Drugs For Gastroesophageal Reflux Disease Research Articles

Drug classes affecting intracranial aneurysm risk: Genetic correlation and Mendelian randomization.

There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach. Using genome-wide association summary statistics we calculated genetic correlation between unruptured IA (N = 2140 cases), ASAH (N = 5140) or the combined group, and liability to drug usage from 23 drug classes (N up to 320,000) independent of the risk factor high blood pressure. Next, we evaluated the causality and therapeutic potential of correlated drug classes using three different Mendelian randomization frameworks. Correlations with IA were found for antidepressants, paracetamol, acetylsalicylic acid, opioids, beta-blockers, and peptic ulcer and gastro-esophageal reflux disease drugs. MR showed no evidence that genetically predicted usage of these drug classes caused IA. Genetically predicted high responders to antidepressant drugs were at higher risk of IA (odds ratio [OR] = 1.61, 95% confidence interval (CI) = 1.09-2.39, p = 0.018) and ASAH (OR = 1.68, 95% CI = 1.07-2.65, p = 0.024) if they used antidepressant drugs. This effect was absent in non-users. For beta-blockers, additional analyses showed that this effect was not independent of blood pressure after all. A complex and likely pleiotropic relationship was found between genetic liability to chronic multisite pain, pain medication usage (paracetamol, acetylsalicylic acid, and opioids), and IA. We did not find drugs decreasing liability to IA and ASAH but found that antidepressant drugs may increase liability. We observed pleiotropic relationships between IA and other drug classes and indications. Our results improve understanding of pathogenic mechanisms underlying IA.

Identification of Competing Endogenous RNA Networks and Potential Therapeutic Drugs for Gastroesophageal Reflux Disease

Background: The diagnosis and cure rate of gastroesophageal reflux disease (GERD) is low, and its pathogenesis remains unclear. Aims: In this study, we aimed to construct the competing endogenous RNA (ceRNA) of GERD by bioinformatics and explore the potential therapeutic drugs for GERD. Methods: The differentially expressed genes (DEGs) were got by limma package and visualized by ggplot2 and pheatmap package in R version 4.1.3 from the GSE63401 gene microarray data. The pro-tein-protein interaction (PPI) network was constructed by the STRING database. The hub genes and subnetwork modules were obtained by Cytoscape software. The microRNA and lncRNA were pre-dicted by the miRTarBase and miRNet databases to construct the ceRNA network. Potential drugs tar-geting DEGs were screened by the CMAP database. Results: In this study, a total of 571 GEDs were obtained, including 462 up-regulated genes and 109 down-regulated genes, which mainly participated in the leukocyte migration process and the cytokine-cytokine receptor interaction pathway. Seventeen miRNAs and three key lncRNAs involved in regulat-ing hub genes were screened through miRTarBase and miRNet databases. Finally, nine ceRNA net-works were obtained, including TTN-AS1/NEAT1/XIST - miR-139-5p - CXCR4 axis, TTN-AS1/NEAT1/XIST - miR-185-5p - IL1B axis and TTN-AS1/NEAT1/XIST - miR-495-3p - LYN axis. In addition, five potential drugs (Pimavanserin, BMS-182874, CL-218872, Losartan, and Laropiprant) for GERD were obtained through the CMAP database. Conclusion: We constructed nine GERD-related ceRNA networks and screened five potential thera-peutic drugs for GERD, providing a theoretical basis for further research on the pathogenesis of GERD.

A comparison of different symptomatic reflux esophagitis treatments: A real-world study.

Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover, whether prokinetics or barrier drugs used alongside PPIs are more effective remains under debate. The aim of the study was to assess the efficacy of different therapeutic approaches to GERD treatment. We enrolled 211 grade A reflux esophagitis patients who consented to participate in this non-randomized, open-label trial. The study consisted of 6 sequentially administered medical treatments for GERD, lasting 2 months, with a 3-week washout period between each drug schedule: Group A: PPI (esomeprazole 40 mg/day before breakfast); Group B: mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, 3 times daily after a meal); Group C: prokinetics (levosulpiride 25 mg or domperidone 10 mg, 3 times daily before a meal); Group D: barrier drug (alginate 3 times daily after a meal); Group E: PPI (esomeprazole 40 mg/day before breakfast) and mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, before sleep); Group F: PPI (esomeprazole 40 mg/day before breakfast) and prokinetics (levosulpiride 25 mg or domperidone 10 mg before lunch and dinner). Symptoms were evaluated using the visual analogue scale (VAS) and global symptomatic score (GSS), as follows: heartburn: 0-3; retrosternal chest pain: 0-3; regurgitation: 0-3. All but 2 treatments (groups C and D) significantly improved VAS and GSS, with group E showing the most significant GSS improvement. Group C had the highest number of dropouts due to treatment failure and reported more side effects. Using PPIs and mucosal protective drugs resulted in significant symptom alleviation. However, the administration of prokinetics caused higher dropouts due to treatment failure.

A Cross-Sectional Survey on the Dispensing Practice and its Determinants from the Retailers’ Perspective in Rural Areas of Gazipur

Being the de facto primary healthcare contacts in rural Bangladesh, retail pharmacy shops (RPSs) influence the medication usage by the people. Therefore, identifying dispensing activities of RPSs can be a key indicator of medicine use. The aim of the current study is to explore the drug dispensing practice of retail pharmacists in the rural areas of Gazipur district. A cross-sectional study was designed to find out drug dispensing practice of analgesic, antipyretic, Gastro Esophageal Reflux Disease (GERD), sedative & hypnotic, ED and multivitamin drugs, assess determinants impacting the practice, and acceptance level of retailers’ suggestions. Forty seven RPSs were selected by random sampling out of 92 in rural areas of Gazipur Sadar from the list of registered allopathic RPSs by the Directorate General Drug Administration (DGDA). Dispensers were interviewed with structured validated questionnaire and data was analyzed using ‘Microsoft Office Excel 2016’. Diclofen, Napa extra, Rivotril, Seclo, Niagra and Filwel Gold were reported to be as the highest dispensed brands at that time. The lowest dispensed brands were found to be Apeclo, Zerin, Relaxen, Procap, Adegra and Biovit Gold. Among determinants impacting dispensing practice, ‘prescriber’s choice’ dominated most in Multivitamin (94%), Sedative & Hypnotic (87%), and Analgesic (77%) groups. ‘Dispenser’s choice’ emerged as a primary determinant in the ED drug group (62%) which is alarming. Moreover, an unlicensed foreign brand, Senegra was found to be dispensed in many drugstores. Buyer’s choice (self-medication) was more remarkable in Antipyretic (38%) and GERD drugs (21%). Although only a few of the reported drugs were over-the-counter (OTC), almost all drugs were being dispensed without prescriptions. As per retailers’ perception, buyers did not seem to be much affected by medicine price (72%) indicating that studied drugs’ price is affordable. A total of 66% dispensers were found to suggest an alternative brand in the absence of a sought brand (brand-substitution) implying to the fact that untrained dispensers may potentially influence drug choice and 77% claimed that buyers usually accept their suggestions which is of no surprise considering the reality of our medication buy-sale practice. Retailers’ perspective might be a great tool to understand drug usage scenario on the ground. Effective regulatory and social initiatives can be devised accordingly to strengthen the rational dispensing and use of medicine. Dhaka Univ. J. Pharm. Sci. 22(1): 55-63, 2023 (June)

Usage Pattern of Fixed-dose Combinations at ICMR Network of Rational Use of Medicine Centres across India: Recommendations for Policymakers and Prescribers.

Irrational use of medicines is a global problem. In India, one contributing factor is the availability of a large number of fixed-dose combinations (FDCs). To improve rational use and to strengthen policies, it is important to assess the usage patterns and rationality of FDCs. This study was conducted as part of a 1-year prospective cross-sectional analysis of prescriptions in the outpatient clinics of broad specialities from 13 tertiary care hospitals across India. Five most commonly prescribed FDCs in each center were analyzed. In addition, all the prescribed FDCs were classified as per the Kokate Committee classification and it was noted whether any of the FDCs were irrational or banned as per the reference lists released by regulatory authorities. A total of 4,838 prescriptions were analyzed. Of these, 2,093 (43.3%) prescriptions had at least one FDC. These 2,093 prescriptions had 366 different FDCs. Of the 366 FDCs, 241 were rational; 10 were irrational; 14 required further data generation; and the remaining 96 FDCs could not be categorized into any of the above. Vitamins and minerals/supplements, antibacterial for systemic use, and drugs for gastroesophageal reflux disease (GERD) and peptic ulcer were the most used FDCs. Based on the finding that some prescriptions contained irrational FDCs, it is recommended that a rigorous, regular, and uniform method of evaluation be implemented to approve/ban FDCs and that prescribers be periodically notified about the status of the bans.

General practitioner prescribing trends among pediatric patients in the United Kingdom: 1998-2018.

To describe the prescribing trends of 17 therapeutic drug categories and the specific drug classes of systemic antibiotics, analgesics, and antidepressants in children and adolescents in the United Kingdom between 1998 and 2018. A population-based retrospective cohort study including children and adolescents aged 018 years. Overall and annual prescription rates per 10 000 person-years and corresponding 95% confidence intervals (CIs) were calculated. Rate ratios and 95% CIs were calculated to assess changes in prescription rates during the study period using Poisson regression. Among 4 075 527 children and adolescents during the study period from 1998 to 2018, the prescribing rates increased by 15% for attention deficit hyperactivity disorder drugs (rate ratio: 1.15, 95% CI: 1.12-1.18), 14% for anxiolytics and hypnotics (rate ratio: 1.14, 95% CI: 1.13-1.16), and 8% for drugs for gastroesophageal reflux disease (GERD) (rate ratio: 1.08, 95% CI: 1.07-1.09). Prescribing rates decreased by 6% for cough preparations (rate ratio: 0.94, 95% CI: 0.92-0.95) and by 3% for analgesics (rate ratio: 0.97, 95% CI: 0.96-0.99). No meaningful changes were observed for systemic antibiotics (rate ratio: 1.02, 95% CI: 0.99-1.04). Among specific drug classes, prescribing rates decreased for broad-spectrum penicillins and cephalosporins, and they increased for selective serotonin reuptake inhibitors, opioids, and drugs for migraine. Between 1998 and 2018, the prescribing of centrally acting drugs and drugs for GERD increased among pediatric patients, whereas prescribing of cough preparations and analgesics declined in this population.

Long-term proton pump inhibitor use does not raise hip fracture risk

Proton pump inhibitors (PPIs) reduce the production of stomach acid and are effective drugs for gastro-oesophageal reflux disease that are commonly prescribed to older people.

Association Between Academic Medical Center Pharmaceutical Detailing Policies and Physician Prescribing

In an effort to regulate physician conflicts of interest, some US academic medical centers (AMCs) enacted policies restricting pharmaceutical representative sales visits to physicians (known as detailing) between 2006 and 2012. Little is known about the effect of these policies on physician prescribing. To analyze the association between detailing policies enacted at AMCs and physician prescribing of actively detailed and not detailed drugs. The study used a difference-in-differences multivariable regression analysis to compare changes in prescribing by physicians before and after implementation of detailing policies at AMCs in 5 states (California, Illinois, Massachusetts, Pennsylvania, and New York) that made up the intervention group with changes in prescribing by a matched control group of similar physicians not subject to a detailing policy. Academic medical center implementation of policies regulating pharmaceutical salesperson visits to attending physicians. The monthly within-drug class market share of prescriptions written by an individual physician for detailed and nondetailed drugs in 8 drug classes (lipid-lowering drugs, gastroesophageal reflux disease drugs, diabetes drugs, antihypertensive drugs, hypnotic drugs approved for the treatment of insomnia [sleep aids], attention-deficit/hyperactivity disorder drugs, antidepressant drugs, and antipsychotic drugs) comparing the 10- to 36-month period before implementation of the detailing policies with the 12- to 36-month period after implementation, depending on data availability. The analysis included 16 121 483 prescriptions written between January 2006 and June 2012 by 2126 attending physicians at the 19 intervention group AMCs and by 24 593 matched control group physicians. The sample mean market share at the physician-drug-month level for detailed and nondetailed drugs prior to enactment of policies was 19.3% and 14.2%, respectively. Exposure to an AMC detailing policy was associated with a decrease in the market share of detailed drugs of 1.67 percentage points (95% CI, -2.18 to -1.18 percentage points; P < .001) and an increase in the market share of nondetailed drugs of 0.84 percentage points (95% CI, 0.54 to 1.14 percentage points; P < .001). Associations were statistically significant for 6 of 8 study drug classes for detailed drugs (lipid-lowering drugs, gastroesophageal reflux disease drugs, antihypertensive drugs, sleep aids, attention-deficit/hyperactivity disorder drugs, and antidepressant drugs) and for 9 of the 19 AMCs that implemented policies. Eleven of the 19 AMCs regulated salesperson gifts to physicians, restricted salesperson access to facilities, and incorporated explicit enforcement mechanisms. For 8 of these 11 AMCs, there was a significant change in prescribing. In contrast, there was a significant change at only 1 of 8 AMCs that did not enact policies in all 3 areas. Implementation of policies at AMCs that restricted pharmaceutical detailing between 2006 and 2012 was associated with modest but significant reductions in prescribing of detailed drugs across 6 of 8 major drug classes; however, changes were not seen in all of the AMCs that enacted policies.

Association of Proton Pump Inhibitor with Hypomagnesaemia: A Cross-Sectional Study at a Tertiary Care Hospital of Anand District

Proton pump inhibitors (PPIs) are one of the most commonly used class of drugs for gastroesophageal reflux disease and number of other common persistent conditions. Hence, risk of potential long-term side effects associated with the use of PPIs is increasing. On March 2, 2011, the US FDA informed the public of the risk of hypomagnesaemia associated with prolonged usage of PPIs. Hence, the present study was undertaken to estimate the risk of development of hypomagnesaemia in patients who have been treatment with PPIs for at least one month and to check whether PPI induced hypomagnesaemia is a long term side effect with all PPIs. General demographic data, type of PPI used along with its duration of use and dose, morbid conditions, concomitant illness and several other confounders available from the basic metabolic panel of 60 patients (30 long term PPI users and 30 non PPI users), was collected and documented using a structured questionnaire. Serum magnesium levels of all 60 patients were estimated and data collected was analysed using T-test and ANOVA. Users on PPIs and non users had a mean serum magnesium level of 1.848 ± 0.023 mg/dL and 2.167 ± 0.34 mg/dL respectively, with the difference being statistically significant (p=0.00) and was independent of age, gender and concomitant drugs prescribed. However female PPI users had slightly lower serum Mg levels. Of the 30 recruited PPI users, 4 were asymptomatic hypomagnesaemic (serum Mg levels<1.7 mg/dL). Mean serum Mg levels in esomeprazole users were slightly higher than those on omeprazole or pantoprazole, with a statistically insignificant difference.

Elcatonin is effective for lower back pain and the symptoms of gastroesophageal reflux disease in elderly osteoporotic patients with kyphosis

Elderly osteoporotic patients with kyphosis tend to be frequently accompanied by the symptoms of gastroesophageal reflux disease (GERD) such as heartburn and acid reflux. Elcatonin, which is effective for lower back pain of osteoporosis, has a physiological action of reducing gastric acid. We examine whether or not this drug would alleviate GERD symptoms as well as lower back pain in patients with osteoporosis. Elcatonin was administrated at a dose of 20 units once weekly for 3 months. The visual analog scale (VAS) and the frequency scale for the symptoms of GERD (FSSG) were used to evaluate lower back pain and GERD symptoms, respectively. Both VAS and FSSG scores significantly decreased after 1, 2 and 3 months of elcatonin administration (at least P < 0.001). Even after the cessation of elcatonin, both scores remained significantly low for an extra 1 and 3 months, respectively. These beneficial effects were also observed in non-steroidal anti-inflammatory drug (NSAID) or GERD drug users. The present findings suggest that elcatonin could improve the symptoms of GERD as well as osteoporosis-invoked back pain in elderly patients with kyphosis, and that these effects are long-lasting and independent of NSAID or GERD drugs.

Prevalence and appropriateness of drug prescriptions for peptic ulcer and gastro-esophageal reflux disease in a cohort of hospitalized elderly

Background Proton pump inhibitors (PPI) are among the most commonly prescribed medicines and their overuse is widespread in both primary and secondary care. Inappropriate prescription is of particular concern among elderly patients, who have often multiple comorbidities and need many drugs. Methods We evaluate the appropriateness of drugs for peptic ulcer or gastro-esophageal reflux disease (GERD) in a sample of elderly patients (65 years old or older) at admission and discharge in 38 internal medicine wards between January 2008 and December 2008, according to the presence of specific conditions or gastro-toxic drug combinations. Results Among 1155 patients eligible for the analysis, 466 (40.3%) were treated with drugs for GERD or peptic ulcer were at hospital admission and 647 (56.0%) at discharge; 62.4% of patients receiving a drug for peptic ulcer or GERD at admission and 63.2% at discharge were inappropriately treated. Among these, the number of other drugs prescribed was associated with greater use of drugs for peptic ulcer or GERD, even after adjustment for age, sex and number of diagnoses at admission (OR 95% CI = 1.26 (1.18–1.34), p = .0001) or discharge (OR 95% CI = 1.11 (1.05–1.18), p = 0.0003). Conclusions Prevalence of inappropriate prescription of drugs for peptic ulcer or GERD remained almost the same at admission and discharge. Inappropriate use of these drugs is related to the concomitant use of other drugs. Careful assessment of clinical conditions and stricter adherence to evidence-based guidelines are essential for a rational and cost-effective use of drugs for peptic ulcer or GERD.

Emerging drugs for gastroesophageal reflux disease

Proton pump inhibitors (PPIs) are very effective and safe drugs for the treatment of erosive and non-erosive gastroesophageal reflux disease (GERD). Nevertheless, a significant proportion of GERD patients (30 – 40%) continue to suffer from symptoms during PPI treatment, which has stimulated the search for better drugs. Improvement of PPI pharmacokinetics and pharmacodynamics has been the main focus of drug development in the past decade with the ultimate goal of optimizing acid inhibition. New inhibitors of the proton pump with a longer half-life, acting faster and longer, have been developed, including potassium-competitive acid blockers. Recent data, however, suggest that the therapeutic efficacy of acid suppression may have reached its maximum and other mechanisms may have to be targeted to further improve symptom control. Potential drugs interacting with different targets are reflux inhibitors such as GABAB receptor agonists and mGluR5 antagonists. These agents reduce the number of transient lower esophageal sphincter relaxation thereby reducing both acid and non-acid reflux. Theoretically, visceral analgesics to modulate visceral perception or even growth factors to enhance mucosal healing may be other emerging drugs to treat GERD.

Emerging drugs for gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease is a common medical problem caused by the exposure of the distal oesophagus to gastric contents. Existing medical therapy is very effective, but symptomatic relief with acid suppressants is often delayed. Treatment focuses on the suppression of gastric acid rather than on the underlying pathophysiological abnormalities, such as transient non-swallow-related lower oesophageal sphincter relaxation. Current pharmacological developments concentrate on drugs with lasting acid suppression and a faster onset of action. Compounds interacting with the complex neuromuscular regulation of the gastro-oesophageal junction are also being developed and offer exciting prospects.

The ethics of placebo-controlled trials: The case of asthma

Some have argued that placebo-controlled trials (PCTs) are unnecessary and unethical in conditions such as asthma for which there is standard therapy. This article, by using asthma clinical trials as an example, examines the ethics of PCTs. There remain several scientifically sound reasons to conduct PCTs: (1) ensuring scientific validity of the trial, (2) evaluating new therapies less effective than the gold standard, (3) minimizing the number of patients exposed to potentially inefficacious or dangerous therapy, (4) studying clinical situations in which withdrawal of therapy might be considered, and (5) determining the true incidence of side effects. Opponents of PCTs err by conflating clinical research with clinical practice and ignoring the fact that all clinical research involves some sacrifice on the part of the subject for the ends of the research and the good of future patients. PCTs do not per se violate major ethical codes. Properly conducted, PCTs remain a valuable and ethical tool in the armamentarium of modern scientific medicine.