Background/Objectives: Diabetes mellitus type 2 (T2DM) is often associated with hypertension, necessitating treatment with combinations of medications that address both glycemic control and blood pressure. Whether commonly co-prescribed antihypertensives modify the glycemic efficacy of a sulfonylurea remains insufficiently characterized in controlled preclinical models. Methods: One hundred adult male Wistar rats were allocated to ten parallel groups (n = 10): healthy and diabetic untreated controls; glimepiride, bisoprolol or amlodipine monotherapy (in healthy and diabetic animals); and the diabetic combinations glimepiride+bisoprolol and glimepiride+amlodipine. T2DM was induced with a high-fat diet plus low-dose streptozotocin (35 mg/kg, i.p.) and confirmed by fasting blood glucose ≥ 200 mg/dL. Glycated hemoglobin (HbA1c) was measured weekly for 11 weeks. Non-parametric inference (Kruskal-Wallis, Dunn's with Bonferroni correction, Mann-Whitney U, Wilcoxon signed-rank) was complemented by Random Forest regression and PCA/K-means clustering. Results: Week-11 HbA1c differed markedly across groups (Kruskal-Wallis H = 94.3, p < 0.001). Glimepiride + bisoprolol achieved near-normal control (4.37% ± 0.15), statistically indistinguishable from healthy groups (p ≥ 0.33), and was the only diabetic regimen with a declining trajectory (-0.66 percentage points; Wilcoxon p = 0.004). Adding either antihypertensive to glimepiride did not worsen glycemic control. Amlodipine monotherapy did not attenuate hyperglycemia (8.47% ± 0.20), approaching that of untreated diabetic controls (9.31% ± 0.18), consistent with the absence of intrinsic glucose-lowering activity. All agents showed pronounced disease-state dependence (healthy-diabetic divergence 2.33-3.13 points). Random Forest prediction was accurate (R[2] = 0.985), and unsupervised clustering separated effective from ineffective regimens, corroborating the statistical findings. Conclusions: In this model, bisoprolol co-administration enhanced and amlodipine co-administration preserved glimepiride-mediated glycemic control. Glimepiride+bisoprolol emerged as the most effective regimen, supporting cardioselective β-blockade as a metabolically favorable antihypertensive partner for sulfonylurea therapy and warranting clinical confirmation. More broadly, these results provide a preclinical, evidence-based rationale for selecting metabolically favorable antihypertensives in patients with coexisting T2DM and hypertension, with the potential to improve glycemic outcomes and reduce the risk of adverse drug-disease interactions during combination therapy.

Cardiovascular diseases, such as hypertension, coronary artery diseases (CAD), arrhythmias, and chronic heart failure (CHF), often require treatment with beta-blockers. These conditions frequently coexist with chronic obstructive pulmonary disease (COPD), which can complicate therapeutic decisions. Indeed, patients with moderate-to-severe COPD are frequently not given these agents out of concern for possible bronchoconstriction arising from blockade of β2-adrenoceptors in the airways. Observational studies, and meta-analyses support the cardiovascular benefits of β-blockade in people with COPD and cardiovascular diseases. Recent trials evaluating cardioselective β-blockade suggest that cardioselective beta-blockers such as bisoprolol, metoprolol and nebivolol are safe and likely beneficial in those patients that would benefit from their intake due to presence of cardiac comorbid diseases. The aim of this systematic review is to summarise the recent trials and indications for use of cardioselective β-blockers in patients with COPD.

Hypertension is a leading chronic disease globally, with rising prevalence in China. A considerable number of hypertension patients struggle to achieve target blood pressure levels with monotherapy alone. The bisoprolol/amlodipine FDC shows promise for blood pressure control and adherence, whereas clinical evidence for Chinese patients is limited. This prospective study evaluated efficacy and safety in patients inadequately controlled by free combination of bisoprolol/metoprolol and amlodipine. In a prospective trial spanning 12 weeks across multiple centers, 78 patients were enrolled who failed 4-week free combinations (e.g., bisoprolol 2.5 mg/day or metoprolol formulations + amlodipine/levamlodipine). Inclusion required office systolic blood pressure (SBP) ≥140 mmHg and/or office diastolic blood pressure (DBP) ≥90 mmHg, with resting heart rate (RHR) ≥70 beats per minute (bpm). Assessments included office BP (OBP) at 4th, 8th, 12th weeks; home BP (HBP) at 0, 1st, 5th, 9th weeks; ambulatory BP at 0, 11 weeks; and time in target range (TTR) at 12 weeks. Patients averaged 49±12.4 years, 73.1% male. After 1 week, home SBP decreased by 6.6 mmHg, DBP by 4.2 mmHg, RHR by 5.5 bpm (all p < 0.0001). OBP significantly reduced at 4 and 8 weeks. By 12 weeks, office SBP dropped by 13.9 mmHg, DBP by 11.2 mmHg, and RHR by 11.3 bpm (all p < 0.0001). The mean Clinic TTR significantly increased by 47.9 percentage points (from 31.3% to 79.2%, p < 0.0001), with the proportion of patients achieving Clinic TTR >70% rising from 19.2% to 66.7% (p < 0.0001). At 11 weeks, ambulatory SBP and HR fell substantially (p < 0.001), and Ambulatory TTR also significantly improved across 24-hour, daytime, and nighttime periods. Bisoprolol/amlodipine FDC is safe and effective for Chinese patients with hypertension not adequately controlled by free combinations of bisoprolol/metoprolol and amlodipine.

Urine drug screening is a valuable diagnostic tool for assessing acute intoxications in the emergency department. Enzyme immunoassay (IA) and immunochromatography (IC) are the two main techniques routinely used due to their rapid turnaround, low cost, and high sensitivity. However, results must be interpreted with caution, as structural cross-reactivity may cause false-positive (FP) findings. We retrospectively analyzed 55 urine samples from emergency patients initially screened for amphetamines by IA and confirmed by gas chromatography-mass spectrometry (GC-MS). Samples containing amphetamine derivatives or potentially cross-reactive substances (tetracaine, trazodone, methylphenidate, ritalinic acid, phentermine, procainamide, ephedrine, bisoprolol, and synthetic cathinones) were subsequently analyzed using an IC assay. Diagnostic performance and cross-reactivity were compared between both screening methods. Of the 55 samples selected by IA, 34 were true positives (TP), 8 true negatives (TN), 2 false negatives (FN), and 11 FP. FP by IA were mainly due to tetracaine, trazodone, phentermine, ephedrine, and procainamide. In comparison, IC yielded 32 TP, 17 TN, 2 FP (phentermine and bisoprolol), and 4 FN. No cross-reactivity with methylphenidate and synthetic cathinones was observed in either technique. IC showed frequent misclassifications between amphetamine and methamphetamine while MDMA detection was more specific. IC is a reliable and rapid alternative for amphetamine screening in the emergency setting, providing improved specificity and fewer false positives than IA. Given its limited discrimination between amphetamine and methamphetamine, IC results should be reported as 'amphetamine derivatives'. These findings highlight assay-dependent cross-reactivity and the importance of understanding methodological limitations for an accurate interpretation.

This study explores a dual-action approach for hypertension management based on a co-formulated suspension containing Candesartan cilexetil (CC) - Bisoprolol fumarate (BF) system, combining FTIR characterisation with computational modelling to evaluate molecular compatibility, binding behaviour, and pharmacokinetic properties.Direct in situ FTIR-ATR spectral analysis confirmed the successful interfacial wetting and co-dispersion of both drugs within the surfactant matrix, driven by robust hydrophobic interactions and cooperative hydrogen bonding. Hirshfeld surface analysis revealed complementary intermolecular interaction patterns between BF and CC, with BF exhibiting flexible hydrogen-bond networks and CC showing directional hydrogen bonding, π-π stacking, and electrostatic interactions.These distinct yet complementary profiles suggest favourable molecular packing and potential co-formulation. Molecular docking further demonstrated balanced binding of the dual system to both β1 and AT1 receptors, with binding energies of -5.19 and -4.88 kcal/mol, respectively. Furthermore, ADMET results indicate poor gastrointestinal absorption and low oral bioavailability, mainly due to high lipophilicity, which may limit in vivo efficacy, although the compound shows an overall acceptable safety profile.In summary, while the CC-BF system appears promising as a dual-target antihypertensive strategy, further formulation improvements and experimental in vitro and in vivo validation are required to confirm its therapeutic potential.

Takotsubo cardiomyopathy (TTC) is a transient and reversible form of left ventricular systolic dysfunction that often mimics acute coronary syndrome and is usually precipitated by emotional or physical stress. We describe an unusual presentation of mid-ventricular TTC in which ventricular arrhythmia was the dominant clinical feature and a probable precipitating factor. A 71-year-old woman presented with left shoulder pain and palpitations in the absence of chest pain or an identifiable emotional stressor. Initial electrocardiography demonstrated frequent runs of rapid non-sustained ventricular tachycardia, with a markedly elevated troponin I level of 2188 ng/L. Coronary angiography showed unobstructed epicardial coronary arteries with delayed contrast clearance. Cardiac magnetic resonance imaging revealed severe left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) 20%-25%) with isolated mid-ventricular akinesia and preserved basal and apical contractility, consistent with a mid-ventricular variant of TTC. Management focused on arrhythmia control and supportive heart failure therapy, with acute stabilisation using intravenous amiodarone followed by beta-blockade with bisoprolol and guideline-directed medical therapy. The ventricular arrhythmia resolved, and left ventricular systolic function improved significantly, with follow-up cardiac magnetic resonance imaging demonstrating recovery of LVEF to 50%. Device therapy was not pursued, given the reversible nature of TTC. This case highlights ventricular arrhythmia as both a presenting manifestation and a possible trigger of TTC and emphasises the importance of considering atypical variants in patients presenting with unexplained cardiomyopathy and ventricular arrhythmias. Multimodality imaging remains essential for accurate diagnosis and for guiding appropriate management in such cases.

Urban aquatic continuums drain emerging organic micropollutants, including WADA-prohibited compounds, which may pose risks to resident health and potentially affect athletes' careers. In this study, 36 WADA-prohibited compounds were selected and quantified along an urban aquatic continuum in Shenzhen, China, spanning WWTP influent and effluent, river inlets (surface water), and ultimately Shenzhen Bay (surface sediment), with caffeine (CAF) and nicotine (NCT) included as reference stimulants. Four β-blockers (bisoprolol, metoprolol, propranolol, and sotalol), cocaine, and furosemide were quantified throughout the continuum, alongside CAF and NCT. During a week-long AM/PM sampling campaign, total loadings of the 24 quantified WADA-prohibited compounds (633 - 2326 ng L[-1], median: 955 ng L[-1]) were approximately one-tenth of those of CAF and NCT in WWTP influent. Removal rates in the WWTP varied widely among the quantified compounds, ranging from negligible to 100%. Within the urban river (Dasha River), attenuation evaluated by comparing compound loadings in WWTP effluent (18 compounds at 143 - 577 ng L[-1], median: 302 ng L[-1]) with those in surface water at the bay inlet (21 compounds at 167 - 512 ng L[-1], median: 315 ng L[-1]) indicated slight increases in both number and concentrations of the quantified compounds, suggesting additional inputs beyond WWTP effluents. A similar pattern was observed for CAF and NCT. As a sink, surface sediment in the bay retained only 10 WADA-prohibited compounds across 4 seasonal sampling events, including fentanyl and betaxolol, which were below quantification limits in water samples, likely due to particulate-bound transport and sedimentation. Gender differences on consumption patterns might also influence environmental loadings of WADA-prohibited compounds, in contrast to CAF (with comparable coffee consumption between male and female populations) and NCT (with male-biased smoking prevalence) in the region. This catchment-based study provides a comprehensive understanding of the environmental behaviors of the WADA-prohibited compounds within an urban aquatic system.

A woman in her 30s presented with acute flaccid paraparesis secondary to severe hypokalaemia. She had a known history of hypertension controlled on amlodipine and bisoprolol. Biochemical workup revealed metabolic alkalosis, renal potassium loss, suppressed plasma renin activity and markedly elevated aldosterone levels. CT imaging identified a left adrenal adenoma consistent with an aldosterone-producing adenoma. The patient underwent laparoscopic adrenalectomy, after which she no longer required antihypertensive medication and maintained normal serum potassium. This case highlights a reversible but often under-recognised cause of secondary hypertension presenting with hypokalaemic paraparesis.

Patients with hypertension, especially when complicated by cardiovascular disease (CVD) and/or comorbidities, require long-term treatment with a combination of antihypertensive drugs, which often gives rise to complex drug regimens. Dual-agent combination antihypertensive therapy is recommended in most patients with hypertension, and where available, a fixed-dose single-pill combination (SPC) is recommended. The combination of antihypertensive drugs should take into account the patient's overall CVD risk profile (other CVD risk factors and diagnoses). The combination of a beta-blocker and angiotensin-converting enzyme inhibitor (ACEi) acts on two neuroendocrine systems implicated in the pathophysiology of hypertension and multiple CVD: beta-blockers on the sympathetic nervous system and ACEis on the renin-angiotensin system (RAS). A large body of solid evidence states that, in addition to their antihypertensive effects, both beta-blockers and ACEis provide cardioprotection and guarantee reductions in CV morbidity and mortality in patients with coronary artery disease (CAD), atrial fibrillation, and heart failure. For these reasons, such a combination might be beneficial for many patients. This review summarizes the evidence supporting the use of beta-blockers and ACEis, as well as the rationale behind their combined administration, particularly in patients with a high risk of CVD, such as those with ischemic heart disease, atrial fibrillation, or heart failure.