Pharmacological Acid Suppression Research Articles

Potential factors of Helicobacter pylori resistance to clarithromycin.

A comparative dissolution kinetics test (CDKT) and bioequivalence studies of generic proton pump inhibitors (PPIs) do not model pharmacological acid suppression (PAS) and pathological duodenogastric reflux (PDGR). This study aimed to model them in CDKT to assess drugs stability and potential pantoprazole-clarithromycin interactions. In CDKT, PDGR (dissolution medium pH 7.00±0.05, preexposure at pH 1.20±0.05) and PAS (pH 4.00±0.05) were modelled for original pantoprazole (OP) and its generics (GP1-4). In CDKT with high-performance liquid chromatography, dissolution gastric medium in adequate (pH 4.00±0.05) and inadequate (pH 1.20±0.05) PAS were modelled for original clarithromycin (OC) and its generics (GC1-4). After exposure in pH 7.00±0.05, pantoprazole was released from GP1 within 10min in the amount of 68.8%. In рН 4.00±0.05, 83.0% and 81.5% of pantoprazole were released from GP1 and GP4. When OP, GP2 and GP3 were placed in pH 7.00±0.05, pantoprazole was released in amount: 99.4%, 88.0% and 98.2%. Clarithromycin releasing from OC, GC1, GC2, GC3, GC4 in pH 4.00±0.05 was 93.5%, 91.6%, 92.9%, 79.4% and 83.0%. In pH 1.20±0.05: 9.7%, 6.7%, 8.5%, 33.3%, 28.8%. Destruction of enteric coats of some local pantoprazole generics in CDKT-models might be a potential factor for inadequate therapy.

Дискуссионные проблемы оценки качества воспроизведенных препаратов эзомепразола

Выполнен тест сравнительной кинетики растворения, моделирующий воздействие патологического дуоденогастрального рефлюкса и лекарственной кислотосупрессии на устойчивость препаратов эзомепразола 3 разных производителей. После экспозиции в растворах с pH (1,2 ± 0,05) или (4,0 ± 0,05) препараты перемещались в среду с pH (7,0 ± 0,05), откуда забирались аликвоты через 0, 4, 10, 15, 20, 30, 45, 60 мин для определения в них концентраций эзомепразола. Время воздействия патологического дуоденогастрального рефлюктата на лекарственную форму эзомепразола равно 4 мин. Показано, что в заданных тестом условиях ВЛС1 и ВЛС2 не являются эквивалентными референтному препарату (РП), лекарственная форма РП, вероятно, подвержена влиянию патологического дуоденогастрального рефлюкса в желудке, ВЛС2 полностью разрушается в умеренно кислой среде с pH 4,0, что свидетельствует о возможном негативном воздействии его основного антисекреторного фармакодинамического эффекта на стабильность в желудке собственной лекарственной формы и действующего вещества.

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p=0.03). On multivariate analyses, acid suppression (HR 0.39, p=0.04) and lower BMI (HR 0.67, p=0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

Prophylactic Acid-Suppressive Therapy in Hospitalized Adults: Indications, Benefits, and Infectious Complications.

Acid-suppressive therapy for prophylaxis of stress ulcer bleeding is commonly prescribed for hospitalized patients. Although its use in select, at-risk patients may reduce clinically significant gastrointestinal bleeding, the alteration in gastric pH and composition may place these patients at a higher risk of infection. Although any pharmacologic alteration of the gastric pH and composition is associated with an increased risk of infection, the risk appears to be highest with proton pump inhibitors, perhaps owing to the potency of this class of drugs in increasing the gastric pH. With the increased risk of infection, universal provision of pharmacologic acid suppression to all hospitalized patients, even all critically ill patients, is inappropriate and should be confined to patients meeting specific criteria. Nurses providing care in critical care areas may be instrumental in screening for appropriate use of acid-suppressive therapy and ensuring the drugs are discontinued upon transfer out of intensive care or when risk factors are no longer present.

Is There Any Association Between Pharmacological Gastric Acid Suppression and Spontaneous Bacterial Peritonitis? An Updated Meta-analysis

Is There Any Association Between Pharmacological Gastric Acid Suppression and Spontaneous Bacterial Peritonitis? An Updated Meta-analysis

Acid‐suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: A meta‐analysis

Proton pump inhibitors (PPI) and H(2) -receptor antagonists (H2RA) are frequently prescribed in hospitalized patients with cirrhosis. There are conflicting reports regarding the role of acid-suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis (SBP). The aim of this meta-analysis was to evaluate the association between acid-suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis. We searched MEDLINE and four other databases for subject headings and text words related to SBP and acid-suppressive therapy. All observational studies that investigated the risk of SBP associated with PPI/H2RA therapy and utilized SBP as an endpoint were considered eligible. Data from the identified studies were combined by means of a random-effects model and odds ratios (ORs) were calculated. Eight studies (n = 3815 patients) met inclusion criteria. The risk of hospitalized cirrhotic patients developing SBP increased when using acid-suppressive therapy. The risk was greater with PPI therapy (n = 3815; OR 3.15, 95% confidence interval 2.09-4.74) as compared to those on H2RA therapy (n = 562; OR 1.71, 95% confidence interval 0.97-3.01). Pharmacologic acid suppression was associated with a greater risk of SBP in hospitalized patients with cirrhosis. Cirrhotic patients receiving a PPI have approximately three times the risk of developing SBP compared with those not receiving this medication. Prospective studies may help clarify this relationship and shed light on the mechanism(s) by which acid-suppressive therapy increases the risk of SBP in hospitalized patients with cirrhosis.

Spontaneous bacterial peritonitis and pharmacologic acid suppression in patients with cirrhosis

Spontaneous bacterial peritonitis and pharmacologic acid suppression in patients with cirrhosis

Management of non-variceal upper gastrointestinal tract hemorrhage: controversies and areas of uncertainty.

Upper gastrointestinal tract hemorrhage (UGIH) remains a common presentation requiring urgent evaluation and treatment. Accurate assessment, appropriate intervention and apt clinical skills are needed for proper management from time of presentation to discharge. The advent of pharmacologic acid suppression, endoscopic hemostatic techniques, and recognition of Helicobacter pylori as an etiologic agent in peptic ulcer disease (PUD) has revolutionized the treatment of UGIH. Despite this, acute UGIH still carries considerable rates of morbidity and mortality. This review aims to discuss current areas of uncertainty and controversy in the management of UGIH. Neoadjuvant proton pump inhibitor (PPI) therapy has become standard empiric treatment for UGIH given that PUD is the leading cause of non-variceal UGIH, and PPIs are extremely effective at promoting ulcer healing. However, neoadjuvant PPI administration has not been shown to affect hard clinical outcomes such as rebleeding or mortality. The optimal timing of upper endoscopy in UGIH is often debated. Upon completion of volume resuscitation and hemodynamic stabilization, upper endoscopy should be performed within 24 h in all patients with evidence of UGIH for both diagnostic and therapeutic purposes. With rising healthcare cost paramount in today's medical landscape, the ability to appropriately triage UGIH patients is of increasing value. Upper endoscopy in conjunction with the clinical scenario allows for accurate decision making concerning early discharge home in low-risk lesions or admission for further monitoring and treatment in higher-risk lesions. Concomitant pharmacotherapy with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents, such as clopidogrel, has a major impact on the etiology, severity, and potential treatment of UGIH. Long-term PPI use in patients taking chronic NSAIDs or clopidogrel is discussed thoroughly in this review.

Increased Rate of Spontaneous Bacterial Peritonitis Among Cirrhotic Patients Receiving Pharmacologic Acid Suppression

Patients with cirrhosis frequently receive proton pump inhibitor (PPI) or H2-receptor antagonist therapies. We investigated whether acid-suppressive therapy is associated with spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. We compared data from 65 hospitalized cirrhotic patients with paracentesis-proven SBP, collected from 2006 to 2009, with those of 65 contemporaneous, hospitalized cirrhotic patients without SBP (controls). We evaluated PPI use and analyzed the effects of covariates. Patients with SBP had a significantly higher incidence of recent (past 7 days) PPI use (71%) than controls (42%). Of patients with SBP, 68% had no documented indication for PPI therapy. Based on multivariable logistic regression analysis, subjects who had not taken PPIs in the past 90 days were almost 70% less likely to develop SBP than those who had taken PPIs in the previous 7 days. Subjects who took PPIs within 8 to 90 days before hospitalization were 79% less likely to develop SBP than those who took PPIs within 7 days before hospitalization. There was no significant difference between patients who received no PPI therapy in the previous 90 days versus those who had taken PPIs in the previous 8 to 90 days (P = .58). Hyponatremia was associated significantly with SBP. There were no significant differences in length of hospital stay or 30-day survival for the SBP and control groups. Pharmacologic acid suppression is associated with SBP in patients with advanced cirrhosis. Prospective studies are needed to determine the mechanism of this association and to determine whether reduced use of PPIs and H2-receptor antagonists reduce the incidence of SBP.

Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection

The incidence and severity of Clostridium difficile infections are increasing. Acid-suppressive therapy has been suggested as a risk factor for C difficile, but this remains controversial. We conducted a pharmacoepidemiologic cohort study, performing a secondary analysis of data collected prospectively on 101 796 discharges from a tertiary care medical center during a 5-year period. The primary exposure of interest was acid suppression therapy, classified by the most intense acid suppression therapy received (no acid suppression, histamine(2)-receptor antagonist [H(2)RA] therapy, daily proton pump inhibitor [PPI], and PPI more frequently than daily). As the level of acid suppression increased, the risk of nosocomial C difficile infection increased, from 0.3% (95% confidence interval [CI], 0.21%-0.31%) in patients not receiving acid suppressive therapy to 0.6% (95% CI, 0.49%-0.79%) in those receiving H(2)RA therapy, to 0.9% (95% CI, 0.80%-0.98%) in those receiving daily PPI treatment, and to 1.4% (1.15%-1.71%) in those receiving more frequent PPI therapy. After adjustment for comorbid conditions, age, antibiotics, and propensity score-based likelihood of receipt of acid-suppression therapy, the association persisted, increasing from an odds ratio of 1 (no acid suppression [reference]) to 1.53 (95% CI, 1.12-2.10) (H(2)RA), to 1.74 (95% CI, 1.39-2.18) (daily PPI), and to 2.36 (95% CI, 1.79-3.11) (more frequent PPI). Similar estimates were found with a matched cohort analysis and with nested case-control techniques. Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.

Proton pump inhibitors: the beginning of the end or the end of the beginning?

Despite the dramatic success of pharmacological acid suppression in healing peptic ulcers (PUs) and managing patients with gastro-esophageal reflux disease (GERD) a number of challenges remain in the management of acid-related disorders. Several new drugs are currently being investigated to provide a significant advance over current treatments. These include new drug formulations, novel proton pump inhibitors (PPIs) as well as potassium-competitive acid blockers (P-CABs), which have already reached clinical testing. Some others (like NO-releasing antisecretory compounds) are still in preclinical development and require proof of concept in humans. While H(2)-receptor antagonists (especially soluble or OTC formulations) will become the 'antacids of the third millennium' and will be particularly useful for on-demand symptom relief, clinicians will continue to rely on PPIs to control acid secretion in GERD and other acid-related diseases. Since an increasing proportion of patients fail to respond to the best PPI treatment, more potent and long-acting drugs and more effective regimens are needed.

Multichannel intraluminal impedance and pH monitoring in gastroesophageal reflux disease

The role of acid is very well established in the pathogenesis of gastroesophageal reflux disease and acid suppression constitutes the main approach to its medical treatment. With the current frequent use of proton pump inhibitors, we are seeing increasing numbers of patients in whom symptoms persist despite pharmacological acid suppression. Reflux monitoring has been traditionally performed through esophageal pH measurement to detect acid reflux (i.e., drops in esophageal pH to below 4.0). Multichannel intraluminal impedance and pH measurement constitutes an important development in reflux monitoring because, in addition to detecting acid reflux, it enables measurement of nonacid reflux (i.e., with a pH > 4.0, also known as ‘weakly acidic’ for pH > 4 but < 7, or ‘weakly alkaline’ if pH > 7), which may be responsible for symptoms in some patients who are being treated with proton pump inhibitors. This review describes the approach to measuring nonacid reflux, the possible mechanisms responsible for symptoms due to this type of reflux, the clinical importance of this phenomenon and available treatment options; and the role of multichannel intraluminal impedance and pH monitoring in the evaluation of refractory gastroesophageal reflux disease.

Barrett's oesophagus: effect of antireflux surgery on symptom control and development of complications.

Forty-five patients with histologically proven Barrett's columnar-lined oesophagus (CLO) were treated in one unit over a 9-year period. Patients were studied prospectively as part of a surveillance programme; all initially received standard conservative treatment including high-dose H2-receptor antagonists. A satisfactory initial response was seen in 21 patients, but in 24 the symptoms were unchanged or progressed; 19 patients in the latter group were considered suitable for antireflux surgery and underwent fundoplication. Symptoms of heartburn or dysphagia persisted or recurred in 88 per cent of patients receiving medical treatment alone and complications developed in 38 per cent, including nine strictures and one adenocarcinoma. In patients undergoing antireflux surgery, symptoms persisted or recurred in 21 per cent and complications developed in 16 per cent (P < 0.01). Complete regression of Barrett's CLO occurred in two patients (11 per cent) after antireflux surgery. The results of this study suggest the superiority of antireflux surgery over pharmacological acid suppression in the control of symptoms and prevention of complications in patients with Barrett's CLO.

Emerging Strategies in Pharmacologic Management for Non-Variceal Upper Gastrointestinal Hemorrhage

Our understanding of the pathophysiology of non-variceal upper gastrointestinal haemorrhage point to the potential role of acid suppressive therapy in improving haemostasis. Use of antihistamine antagonists in clinical studies on gastrointestinal haemorrhage did not demonstrate any significant benefit. With an improved understanding of drug pharmacokinetics, use of antihistamine antagonists are shown to have a significant tolerance effect and a failure to maintain a sustained intragastric acid suppression which may account for the lack of clinical benefit. Proton pump inhibitors have been shown to provide a sustained acid suppression and clinical studies have supported the use of proton pump inhibitors in acute upper gastrointestinal haemorrhage. A combination of pharmacological acid suppression and endoscopic therapy appears to act synergistically and provide the most effective means for achieving haemostasis particularly in the setting of actively bleeding peptic ulcers.

Quantitative result of 13C-Urea breath test does not correlate with Helicobacter pylori density in the stomach by assessing histopathology and grade of phenol red staining

'Significant difference using Mann·Whitney U. All values displayed for 1M and non-1M medians 24 hour acid clearance for the two groups was examined. Results for percentage total acid exposure time (At), total number of reflux episodes (El)' total acid clearance time (ACTl).percentage erect acid exposure time (Ae ) , erect reflux episodes (Ee) , percentage supine acid exposure time (As)and supine reflux episodes (E,) were compared for the 1M and NIM groups using the Mann-Whitney U test. The median acid exposure of the 1M group of patients was shown to be significantly higher than the non-1M group (5.2% vs 2.8%). This was most clearly displayed in the supine period where both the number of reflux episodes (2 vs I) and the acid exposure (1.4% vs 0.2%) were increased with respect to the non-1M group. Overall, the 1M group showed a significant delay in their median oesophageal acid clearance time (2.9 min vs 2.1 min). Oesophageal manometry provides important evidence of the ability of patients to effectively clear refluxate. Therefore, in addition to providing valuable pre-surgical information, manometry assist in therapeutic management. Patients with 1M should be advised to incline the upper body during rest and be provided with prolonged pharmacological acid suppression at night.

Outcomes of atypical symptoms attributed to gastroesophageal reflux treated by laparoscopic fundoplication

Background: The introduction of laparoscopic fundoplication (LF) has lowered the threshold for operation in patients with symptoms attributed to gastroesophageal reflux. We sought to determine whether the outcomes in patients referred for atypical symptoms (pulmonary, pharyngolaryngeal, and pain syndromes) were as good as those referred for correction of heartburn and regurgitation (typical symptoms). Methods: Thirty-five of 150 consecutive patients undergoing LF with a minimum of 12 months of follow-up were referred primarily for correction of atypical symptoms. A standard preoperative evaluation included endoscopy, manometry, upper gastrointestinal contrast radiography, and 24-hour pH probe testing (33 of 35 patients with atypical symptoms). Patients completed a symptom questionnaire administered by a study nurse before the operation and 3 and 12 months after the operation. Symptoms were scored from 0 to 10. Results: Heartburn was relieved by LF in 93% of patients, whereas only 56% of patients had relief of atypical symptoms. Furthermore, the degree of improvement in typical symptoms was greater than that seen for atypical symptoms as measured by the 0 to 10–symptom rating score (improvement in typical symptoms = 6.2 vs improvement in atypical symptoms = 4.4 [p = 0.01]). The response rate for laryngeal, pulmonary, and epigastric/chest pain symptoms was 78%, 58%, and 48%, respectively. Analysis of factors associated with relief of atypical symptoms revealed that response to a preoperative trial of omeprazole or H2-blockers was significantly associated with successful surgical outcome (p = 0.03). Six of seven patients with laryngeal symptoms who had acid reflux above the cricopharyngeal level shown by dual-probe pH testing had relief of the symptoms after LF. Manometric findings (amplitude of esophageal body contractions, propagation of contractions, and lower esophageal sphincter resting pressure) neither predicted nor correlated with relief of atypical symptoms after the operation. Conclusions: Relief of atypical symptoms attributed to gastroesophageal reflux by LF is less satisfactory and more difficult to predict than relief of heartburn and regurgitation. The only useful preoperative predictors of relief of atypical symptoms in this study were the response to pharmacologic acid suppression and dual-probe pH testing (only in patients with laryngeal symptoms). (Surgery 1998;124:28-32.)

Outcomes of atypical symptoms attributed to gastroesophageal reflux treated by laparoscopic fundoplication

Background: The introduction of laparoscopic fundoplication (LF) has lowered the threshold for operation in patients with symptoms attributed to gastroesophageal reflux. We sought to determine whether the outcomes in patients referred for atypical symptoms (pulmonary, pharyngolaryngeal, and pain syndromes) were as good as those referred for correction of heartburn and regurgitation (typical symptoms). Methods: Thirty-five of 150 consecutive patients undergoing LF with a minimum of 12 months of follow-up were referred primarily for correction of atypical symptoms. A standard preoperative evaluation included endoscopy, manometry, upper gastrointestinal contrast radiography, and 24-hour pH probe testing (33 of 35 patients with atypical symptoms). Patients completed a symptom questionnaire administered by a study nurse before the operation and 3 and 12 months after the operation. Symptoms were scored from 0 to 10. Results: Heartburn was relieved by LF in 93% of patients, whereas only 56% of patients had relief of atypical symptoms. Furthermore, the degree of improvement in typical symptoms was greater than that seen for atypical symptoms as measured by the 0 to 10–symptom rating score (improvement in typical symptoms = 6.2 vs improvement in atypical symptoms = 4.4 [ p = 0.01]). The response rate for laryngeal, pulmonary, and epigastric/chest pain symptoms was 78%, 58%, and 48%, respectively. Analysis of factors associated with relief of atypical symptoms revealed that response to a preoperative trial of omeprazole or H 2-blockers was significantly associated with successful surgical outcome ( p = 0.03). Six of seven patients with laryngeal symptoms who had acid reflux above the cricopharyngeal level shown by dual-probe pH testing had relief of the symptoms after LF. Manometric findings (amplitude of esophageal body contractions, propagation of contractions, and lower esophageal sphincter resting pressure) neither predicted nor correlated with relief of atypical symptoms after the operation. Conclusions: Relief of atypical symptoms attributed to gastroesophageal reflux by LF is less satisfactory and more difficult to predict than relief of heartburn and regurgitation. The only useful preoperative predictors of relief of atypical symptoms in this study were the response to pharmacologic acid suppression and dual-probe pH testing (only in patients with laryngeal symptoms). (Surgery 1998;124:28-32.)

Acid suppression and gastri atrophy: sifting fact from fiction

Prolonged pharmacological acid suppression is associated with various histological changes in the gastric mucosa, particularly in Helicobacter pylori infected patients. In a number of subjects these changes include a shift...