Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers...Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.展开更多
Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are m...Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are many regimens offered for H.pylori eradication which include triple,quadruple,or sequential therapy regimens.The central aim of this systematic review is to evaluate the evidence for H.pylori therapy from a meta-analytical outlook.The consequence of the dose,type of proton-pump inhibitor,and the length of the treatment will be debated.The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.展开更多
Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia （PPIH） has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations ...Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia （PPIH） has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations have confirmed the association of PPI exposure and serum magnesium concentrations, there are no prospective,controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may be a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition. This review explores the current state of research in the feld of PPIH and the proposed mechanisms of this effect.展开更多
Objective： To determine whether patients maintain symptom control after discontinuation of PPI （proton-pump inhibitor） therapy through intervention of a pharmacist-led medication utilization program and determine a...Objective： To determine whether patients maintain symptom control after discontinuation of PPI （proton-pump inhibitor） therapy through intervention of a pharmacist-led medication utilization program and determine annual clinic cost-savings per prescription. Design： The study was conducted as a prospective, medication use evaluation. Using an electronic medical record system at a clinic, reports generated all patients receiving PP1 therapy from January 2013-June 2015. Patients were encouraged to participate in a PPI discontinuation trial through a pharmacist-led educational session. Participants were followed-up three months post enrollment to assess their quality of life through a survey assessing severity and frequency of symptoms. Participants unable to maintain symptom control after the intervention were referred back to their primary care physician for further evaluation. Results： Of one hundred participants, 25% （n = 25） were able to discontinue the use of PPI by lifestyle modifications, 43% （n = 43） refused to discontinue PP1 therapy and lifestyle changes due to the severity of their symptoms, 17% （n = 17） switched to over-the-counter H2 receptor antagonist daily to control their symptoms, 9% （n = 9） used PPIs only as needed, and 6% （n = 6） of participants were dropped from the study after three failed communication attempts. The clinic saved approximately $11 thousand annually for every one prescription of PPI＇s. Conclusions： Discontinuation of PPI or step-down therapy was possible for patients with mild-moderate GERD （Gastroesophageal Reflux Disease） symptoms when mediated by pharmacist counseling and follow-up. Also, the annual PPI expenditure at this clinic will decrease due to participant＇s discontinuation of therapy.展开更多
BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential thera...BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.展开更多
Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestin...Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.展开更多
This study aimed to explore the relationship between proton pump inhibitors(PPIs)and gastric tumors and determine the reasons behind these connections.We reviewed studies on PPIs and stomach tumors.We explored the rel...This study aimed to explore the relationship between proton pump inhibitors(PPIs)and gastric tumors and determine the reasons behind these connections.We reviewed studies on PPIs and stomach tumors.We explored the relationship between PPIs and different types of gastric neoplasms according to the classification of gastric neoplasms.Long-term use of PPIs is associated with stomach infection,high gastrin levels,and rebound acid hypersecretion,which are directly or indirectly related to the development of gastric neoplasms.PPIs can increase the risk of gastric fundal polyps.Further evidence is needed to prove that it can increase the risk of gastric cancer.展开更多
Background: The development of esophageal stricture during treatment with high dose chemotherapeutic agents is well known and documented in the literature. With the introduction of proton pumps inhibitors (PPI), the g...Background: The development of esophageal stricture during treatment with high dose chemotherapeutic agents is well known and documented in the literature. With the introduction of proton pumps inhibitors (PPI), the gastroesophageal reflux disease (GERD) induced stricture has shown significant improvement. The aim of this report is to remind of the fact that the chemotherapy induced strictures show poor response and their treatment is still a challenge. Case presentation: Here, we reported a boy with Down syndrome and congenital heart disease who developed acute lymphoblastic leukemia and subsequent esophageal stricture during treatment with a PPI. Conclusion: It is important to be aware of this potential complication of gastroesophageal reflux or antineoplastic treatment, even in cases thought to be adequately treated with a proton pump inhibitor, and that the start of PPI’s is also the start of an evaluation of the use of this medication.展开更多
Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource util...Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource utilization.In fact,the management of patients with GERD is complex and poses several questions to the clinician who faces them in clinical practice.For instance,many aspects should be considered,including the appropriateness of indication to endoscopy,the quality of the endoscopic examination,the use and interpretation of ambulatory reflux testing,and the choice and management of anti-reflux treatments,i.e.,protonpump inhibitors and surgery.Aim of the present review was to provide a comprehensive update on the clinical management of patients with GERD,through a literature review on the diagnosis and management of patients with GER symptoms.In details,we provide practice-oriented concise answers to clinical questions,with the aim of optimising patient management and healthcare resource use.展开更多
基金Supported by Zhejiang Provincial Bureau of Education, No. 20070227Zhejiang Medical Association, No.2007ZYC18Association of Zhejiang Hospital Administration, No. 2007AZHA-KEB312
文摘Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.
文摘Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are many regimens offered for H.pylori eradication which include triple,quadruple,or sequential therapy regimens.The central aim of this systematic review is to evaluate the evidence for H.pylori therapy from a meta-analytical outlook.The consequence of the dose,type of proton-pump inhibitor,and the length of the treatment will be debated.The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.
文摘Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia （PPIH） has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations have confirmed the association of PPI exposure and serum magnesium concentrations, there are no prospective,controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may be a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition. This review explores the current state of research in the feld of PPIH and the proposed mechanisms of this effect.
文摘Objective： To determine whether patients maintain symptom control after discontinuation of PPI （proton-pump inhibitor） therapy through intervention of a pharmacist-led medication utilization program and determine annual clinic cost-savings per prescription. Design： The study was conducted as a prospective, medication use evaluation. Using an electronic medical record system at a clinic, reports generated all patients receiving PP1 therapy from January 2013-June 2015. Patients were encouraged to participate in a PPI discontinuation trial through a pharmacist-led educational session. Participants were followed-up three months post enrollment to assess their quality of life through a survey assessing severity and frequency of symptoms. Participants unable to maintain symptom control after the intervention were referred back to their primary care physician for further evaluation. Results： Of one hundred participants, 25% （n = 25） were able to discontinue the use of PPI by lifestyle modifications, 43% （n = 43） refused to discontinue PP1 therapy and lifestyle changes due to the severity of their symptoms, 17% （n = 17） switched to over-the-counter H2 receptor antagonist daily to control their symptoms, 9% （n = 9） used PPIs only as needed, and 6% （n = 6） of participants were dropped from the study after three failed communication attempts. The clinic saved approximately $11 thousand annually for every one prescription of PPI＇s. Conclusions： Discontinuation of PPI or step-down therapy was possible for patients with mild-moderate GERD （Gastroesophageal Reflux Disease） symptoms when mediated by pharmacist counseling and follow-up. Also, the annual PPI expenditure at this clinic will decrease due to participant＇s discontinuation of therapy.
文摘BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.
文摘Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.
文摘This study aimed to explore the relationship between proton pump inhibitors(PPIs)and gastric tumors and determine the reasons behind these connections.We reviewed studies on PPIs and stomach tumors.We explored the relationship between PPIs and different types of gastric neoplasms according to the classification of gastric neoplasms.Long-term use of PPIs is associated with stomach infection,high gastrin levels,and rebound acid hypersecretion,which are directly or indirectly related to the development of gastric neoplasms.PPIs can increase the risk of gastric fundal polyps.Further evidence is needed to prove that it can increase the risk of gastric cancer.
文摘Background: The development of esophageal stricture during treatment with high dose chemotherapeutic agents is well known and documented in the literature. With the introduction of proton pumps inhibitors (PPI), the gastroesophageal reflux disease (GERD) induced stricture has shown significant improvement. The aim of this report is to remind of the fact that the chemotherapy induced strictures show poor response and their treatment is still a challenge. Case presentation: Here, we reported a boy with Down syndrome and congenital heart disease who developed acute lymphoblastic leukemia and subsequent esophageal stricture during treatment with a PPI. Conclusion: It is important to be aware of this potential complication of gastroesophageal reflux or antineoplastic treatment, even in cases thought to be adequately treated with a proton pump inhibitor, and that the start of PPI’s is also the start of an evaluation of the use of this medication.
文摘Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource utilization.In fact,the management of patients with GERD is complex and poses several questions to the clinician who faces them in clinical practice.For instance,many aspects should be considered,including the appropriateness of indication to endoscopy,the quality of the endoscopic examination,the use and interpretation of ambulatory reflux testing,and the choice and management of anti-reflux treatments,i.e.,protonpump inhibitors and surgery.Aim of the present review was to provide a comprehensive update on the clinical management of patients with GERD,through a literature review on the diagnosis and management of patients with GER symptoms.In details,we provide practice-oriented concise answers to clinical questions,with the aim of optimising patient management and healthcare resource use.
