Histamine-2 Research Articles

Promoting Activity of Terpenes on Skin Permeation of Famotidine.

Famotidine (FMT) is a competitive histamine-2 (H2) receptor antagonist that inhibits gastric acid secretion for the treatment of Gastroesophageal reflux disease. To study the promoting effect and mechanism of terpenes, including l-menthol, borneol, and geraniol, as chemical enhancers, FMT was used as a model drug. Attenuated total reflectance-Fourier transform IR spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to explore the effects of terpenes on the skin. Hairless mouse skin was mounted on Franz-type diffusion cell, and skin permeation experiment of FMT hydrogel was carried out. The results suggested that the thermodynamic activity influenced the permeability of the drug, and the main mechanism of terpenes to enhance skin permeation of the drug was based on increasing the fluidity of the intercellular lipids. Moreover, it was revealed that l-menthol simultaneously relaxed the packing structure and lamellar structure, whereas geraniol had a great influence on the lamellar structure only. Collectively, all terpenes had a promoting effect on skin permeation of FMT, indicating their potential as chemical enhancers to change the microstructure of stratum corneum and improve the permeation of FMT through the skin, and it has great potential to be used in transdermal formulations of FMT.

Long-term vonoprazan administration causes gastric fundic gland-type hyperplastic polyps and chronic bleeding.

A patient experienced gastric fundic gland-type hyperplastic polyps, consisting of foveolar epithelium and parietal cells, complicated with chronic bleeding due to long-term treatment with vonoprazan. The patient had progressive anemia, probably caused by bleeding from the polyps. After switching from vonoprazan to a histamine-2 (H2) receptor antagonist, the polyps markedly shrank and the anemia improved. Vonoprazan can produce reversible hyperplastic polyps and anemia. In case of anemia in patients receiving long-term vonoprazan, it is important to consider drug cessation or change to an H2 blocker.

Pharmacological Screening Model and Its Treatment of Peptic Ulcer Disease

Peptic ulcer is a ceaseless sickness influencing up to 10% of the total population. Peptic ulcer created by the unevenness of gastric juice pH and mucosal protections. Two fundamental components delivered Peptic ulcer. Frist is central point it included bacterial disease, for example, Helicobacter Pylori (H. Pylori) and medicine non-steroidal anti-inflammatory medication and synthetic E.g., HCL, Ethanol. Second is minor factor it included pressure, smoking, fiery food and nourishment lopsidedness. Ordinary treatment of Peptic ulcer, for example, proton siphon inhibitor (PPI) and Histamine-2 (H2) Receptor Antagonist. Also, other Hand therapeutic plant and their concoction compound are valuable in the counteraction and treatment of peptic ulcer infection. Various creature models are utilizing to influenced ulcer to identifying the antiulcer activity of many new existed drugs such as Pylorus ligated (shay) rats, Stress ulcers, Restraint ulcer in rats, Water immersion-induced restraint ulcers, Cold and restraint ulcers, Gastric mucosal damage induced by NSAID in rats, Induced solitary chronic gastric ulcer, Acetic acid induced kissing gastric ulcers in rats Histamine induced gastric ulcer in guinea pig, Duodenal anti-ulcer activity, Gastric cytoprotective action.

The Review on Peptic Ulcer Disease

Peptic ulcer is a chronic disease affecting up to 10% of the world’s population. The formation of peptic ulcers depends on the presence of gastric juice pH and the decrease in mucosal defenses. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major factors disrupting the mucosal resistance to injury. Conventional treatments of peptic ulcers, such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, have demonstrated adverse effects, relapses, and various drug interactions. Peptic ulcer disease is characterized by discontinuation in the inner lining of the gastrointestinal (GI) tract because of gastric acid secretion or pepsin. It extends into the muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. It may involve the lower esophagus, distal duodenum, or jejunum. Hence, this review presents common medicinal plants that may be used for the treatment or prevention of peptic ulcers. Peptic ulcer disease results from an imbalance between factors that protect the mucosa of the stomach and duodenum, and factors that cause damage to itPeptic ulcer disease presents with gastrointestinal symptoms similar to dyspepsia and can be difficult to distinguish clinically. It can have potentially serious complications such as bleeding or perforation, with a high risk of mortality.

Association of Proton Pump Inhibitor/Histamine-2 Blocker Use and Ocular Toxoplasmosis: Findings from a Large US National Database

To test the hypothesis that the use of proton pump inhibitors (PPIs) is associated with an increased risk of being diagnosed with toxoplasmic retinochoroiditis. Retrospective, matched case-control study using data from 2000 to2020. Patients with ocular toxoplasmosis and controls were matched 5:1 for age, sex, and race, with the eligibility date ± 3 months from the index date of exposed match. Patients aged < 18 years with congenital toxoplasmosis, having < 2 years in the insurance plan before the index date, and without ≥ 1 visit to an eyecare provider before the index date were excluded from the study. Patients with ocular toxoplasmosis were identified using the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes, and PPI use or diseases highly associated with PPIs were identified using national drug codes from an administrative medical claims database. The primary outcome was defined as having a prescription for a PPI or histamine-2 (H2) blocker. Multivariable logistic regression analyses were performed, controlling for demographic and systemic health variables. A total of 4069 cases and 19 177 controls met the eligibility criteria. Of the 4069 patients with ocular toxoplasmosis, 989 (24.3%) were on PPI/H2 blockers compared with 3763 of 19 177 (19.2%) controls. The adjusted logistic regression model demonstrated 1.28 greater odds of PPI/H2 blocker use in cases of ocular toxoplasmosis than matched controls (95% confidence interval, 1.17-1.40; P < 0.001). Proton pump inhibitor/H2 blocker exposure was associated with an increased risk of being diagnosed with ocular toxoplasmosis, corroborating findings from a prior case series. Proprietary or commercial disclosure may be found after the references.

Cimetidine-Based Cationic Amphiphiles for In Vitro Gene Delivery Targetable to Colon Cancer

Cimetidine, a histamine-2 (H2) receptor antagonist, has been found to have anticancer properties against a number of cancer-type cells. In this report, we have demonstrated that cimetidine can acts as a hydrophilic domain in cationic lipids and targetable to the gastric system by carrying reporter genes and therapeutic genes through in vitro transfection. Two lipids, namely, Toc-Cim and Chol-Cim consisting cimetidine as the main head group and hydrophobic moieties as alpha-tocopherol or cholesterol, respectively, were designed and synthesized. 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) is a well-known co-lipid employed to produce liposomes as uniform vesicles. The liposomes and lipoplexes were structurally and functionally evaluated for global surface charges and hydrodynamic diameters, and results found that both liposome and lipoplex size and surface charges are optimal to screen the transfection potentials. DNA-binding studies were analyzed as complete binding at all formulated N/P ratios. The liposomes and lipoplexes of both the lipids Toc-Cim and Chol-Cim show minimal cytotoxicity even though at higher concentrations. The results of the transfection experiments revealed that tocopherol-based cationic lipids (Toc-Cim) show finer transfection efficacy with optimized N/P ratios (2:1 and 4:1) in the colon cancer cell line. Toc-Cim lipoplexes show higher cellular uptake compare to Chol-Cim in the colon cancer cell line at 2:1 and 4:1 N/P ratios. Toc-Cim and Chol-Cim lipids showed highly compatible serum, examined up to 50% of the serum concentration. To evaluate the apoptotic cell death in CT-26 cells, exposed to Toc-Cim:p53 and Chol-Cim:p53 lipoplexes at 2:1 N/P ratios, superior results showed with Toc-Cim:p53. An effect of TP53 protein expression in CT-26 cell lines assayed by western blot, transfected with Toc-Cim:p53 and Chol-Cim:p53 lipoplexes, demonstrated the superior efficacy of Toc-Cim. All of the findings suggest that Toc-Cim lipid is relatively secure and is an effective transfection agent to colon cancer gene delivery.

Anti-ulcer Activities of Herbal Remedies as Alternative Therapy

Peptic ulcer is a disorder that commonly has an effect on the digestive system. It is a chronic illness which has impact on approximately, 10% of the mankind. The majority of current therapy regimens are based on western medicine. Proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, which are commonly used to treat peptic ulcers, have been linked to side effects, relapses, and drug interactions. However, several investigations have shown that herbal medications can efficiently heal stomach ulcers in humans and animals using different processes. As a result, this review will focus on common plants with medicinal value which can be utilized to cure or prevent peptic ulcers.

Histamine-2 (H2 ) antagonists can be safely removed from standard paclitaxel premedication regimens.

AimsThe aim of this study is to investigate the rates of hypersensitivity reactions (HSRs) in patients receiving paclitaxel chemotherapy, with and without a histamine‐2 (H2) antagonists.MethodThis prospective, multi‐centre, cohort study compared patients receiving paclitaxel treated with premedication regimens containing chlorphenamine, dexamethasone and an H2 antagonist vs patients treated without an H2 antagonist. Rates of HSRs were described and logistic multivariable regression was used to investigate any associations with H2 antagonist treatment, adjusting for confounding variables.ResultsA total of 1043 individuals were included in the study; of these, 638 (61%) patients received an H2 antagonist and 405 (49%) were not given an H2 antagonist. Incidence of HSR in the cohort treated with H2 antagonists was 11.31% (n = 70) vs 9.86% (n = 41) in the cohort without. There was no statistically significant difference between the rates of HSR observed in those receiving and not receiving an H2 antagonist (odds ratio 1.04, 95% CI 0.65, 1.66, P = .9).ConclusionsResults presented within the study are consistent with other recently published evidence to suggest that H2 antagonists do not confer any advantage as part of premedication regimens in reducing the incidence of HSR in patients treated with paclitaxel.

Activation of histamine type 2 receptors enhances intrinsic excitability of medium spiny neurons in the nucleus accumbens.

Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, from where they project to many brain areas including the nucleus accumbens (NAc), a brain area that integrates diverse monoaminergic inputs to coordinate motivated behaviours. While the NAc expresses various histamine receptor subtypes, the mechanisms by which histamine modulates NAc activity are still poorly understood. Using whole‐cell patch‐clamp recordings, we found that pharmacological activation of histamine 2 (H2) receptors elevates the excitability of NAc medium spiny neurons (MSNs), while activation of H1 receptors failed to significantly affect MSN excitability. The evoked firing of MSNs increased after seconds of local H2 agonist administration and remained elevated for minutes. H2 receptor (H2R) activation accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, diminished action potential afterhyperpolarization and increased the action potential half‐width. The increased excitability was protein kinase A‐dependent and associated with decreased A‐type K+ currents. In addition, selective pharmacological inhibition of the Kv4.2 channel, the main molecular determinant of A‐type K+ currents in MSNs, mimicked and occluded the increased excitability induced by H2R activation. Our results indicate that histaminergic transmission in the NAc increases MSN intrinsic excitability through H2R‐dependent modulation of Kv4.2 channels. Activation of H2R will significantly alter spike firing in MSNs in vivo, and this effect could be an important mechanism by which these receptors mediate certain aspects of goal‐induced behaviours.Key points Histamine is synthesized and released by hypothalamic neurons of the tuberomammillary nucleus and serves as a general modulator for whole‐brain activity including the nucleus accumbens.Histamine receptors type 2 (HR2), which are expressed in the nucleus accumbens, couple to Gαs/off proteins which elevate cyclic adenosine monophosphate levels and activate protein kinase A.Whole‐cell patch‐clamp recordings revealed that H2R activation increased the evoked firing in medium spiny neurons of the nucleus accumbens via protein kinase A‐dependent mechanisms.HR2 activation accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, diminished action potential medium after‐hyperpolarization and increased the action potential half‐width. HR2 activation also reduced A‐type potassium current.Selective pharmacological inhibition of the Kv4.2 channel mimicked and occluded the increased excitability induced by H2R activation.

A review on peptic ulcer

Peptic ulcer is a chronic disease affecting up to 10% of the world’s population. The formation of peptic ulcers depends on the presence of gastric juice pH and the decrease in mucosal defences. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major factors disrupting the mucosal resistance to injury. Peptic ulcer disease (PUD) is characterized by discontinuation in the inner lining of the gastrointestinal (GI) tract because of gastric acid secretion or pepsin. It extends into the muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. It may involve the lower esophagus, distal duodenum, or jejunum. Epigastric pain usually occurs within 15-30 minutes following a meal in patients with a gastric ulcer; on the other hand, the pain with a duodenal ulcer tends to occur 2-3 hours after a meal. The treatments of peptic ulcers, such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, have demonstrated adverse effects, relapses, and various drug interactions. On the other hand, medicinal plants and their chemical compounds are useful in the prevention and treatment of numerous diseases. Hence, this review presents common medicinal plants that may be used for the treatment or prevention of peptic ulcers.

Functional interaction of H2-receptors and 5HT4-receptors in atrial tissues isolated from double transgenic mice and from human patients

In the past, we generated transgenic mice that overexpress the human histamine 2 (H2)-receptor (H2-TG) or that overexpress the human serotonin 4 (5-HT4)-receptor (5-HT4-TG) in the heart. Here, we crossbred these lines of mice to generate double transgenic mice that overexpress both receptors (DT). This was done to study a conceivable interaction between these receptors in the mouse heart as a model for the human heart. When in left atria, initially, force of contraction was elevated maximally with 1 µM serotonin, and subsequently, histamine was cumulatively applied; a biphasic effect of histamine was noted: the force of contraction initially decreased, maximally at 10 nM histamine, and thereafter, the force of contraction increased again at 1 µM histamine. Notably, functional interaction between 5-HT and histamine was also identified in isolated electrically stimulated trabeculae carneae from human right atrium (obtained during cardiac surgery). These functional and biochemical data together are consistent with a joint overexpression of inotropically active H2-receptors and 5-HT4-receptors in the same mouse heart. We also describe an antagonistic interaction on the force of contraction of both receptors in the mouse atrium (DT) and in the human atrial muscle strips. We speculate that via this interaction, histamine might act as a “brake” on the cardiac actions of 5-HT via inhibitory GTP-binding proteins acting on the activity of adenylyl cyclase.

#21: Risk Factors and Clinical Characteristics of Stenotrophomonas Maltophilia Infections in Neonates &amp; Children from Day 1 to 21-Year Old Between the Years 2008 to 2020

Abstract Background Stenotrophomonas maltophilia is a ubiquitous organism associated with opportunistic infections. In the immunocompromised host, increasing prevalence and severity of illness is observed, particularly opportunistic bloodstream infections and pneumonia syndromes. S. maltophilia is intrinsically resistant to most currently available broad-spectrum antibiotics, including carbapenems and beta-lactams. This intrinsic resistance is due to the presence of chromosomally expressed beta-lactamases, L1 (a metallo-carbapenemase), and L2 (an extended-spectrum beta-lactamases), which together can hydrolyze nearly all betalactam antibiotics including carbapenems. In vitro activity is observed with tetracyclines and fluoroquinolones, but resistance can be rapidly induced mainly due to efflux pumps. Trimethoprim/sulfamethoxazole (TMP-SMX) generally is considered the treatment of choice for S. maltophilia infection, although consideration of S. maltophilia in treatment guidelines is sparse. Additionally, a recent study suggests that S. maltophilia susceptibility to TMP-SMX may be decreasing globally, due in part to acquired antibiotic resistance. Though historically identified as a cause of nosocomial infections, communityonset infections increasingly are being reported. From 1996 to 2016, S. maltophilia was commonly isolated from patients hospitalized with pneumonia and bloodstream infection (BSI), and the incidence of S. maltophilia infection is increasing Methods A retrospective analysis of characteristics and outcomes in patients with S. maltophilia–positive cultures were conducted using the Healthbridge EHR. Study Population This retrospective matched case control study was carried out in neonates with S. maltophilia infections at UHB DOWNSTATE MEDICAL CENTER NICU and Pediatric Department between 2008 and 2020. To identify the case patients, we reviewed the admission and medical records of patients and records from the Microbiology Department in the study period. Control patients were selected from the patients who admitted for at least 72 hours and had pneumonia and/or nosocomial sepsis caused by pathogens other than S. maltophilia. To determine the risk factors for S. maltophilia infections among 35 case patients were compared with 35 control patients. Medical charts of all infants with positive cultures for S. maltophilia and control cases were reviewed for birth weight; gestational age; delivery type; postnatal age at hospitalization; prolonged rupture of membranes; invasive procedures (mechanical ventilation, intubation, urinary catheter, umbilical catheter); duration of mechanical ventilation (day); exposure to antimicrobial agents (aminoglycosides, carbapenems, cephalosporins, penicillins); administration of total parenteral nutrition (TPN); duration of TPN; histamine 2 (H2) blockers; exposure to steroids; cholestasis; elevated liver enzymes; death; sepsis-related death; and duration of hospitalization. All the risk factors for infection were calculated before the onset of infection in both groups. Results in progress Conclusions:

Awareness about FDA announcement on voluntary recall of ranitidine among physicians and pharmacists in and around Chennai, India: a cross-sectional study

BackgroundRanitidine is a histamine-2 (H2) blocker, which decreases the amount of acid created by the stomach. In September 2019, the drug was recalled due to impurities N-nitrosodimethylamine (NDMA) by the Food and Drug Administration (FDA), European Medicines Agency (EMA), and Health Canada. NDMA is a carcinogen based on results from laboratory tests. The objective of the study is to assess the awareness among the physicians and pharmacists in and around Chennai about the ranitidine recall notification and its related issues. A descriptive, cross-sectional study was carried out where a questionnaire was administered on 198 physicians and 113 pharmacists who were enrolled in the study. Awareness, knowledge, and issues related to recall notification were recorded from the participants.ResultsResults showed that only 75% of the study participants were aware of the notification and the issues related, with significantly more participants from the urban area compared with the rural area. When the notification was known by many, the reasons pertaining to the notification were not known.ConclusionOverall, the awareness assessed among physicians and pharmacists was not satisfactory. Physicians and pharmacists are the most responsible healthcare providers and to be updated with every notification on medication published by regulatory bodies.

Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review.

COVID-19 caused by SARS-CoV-2 was declared as a global pandemic by the WHO. Famotidine is a histamine-2 (H2) receptor antagonist which blocks the H2 receptors in the parietal cells, decreasing gastric acid secretion. Our review aims to study all the available scientific evidence on famotidine research outcomes systematically to introspect its clinical efficacy and probable mechanisms and clinical efficacy against SARS-CoV-2. An electronic search of PubMed, Scopus and Google Scholar was performed using MeSH terms "SARS CoV-2" OR "COVID-19" AND"FAMOTIDINE". Relevant informationwas extracted from studies reporting the efficacy of famotidine in COVID-19. We found a total of 32 studies, out of which only 14 were relevant and were included in our review.Molecular computational studies showed that famotidine selectively acts on viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro). Additionally, it acts via inverse-agonism on the H2 receptors present in neutrophils and eosinophils which leads to inhibition of cytokine release. Clinical study findings have pointed toward significant improvements in COVID-19 patient-reported symptoms in non-hospitalized patients and reduction in intubation or death in critically ill patients associated with the usage of famotidine. However,in one of the studies,famotidine has failed to show any significant benefit in reducing mortality due to COVID-19. Famotidine has the potential to answer the ongoing global challenge owing to its selective action on viral replication. Additionally, clinical findings in COVID-19 patients support its efficacy to reduce clinical symptoms of COVID-19.We suggest that further optimally powered randomized clinical trials should be carried out to come up with definitive conclusions.

Peptic Ulcer Disease: An Overview of Aetiology, Pathophysiology, Clinical Presentation, Diagnosis and Treatment Options

Introduction: Peptic ulcer disease (PUD) is endemic in all parts of the world. It is estimated that as high as 5-10% of the world’s population is affected by PUD. Disruption in the gastric protective factors within the gastrointestinal lumen is responsible for the development of PUD. Aggravating factors that promote formation of peptic ulcers include gastric acids, decreased bicarbonate and general decrease in mucosal defences. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major aetiologic factors contributing to damages to the mucosal defence. The major clinical symptom of PUD is epigastric pain. Others includes bloating, heartburn, nausea or vomiting. Testing for H. pylori is important in treatment of PUD. The major complications of H pylori-associated and NSAID-induced ulcers include upper gastrointestinal bleeding, perforation, penetration, gastric outlet obstruction and gastric adenocarcinoma. Purpose: The purpose of this review is to present a general overview of the aetiology, pathophysiology, clinical presentation, diagnosis and treatment options for peptic ulcer disease (PUD). Conclusion: PUD remains a global health challenge requiring that all patients should be treated. Conventional treatments include gastric acid suppressing agents such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists as well as mucosal protective agents. Eradication of H. Pylori is critical in pharmacotherapy of H. pylori associate PUD. New approaches to treatments may include the use of antioxidants containing medicinal plants.

Mucoprotective drugs can prevent and treat nonsteroidal anti-inflammatory drug-induced small bowel enteropathy: a systematic review and meta-analysis of randomized controlled trials.

Background:Small bowel enteropathy (SBE) is a complication of nonsteroidal anti-inflammatory drug (NSAID) therapy occurring in 71% of NSAID users. We aimed to analyse the efficacy and safety of medications to prevent and treat NSAID-induced SBE in randomized controlled trials (RCTs).Methods:This review was registered on PROSPERO (CRD42021223371). We systematically searched four databases until 20 October for comparing mucoprotective (MP), antibiotic and probiotic treatments to placebo, proton-pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists in NSAID-associated small intestinal injuries. The main outcomes were mucosal integrity, mucosal breaks after treatment, mucosal injury improvement and complete healing of mucosal breaks. Meta-analytical calculations for weighted mean differences (WMDs) and odds ratios (ORs) were performed with the random-effects model and interpreted with 95% confidence intervals (CIs).Results:A total of 18 RCTs were included in the quantitative synthesis. MP medications administered preventively reduced the number of mucosal erosions (WMD = −1.24, CI: −2.15 to −0.34) and lead to a significantly lower chance of developing mucosal breaks after treatment (OR = 0.38, CI: 0.16–0.93). MP therapy was associated with a higher rate of complete healing of mucosal breaks (OR = 5.39, CI: 2.79–10.42). In the qualitative synthesis, there were tendencies for a lower increase in the mean number of mucosal breaks and reddened lesions with prophylactic and a higher decrease in mucosal breaks with therapeutic MP drug administration.Conclusion:MP treatment administered with NSAIDs can prevent and reduce small intestinal mucosal lesions.

Physiology of the distal convoluted tubule and collecting duct

Antacids are usually alkaline substances that are used to neutralise excess acid in the stomach. Antacids were developed based on the hydroxides and carbonates of the group II and III metals, as well as the bicarbonates of the alkali metals. Antacids can be classified into two main classes being non-absorbable or absorbable antacids. Non-absorbable antacids have fewer side effects and further advantageous properties. Each antacid has a specific active ingredient which has a different effect on the gastric acid. Antacids act similar to when an acid reacts with a hydroxide; a salt and water are produced. Antacids are more effective in the form of suspension. The average therapeutic dose of an antacid is 10–15 ml of liquid or one to two tablets three to four times a day. These drugs have small volumes of distribution, undergo minimal hepatic metabolism and are excreted in faeces. Antacids that contain calcium, magnesium and aluminium ions are chelators. To avoid undesirable interactions, antacids are usually used two hours before or after taking any medication. Stress ulcerations are common in intensive care unit (ICU) patients. The pathophysiology of the ulceration probably results from an imbalance between mucosal protection and gastric acid hypersecretion. Whilst prophylaxis was provided to every patient previously, it is wise to individualise the decision and to only provide it to high risk patients. For critically ill patients who are able to receive enteral medications and in whom prophylaxis is indicated, an oral proton pump inhibitor (PPI) is preferred rather than an alternative prophylactic agent. For critically ill patients who cannot receive enteral medications, an intravenous (IV) histamine 2 (H2) receptor blocker or IV PPI can be administered. Where PPIs or H2 blockers cannot be administered, sucralfate is a suitable oral alternative.

Pharmacology of antacids

Antacids are usually alkaline substances that are used to neutralise excess acid in the stomach. Antacids were developed based on the hydroxides and carbonates of the group II and III metals, as well as the bicarbonates of the alkali metals. Antacids can be classified into two main classes being non-absorbable or absorbable antacids. Non-absorbable antacids have fewer side effects and further advantageous properties. Each antacid has a specific active ingredient which has a different effect on the gastric acid. Antacids act similar to when an acid reacts with a hydroxide; a salt and water are produced. Antacids are more effective in the form of suspension. The average therapeutic dose of an antacid is 10–15 ml of liquid or one to two tablets three to four times a day. These drugs have small volumes of distribution, undergo minimal hepatic metabolism and are excreted in faeces. Antacids that contain calcium, magnesium and aluminium ions are chelators. To avoid undesirable interactions, antacids are usually used two hours before or after taking any medication. Stress ulcerations are common in intensive care unit (ICU) patients. The pathophysiology of the ulceration probably results from an imbalance between mucosal protection and gastric acid hypersecretion. Whilst prophylaxis was provided to every patient previously, it is wise to individualise the decision and to only provide it to high risk patients. For critically ill patients who are able to receive enteral medications and in whom prophylaxis is indicated, an oral proton pump inhibitor (PPI) is preferred rather than an alternative prophylactic agent. For critically ill patients who cannot receive enteral medications, an intravenous (IV) histamine 2 (H2) receptor blocker or IV PPI can be administered. Where PPIs or H2 blockers cannot be administered, sucralfate is a suitable oral alternative.

Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations

The long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria and in some cases to achlorhydria when compared to other acid-suppressing agents like histamine-2 (H2) receptor blockers and antacids. These consequences by the use of long-term PPIs may lead to significant vitamin (B12 and C) and mineral (iron, calcium and magnesium) deficiencies which needs gastric acid for their absorption and bioavailability. Long-term use of PPIs by the pregnant patients may impose a potential risk of congenital malformations. Various studies have recommended the life style modifications and antacid use as first choice among pregnant womens by preserving PPIs (omeprazole as a safe choice of PPI) for severe conditions of gastroesophageal reflux disease. The long-term acid suppression by PPIs can also lead to enteric, respiratory and urinary tract infections. The hypochlorhydria by chronic PPIs use may induce hypergastrinemia, which ultimately mediates the gastric polyps, gastric carcinoids and gastric cancer. The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose the patients to major adverse cardiac events. This review has enlisted the comprehensive information regarding the adverse effects induced by long-term use of PPIs and their possible relations. Considerable studies like case-control, randomized trials, cohort studies and meta-analysis were reported in supporting these adverse effects. The clinicians and patients should be cautious about these effects so that they can avoid the serious outcomes. PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication.

ROLE OF BOSWELLIC ACID IN THE TREATMENT OF PEPTIC ULCER DISEASE

A peptic ulcer is a chronic disease. Its main features are the incompetent defense of the mucosal and the existence of the gastric juice. The two most important factors that disrupt the balance between the acid and the mucus are the Helicobacter pylori infection (H. pylori) and Non-steroidal anti-inflammatory drugs (NSAIDs). The known treatments like proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists have demonstrated adverse effects and various drug interactions. So the desired approach nowadays is alternative therapies and the usage of herbal products. Boswellic acids provide a potential alternative to the treatment of non-steroidal anti-inflammatory drugs induced peptic ulcer.