The clinical efficacy of many antihypertensive medications is constrained by their poor water solubility, low membrane permeability, significant first-pass metabolism, and uncertain oral bioavailability, even though hypertension is still a major worldwide health concern. For BCS Class II and IV medications like telmisartan, amlodipine, nifedipine, and carvedilol, these restrictions are especially important and call for creative delivery methods. Because of their unique dual hydrophilic-hydrophobic structure, amphiphilic chitosan derivatives have emerged as adaptable nanocarriers that may overcome these limitations. Chitosan can self-assemble into micelles, nanoparticles, nanoemulsions, and hybrid systems, with high encapsulation efficiency for lipophilic drugs when chemically modified with alkyl chains, fatty acids, bile acids, sterols, or synthetic polymer segments. By keeping medications in an amorphous, molecularly dispersed state and providing protection against gastrointestinal degradation, these nanostructures improve solubility. In addition to increasing solubility, amphiphilic chitosan improves drug permeation and systemic absorption by providing strong mucoadhesion, extended intestinal residence, and temporary modulation of tight junctions. Combined oral delivery with these carriers often results in a 2- to 3- fold increase in bioavailability and extended antihypertensive action in preclinical studies. Moreover, amphiphilic chitosan systems can provide sustained and extended release, with reduced peak-trough fluctuations and enhanced therapeutic stability. Their natural origin, biodegradability, acceptable safety profile, and regulatory acceptability strengthen their translation potential. This review carefully scrutinizes the chemistry and self-assembly processes, formulation strategies, pharmacokinetic advantages, safety-related issues, and potential uses of amphiphilic chitosan-based nanocarriers. All things considered, these technologies represent an interesting emerging delivery approach that may improve the oral bioavailability and therapeutic efficacy of poorly soluble antihypertensive drugs.

The dissemination of antibiotic resistance driven by non-antibiotic pharmaceuticals is an emerging concern warranting further investigation. Calcium channel blockers (CCBs), frequently detected in aquatic environments, have rarely been studied for their role in the spread of antibiotic resistance genes (ARGs). This study examines the impact of two representative CCBs, amlodipine (AML) and verapamil (VER), on conjugative horizontal gene transfer (HGT) under low-level chlorine conditions. A bacterial conjugation system was established using Escherichia coli harboring the conjugative plasmid RP4, under simulated residual chlorine exposure typical of water distribution networks (0.3 mg/L). Conjugation assays revealed that, in the absence of residual chlorine, AML and VER at environmentally relevant concentrations (0.01-100 μg/L) exerted negligible effects on ARG conjugative transfer. Similarly, residual chlorine alone did not significantly enhance HGT. However, the co-occurrence of CCBs and residual chlorine synergistically promoted HGT, yielding a maximal 15.2-fold increase in conjugation frequency. This promotional effect was not mediated by increased cell membrane permeability but was driven by elevated reactive oxygen species production, upregulation of efflux pumps and outer membrane porins, and modulated transcription of conjugation-related genes. Notably, the oxidative stress response gene rpoS was upregulated by over 20-fold, while korA/korB (negative regulators) and kilA/kilB (repressors of vertical transfer) were both downregulated, collectively relieving the repression on conjugative transfer. These findings demonstrate that environmental non-antibiotic pharmaceuticals can synergistically promote ARG dissemination under residual chlorine in water supply systems. This study provides a scientific basis for refining risk assessment frameworks for pharmaceutical contaminants in water.

Plasma prorenin is commonly elevated in patients with diabetes and has been associated with the development of albuminuria and progression of diabetic nephropathy. Because albuminuria often reflects podocyte injury, the pathogenic role of prorenin in podocyte dysfunction warrants further investigation. In this study, we examined the association between prorenin and podocyte injury, as well as glomerular fibrosis, using a transgenic rat model in which prorenin is inducibly expressed and secreted from the liver. cyp1a1-prorenin transgenic rats were randomized to receive diets containing increasing concentrations of the gene activator indole-3-carbinol (I3C; 0.05%, 0.15%, or 0.3%) for 4 weeks. Wild-type rats maintained on a normal diet served as controls. I3C administration resulted in a dose-dependent increase in plasma prorenin levels in transgenic rats. Elevated prorenin was associated with increased mean arterial pressure and urinary albumin excretion, accompanied by a dose-dependent reduction in podocyte number and slit diaphragm protein expression, as well as segmental foot process effacement and podocyte hypertrophy. In addition, increased prorenin stimulated renal expression of profibrotic factors and promoted glomerular fibrosis. Treatment with either amlodipine or enalapril for 6 weeks prevented the development of hypertension and partially attenuated podocyte injury, albuminuria, and renal fibrosis, without fully reversing these changes. These protective effects were associated with suppression of NF-κB- and Nox2-mediated inflammatory and oxidative stress pathways. Collectively, these findings demonstrate that prorenin promotes podocyte injury and glomerular fibrosis through mechanisms that are partially dependent on hypertension and angiotensin II but also involve angiotensin II-independent pathways.

Limited information indicates that milk levels of amlodipine are usually low and plasma levels in breastfed infants are undetectable. Maternal use of amlodipine during breastfeeding has not caused any adverse effects in breastfed infants. If amlodipine is required by the mother, it is not a reason to discontinue breastfeeding.

Several studies have supported Dr Gideon Koren’s 1993 landmark article, “Medications Which Can Kill a Toddler with One Tablet or Teaspoonful.” Although each study has its own merits, most focus solely on pediatric overdoses, and few provide an exhaustive reference list for real-time evaluation of ingestions in children and adults. The following xenobiotics warrant special attention because of their potential to cause serious outcomes, even after exposure to small volumes. This list does not imply that all pediatric exposures to these agents result in fatality, and the absence of a xenobiotic from this list does not indicate that it is necessarily safe. α1-Adrenergic agonists and imidazoline receptor agonists: Clonidine, guanfacine, naphazoline, oxymetazoline, tetrahydrozoline, xylazine (veterinary). Sulfonylureas: Chlorpropamide, glyburide, glipizide, glimepiride. Calcium channel blockers: Verapamil, diltiazem, nifedipine, amlodipine, nicardipine, nimodipine; β-Blockers: Metoprolol, labetalol, propranolol, sotalol. Tricyclic antidepressants: Imipramine, desipramine, amitriptyline, nortriptyline. Opioids: Codeine, hydrocodone, methadone, morphine, heroin. Antidiarrheals: Diphenoxylate plus atropine, loperamide. Salicylates and methyl salicylate: Oil of wintergreen, bismuth subsalicylate, mentholated balms, paramao or lawang root oil . Antipsychotics: Loxapine, thioridazine, chlorpromazine. Antimalarials: Chloroquine, hydroxychloroquine, quinine, primaquine. Antiarrhythmics: Quinidine, disopyramide, procainamide, flecainide, amiodarone. Camphor: A terpenoid used as an analgesic, antipruritic agent, and component of cooling gels, ointments, balms, mothballs, household fragrances, and essential oils. Oral camphor use occurs in some regions for religious ceremonies, traditional remedies, aphrodisiacs, or lactation suppression. Nonalkaloid toxic lignan: Podophyllin, podofilox. Unique plant toxins: Colchicine. Oral acetylcholinesterase inhibitors: Rivastigmine, donepezil, galantamine, carbamate pesticides. Methylxanthines: Theophylline, 1,3-dimethylxanthine, caffeine. Other opioids: Buprenorphine, fentanyl. Toxic alcohols: Methanol, ethylene glycol, diethylene glycol. Caustics and other household products: Acidic or alkaline household products, hydrofluoric acid, selenious acid, acetonitrile, methylene chloride. Accidental overdoses continue to occur regularly despite the implementation of various safety measures, including widespread public education, the use of childproof containers, and easy access to poison control centers. In the US, poison control centers receive more than 2.4 million calls annually, with more than 50% involving children younger than 6 years. Most pediatric accidental ingestions involve household cleaning products and analgesics, followed by cosmetics, foreign objects, and dietary supplements. Adult overdoses may be unintentional but often involve larger total doses or high-risk medications, including opioids and sedative-hypnotics. America's Poison Centers identify the 5 most common substance classes as analgesics, household cleaners, antidepressants, cosmetic or personal care items, and cardiovascular drugs. The number of ingestions involving cleaning products increased sharply during the COVID-19 pandemic but has since declined.

We investigated seasonal variation in the office and ambulatory blood pressure control in hypertensive patients treated with two single-pill dual-combination antihypertensive therapies. The study participants (n = 560) were hypertensive patients enrolled in a 24-week therapeutic study. Antihypertensive treatment was initiated with amlodipine/benazepril 5/10 mg/day or benazepril/hydrochlorothiazide 10/12.5 mg/day, with the possible up-titration to 10/20 mg/day or 20/25 mg/day during follow-up, respectively. Office blood pressure was measured at each clinic visit, and ambulatory blood pressure monitoring was performed at baseline and 24-week follow-up. At 24 weeks of follow-up, in patients who continued antihypertensive treatment (n = 511), the proportion of up-titration to higher dosages was significantly different across seasons of treatment commencement in the benazepril/hydrochlorothiazide group (P = 0.002), but not in the amlodipine/benazepril group (P = 0.84). The between-group difference was significantly different in 134 patients who commenced treatment in winter (18.9% vs. 5.0%, P = 0.02), but not in 377 patients who commenced treatment in the other seasons (P ≥ 0.33). The control rate of office blood pressure (<140/90 mmHg) was significantly different across seasons of treatment commencement in the amlodipine/benazepril group (P = 0.01), but not in the benazepril/hydrochlorothiazide group (P = 0.16). The mean changes from baseline to 24-week follow-up tended to be smaller in the benazepril/hydrochlorothiazide than amlodipine/benazepril group in 24-h (mean between-group difference, -2.8 mmHg) and daytime diastolic blood pressure (mean between-group difference, -3.2 mmHg) in patients who commenced treatment in winter, though statistical significance was not achieved (P ≥ 0.07). In conclusion, there was seasonality in the clinic and ambulatory blood pressure-lowering effect of antihypertensive drug combinations, with a marginally significant difference in treatment intensity and blood pressure control between treatment with amlodipine or hydrochlorothiazide in combination with benazepril.

Many hypertensive patients require three or more antihypertensive agents to achieve target blood pressure. This randomized, double-blind, multicenter phase 3 trial conducted in South Korea evaluated the efficacy and safety of a single-pill triple combination therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients whose blood pressure remained inadequately controlled on Val/Aml dual therapy. Patients uncontrolled after 4 weeks of Val/Aml 80/5 mg were randomized 1:1 to either Val/Aml/CTD 80/5/12.5 mg or Val/Aml 80/5 mg using a double-dummy design. After 2 weeks, doses were escalated to Val/Aml/CTD 160/5/25 mg or Val/Aml 160/5 mg, respectively, for a total treatment duration of 6 weeks. The primary endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Of 193 randomized patients, 178 completed the study. The least squares mean ± SE change in MSSBP was -19.70 ± 1.31 mmHg in the Val/Aml/CTD group versus -8.71 ± 1.26 mmHg in the control group, yielding a statistically significant between-group difference of -10.99 ± 1.81 mmHg (95% CI, -14.56 to -7.41; p < 0.0001). No serious adverse events occurred in the Val/Aml/CTD group, compared with an incidence of 1.98% in the control group (p = 0.4985). Triple combination therapy with Val/Aml/CTD demonstrated superior blood pressure reduction and a favorable safety profile in patients with essential hypertension inadequately controlled on Val/Aml dual therapy, supporting its use as an effective treatment option in this population. Trial Registration: This trial was prospectively registered at ClinicalTrials.gov (identifier: NCT06416865).

The One Health philosophy highlights the need to sustainably balance and optimise the health of humans, animals, and ecosystems. Pharmaceuticals are essential for human health, but their usage poses downstream risks to aquatic life. Thus, pharmaceuticals need to be environmentally friendlier whilst delivering the same intended health outcomes. Chiral switch, whereby racemic formulations are replaced with enantiopure versions, is proposed to reduce the environmental burden of pharmaceuticals under the One Health philosophy. This research aimed to develop enantioselective methodologies applicable to complex environmental matrices to inform the chiral switch of commonly prescribed pharmaceuticals. This was achieved using cation exchange solid-phase extraction (SPE) and two separate chiral-high performance liquid chromatography (HPLC) methods for selective detection and quantification of 16 pharmaceuticals (anti-depressants, beta-blockers, calcium-channel blocker, central nervous system stimulant, skeletal muscle relaxant) and primary metabolites in wastewaters. An InfinityLab Poroshell 120 Chiral-V was used to separate cationic enantiomers and CHIRALPAK® ZWIX(+) for zwitterions with enantioresolutions ranging from 0.6 to 4.2. Quantitation limits and trueness values of the SPE-chiral HPLC methods ranged from 6.5 × 10[-2] ng L[-1] to 42 ng L[-1] and from 60% to 119%, respectively. Application of the methodology to wastewater samples revealed several analytes were in non-racemic composition including citalopram, fluoxetine, mirtazapine, desmethylmirtazapine, and ritalinic acid. Greatest enantiomer enrichment was observed for desmethylmirtazapine with a maximum enantiomeric fraction of 0.80. Furthermore, to the best of our knowledge this is the first study to report the enantiomeric composition of baclofen, amlodipine, hydroxyatenolol and ritalinic acid in wastewater. Further application of these newly developed methods can help develop more accurate environmental risk assessments of pharmaceutical enantiomers to inform the proposed chiral switch decision making process in healthcare.

Hypertension may adversely affect bone health, but the skeletal effects of commonly prescribed antihypertensive drugs remain inadequately u nderstood. In this 24-week prospective study, 96 newly diagnosed Stage I hypertensive patients received either Amlodipine (5-10 mg) or Telmisartan (40-80 mg), with serial assessment of bone metabolism markers. Both drugs achieved comparable blood pressure control throughout the study period. Telmisartan significantly reduced PTH and IL-6 levels while enhancing BS-ALP and transiently increasing osteocalcin, whereas Amlodipine demonstrated only a temporary rise in BS-ALP. Thus, data shows the telmisartan may provide additional benefits on bone remodeling and skeletal health in hypertensive patients at risk of fragility.

A man in his early 60s with previously well-controlled hypertension developed sudden deterioration in blood pressure control 2 weeks after starting isoniazid-rifampin therapy for latent tuberculosis infection. His blood pressure had previously been stable on an angiotensin receptor blocker and a calcium channel blocker. He presented with a headache and newly uncontrolled hypertension. Rather than representing progression of essential hypertension, the deterioration was temporally associated with rifampicin-induced cytochrome P450 enzyme induction. Rifampin is a potent inducer of CYP3A4 and can reduce plasma concentrations of calcium channel blockers such as amlodipine by up to approximately 80%, substantially diminishing their antihypertensive effect. Blood pressure improved after escalation of antihypertensive therapy while antituberculosis treatment continued without interruption. This case highlights the importance of structured medication review when evaluating sudden loss of blood pressure control in primary care.