Safety of the long-term use of proton pump inhibitors
تعليق: مقالة مرجعية من عام 2010 لكن يلاحظ عدم الإشارة لمشاكل الإبصار في الكلمات المفتاحية بالمقالة على الرغم من الإشارة لها في داخل النص. ربما لأنه لا يوجد دليل واضح مع او ضد والسبب غياب الدراسات وهذا ما نحتاجه. وهذه الدراسة توضح أن هذا الدواء هام تقنين إستخدامه للمسنين ربما أكثر من الفئات العمرية الأخرى بسبب أن المشاكل المحتملة له مشهورة في المسنين وأيضاً بسبب زيادة إستهلاكه في المسنين بداعي وبدون داعي. --احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
معلومات المقالة
Safety of the long-term use of proton pump inhibitors
World J Gastroenterol. 2010 May 21; 16(19): 2323–2330.
doi: 10.3748/wjg.v16.i19.2323
PMCID: PMC2874135
Alan BR Thomson, Michel D Sauve, Narmin Kassam, and Holly Kamitakahara
Abstract
The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaffin-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-term use of PPIs. Long-term use of PPIs does not lead to vitamin B12 deficiencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use long-term in persons in whom there is a clear need for the maintenance of extensive acid inhibition.
كلمات مفتاحية
Keywords: Acid inhibition, Drug safety, Osteoporosis, Pneumonia, Enteric infections
تعليقات
طريقة إجراء البحث لكتابة المقالة تعتبر ممتازة ومهمة وقدوة: This review fits in that important tradition, and purports to fill a need for a comprehensive review on the safety of long-term use PPIs. Mulrow published criteria for minimizing bias in narrative reviews[19]. Deeks summed up these as being rigorous, informative, comprehensive, and explicit[20]. Collins and Fauser, in their editorial, enforced the view of the importance of “balancing the strengths of systemic and narrative reviews”[21]. To achieve this balance and complement a primarily journalistic approach, a search of PubMed, Google Scholar and UpToDate for articles published since 1999 on the topic of “PPI” and “safety” (and related MESH terms) was conducted to identify English language meta-analysis, publications in one of the top biomedical journals in this field (NEJM, Annals, Lancet, JAMA, American Journal of Gastroenterology, Gastroenterology, American Journal of Gastroenterology, Alimentary Pharmacology and therapeutics, Drugs, BMJ) as well as major North American and European guidelines. Checklists have been proposed for systematic and qualitative research[22,23], aiding in the review. We present this information on the long-term safety of PPIs with a series of questions, a summary of the literature, and our proposed answer. --احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
المشاكل الكبيرة ومنها مشاكل الإبصار لم يتحدث عنها المؤلف كثيراً: Serious adverse events are rare, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole[10-12], and disputed visual disturbances with pantoprazole and omeprazole[13,14]. يلاحظ أنه في عام 2010 لم يكن المؤلف قد رصد إلا دراستين عن مشاكل البصر. وصدرت بعده العديد من المنشورات عن هذا الموضوع (اليابان عام 2000 مثلاً وتقرير حالة من الدانيمارك). وأيضاً المؤلف لم يكن على معرفة بإحتمال وجود علاقة بين الدمنشيا وهذه الأدوية. وأيضاً يلاحظ في التجارب المسجلة في سجل الأمريكي للتجارب أن الكثير منها الذي يستخدم هذه الأدوية يضع أحد خصائص الإستبعاد من الدراسة وجود مشاكل كبد أو فيروسات او مشاكل كلى. ودراسة واحد (في مجلد التصنيف من جامعة إيمروي) تضع مشاكل البصر من خصائص الإستبعاد Exclusion criteria. --احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
وبها تنويه خاص بالمسنين: In elderly patients who may already have gastric atrophy (possibly from H. pylori infection), PPIs used long-term may reduce serum vitamin B12 concentrations[85-87]--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
وشئ هام قد يكون له علاقة بمشاكل الإبصار: What is the physiological background to speculating that PPIs might result in pulmonary complications? PPI use is associated with increased intragastric aerobic bacteria, and with the production of acetaldehyde from alcohol[108]. فهل نوع الكحول الإيثيلي أو الميثانول المعروف بخطورته على البصر؟؟؟؟ ما هي الأغذية التي تتحول لمكوناتها لميثانول وما علاقة البكتريا بذلك وهل لحامض المعدة دور في تقليل خطر الميثانول؟؟--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
وشئ آخر له علاقة بالمسنين ويدفعنا للقول لقد حان الوقت لمراجعة كيفية كتابة هذه الأدوية للمسنين وتقليل إستهلاكهم لها. In case controlled studies, PPI use long-term is associated with an increased risk of bone fractures, and this increased risk depends on the duration and dose of chronic use of the PPI[102] (e.g. Manitoba Population Health Research Data Repository[103]). Use of PPI ≥ 5 years can increase the risk of osteoporotic fractures by 1.62-fold (95% CI: 1.02-2.58). Other studies confirm that use of PPI ≥ 7 years increases the risk of osteoporotic hip fractures by 4.55-fold (95% CI: 1.68-12.29) and PPI use for 6-12 mo has been reported to be associated with an increased risk of osteoporotic hip and spine fractures[103-105]. Osteoporotic fractures of the hip and spine may be associated with many factors, which must be carefully taken into account in any case-controlled study which suggests a new association, such as the use of PPIs. However, case control studies on the risk of OP may be criticized on a methodological basis, such as the lack of appropriate stratification of the risk of other factors known to be associated with an increased risk of OP[106]. The Canadian Association of Gastroenterology (CAG) position paper suggests that “current data would not support particular care in prescribing PPI therapy due to concern about risk of hip fracture”[107].--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
وطبعاً التداخلات الدوائية على كل لون يا باتستا ومنها أدوية جلطات القلب: PPIs reduce gastric acid, and thereby reduce the bioavailability of drugs requiring intragastric acidity to maximize their absorption and bioavailability[51]. Examples of such drugs would include ketoconazole, itraconazole and indinipur[72], and may reduce the effects of locally acting drugs such as sucralfate. PPIs may alter the intestinal first pass metabolism or the hepatic clearance of some drugs, and thereby modify their pharmacodynamics[72]. They have no effect on n-acetyl-transfer or xanthine oxidase activities[73], and may show a rare class action effect on vitamin K antagonists[74]. PPIs have a low drug interaction through phase I/II effects[5,75], and may differ in their possibility of causing drug interactions. Omeprazole and lansoprazole have a high affinity for CYP2C19 and CYP3A4 but these cytochromes contribute little to rabeprazole metabolism. Pantoprazole is completely metabolized by these cytochrome enzymes, but it uniquely has no drug interactions with a wide range of drugs[72,76-78]. PPIs, with the exception of pantoprazole, have been associated with reduced effectiveness of clopidogrel and a resulting 40% increased risk of coronary stent occlusions[79]. There is no consensus yet on how to manage this[80]. Thus, PPIs have an effect in common with all acid lowering therapy to reduce the absorption of acid-dependent medications. The metabolism of PPIs by hepatic cytochrome enzymes varies significantly between drugs.--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
وأيضاً يهم المسنين:ome observational studies show an association between PPI use and risk of CDAD[121-132]. For example, for PPI use and CDAD in chronic renal failure patients, the AOR is 5.7 (95% CI: 1.3-39.1) (P = 0.02)[133]. In meta-analyses of studies of CDAD and PPIs, the AOR is 1.96 (95% CI: 1.28-3.00). Some of these reports involve a hypervirulent strain of C. difficile, and after correcting for other factors such as antibiotic use, there is no association with PPIs[134]. The bottom line is that there is no convincingly proven data that PPIs increase the risk of CDAD[134,135].--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
وأيضاً: SMALL BOWEL CONTAMINATION SYNDROME AND ENTERIC INFECTIONS It is thought that PPIs have a minor effect on altering the intestinal bacterial microbiota[136]. Observational studies have suggested that PPIs may[137] or may not[138] increase risk of enteric infections. Thus, PPIs do not have a convincingly proven adverse effect on the enteric microbiota, and if such an effect does exist, there is no proven clinically important adverse effect[139,140].--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
وهنا المؤلف يعلق على طريقة إستهلاك هذه الأدوية بقوله: PPIs are a medication that is generously prescribed for a variety of symptoms that are thought, and not necessarily confirmed, to be acid-induced. One reason for this is the relatively low number of adverse effects that have been shown in the short- or long-term وهو لا يتحدث عن أنواع عسر الهضم الغير مرتبطة بالقرح او الحمض Non-ulcer dyspepsia.--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
كما يعلق على مدى تسببها في حدوث حموضة بعد وقفها: One study suggests that symptoms that commence following the discontinuation of PPIs due to rebound acid hypersecretion may be as troublesome as the symptoms that the PPIs were being used to treat in the first place[141]. Because of these rebound symptoms, there may be a need for further and continuous PPI use. وهذا طبعا قد يسبب شعور كاذب أن هذه الأدوية كانت تقي من الحموضة وبالتالي يستمر في تناولها إلى ما لا نهاية لكن بدون حاجة مؤكدة. نحتاج لمقارنة تأثير هذه الأدوية مع البلاسيبو فمن المؤكد أن البلاسيبو له دور هام في علاج القولون العصبي وهو مشابه لعسر هضم القرح. والله أعلم. --احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
لهذا ينصح المؤلف ويقول: As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. وهذا النصح يحتاج لتمحيص ودراسات أخرى. وهذه النصيحة قد تكون المدخل لمقالة تجميعية.--احمد شوقي محمدين 20:52، 15 أكتوبر 2016 (ت ع م)
