Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed, and two additional oral products received US approval in 2025 and 2026. All eleven US labels examined describe delayed gastric emptying as potentially affecting the absorption of co-administered oral medications. Since the exenatide program, no study has evaluated a narrow therapeutic index victim across more than one administration schedule; the original warfarin and digoxin studies each used a single schedule. The omission may reflect an interaction paradigm built around enzymes and transporters. Current frameworks do not routinely trigger motility-specific studies because the standard in vitro screening cascade does not address gastric emptying. Total area under the concentration-time curve (AUC) may also fail to characterize rate-dependent effects in some victim drugs. Once a class warning is established, further study may receive less priority, and interactions managed by routine dose adjustment may go unreported. Of eleven US prescribing-information documents screened, six contributed quantitative data showing that the direction of effect is not uniform: thyroxine, atorvastatin and ramipril exposures have all been reported to increase under specific conditions, so a reduction in exposure should not be assumed. The class is also pharmacologically heterogeneous; ICH M12 places absorption-mediated interactions outside its scope, and the European Medicines Agency has adopted a concept paper proposing guidance covering them. I propose an evaluation framework built on biopharmaceutically stratified probe panels, timing- and titration-explicit designs, selective use of prespecified partial AUC endpoints for rate-sensitive victims, and physiologically based pharmacokinetic models qualified against human gastric emptying data.

ObjectiveAngiotensin-converting enzyme inhibitors are widely prescribed for cardiovascular disease and are a well-recognized cause of cough. However, cough in patients treated with angiotensin-converting enzyme inhibitor may also reflect underlying pulmonary disease. This study compared the clinical, laboratory, and medication-related characteristics of angiotensin-converting enzyme inhibitor users presenting with pulmonary and non-pulmonary cough.MethodsThis retrospective single-center study included 199 angiotensin-converting enzyme inhibitor-treated patients who presented with cough to the Chest Diseases Outpatient Clinic of Giresun Training and Research Hospital between October 2021 and January 2025. Patients were classified as having cough with pulmonary or non-pulmonary causes according to available clinical, laboratory, and radiological findings. Non-pulmonary cough was not considered synonymous with confirmed angiotensin-converting enzyme inhibitor-induced cough; however, it indicated the absence of identifiable pulmonary pathology based on retrospective data. Demographic, clinical, laboratory, and angiotensin-converting enzyme inhibitor subtype characteristics were compared.ResultsAmong 199 patients, 153 (76.9%) had pulmonary cough and 46 (23.1%) had non-pulmonary cough. Cough duration was longer (p = 0.044) and dyspnea was more frequent (54.2% vs. 13.0%, p < 0.001) in the pulmonary group. Perindopril use was more common in the non-pulmonary group, whereas ramipril use was more common among patients with pulmonary cough (p = 0.015). In a post hoc analysis limited to patients with documented angiotensin-converting enzyme inhibitor discontinuation and evaluable follow-up notes (n = 78), the overall distribution of cough-response categories differed between the groups (Fisher-Freeman-Halton exact p = 0.039), with complete resolution observed in 33.3% of the patients in the non-pulmonary group and 7.9% patients in the pulmonary group. C-reactive protein levels were higher in the pulmonary group (10.87 vs. 5.67 mg/L, p = 0.010), whereas other hematological parameters did not differ significantly.ConclusionsIn the angiotensin-converting enzyme inhibitor-treated patients presenting with cough, shorter symptom duration, absence of dyspnea, and lower C-reactive protein levels may be more compatible with non-pulmonary or presumed angiotensin-converting enzyme inhibitor-related cough, whereas prolonged cough, dyspnea, and elevated C-reactive protein levels may support the consideration of a pulmonary pathology. These findings are hypothesis-generating and require prospective validation.

Background/Objectives: The global rise in obesity-related hypertension, metabolic syndrome, and chronic inflammation calls for a precise characterization of the safety profiles of first-line therapies. While amlodipine is considered metabolically neutral, its real-world impact on dysglycemia and inflammatory biomarkers remains incompletely defined. This study aims to characterize the metabolic and inflammatory adverse drug reaction profile of amlodipine, using the EudraVigilance database. Methods: Descriptive and disproportionality analyses were performed on 41,872 Individual Case Safety Reports recorded prior to 17 May 2026. Amlodipine was compared against major antihypertensive classes (beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartans, and diuretics), calculating reporting odds ratios (ROR) and 95% confidence intervals. Results: "Hyperglycaemia" could be considered a safety signal for amlodipine, compared to beta-blockers (e.g., bisoprolol-ROR: 2.56), ACE inhibitors (e.g., ramipril-ROR: 2.82), and sartans (e.g., candesartan-ROR: 3.85). "Metabolic syndrome" was reported for amlodipine with a lower probability than for hydrochlorothiazide (ROR: 0.35). Inflammatory signals (e.g., increased C-reactive protein) appeared less frequently for amlodipine than for certain renin-angiotensin-aldosterone system inhibitors (e.g., perindopril-ROR: 0.53). Conclusions: The disproportionality analysis identified relatively lower reporting frequencies for several metabolic and inflammatory adverse drug reactions, compared with selected antihypertensive agents. These findings represent pharmacovigilance signals that warrant further investigation in analytical epidemiological and clinical studies. Although hyperglycemia was reported disproportionally relative to several comparator drugs, reports of T2DM were less frequently reported for amlodipine. However, these observations should not be interpreted as evidence of differences in clinical risk, because disproportionality analyses cannot establish incidence or causality. Reports of inflammation likely reflect patient comorbidities rather than a direct drug effect. These findings demonstrate that post-marketing surveillance remains essential, even when accounting for the methodological limitations of spontaneous reporting.

Cardiovascular risk factors are often undertreated in patients with dementia. Renin-angiotensin system inhibitors (RASI) are first-line treatments for hypertension. We examined the association between RASI and all-cause mortality in hypertensive patients with and without dementia, comparing angiotensin-converting enzyme inhibitors (ACEI) to angiotensin receptor blockers (ARB); and selected individual agents. This nationwide register-based cohort study included data from Swedish national registries 2007-2018. The study included 158 176 hypertensive patients with exposure to RASI medications (21 152 RASI users and 137,024 non-users), after excluding prevalent users. Propensity score matching was used to balance measured confounders. Cox regressions compared mortality risk among RASI users versus non-users, ACEI users versus ARB users, and users of enalapril, ramipril, losartan, and candesartan versus other RASI users. RASI use was associated with lower all-cause mortality (hazard ratio[HR] 0.93, 95% confidence interval[CI] 0.91-0.95, p< 0.001) in the full cohort, and among patients with dementia (HR 0.88, 95% CI 0.85-0.92). Compared to ACEI, ARB were associated with lower mortality in the full cohort (HR 0.90, 95% CI 0.85-0.96), but results were not significant in patients with dementia. The comparison of the individual drugs were consistent with class-level findings. RASI use was associated with lower all-cause mortality among older hypertensive patients, including those with dementia. These observational findings support continued attention to evidence-based hypertension treatment in patients with dementia.

Pharmaceutical residues are increasingly detected in aquatic environments and are recognized as contaminants of emerging concern. This systematic literature review compiled and evaluated published concentrations of pharmaceutical residues in bottled water, tap water, and surface water in Portugal, applying risk quotient (RQ) and screening-level risk quotient (RQ_screen) approaches to evaluate potential human health risks and prioritize contaminants. Assessment based on the compiled literature data across age groups showed bottled and tap water posed low risk, while surface water presented the highest concern, with compounds spanning the full risk spectrum. Key contributors to potential human health risk included hormones (17-alpha-ethinylestradiol, 17-beta-estradiol, estrone), ramipril, betamethasone, citalopram, and amoxicillin. RQ_screen highlighted compounds relevant for ongoing monitoring even in treated waters, such as carbamazepine, diclofenac, salicylic acid, warfarin, fluoxetine, and erythromycin, due to their persistence and toxicological significance. Both RQ and RQ_screen indicated higher risk values for infants and children, reflecting lower body weight and higher water intake per unit mass, underscoring the need for age-specific evaluations. The RQ_screen method proved useful for contaminant prioritization, identifying substances relevant for monitoring despite low concentrations. Overall, this systematic review highlights pharmaceutical residues as an emerging public and environmental health concern in Portugal and emphasizes the importance of targeted monitoring and risk-based management within a One Health framework.

Because no information is available on the use of ramipril during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Psoriasis is a chronic, immune-mediated skin disorder characterized by excessive inflammation and the overexpression of pro-inflammatory cytokines, including IL-6, IL-1β, IL-17 A, and IFN-γ. Despite the availability of targeted therapies, current treatments often entail high costs, limited accessibility, and adverse side effects. Drug repurposing-utilizing approved medications for novel indications-offers a cost-effective strategy to accelerate the development of alternative therapies with established safety profiles. Twelve FDA-approved antihypertensive drugs-including ACE inhibitors, angiotensin receptor blockers, beta-blockers, and calcium channel blockers-were computationally evaluated for anti-inflammatory potential in psoriasis. Target cytokines were identified using network analysis via STRING and Cytoscape. Molecular docking was performed against IL-6, IL-1β, IL-17 A, and IFN-γ. The top-performing ligands underwent further analysis using ADMET prediction, BOILED-Egg visualization, Density Functional Theory (DFT) calculations, and molecular dynamics (MD) simulations to assess pharmacokinetics, electronic properties, and protein-ligand complex stability. Apremilast, a clinically approved anti-psoriatic agent, served as the reference drug. Lisinopril, Ramipril, Amlodipine, and Atenolol emerged as top candidates based on docking scores and pharmacokinetic profiles. Among them, Lisinopril exhibited the strongest binding affinity across all four cytokines, comparable to or exceeding that of Apremilast. Amlodipine demonstrated the highest electronic reactivity, and all selected drugs showed favorable ADMET properties. MD simulations over 200 ns confirmed the dynamic stability of the Lisinopril-IL-6 complex. Lisinopril has shown potential as a molecular candidate through detailed computational analysis of cytokine interactions. However, these results are purely predictions and should be viewed with caution, especially considering reports of potential ACE inhibitor-related psoriasis worsening. Further thorough laboratory, animal, and clinical studies are necessary to assess its practical application and safety in treating psoriasis.

The development of environmentally sustainable analytical methodologies capable of resolving highly overlapped multicomponent systems remains an important challenge in modern analytical chemistry. UV spectrophotometry offers several practical advantages, including minimal solvent-consumption, rapid analysis, low operational cost, and instrumental simplicity; however, its quantitative application is often constrained by severe spectral-overlap among analytes. In the present study, a dual-matrix chemometric framework was developed for the simultaneous determination of five spectrally overlapping analytes-hydrochlorothiazide (HCD), losartan potassium (LOS), ramipril (RAP), N-nitrosodiethylamine (NDA), and toluene (TLN)-in pharmaceutical formulations and fortified human plasma samples. The proposed methodology integrates a five-factor, five-level multilevel experimental design for calibration, Sobol quasi-random sampling for external validation, and Firefly Algorithm-optimized Partial Least Squares (FA-PLS) modeling for adaptive wavelength selection and multivariate calibration. The developed models demonstrated excellent analytical performance. For pharmaceutical formulations, mean recoveries ranged from 99.68 to 100.57%, with RMSEP values between 0.037 and 0.094 µg/mL. For fortified human plasma samples, mean recoveries ranged from 98.18 to 98.97%, with RMSEP values between 0.059 and 0.146 µg/mL, demonstrating the feasibility of the proposed approach under biologically relevant matrix conditions. The environmental profile of the proposed methodology was comprehensively evaluated using multiple complementary tools, including NEMI, ComplexGAPI, AGREE, the Multicolor Assessment Tool, carbon footprint estimation, and the Need-Quality-Sustainability index. Collectively, these assessments confirmed the favorable greenness and overall sustainability characteristics of the developed spectrophotometric approach. To the best of our knowledge, no previous UV spectrophotometric chemometric method has been reported for the simultaneous determination of LOS, RAP, and HCD in the presence of both NDA and TLN within a single analytical workflow without a prior separation step. The proposed dual-matrix FA-PLS framework demonstrates that UV spectrophotometry, when coupled with advanced chemometric optimization and statistically designed calibration strategies, can provide an accurate, sensitive, and environmentally sustainable platform for multicomponent pharmaceutical analysis and proof-of-concept application to biological matrices.