Common gastrointestinal drug-drug interactions in geriatrics and the importance of careful planning.

INTRODUCTION: Polypharmacy, which uses multiple medications to treat chronic illnesses, is common among elderly patients. However, it can lead to drug interactions, especially with gastrointestinal (GI) medicines that are extensively used. These drug interactions can have severe consequences and pose a significant challenge to healthcare providers. Therefore, it is crucial to identify the underlying mechanisms of these interactions and develop strategies to minimize medication errors. AREAS COVERED: We analyzed databases on GI illnesses common in older adults, including GERD, peptic ulcer disease, IBS, IBD, constipation, and diarrhea. Our research identified noteworthy drug interactions and utilized major electronic databases such as USFDA, PubMed, Scopus, and Google Scholar until 15 May 202315 May 2023, along with a review of reference lists. EXPERT OPINION: Aging can affect how the body processes drugs, leading to an increased risk of drug interactions. Therefore, healthcare professionals must carefully evaluate a patient's medical history and health condition to design personalized treatment plans.

Is there an appropriate strategy for treating co-morbid irritable bowel syndrome and bladder pain syndrome?

INTRODUCTION: Two of the most frequent components of chronic pelvic pain syndrome (CPPS) are irritable bowel syndrome (IBS) and bladder pain syndrome (BPS), characterized by considerable overlapping symptoms and pathophysiology. Currently, its management is challenging meaning there is high the demand for novel efficient therapeutics to aid patient care and to tackle the socioeconomic burden of IBS and BPS. As there are presently no sufficient treatment strategies, identifying the mechanisms that result in their main symptoms is the opportunity for developing appropriate therapies. Areas covered: Herein, the authors explore the potential common treatment strategies for co-morbid IBS and BPS and highlight the absolute need for further research of these deliberating clinical entities. Expert opinion: In the future, the authors summise that the discovery of predictive molecular biomarkers combined with clinical phenotypic categorization will likely allow for more definitive differentiation of patients and thus for better treatment options. Furthermore, it has been suggested that effective IBS treatment strategies would be of great value to co-morbid IBS and BPS therapy.

Investigational opioid antagonists for treating opioid-induced bowel dysfunction.

INTRODUCTION: Opioids have been highlighted for their role in pain relief among cancer and non-cancer patients. Novel agents have been investigated to reduce opioid-induced constipation (OIC) as the main adverse effect that may lead to treatment discontinuation. Development of peripherally acting mu-opioid receptor antagonists (PAMORA) has resulted in a novel approach to preserve the efficacy of pain control along with less OIC. AREAS COVERED: Clinical evidence for investigational PAMORAs was reviewed and clinical trials on investigational agents to reduce OIC were included. TD-1211 is currently being evaluated in Phase II clinical trial. Oxycodone-naltrexone and ADL-5945 went through Phase III clinical trials, but have been discontinued. EXPERT OPINION: There is a substantial need to develop agents with specific pharmacokinetic properties to meet the needs of patients with underlying diseases. Holding the efficacy of a medicine with the highest selectivity on targeted receptors and the least adverse effects is the main approach in upcoming investigations to improve patients' quality of life (QoL). Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature.

Tumor Necrosis Factor-alpha Antibodies in Fistulizing Crohn's Disease: An Updated Systematic Review and Meta-analysis.

Medical treatment for fistulizing Crohn's disease (FCD) is changing rapidly over the time by the introduction of novel therapeutic medicines, while no global consensus is available. This study aims to accomplish a systematic review and meta-analysis on the efficacy of tumor necrosis factor-alpha antibodies (anti-TNF-α antibodies) versus placebo in FCD. A systematic review of published literature was carried out till December 2016, and a meta-analysis of identified studies was done. Data have been explored from PubMed, Scopus, Cochrane Library Database, and Web of Science. Predefined exclusion criteria for included studies in meta-analysis are based on search methodology and are as follows: Randomized clinical trial about Crohn's disease (CD) patients without fistula, pediatrics CD, randomized clinical trials about pregnant women with FCD, nonhuman studies, randomized clinical trials with surgical therapies interventions, conference abstracts, case reports, and language other than English studies. All randomized placebo-controlled trials were included. To assess risk of bias, Jadad score was applied to evaluate trials' methodological quality. Relative risk (RR) and 95% confidence intervals were computed using Mantel-Haenszel and/or Rothman-Boice (for fixed effects) or Der Simonian-Laird (for random effects) techniques. Nine studies attained defined inclusion criteria. The meta-analysis results showed that anti-TNF-α antibodies are remarkably more effective in comparison to placebo for fistula closure maintenance (RR = 2.36; 95% confidence interval: 1.58-3.55; P < 0.0001) in patients with FCD, whereas anti-TNF-α antibodies were not superior to placebo neither in fistula improvement nor in fistula closure. We concluded that adalimumab and certolizumab pegol are both effective in fistula closure maintenance in adult patients with FCD.

Inflammatory bowel disease therapies discontinued between 2009 and 2014.

INTRODUCTION: New therapeutic approaches are currently under development, which consider the fundamental mechanisms involved in the pathogenesis of inflammatory bowel disease (IBD). The disease is associated with inflamed intestinal and colonic mucosa in response to the dysregulated immune system. AREAS COVERED: The aim of this article is to review drugs that have been designed for the treatment of IBD and discontinued between 2009 and 2014. Herein, nine molecules with different mechanisms of action are under review. Brodalumab, daclizumab, elubrixin and vatelizumab were withdrawn from the Phase II trial due to the lack of efficacy. Abatacept was not significantly superior to the placebo in the rate of remission and its Phase III trials were stopped. CNDO-210 and Catridecacog were discontinued due to safety concerns and lack of efficacy, respectively. Finally, NU-206 and alkaline phosphatase also ceased in development during Phase I and II tests. EXPERT OPINION: The development in our knowledge and understanding of the pathophysiology of IBD and the identification of key objectives for the future play significant roles in IBD therapeutic development. Furthermore, well-planned clinical trials with concise measures of efficacy and safety are required to better decide whether to extend or terminate the development process. Some anti-inflammatory cytokines such as IL-2, IL-12, IL-17, IL-18, IL-23 and INF-γ could garner more attention in the future.

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis.

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model. METHODS: Rats were divided into seven groups. Four groups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha (TNF-α) and interlukin-1ß (IL-1ß), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), and ferric reduced ability of plasma (FRAP) were determined in the colon. RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α (114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1ß (24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS (0.2 ± 0.03 vs 0.49 ± 0.04 µg/mg protein, P < 0.01), MPO (15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP (23.46 ± 1.2 vs 15.02 ± 2.37 µmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO. CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.

New biologic therapeutics for ulcerative colitis and Crohn's disease.

INTRODUCTION: Some inflammatory bowel disease (IBD) patients especially those with refractory Crohn's disease (CD) or relapsing ulcerative colitis (UC) do not respond to current therapies. The newly introduced biological drugs have got some interest due to their specificity and selectivity in modulation of inflammatory elements. AREAS COVERED: In 46 included randomized, placebo-controlled clinical trials, the efficacy and safety of different biologic drugs have been evaluated in moderately to severely active CD or UC patients. Current investigated drugs include new anti-TNF drugs (adalimumab, certolizumab pegol, etanercept, onercept and golimumab), anti-CD20 (rituximab), T-cell inhibitors (abatacept) and anti-α4 integrins (natalizumab and vedolizumab). Adalimumab, certolizumab, and golimumab showed significant efficacy in induction of remission and maintenance in CD and UC patients with a rate of adverse events similar to placebo in the major trials. Natalizumab and vedolizumab were effective in the treatment of moderately to severely active CD and UC patients. However, vedolizumab caused less adverse effects than natalizumab. onercept, etanercept, rituximab and abatacept were all well tolerated but were not effective in CD or UC patients. EXPERT OPINION: Anti-TNF drugs, except for onercept and etanercept, and anti-α4 integrins exhibit beneficial therapeutic effects. Although they were all well tolerated, the incidence of progressive multifocal leukoencephalopathy associated with natalizumab should not be missed.

Benefit of Aloe vera and Matricaria recutita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects.

OBJECTIVE: To evaluate the beneficial effects of a mixture of Aloe vera (AV) and Matricaria recutita (German chamomile, GC) in an experimental model of irritable bowel syndrome (IBS). METHODS: IBS was induced by a 5-day restraint stress in rats including the groups of control (water), GC (300 mg/kg), loperamide (10 mg/kg), mixed AV and GC (50: 50 at doses of 150, 300 or 450 mg/kg assigned as Mix-150, Mix-300 and Mix-450, respectively) and the sham group which did not receive any restraint stress and was fed with saline. All medications were administered intragastrically by gavage for 7 days, 2 days as pre-treatment followed by 5 days during induction of IBS every day before restraining. RESULTS: The increased tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO) activity, and lipid peroxidation (LPO) in colonic cells in the control group were significantly decreased in the treatment groups. GC inhibited only small bowel transit while the AV/GC mixture delayed gastric emptying at the doses of 150 and 300 mg/kg. The AV/GC mixture also reduced colonic transit and small bowel transit at the dose of 150 mg/kg. CONCLUSIONS: The severity of stress-induced IBS was diminished by the AV/GC mixture at all doses used but not dose-dependently, via inhibiting colonic MPO activity and improving oxidative stress status. The effect of the mixture was more effective than GC alone. The present results support effectiveness of the AV and GC combination in IBS.

Effects of Hypericum perforatum extract on rat irritable bowel syndrome.

CONTEXT: In irritable bowel syndrome (IBS), disturbance of bowel motility is associated with infiltration of inflammatory mediators and cytokines into the intestine, such as neutrophils, myeloperoxidase (MPO), tumor necrosis factor alfa (TNF-α), and lipid peroxide. AIMS: Regarding promising anti-inflammatory and anti-oxidative effects of Hypericum perforatum (HP) extract, besides its anti-depressant effect, this study was designed to evaluate the effects of HP in an experimental model of IBS. SETTINGS AND DESIGN: IBS was induced by a 5-day restraint stress in rats. The HP extract was administered by gavage in doses of 150, 300, and 450 mg/kg for 26 days. Fluoxetine and loperamide were used as positive controls. Gastric emptying and small bowel and colon transit, besides the levels of TNF-α, MPO, lipid peroxidation, and antioxidant power, were determined in colon homogenates. STATISTICAL ANALYSIS USED: Data were analyzed by one-way ANOVA followed by Tukey's post hoc test for multiple comparisons. RESULTS: A significant reduction in small bowel and colonic transit (450 mg/kg), TNF-α, MPO, and lipid peroxidation and an increase in antioxidant power in all HP-treated groups (150, 300, and 450 mg/kg) were seen as compared with the control group. Gastric emptying did not alter significantly when compared with the control group. Treatment with loperamide (10 mg/kg) significantly inhibited gastric emptying and small bowel and colonic transit, while flouxetine (10 mg/kg) decreased gastric emptying, TNF-α, MPO, and lipid peroxidation and increased the antioxidant power of the samples in comparison with the control group. CONCLUSIONS: HP diminished the recruitment of inflammatory cells and TNF-α following restraint stress not in a dose-dependent manner, possibly via inhibition of MPO activity and increasing colon antioxidant power, without any difference with fluoxetine. The HP extract inhibits small bowel and colonic transit acceleration like loperamide but has minimal effect on gastric emptying.