight loss, and nausea.1 In some cases, these symptoms are associated with other illnesses, such as gastroesophageal reflux disease, general dyspepsia, or gastritis, which makes evaluation more challenging. Asymptomatic ulcers may go undetected until clinical presentation of a GI bleed.1 Physicians, including cardiologists, may be unaware of the occurrence of asymptomatic ulcers in patients taking LDA for cardioprotection, as these patients do not present with clinical signs or concerns after beginning the aspirin regimen. Awareness of PUD risk factors may help clinicians to identify patients at risk for ulcer formation and initiate appropriate gastric protection therapy.

All patients with an ulcer, regardless of whether they are taking aspirin, should be tested for H. pylori infection to determine the best treatment.11 Surprisingly, up to 35% of patients at high-risk for GI bleeding are neither tested for H. pylori infection nor given proton pump inhibitor (PPI) gastroprotection during the course of their NSAID therapy.49 Several invasive (eg, histology, rapid urease testing) and noninvasive (eg, antibody detection, nonendoscopic urease testing, fecal antigen testing) methods are used to diagnose ulcers and detect H. pylori infection.11 Once a clinician has decided to test a patient for infection, the next step is to determine if endoscopy is necessary for the procedure, based on the patient’s clinical presentation of symptoms.

Treatment, management, and prevention of ulcers

Upon diagnosis of an ulcer, patients’ need for aspirin therapy should be reviewed on a case-by-case basis to evaluate their risk-to-benefit ratio. Patients using LDA for primary prevention have a lower benefit of cardiovascular risk reduction than those using it for secondary prophylaxis. In cases of secondary prevention, failure to resume LDA after ulcer bleeding is associated with an increased mortality rate.70,71 Alternative methods of antiplatelet therapy may be considered in patients with a high risk of GI bleeding who are using aspirin for primary prevention. Previously, clopidogrel was a substitute therapy for LDA in patients with major upper GI intolerance. In 2008, however, guidelines were revised by the American College of Cardiology Foundation, American College of Gastroenterology, and American Heart Association to state that the use of clopidogrel is inferior to the combination of LDA and PPI for gastroprotection and is not recommended.25

Aspirin modifications have been made in attempts to make aspirin more tolerable in the GI tract. For example, enteric-coated aspirin with cellulose or silicon resists disintegration in the stomach, allowing aspirin to dissolve specifically in the duodenum where the pH is more alkaline.72 In other cases, buffering agents, such as calcium carbonate, magnesium oxide, or magnesium carbonate, are used to lower the hydrogen ion concentration in the GI tract, resulting in an increased solubility of aspirin in the stomach, which increases the rate of absorption and reduces the contact time aspirin has with the gastric mucosa, thereby reducing GI irritation.73 Although these modifications may reduce stomach upset in some people, they may not reduce the risk of GI bleeding.19,72 Enteric-coated aspirin has even been found to induce significant injury to the lower gut.28

Many different types of drugs have been used over the years to treat ulcers; those aimed at inhibiting gastric acid secretion have been the most successful (). Originally, H2-receptor antagonists were used to treat ulcers and were often used in maintenance therapy. Over time, they were gradually replaced with PPIs, which offer more potent acid inhibition and more rapid ulcer healing.1 Although other classes of drugs can be used, including misoprostol (a prostaglandin analog) and bismuth salts, PPIs have become the hallmark in ulcer therapy. Fixed-dose combination medication consisting of aspirin plus a PPI offers an alternative to prescribing patients two separate medications and provides more convenient dosing. Several studies have shown that fixed-dose combination therapy with aspirin and the PPI esomeprazole reduced the incidence of peptic ulcers and dyspeptic symptoms when compared with aspirin with placebo.74–76 Although PPIs are known to reduce gastric symptoms, patient adherence to an aspirin and PPI cotherapy regimen for gastroprotection is poor.34 A fixed-dose combination regimen, therefore, would likely increase patient adherence to an LDA treatment schedule. An additional class of drugs designed to treat ulcers is a noncovalent complex of aspirin and phosphatidylcholine.34 This approach, currently in clinical development, is targeted at reducing aspirin-induced GI toxicity in patients with H. pylori-negative ulcers and may have potential as an alternative to PPIs in certain patient populations.

Table 3

Classification of treatments for peptic ulcers

Ulcer treatment Typical use Rating H. pylori status
PPI Standard treatment of H. pylori-positive and -negative ulcers; prevention of NSAID/aspirin-induced ulcers; intravenous administration for bleeding ulcers Most potent acid inhibition + or −
– Omeprazole
– Pantoprazole
– Lansoprazole
– Rabeprazole
– Esomeprazole
H. pylori eradication + PPI Standard for H. pylori-positive ulcers Most potent acid inhibition + cure for infection +
H2 receptor antagonists H. pylori-negative ulcers Acid inhibition
– Cimetidine
– Ranitidine
– Famotidine
– Nizatidine
– Roxaditine
Prostaglandin analogs H. pylori-negative ulcers; prevention of NSAID/aspirin-induced ulcers Weak acid inhibition
– Misoprostol
Bismuth salts Quadruple therapy for H. pylori eradication weak antibacterial effect +
– Subcitrate
– Subsalicylate
Phosphatidylcholine-aspirin H. pylori-negative ulcers; prevention of aspirin-induced ulcers Acid inhibition
– PL2200

For the treatment and long-term prevention of recurrent bleeding ulcers, recommendations differ based on the nature of the ulcer. Patients with H. pylori-associated ulcers should receive therapy specific to H. pylori eradication, whereas patients taking aspirin are recommended to take gastroprotective measures, such as a daily PPI or fixed-dose combination therapy ().3 If untreated, long-term infection with H. pylori could potentially lead to asymptomatic chronic gastritis, chronic dyspepsia, duodenal ulcer disease, gastric ulcer disease, or gastric malignancy.77 The gold standard in the eradication of H. pylori is a 1-week regimen of triple therapy, consisting of PPI treatment with two antibiotics.78 In general, H. pylori-positive LDA users with bleeding ulcers showed a reduction in the rate of recurrent bleeding when H. pylori was eradicated or when a PPI was administered in conjunction with LDA.79,80 Another study found that eradicating H. pylori alone in patients undergoing LDA therapy, with a history of ulcer bleeding, was sufficient to reduce the long-term risk of recurrent bleeding.81 These data suggest a possible risk-reduction strategy by employing a test-and-treat tactic for the eradication of H. pylori; however, whether this method of reducing ulcer bleeding is cost-effective remains to be evaluated.

Flow chart of recommended management to prevent recurrent ulcer bleeding based on type. Reprinted by permission from Macmillan Publishers Ltd: American Journal of Gastroenterology. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345–360. Copyright 2012.3

Abbreviations: LDA, low-dose aspirin; PPI, proton pump inhibitor; NSAID, nonsteroidal anti-inflammatory drug; coxib, cyclooxygenase-2 inhibitor; H. pylori, Helicobacter pylori.

Raising awareness of possible asymptomatic ulcers

From 2007 to 2008, physicians prescribed aspirin and other antiplatelet medications in 46.9% of patient visits for patients with ischemic vascular disease.82 These data also showed that cardiologists prescribed antiplatelet drugs more frequently than primary care physicians (68% versus 35%, respectively),82 for unclear reasons.

Awareness of the GI adverse events related to aspirin use should rise in tandem with aspirin prescriptions. In fact, the American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association Task Force recommends that aspirin doses >81 mg should not be routinely prescribed, since the risk of GI adverse events increases with dose escalation.25 Because the use of enteric-coated or buffered formulations of aspirin for cardioprotection is not sufficient to reduce the risk of GI bleeding, patients at risk of GI adverse events should be prescribed gastroprotection at the initiation of LDA therapy.

Proper review of patient history and follow-up are essential in the cardiology setting to appropriately risk stratify, manage, and educate patients about GI adverse events. One suggested strategy is to administer a patient history questionnaire with a special focus on the risk factors for GI bleeds at the time of prescription. Cardiologists will become aware of the patient’s need for gastroprotection or H. pylori screening if the patient has a previous history of infection. This approach may help prevent future complications and ulcers. Overall, for patients with an increased ulcer risk, H. pylori screening is recommended to avoid the additive effect of aspirin use with H. pylori infection. A dialogue about the symptoms of peptic ulcers may help both the patient and physician to recognize a potential peptic ulcer before it worsens, and potentially avoid any other serious complications.

Proper patient evaluation and physician awareness provide more than the obvious health benefits. Preventive and follow-up screening have the potential to both decrease adverse events and generate cost-savings to patients who fall within the high-risk population for GI bleeds and are prescribed an antibiotic eradication regimen.12 Economic analysis has demonstrated the benefit of initial noninvasive H. pylori testing for patients with suspected PUD.83 Cost-effectiveness data suggest that H. pylori testing and treatment are appropriate for all patients with suspected PUD, even if the majority of patients will not benefit.83 Although clinicians are faced with several alternatives to eradicate H. pylori, few regimens are able to meet the criteria of being simple, inexpensive, and effective.84 Moreover, even though the early detection of asymptomatic H. pylori infection may help to reduce the risk of ulcer formation, it is more difficult to diagnose an H. pylori-negative asymptomatic ulcer due to aspirin use alone. Endoscopic methods are available and sensitive to this detection; however, endoscopy is not always accessible or covered by health insurance for asymptomatic patients. Although early detection is not always possible, it can prevent serious complications and provide a cost benefit to patients.

Conclusion and future directions

Cardiovascular disease is well recognized as the leading cause of death in the US, as well as in many developing countries around the world.85 Although the benefits of LDA use for cardioprotection are clear, GI side effects result in substantial morbidity for both symptomatic and asymptomatic patients. Gastroduodenal ulcers and erosions are observed in approximately one third of asymptomatic patients taking LDA and gastroprotective agents,30 leading guidelines to recommend aspirin use only in patients with a risk of cardiovascular disease over a particular threshold.26,34,86–89 However, results from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey demonstrate that aspirin is prescribed in <50% of patients deemed appropriate for LDA therapy.82

Although the GI effects of aspirin may result in substantial morbidity and mortality, a continued downward trend is observed for the rate of hospitalizations due to PUD over the past decade. The decline in PUD hospitalization rates is attributed in part to a decline in H. pylori infections due to awareness, improvements in antibiotic treatment regimens, and possibly trends in safer use of NSAIDs and gastroprotective agents.2 Data such as these suggest an optimistic future where physician and patient awareness may reduce aspirin-induced GI bleeding.

Footnotes

Disclosure

POZEN Inc. (Chapel Hill, NC, USA) provided funding for coordination and editorial support of a review on the general topic of aspirin and ulcers. Content and direction were the sole discretion of the authors without review by POZEN Inc. employees. Scientific editorial support was provided by Courtney Mezzacappa Zeni, PhD (QSci Communications, King of Prussia, PA, USA). BC discloses that he has consulting relationships with AstraZeneca Inc., Horizon Therapeutics, Inc., POZEN Inc., Ritter Pharmaceuticals, and Sucampo, Inc. He has received research grants from PLx Pharma and Pfizer Inc. KWM discloses that he has served as a consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Merck, Ortho-McNeil, Pfizer, Polymedix Inc., and Sanofi. He also discloses that he has received institution grant support from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Merck, Portola Pharmaceuticals, POZEN Inc., Regado Biosciences, Sanofi, Schering-Plough (now Merck), and The Medicines Company.

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Preventing Ulcer in Aspirin, Advil Users

Jan. 4, 2002 — Ulcers were once blamed on stress and spicy foods, but today doctors know that they are most often caused by two things — a common gut bacteria known as Helicobacter pylori and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and Advil. Now, research suggests that ulcer risk can be reduced dramatically for patients taking NSAIDs by screening for and eradicating H. pylori infection.

Two studies, published in the Jan. 5 issue of The Lancet, offer the best evidence yet that H. pylori infection and prolonged NSAID use have a synergistic effect on the development of ulcers. An analysis of 25 major studies found that NSAID takers who also had H. pylori infection were 61 times more likely to develop ulcers than those who were not infected and did not take NSAIDs.

“We have known for years that NSAIDs cause ulcers and they cause pre-existing ulcers to bleed,” gastroenterologist Richard H. Hunt, MD, tells WebMD. “Serious complications from regular NSAID use occur in about 4% of users each year.”

Pain relievers such as aspirin, ibuprofen (Advil, Motrin) and naproxen sodium (Aleve) interfere with the stomach’s ability to protect itself from damaging acids. These NSAIDs promote ulcers by disrupting the mucus that coats the stomach lining, and by disturbing other natural defenses against digestive juices.

H. pylori‘s role in promoting ulcers has been known for several decades, but it has been unclear whether the infection increases ulcer risk in NSAID users. A study from the United Kingdom suggested that infection with the bacterium is actually protective against ulcers in people who routinely take anti-inflammatory drugs.

In their analysis of the best available research, Hunt and colleagues from Ontario’s McMaster University Medical Center found that 42% of NSAID users with H. pylori infection developed ulcers, compared with 26% of users without the infection. H. Pylori infection and NSAID use increased the risk of bleeding ulcers by nearly 2-fold and 5-fold, respectively. But when patients both took NSAIDs and were infected, they had a 6-fold greater risk.

“What we found is that these are two independent risk factors that carry a similar level of risk,” Hunt says. “But when they occur together, the risk is far greater.”

In a separate report, researchers from The Chinese University of Hong Kong expanded on earlier intervention studies. All patients were beginning NSAID therapy, had a history of stomach problems, and were infected with H. pylori. Half of the patients received treatment to eradicate the infection and the other half did not. Six months later, patients in the group that did not receive eradication therapy were more nearly three times more likely than those in the eradication therapy group to have developed an ulcer.

Gastroenterologist Roy E. Pounder, MD, who wrote an editorial accompanying the new research, says that together the two studies prove that H. pylori infection increases the chances of developing ulcers in people taking conventional NSAIDs. But, he tells WebMD, there is not yet a clear course of action to protect those at risk.

He says people who are infected or have a history of stomach problems might consider taking the newer NSAIDS known as Cox-2 inhibitors that are designed to avoid stomach problems. But the drugs have not been tested among patients with known H. pylori infection. Those taking traditional NSAIDs might also consider adding over-the-counter acid-reducing drugs or the newer proton pump inhibitors to their regimen.

Hunt says the main message to be drawn from the two studies is that people taking conventional NSAIDs should discuss ulcer risk with their doctor, especially if they have a history of stomach problems.

“I don’t want to overstate this and say that everybody should be tested for H. pylori infection,” he says. “I think it is way too early to say this. But it is clear from these studies that anyone being put on traditional NSAIDs needs to have a very careful medical history taken.”

The Effects of Aspirin and Acetaminophen on the Stomach in Healthy Volunteers – Full Text View

Aspirin is a medication commonly used to relieve minor pains. Aspirin has also been used to prevent heart attacks and strokes. Aspirin, however, can also cause damage to the stomach and/or intestinal lining leading to the development of erosions (“small sores”) and/or ulcers (“large sores”). Erosions may cause bleeding (“bleeding ulcers”) and/or perforations (“holes in the stomach”). Acetaminophen, often referred by the brand name, Tylenol, is also used to treat minor pains but is not commonly recognized to cause damage to the stomach lining.

Many patients often take both of these medications together. While the effects on the stomach lining of each medication, when used alone, are known, the effects of both medications, when used together, are not.

The purpose of this study is to show whether or not the collective effects of both aspirin and acetaminophen, when used together, increase the damage on the stomach lining when compared to either medication alone.

Low dose aspirin is used for the primary and secondary prevention of cardiovascular thromboembolic events. As a non-selective inhibitor of cyclooxygenase, aspirin use results in irreversible COX-1 inhibition leading to impaired platelet aggregation. However, aspirin also inhibits COX-1 activity in the gastric mucosa by suppressing the synthesis of protective prostaglandins. In doing so, this creates a state of propensity for the development of aspirin-associated gastrointestinal ulcers and ulcer complications.

A high proportion of aspirin users also require concomitant use of anti-inflammatory medications for the treatment of pain and arthritis. However, evidence suggests that the risk of developing gastroduodenal ulcers and ulcer complications is significantly increased when aspirin is co-administered with other nonselective NSAIDs. In a previous study, concomitant aspirin (325 mg daily) in healthy subjects taking naproxen (500mg bid) was associated with endoscopic ulcer rates of 27.3% as compared to aspirin alone (7.6%). In a separate and independent trial of similar design, patients using 81 mg of aspirin in conjunction with daily naproxen also resulted in a higher incidence of gastric and duodenal ulcers than aspirin therapy alone. Beyond endoscopic ulcer rates, the risk of upper gastrointestinal hemorrhage has been reported to be substantially increased with concurrent administration of low-dose aspirin with nonselective NSAIDS. These data suggest that the gastrointestinal toxicity of combined aspirin with other NSAIDs may be more than additive.

When Should Low-dose Aspirin be Resumed After Peptic Ulcer Bleeding? – Full Text View

Acute upper gastrointestinal (GI) bleeding associated with the use of low-dose aspirin (ASA) is a major cause of peptic ulcer bleeding worldwide. Among survivors of acute myocardial infarction, a study of over 14,000 patients reported that the risk of life-threatening GI bleeding in the first two months is 7 times higher than that in the subsequent months (1). After endoscopic control of ulcer bleeding, most patients with cardiovascular (CV) diseases will need to resume ASA. Clinicians often face the dilemma: when should ASA be resumed? Furthermore, patients who suffer from acute peptic ulcer bleeding are often elderly patients with significant co-morbidities. Mortality in these patients remains high. Clinicians are facing an increasing number of patients who are on antiplatelet drugs or anticoagulants.

However, there are very limited data to guide the best timing for resumption of ASA in these high risk patients. To date, our group has conducted the only randomized controlled trial in the literature that has partially addressed this issue. Importantly, the investigator found that immediate resumption of ASA saves life but at the expense of higher risk of recurrent bleeding (2). Accordingly, current international guidelines recommend early resumption of ASA but the optimal timing is unknown.

In the setting of acute GI bleeding, it is often a dilemma whether to stop or to restart these drugs. The balance between bleeding and thrombotic risks is difficult and treatment is often empirical and not evidence-based.

The investigator aims to test the hypothesis that in ASA users complicated by peptic ulcer bleeding, withholding ASA till day 3 reduces the risk of recurrent bleeding compared to immediate resumption of ASA without a significant increase in mortality.

References

  1. Moukarbel GV, Signorovitch JE, Pfeffer MA et al. Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. Eur Heart J 2009;30(18):2226-32.
  2. Sung JJ, Lau JY, Ching JY et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med 2010;152(1):1-9.

Nonsteroidal Anti-Inflammatory Drugs and Peptic Ulcers

A peptic ulcer is the term used for a sore that occurs in the mucosal lining of the stomach, small intestine, or esophagus. When the ulcer is in the stomach it might also be called a gastric ulcer. Ulcers in the first part of the small intestine (duodenum) may be called a duodenal ulcer.

The most common cause of a peptic ulcer is a type of bacteria called Helicobacter pylori (H. pylori). A second, less common cause of peptic ulcers that’s steadily increasing in importance is the use of non-steroidal anti-inflammatory medications (NSAIDs) such as aspirin, ibuprofen, and naproxen.

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Using over-the-counter NSAIDs for the occasional headache or achy back won’t typically cause a peptic ulcer. Rather, peptic ulcer disease is something that can occur with longer-term use of NSAIDs, especially at high doses, such as for chronic pain associated with arthritis or other inflammatory conditions.

People who have any concerns about the use of NSAIDs and how the digestive system will be affected should speak to a healthcare provider.

Why NSAIDs Can Cause Ulcers

NSAIDs can cause ulcers by interfering with the stomach’s ability to protect itself from gastric acids. While these acids are vital to the digestive process, they can cause damage if the protective barriers of the stomach are compromised.

Normally, the stomach has three protections against gastric acid:

  • Mucus produced by foveolar cells that line the stomach
  • Bicarbonate produced by foveolar cells, which helps neutralize stomach acid
  • Blood circulation that aids in the repair and renewal of cells in the stomach’s mucosal layer

NSAIDs slow the production of protective mucus in the stomach and change its structure.

A class of lipids made by the body called prostaglandins have an effect on pain receptors. NSAIDs work to reduce pain by blocking the enzymes that are involved in the production of certain prostaglandins. Prostaglandins are also protective in the mucosal layer of the stomach, and when they are depleted, there can be a break in that layer.

The suppression of the body’s natural defenses against gastric acids can lead to inflammation in the stomach lining. Over time, this can cause the rupture of a capillary blood vessel, causing bleeding and the development of an open, ulcerative sore in the mucosal lining.

Symptoms

A peptic ulcer may cause symptoms in the digestive tract, but some people have no symptoms at all.

The most common symptom is upper abdominal pain (where the stomach is located) that can feel dull or burning. The pain can range in severity, with some experiencing mild discomfort and others having severe pain. Most of the time the pain will occur after a meal but for some people, it might also occur at night. It could go on for anywhere from a few minutes to a few hours.

Other symptoms are less common but can include bloating, burping, gas, nausea, vomiting, loss of appetite, weight loss, feeling sick to your stomach, and feeling full after even a small meal.

In rare cases, people with peptic ulcers may see blood in their stool or have stools that are black because they contain blood. Blood coming from one or more peptic ulcers could also be visible in vomit.

Call your healthcare provider right away if you notice blood in your stool or vomit. This can be a sign of excessive bleeding or other serious problems.

Diagnosis

When the symptoms of a peptic ulcer are present, a healthcare provider may order several tests to determine the cause and confirm the diagnosis.

In people who are receiving NSAIDs for chronic pain, a healthcare provider may already have a high suspicion that the medication is the cause of, or is contributing to, peptic ulcer disease. Because it is the most common cause of peptic ulcers, infection with H. pylori is normally ruled out through the use of a breath test, blood test, or stool test.

Tests may be done to look for ulcers in the inside of the upper digestive tract. These include:

  • Upper GI series: Patients drink a substance called barium and a series of X-rays are taken. The barium helps the internal organs show up on imaging.
  • Upper endoscopy: A flexible tube with a camera is used to look inside the esophagus, the stomach, and the duodenum. Patients are sedated during this procedure and small pieces of tissue (a biopsy) can be taken from the lining of the digestive tract for further testing.

Risk Factors

All NSAIDs have the potential to cause indigestion, gastric bleeding, and ulcers. However, some people are more susceptible to developing peptic ulcer disease than others.

Peptic ulcers caused by NSAIDs are more likely to occur in people who:

  • Are 70 or older
  • Also take corticosteroids
  • Have a history of ulcers
  • Take high-dose NSAIDs
  • Are taking NSAIDs regularly for a long time
  • Are taking more than two types of NSAIDs
  • Have an infection with H. pylori
  • Use aspirin daily (including low-dose aspirin for cardioprotective purposes)
  • Also take blood thinners
  • Smoke
  • Drink alcohol

While studies suggest that as much as 25% of people who use NSAIDs long-term will develop an ulcer, only a small percentage of those will go on to develop serious complications.

Treatment

NSAID-induced ulcers usually heal once the NSAID is stopped. Treatment may be recommended to speed up the healing process. In other cases, surgery may be needed.

Medications

A healthcare provider may recommend taking one or more medications.

Over-the-counter options include:

Prescription medications that might be recommended include:

  • An h3-blocker, which prevents the production of stomach acid by blocking histamine
  • A proton pump inhibitor (PPI), which lowers the amount of acid in the stomach.
  • Mucosal protective agents (MPAs), which work to keep the body producing the beneficial mucosal layer in the stomach

The larger problem for people experiencing peptic ulcer disease as a result of therapy with NSAIDs is how to manage pain when those medications are discontinued. In the case of chronic pain, this may require the help of a team of specialists, including a pain management healthcare provider.

A class of medications called COX-inhibitors might be used to control pain for some people. COX-inhibitors have been shown to work for pain relief and are associated with fewer digestive side effects than other types of NSAIDs. These drugs have also been shown to have cardiovascular side effects, however, so it’s usually recommended that they be used at the lowest effective dose.

Lifestyle

Some lifestyle changes that may be recommended in order to help heal peptic ulcers include:

  • Avoiding any types of food that worsen symptoms
  • Avoiding caffeine
  • Avoiding alcohol
  • Stopping smoking

Surgery

In some cases, surgery for a peptic ulcer may be needed. This is more often the case when there are complications as a result of the ulcer, such as:

Prevention

Obviously, avoiding long-term/high-dose use of NSAIDs, or not using these medications altogether, can help protect you from peptic ulcers.

If you have to take an NSAID due to a condition you are trying to manage, your healthcare provider may prescribe you one of the medications used to treat peptic ulcers in order to prevent one from occurring in the first place.

Some think that spicy food and everyday stress cause ulcers, but that has been disproven. The above lifestyle changes can, however, help reduce your risk.

A Word From Verywell

Most people who take NSAIDs will not experience peptic ulcer disease. However, people who have chronic pain and who are receiving high doses of these medications should be aware of the possibility.

In some cases, it might be appropriate to ask a healthcare provider if there are ways to prevent ulcers and if those measures should be put into place while receiving high doses of NSAIDs. Because untreated ulcers can lead to complications, it’s important to get a diagnosis and receive treatment right away if an ulcer is suspected.

Low-dose Aspirin And Stomach Ulcer Medications Better For Heart Patients With Gastrointestinal Complications — ScienceDaily

DALLAS – Jan. 20, 2005 – Heart patients with gastrointestinal complications should use low doses of aspirin combined with drugs that treat stomach ulcers rather than taking the anti-platelet drug Plavix, which has been thought to reduce bleeding ulcers, according to a gastroenterologist at UT Southwestern Medical Center and the Dallas Veterans Affairs Medical Center.

Physicians are challenged in treating heart patients who may be at high-risk for gastrointestinal bleeding from aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Factors that place patients at high-risk include a history of ulcers or gastrointestinal complications such as bleeding, increased age and congestive heart failure.

Low-dose aspirin (325 milligrams or less daily) has been shown to lower the risk of cardiovascular and cerebrovascular blood clots. It can, however, cause gastrointestinal ulceration and major bleeding, thereby limiting its overall usefulness even at the lowest effective amount.

In an editorial in the current issue ofThe New England Journal of Medicine, Dr. Byron Cryer, associate professor of internal medicine at UT Southwestern, said current cardiology guidelines suggest patients who cannot take aspirin because of previous bleeding ulcers be given the drug clopidogrel (Plavix), which has been found to be marginally better than low-dose aspirin in preventing heart attacks and reducing bleeding ulcers. But, Plavix’s effectiveness has not been proven in heart patients at greatest risk due to their history of gastrointestinal bleeding, and recent research indicates it actually may impair ulcer healing and markedly increase rates of bleeding.

“Clopidogrel inhibits new growth of small blood vessels in ulcers – which is important for ulcer healing,” said Dr. Cryer, a VA physician. “Although Plavix may not primarily cause gastrointestinal ulcers, through inhibition of new blood vessel growth, it may impair healing of background ulcers. When combined with the propensity to increase bleeding, these agents may convert small, silent ulcers into large ulcers that bleed profoundly.”

Consequently, Dr. Cryer recommends that patients at high-risk for gastrointestinal complications who require blood clot-preventing therapy should consume the lowest effective dose of aspirin combined with drugs used to treat stomach ulcers (such as Aciphex, Nexium, Prevacid, Prilosec or Protonix) rather than take clopidogrel.

The New England Journal of Medicine editorial accompanies a study in the same issue of the journal by researchers from Hong Kong. The study evaluates the use of antiplatelet therapies in patients with a history of aspirin-induced upper gastrointestinal bleeding and found those who took clopidogrel had a 1200 percent increase in recurrent bleeding from ulcers when compared to patients who took aspirin with esomeprazole (Nexium).

Dr. Cryer has been a paid consultant for McNeil Consumer and Specialty Pharmaceuticals and TAP Pharmaceutical Products and a paid speaker for AstraZeneca, the maker of Nexium, and TAP Pharmaceutical Products.

Story Source:

Materials provided by University Of Texas Southwestern Medical Center At Dallas. Note: Content may be edited for style and length.

Stomach ulcer – Causes – NHS

Stomach ulcers are usually caused by Helicobacter pylori (H. pylori) bacteria or non-steroidal anti-inflammatory drugs (NSAIDs).

These can break down the stomach’s defence against the acid it produces to digest food, allowing the stomach lining to become damaged and an ulcer to form.

H. pylori bacteria

H. pylori infections are common, and it’s possible to be infected without realising it because the infection doesn’t usually cause symptoms. 

The bacteria live in the stomach lining, and people of all ages can be infected.

But in some people, the bacteria can irritate the stomach lining and make it more vulnerable to damage from the stomach acid.

It’s not clear exactly why some people are more vulnerable to the effects of H. pylori bacteria than others.

NSAIDs

NSAIDs are medicines widely used to treat pain, a high temperature (fever) and inflammation (swelling).

Commonly used NSAIDs include:

Many people take NSAIDs without having any side effects, but there’s always a risk the medication could cause problems, such as stomach ulcers, particularly if taken for a long time or at high doses.

You may be advised not to use NSAIDs if you currently have a stomach ulcer or if you have had one in the past. 

Paracetamol can often be used as an alternative painkiller, as it’s generally considered safer.

Lifestyle factors

It used to be thought that stomach ulcers may be caused by certain lifestyle factors, such as spicy foods, stress and alcohol.

There’s little hard evidence to confirm that this is the case, but these factors may make the symptoms of ulcers worse.

But it’s thought that smoking increases your risk of developing stomach ulcers and may make treatment less effective.

Page last reviewed: 17 September 2018
Next review due: 17 September 2021

Aspirin stomach ulcer: symptoms and treatment

Aspirin (ASA) is the main representative of the NSAID group, it is successfully used in the treatment of colds and rheumatic diseases accompanied by fever, and is also used as a blood thinner to prevent blood clots in the vessels.

However, doctors discovered the ability of Aspirin to damage the mucous membrane of the stomach and duodenum. In 20-25% of patients taking long-term treatment with ASA or combined NSAIDs, an aspirin ulcer of the gastrointestinal tract occurs, and half of the patients develop erosive gastritis.

Mechanism of ulcer

The process of damage to the gastric mucosa by salicylates does not have a complete explanation. Local corrosive, chemical and toxic effects are highly probable. Aspirin directly affects the lining of the stomach, causing necrosis of the mucous membrane and provoking its allergic irritation.

A stomach ulcer caused by taking Aspirin, in terms of symptoms, is no different from a disease provoked by other factors.It is characterized by:

  • Pain in the epigastric region, especially at night;
  • stool disorder, often with signs of hemorrhage;
  • hiccups, nausea and bouts of vomiting after eating.

If these pathological signs appear while taking Aspirin, treatment should be stopped immediately and a gastroenterologist should be consulted.

After administration of ASA or other salicylates (orally and intravenously) to the patient’s body, during EGD, transformations in the gastric mucosa can be seen.Around the particles of acetylsalicylic acid on the gastric mucosa, there is swelling, redness, tissue necrosis and hemorrhage into the deeper layers, which indicates the allergic nature of the pathological changes.

The ability of aspirin particles to induce inflammatory changes around themselves has been established through clinical trials. The gastric mucous layer coagulates, partially losing its protective ability.

Even a short or one-time use of a large dose of ASA causes an aspirin ulcer of the gastrointestinal tract or erosive gastritis.This is often a consequence of the medical illiteracy of the population, when a person believes that by taking a large amount of a medicine, he can independently stop a cold illness without contacting a therapist.

In this case, uncrushed tablets are in the stomach cavity for a long time without dissolving. The acid eats away at the delicate mucous membrane, damaging the walls of nearby vessels. As a result, latent bleeding may occur.The situation is complicated by the fact that this process can be asymptomatic for a long period. The patient does not feel pain, heartburn and nausea.

Then obvious symptoms of internal bleeding appear sharply:

  • vomit streaked with blood or “coffee grounds”;
  • weakness;
  • black tarry stools;
  • 90,015 signs of anemization.

Patients with such symptoms require hospitalization in a hospital. Sometimes there is a need for surgical treatment.

Studies prove that mucosal defects do not occur in all patients receiving salicylates. In the vast majority of people, the stomach lining is resistant to high doses of aspirin. The risk group for the onset of the disease are patients predisposed to gastrointestinal diseases, weakened and elderly people, as well as those with a history of gastric ulcer and duodenal ulcer. In such patients, gastric hemorrhages and perforations sometimes occur even from short-term use of Aspirin.

Aspirin dosage forms with a special insoluble coating that protects the gastric mucosa reduce the risk of injury, but do not completely remove it. Indeed, the very presence of acetylsalicylic acid in the patient’s body provokes pathological reactions.

The harmful effect of aspirin on the gastric membrane increases with the simultaneous administration of other drugs, especially Prednisolone and Butadion. Inflammation and ulceration of the mucous membrane of the digestive organ disappear after discontinuation of treatment with salicylates and antiulcer pharmacological therapy.

What can replace aspirin

Free sale of non-steroidal anti-inflammatory drugs entails their uncontrolled use. At the same time, the vast majority of patients, as well as some pharmacy workers, do not have a complete understanding of the side effects, and especially the ulcerogenic effect of drugs that contain ASA.

Treatment with Aspirin, and even more long-term, can contribute to the appearance of dangerous complications such as an ulcer with perforation and bleeding.

At the same time, the drug is widely used for the prevention of rheumatism. The therapy involves the use of the drug in large doses for 2-3 months. In general, ASA is well tolerated and does not cause undesirable reactions, but, nevertheless, it is better to use less dangerous drugs.

Also, Aspirin is an inexpensive and popular antipyretic and analgesic agent that is used for all colds accompanied by hyperthermia and headache.However, instead of this dangerous drug, it is wiser to use analgesics of different pharmacological groups that do not have a pronounced ulcerogenic effect, for example:

  • Metamizole,
  • Piroxicam,
  • Sumatriptan,
  • Indomethacin,
  • Ketorolac,
  • Ibuprofen,
  • Celecoxib,
  • Diclofenac.

Paracetamol (aka children’s Panadol) is used instead of ASA all over the world for ARVI or other colds.In pediatric practice, it is the drug that is used first.

The effectiveness of ASA as an antiplatelet agent is beyond doubt. It is still used as a first aid for blood thinning in pulmonary embolism and heart attacks. People with pathologies of the cardiovascular system carry it with them in the first-aid kit along with Nitroglycerin. If necessary, Aspirin is able to quickly and effectively improve the properties of blood.

The most popular antiplatelet drugs are recognized:

  • Cardiomagnyl,
  • Lospirin,
  • Aspeckard,
  • Aspirin cardio.

Peptic ulcer is a contraindication to taking these drugs, so they should be replaced with antiplatelet agents without an ulcerogenic effect (Dipyridamole, Integrilin, Clopidogrel, Ticlopidine).

Aspirin ulcer therapy

Salicylic and aspirin ulcers of the mucous membrane of the digestive organ have meager symptoms, but their complications are always sudden and sometimes very severe. Most often, defects are localized in the antrum of the stomach, closer to the gatekeeper. The manifestations of salicylate damage can be very different, from erosive gastritis to a true ulcer.

At the same time, the medicine taken on an empty stomach irritates the mucous membrane more strongly than that taken after a meal. The damaging effect of Aspirin on the mucous membrane is reduced by ascorbic acid and calcium.

To reduce the irritating effect of ASA, doctors recommend drinking it with plenty of milk. It is contraindicated to take the medicine on an empty stomach or with alcohol.

Treatment of the disease is multicomponent. It starts with stopping the use of Aspirin and prescribing a diet, as well as standard antiulcer therapy, including antisecretory, antacid drugs, PPIs, anticholinergics and antispasmodics.

Thus, uncontrolled treatment with such a popular, inexpensive and effective drug as ASA is dangerous for its formidable complications. First of all, this applies to people with a burdened history and a predisposition to gastrointestinal diseases, as well as elderly and debilitated patients.

90,000 ASPIRIN: CANCER AND PLAGUE IN ONE BOTTLE

Recently, more and more doctors are wary of aspirin. Less and less often they recommend their patients to take this medicine.Primarily due to the so-called Reye’s syndrome. For the first time, Dr. Ray became interested in this syndrome, who discovered a strange pattern: during the rampant viral infections, the number of child deaths increased. Now the world statistics are already known: out of 100,000 children who have had colds and viral diseases, 0.2-4% develop Reye’s syndrome. The symptoms of this disease have been meticulously described and divided into three stages. At first, the child, who has almost coped with the cold, suddenly begins to vomit on the 3rd-7th day.The patient answers questions of adults inappropriately. But he still walks. At the second stage of the development of the disease, the child speaks with difficulty, has almost no contact with others, and no longer moves. The third stage develops rapidly: coma, convulsions, respiratory arrest. And that’s all. For a long time they could not understand where this attack falls on the unfortunate children’s heads. And yet we managed to find out. The culprits were: acetylsalicylic acid, salicylates, tetracyclines, bismuth preparations and anticonvulsants.Moreover, if they were prescribed to children precisely during the period of a viral infection. Concerned specialists have prepared serious reports on this disease with evidence. In this connection, the American and British medical institutions responsible for the life and safety of children have banned children under 12 years of age from taking aspirin. Children are not the only ones affected by aspirin. In medical practice, more than once there were cases when a patient developed internal bleeding, which in its characteristics surprisingly resembled the plague.Having understood the situation, the doctors made another diagnosis – influenza. Moreover, all patients who developed internal bleeding had previously taken aspirin. It turns out that the influenza virus, like the causative agent of the plague, thinns the walls of blood vessels, literally makes holes in the capillaries. And if you take aspirin, which is known to thin the blood, then the risk of bleeding increases a hundredfold. It is especially dangerous if it starts in the lungs. Then death comes very quickly. That is why doctors, who take into account the latest data from scientific research, are categorically opposed to prescribing aspirin or its Russian equivalent, acetylsalicylic acid, to patients during illness with the flu.The third important aspirin problem occurs in the stomach. Aspirin damages the walls of the stomach. Especially if you swallow a pill whole, not a powder. If you also take 100 grams of vodka in addition, then a stomach ulcer is guaranteed. In general, doctors recently, disillusioned with aspirin, strongly recommend lowering the temperature with the help of other drugs. For example, related to paracetamol. You can also use home methods to lower the temperature. For example, wetting (but not rubbing!) The back and chest of the patient with alcohol or vodka.For the same purpose, you can use a solution of acetic acid (a tablespoon of vinegar per liter of water). A cold compress on your head or wrapping your body in a damp sheet still helps to reduce heat. And aspirin in the arsenal of remedies, doctors suggest leaving only as a means of preventing thrombosis. After all, this drug is really effective in thinning the blood.

Aspirin for the heart – City Hospital

All cardiologists in the world argue that acetylsalicylic acid or aspirin should be prescribed to all patients at risk of complications from the cardiovascular system.It is believed that this drug should be taken by everyone who has no contraindications.

What does aspirin do?

It turns out that aspirin prevents platelets from sticking together, it is this property of aspirin that is used to prevent diseases that are accompanied by the formation of blood clots.

These are diseases such as varicose veins, angina pectoris, hypertension, stroke, myocardial infarction. The drug is used specifically for the prevention of complications, that is, it is able to thin the blood.

However, aspirin, like all anti-inflammatory drugs, has an important side effect – the development of inflammatory changes in the stomach, the formation of gastrointestinal ulcers, and after prolonged use, there is a threat of gastric bleeding.

It should be noted that currently the release of enteric-soluble aspirin has been established, the drug is enclosed in a shell that is not dissolved by stomach enzymes, begins to be digested only in the intestine, where the effect of aspirin is not so dangerous.Such aspirins are suitable for everyone and even people who cannot tolerate this drug. They can be prescribed to patients suffering from erosive gastritis, peptic ulcer, but without exacerbation. Take a capsule or tablet without chewing or breaking.

Scientists have found that nitroglycerin preparations that are prescribed in parallel with taking aspirin reduce the negative effect of aspirin on the gastrointestinal tract. Namely, taking nitrates reduces the risk of bleeding ulcers by 40%.

There is a misconception that ascorbic acid is the aspirin’s counterpart. No and no again. These are completely different drugs. Acetylsalicylic acid cannot be substituted with lemon or kiwi, and no dietary supplement is an alternative to aspirin. But nature gives aspirin in the form of meadowsweet or meadowsweet. The main components of this herb are derivatives of salicylic acid. Tavolga has a positive effect on the human body without causing the side effects that are characteristic of salicylates.If the meadowsweet is taken for a long time, let’s say one year, then the cholesterol level decreases, the heart rate is hardened, shortness of breath disappears, and blood pressure normalizes. But in order to start taking meadowsweet, you need to consult with your doctor.

For preventive purposes, herbalists recommend:

1 tsp. brew ground meadowsweet herb in a teapot with green tea, leave for 7-10 minutes and take 1-3 cups a day at any time.

If your blood pressure rises at the age of 30 and if your relatives suffer from CVD, then, after consulting a doctor, you should already take aspirin, that is, start CVD prevention, naturally, based on the state of the cardiovascular system. And we must also remember that after 45 years, the risk of heart complications increases several times . Therefore, we must not forget aspirin!

By the way! Recently, scientists have found that when taken for a long time, aspirin prevents the development of certain types of cancer, such as colon, stomach, esophagus, pharynx, and even breast cancer.And, if the disease is diagnosed in the early stages, then regular intake of aspirin will slow down the growth of malignant tumors.

When leaving the hospital, you must carefully listen to the recommendations of the attending doctor and strictly follow them. Many patients believe that having been treated in a hospital, they have freed themselves from their illness. But this is a delusion. The disease receded thanks to the efforts of the doctor, but in the future it must be kept “in check”, that is, strictly follow the regime of work and rest, take the recommended medicines, including aspirin.And all the time. And then you are not threatened with repeated hospitalizations for complications. And if you want to live a long life without being sick, then consult your local doctor and take aspirin to prevent complications of cardiovascular diseases.

The conversation was:

GBUZ SO “City Hospital of Kamensk-Uralsky”

NP Ronzhina

What is an aspirin test? | Healthy life | Health

Answer doctor-immunologist Anna Shulyaeva :

Aspirin test is a simple and quick non-invasive diagnostic option that allows you to weed out inflammatory or colds.The general strategy is as follows: a person is given a tablet of acetylsalicylic acid to drink, and then the effect is observed. If the temperature does not drop, they talk about thermoneurosis or other pathological diseases. With a decrease in temperature, doctors are inclined to the version of the presence of a viral infection, popularly called the common cold.

Today, paracetamol is more commonly used for such a test. This type of test is offered to those who have acetylsalicylic acid intolerance, gastritis with high acidity, stomach / duodenal ulcer, and children.

There can be two principles of carrying out. In the first case, first, a quarter of a paracetamol tablet is given, after half an hour the result is evaluated, then another quarter must be taken and the effect is evaluated in another half hour. The second option is carried out as follows: half a pill is issued, the result is viewed in half an hour and an hour.

If the temperature does not decrease, doctors have reason to suspect thermoneurosis. This means that a person is affected by some kind of neurological pathology, leading to the appearance of such a symptom as an increased body temperature in a constant mode.

Special attention is paid to children. After all, they have many different conditions that lead to the appearance of subfebrile condition. This may be a variant of the norm at the age of 3-6 years. By the way, because of such a run, doctors often have disputes – to carry out a test at the age of 3 years or wait until 6.

But in any case, no matter what decision is made, a pediatrician should work in conjunction with neurologists, osteopaths and other narrow specialists. In adults, by the way, the principle is the same – when a constant subfebrile temperature of an unknown genesis appears, it is necessary to be examined by different doctors.

See also:

90,000 SFNTSA RAS: Public life

[24.06.2019]

This is an outdated version of the site. The new site is located at: www.sfsca.ru


[23.06.2019]

Project

Reviewed by the Bureau of the Department of Agricultural Sciences of the Russian Academy of Sciences

November 29, 2018 Minutes No. 7


[05.06.2019]
SEED 2019

At the field stations of the Central Experimental Base (p.the village of Krasnoobsk), the North-Klundinsky (the village of Bagan, Novosibirsk region) and the East Siberian departments (the village of Mikhailovka, Uzhursky district of the Krasnoyarsk region) of the Siberian Research Institute of Forage, SFNTSA RAS, sowing work has ended.


[31.05.2019]
SFNTSA RAS received a patent of the Russian Federation for a utility model

SFNTSA RAS received a patent of the Russian Federation for a useful model “Device for determining the tribological characteristics of materials.”


[thirty.05.2019]
“PIG BREEDING VETERINARY 2019”

May 22-23, 2019 Novosibirsk hosted the VIII scientific and practical conference “Veterinary medicine in pig breeding – 2019”.


[05/29/2019]
NOTICE ABOUT THE FUTURE REORGANIZATION OF THE SFNTS RAS

NOTICE ABOUT FUTURE REORGANIZATION


[27.05.2019]
Sowing 2019

At the Kemerovo Research Institute of Agriculture, a branch of the SFNCA RAS, the laying of field experiments was carried out in full accordance with the state assignment.


[27.05.2019]
SFNTSA RAS received a Russian patent for an invention

SFNTSA RAS received the RF patent for invention № 2686990 “Method of cultivation of perennial fodder culture of the horned beetle Lotus corniculatus”.


[24.05.2019]
PARTNERS NEWS

The largest international exhibition of agricultural machinery and equipment “BATA AGRO 2019” was held in Bulgaria from 14 to 17 May. FSUE Omsk Experimental Plant took an active part in the exhibition.


[22.05.2019]
SEED 2019

The 2019 sowing campaign is coming to an end at the SibNIIZiH SFNTSA RAS. In accordance with the State Assignment, research is being carried out to improve the technologies for cultivating grain crops, rapeseed, and potatoes.


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Diclofenac Long eye drops 0.1% 10ml

Diclofenac Long eye drops 0.1% 10ml

Instructions for use Diclofenac
Buy Diclofenac long eye drops 0.1% 10ml
Dosage forms

eye drops 0.1%
Manufacturers
Firn M
Group
Anti-inflammatory drugs – phenylacetic acid derivatives
Composition
The active ingredient is sodium diclofenac.
International non-proprietary name
Diclofenac
Synonyms
Voltaren, Voltaren Akti, Voltaren Ofta, Voltaren Rapid, Voltaren Emulgel, Diclac, Diclac Lipogel, Diclo-F, Diclobene, Diclovit, Diclogen, Diclonat P, Dicloran, Diclofenac sodium, Diclofenaclofenta Diclofenac-Akos, Diclofenac-Acri, Diclofenac-Acri retard, Diclofenac-Altpharm, Diclofenac-MFF, Diclofenac-Ratiopharm, Diclofenac-UBF, Diclofenac-FPO, Naklofenac-Dorzenik-Dorzento , Ortofer, Ortoflex, Panamor AT-50, Rapten Duo, Rapten Rapid
Pharmacological action
Non-steroidal anti-inflammatory agent.Inhibits the biosynthesis of prostaglandins. Prostaglandins play a major role in the development of the main symptoms of inflammation (edema, fever, pain). In rheumatic diseases, the anti-inflammatory and analgesic properties relieve symptoms such as pain at rest and on movement, morning stiffness, swelling of the joints. It has a pronounced analgesic effect for moderate to severe pain of a non-rheumatic nature. In inflammatory processes that occur after operations and injuries, it quickly relieves both spontaneous pain and pain during movement, and reduces inflammatory edema at the site of the wound.In primary dysmenorrhea, relieves pain and reduces bleeding. Suppresses platelet aggregation. With prolonged use, it has a desensitizing effect. In ophthalmology, it eliminates miosis, reduces the likelihood of developing cystoid macular edema during cataract operations. Absorption – fast and complete, food slows down the rate of absorption. The maximum concentration in plasma is reached after 1-2 hours. As a result of the slow release of the active substance, the maximum concentration of diclofenac with prolonged action in the blood plasma is lower than that formed upon administration of the short-acting drug.With intramuscular administration, the maximum plasma concentration is reached after 10-20 minutes, with rectal administration – after 30 minutes. Bioavailability is 50%. The connection with blood plasma proteins is over 99%. When applied topically, the active ingredient is partially absorbed through the skin. When instilled into the eye, the time for the onset of the maximum concentration in the cornea and conjunctiva is 30 minutes, it penetrates into the anterior chamber of the eye, does not penetrate into the systemic circulation in therapeutically significant concentrations. Does not cumulate.It is excreted in the form of metabolites through the kidneys and with bile.
Indications for use
Inflammatory diseases of the joints (rheumatoid arthritis, rheumatism, ankylosing spondylitis, chronic gouty arthritis), degenerative diseases (deforming osteoarthritis, osteochondrosis), lumbago, sciatica, neuralgia, myalgia, diseases of extra-articular tissues soft tissue damage), post-traumatic pain syndromes accompanied by inflammation, postoperative pain, acute gout attack, primary dysmenorrhea, adnexitis, migraine attacks, renal and hepatic colic, ENT infections, residual pneumonia.Locally – injuries of tendons, ligaments, muscles and joints, localized forms of soft tissue rheumatism. In ophthalmology – non-infectious conjunctivitis, post-traumatic inflammation after penetrating and non-penetrating wounds of the eyeball, pain syndrome when using an excimer laser, during lens removal and implantation (pre- and postoperative prevention of miosis, cystoid edema of the optic nerve).
Contraindications
Hypersensitivity, hematopoiesis disorder, stomach and duodenal ulcers, “aspirin” bronchial asthma, childhood (up to 6 years), the last trimester of pregnancy.
Side effect
From the gastrointestinal tract: gastralgia, nausea, vomiting, diarrhea, stomach cramps, dyspepsia, flatulence, anorexia. From the side of the central nervous system: headache, dizziness, fatigue. From the side of hematopoiesis: thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia. There is a burning sensation at the site of the intramuscular injection. When using suppositories, local irritation. From the side of the skin: skin rashes, hives, itching, burning. With long-term use and / or application to large surfaces – systemic side effects due to resorptive action.Immediately after instillation in the eyes – a passing burning sensation and / or blurred vision.
Interaction
Increases blood concentration of lithium, digoxin, indirect anticoagulants, oral antidiabetic drugs (both hypo- and hyperglycemia are possible), quinolone derivatives. Increases the toxicity of methotrexate, cyclosporine, the likelihood of side effects of glucocorticoids (gastrointestinal bleeding), the risk of hyperkalemia against the background of potassium-sparing diuretics, reduces the effect of diuretics.Plasma concentration decreases with the use of acetylsalicylic acid.
Method of administration and dosage
Instilled into the conjunctival sac before surgery, 1 drop 5 times within 3 hours, immediately after surgery – 1 drop 3 times, then 1 drop 3-5 times / day as required for treatment time. Other indications – 1 drop 4-5 times a day. The duration of drug treatment is no more than 28 days. Longer treatment requires a detailed ophthalmological examination and accurate diagnosis.Typically, therapy is extended from one to several weeks.
Overdose
Ingestion: Symptoms: dizziness, headaches, hyperventilation, clouding of consciousness, in children – myoclonic seizures, gastrointestinal disorders, liver and kidney function. Treatment: symptomatic therapy.
Special instructions
In order to quickly achieve the desired effect, oral forms of diclofenac are taken 30 minutes before meals. After removing the contact lenses, instillation is performed after 5 minutes.Topical preparations are applied only to intact skin. With long-term treatment, it is necessary to periodically study the blood count and liver function, analysis of feces for occult blood. In the first 6 months of pregnancy, it should be used according to strict indications and in the lowest dosage. Due to a decrease in the reaction rate, it is not recommended to drive vehicles and work with mechanisms. Restrictions on use. Dysfunction of the liver and kidneys, heart failure, porphyria, work requiring increased attention, pregnancy, breastfeeding (breastfeeding should be avoided).
Storage conditions
Store in a dry, dark place at room temperature.

Museum “World of Time” – March 6

1849 Senator David Rice Atchison (1807-1886) became President of the North American United States for one day. Until 1933, a tradition was observed: American presidents took office on March 4. But in 1849, that day fell on Sunday, and the new president, Zachary Taylor, refused to host the ceremony for religious reasons.According to the then Constitution, Atchison, the leader of the majority party in the Senate, automatically became the interim president. On Monday, Taylor did take the oath. Later Atchison said: “I slept almost all my ‘presidential day’. It was the fairest government in American history. ”

1899 – German chemical company Bayer patented the Aspirin trademark. The technology for producing aspirin (acetylsalicylic acid) was developed by a young German chemist Felix Hoffmann.Hoffman immediately tried the new analgesic and antipyretic drug on his father, who suffered from rheumatism. The effect was immediate: the sharp pain subsided. But Hoffmann’s application was rejected: forty years earlier, the French chemist Charles Gerhardt had already received such a patent. True, its acetylsalicylic acid was not suitable for drug use. Within a couple of years “Bayer” aspirin gained widespread popularity all over the world. The antipyretic effect saved millions of lives during the infamous Spanish flu pandemic.

In Russia, aspirin was produced at a subsidiary of Friedrich Bayer & Co. After the outbreak of the First World War, the Moscow office of the firm suffered greatly from anti-German pogroms, but production did not stop for a single day. Under Soviet rule, aspirin was produced without any license, cost a penny and was readily prescribed by doctors. In addition to its direct purpose, this medicine was also used for household purposes: the tablets were thrown into jars with homemade pickles and into vases with freshly cut roses, crushed aspirin was added to rosin for soldering something tricky.In the meantime, side effects began to appear: acetylsalicylic acid aggravated stomach ulcers and provoked allergies. In the Soviet Mashkovsky reference book even the corresponding terms are given – “aspirin ulcer” and “aspirin asthma”. In children and adolescents, aspirin could cause the most unpleasant disease – Reye’s syndrome. Since 1978, Bayer has started to return to Russia. The initiator of the development of business ties with the USSR was the then president of the concern Bruno Kahl, the former commander of the SS Panzer Regiment “Great Germany”.For battles on the Eastern Front, he was awarded the Knight’s Cross with Oak Leaves – the highest military award of the Third Reich. After the collapse of the USSR, Bayer won a series of patent wars. As a result, the proprietary “Bayer” aspirin returned to us. For some time, there was even an opinion among the people that “real” aspirin – effervescent and instant – does not increase the acidity of the stomach. But this myth soon passed away.

1925 – the first issue of the newspaper “Pionerskaya Pravda” was published.

Pionerskaya Gazeta was at first the organ of the Moscow Committee of the Komsomol, since 1927 – the organ of the Central Committee and MK of the Komsomol, since 1958 – the Central Committee of the Komsomol and the Central Council of the Lenin All-Union Pioneer Organization. It was published twice a week. N.K.Krupskaya, M.I.Ulyanova, Em.Yaroslavsky, M.Gorky, V.V. Mayakovsky, A.P. Gaidar, S.Ya. Marshak, L.A. Kassil took an active part in the newspaper. “Pionerskaya Pravda” helped the pioneer organization and school in the communist upbringing of the younger generation, held all-Union and international children’s events – hikes, shows, contests, exhibitions, sports games.Every year the editorial office received over 200 thousand letters from children, many of which were published on the pages of the newspaper. She was awarded the Order of the Red Banner of Labor (1945) and the Order of Lenin (1950). Circulation reached (1975) up to 9.5 million copies. After the collapse of the USSR, the publication of the newspaper remained under the same name: “Pionerskaya Pravda” – a newspaper for children and adolescents.

1940 – two experimental T-34 tanks, produced at the Kharkov steam locomotive plant, went on their own to Moscow.They were accompanied by two Voroshilovets tracked artillery tractors. The 750-kilometer test run was carried out in an atmosphere of complete secrecy: the tanks were removed from their weapons and camouflaged as tractors, the cars moved only along country roads. After the breakdown of one of the tanks in Belgorod (breakage of the main clutch), the convoy split. The first tank arrived on March 12 in Serpukhov, near Moscow, at machine-building plant No. 37. A couple of days later the second tank also arrived. The vehicles were repaired at the plant, and on the night of March 17, both tanks arrived at the Ivanovskaya Square of the Kremlin to demonstrate to the leaders of the party and government.The designers and the factory workers promised to quickly correct the identified shortcomings, and the T-34 was put into production. Production of “thirty-fours” began at two factories – Kharkov and Stalingrad. By June 22, 1941, 1,066 T-34 tanks were sent to the troops.

1945 – in Hungary, near Lake Balaton, the offensive of German troops began. Hastily deployed from the Western Front, the 6th SS Panzer Army struck at the weakest formations of the 3rd Ukrainian Front – the 1st Bulgarian and 3rd Yugoslav armies.German troops managed to cross the Drava River outright and capture two bridgeheads – each up to 8 km deep along the front and up to 5 km deep. At 7 o’clock in the morning, after an hour-long artillery preparation, German troops launched an offensive in the sector of the 57th Army. At the cost of heavy losses, they managed to break into the defense of the army. But these were distracting actions. The Germans delivered the main blow between the lakes Velence and Balaton, in the sector of the 4th Guards and 26th armies of the 3rd Ukrainian Front. Up to a hundred German tanks and assault guns took part in the attacks simultaneously.Fierce fighting broke out. In the first five days, German troops managed to break through the main and second lines of defense. The newest “Royal Tigers”, equipped with the “Owl” night vision devices, operated successfully even on moonless nights.

But Hitler had no reserves. Having lost 40 thousand people and about 500 tanks, the Germans fizzled out. By March 15, the attacks had ceased, and in a number of sectors the enemy began to retreat. Chief of the General Staff of the Ground Forces Heinz Guderian wrote in his diary: “All chances for a major success have disappeared.The high fighting spirit of the SS divisions, which had been preserved until now, was lost. Under the cover of stubbornly fighting tankers, in spite of the order, entire units retreated. “The battle at Balaton was the last major offensive operation of the German armed forces in World War II. After repelling the onslaught, units of the 3rd Ukrainian Front went on the offensive against Vienna practically without an operational pause.

1984 – Motorola launches the world’s first portable cellular telephone, the DynaTAC 8000X.The development took 15 years, the company spent about $ 100 million on this project. The first commercial model of a mobile phone weighed about a kilogram and worked in standby mode for only 8-9 hours. But consumers were so impressed by the ability to always stay connected that several thousand Americans signed up for the DynaTAC 8000X. They were not deterred even by the price of the device – $ 3995.

It is curious that back in 1957, a Moscow engineer L. Kupriyanovich created a 3-kg mobile phone LK-1, as well as a base station connected to the city telephone exchange.