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In shallow, open-water engineered wetlands, design parameters select for a photosynthetic microbial biomat capable of robust pharmaceutical biotransformation, yet the contributions of specific microbial processes remain unclear. Here, we combined genome-resolved metatranscriptomics and oxygen profiling of a field-scale biomat to inform laboratory inhibition microcosms amended with a suite of pharmaceuticals. Our analyses revealed a dynamic surficial layer harboring oxic-anoxic cycling and simultaneous photosynthetic, nitrifying, and denitrifying microbial transcription spanning nine bacterial phyla, with unbinned eukaryotic scaffolds suggesting a dominance of diatoms. In the laboratory, photosynthesis, nitrification, and denitrification were broadly decoupled by incubating oxic and anoxic microcosms in the presence and absence of light and nitrogen cycling enzyme inhibitors. Through combining microcosm inhibition data with field-scale metagenomics, we inferred microbial clades responsible for biotransformation associated with membrane-bound nitrate reductase activity (emtricitabine, trimethoprim, and atenolol), nitrous oxide reduction (trimethoprim), ammonium oxidation (trimethoprim and emtricitabine), and photosynthesis (metoprolol). Monitoring of transformation products of atenolol and emtricitabine confirmed that inhibition was specific to biotransformation and highlighted the value of oscillating redox environments for the further transformation of atenolol acid. Our findings shed light on microbial processes contributing to pharmaceutical biotransformation in open-water wetlands with implications for similar nature-based treatment systems.

Introducción: la hipertensión perioperatoria constituye una de las principales alteraciones detectadas durante la colecistectomía video endoscópica. Se presume del efecto protector que tiene el atenolol con su acción beta bloqueadora en reducir esta condición morbosa. Objetivo: evaluar la eficacia del atenolol en prevenir la hipertensión perioperatoria durante la colecistectomía video endoscópica. Método: se realizó un estudio observacional, analítico, longitudinal y prospectivo de tipo cohorte con dos grupos paralelos de estudio, uno de tratamiento y un grupo control, en la Unidad Quirúrgica del Hospital Clínico Quirúrgico “Lucía Íñiguez Landín” de Holguín desde enero a diciembre de 2018- El universo estuvo constituido por los 697 pacientes (N=697) atendidos en la consulta de evaluación preoperatoria y se tomó como muestra a 183 hipertensos (n=183) que se operaron por cirugía video endoscópica de litiasis vesicular, de ellos aleatorizados 95 al grupo de tratamiento con atenolol y 88 al grupo control. A los pacientes del grupo tratamiento se les administró atenolol 25 mg diarios durante 15 días antes de la cirugía. Las variables principales que se monitorizaron fueron las presiones arteriales sistólica, diastólica y media, y se emplearon indicadores para evaluar la efectividad del tratamiento. Resultados: las presiones arteriales preoperatorias disminuyeron de forma significativa en el grupo de tratamiento con atenolol. La hipertensión perioperatoria fue más frecuente en el grupo control. El atenolol es un bloqueador selectivo de los receptores beta 1, ejerce su efecto hipotensor a nivel central al deprimir los centros cardiovasculares simpáticos como el vasomotor bulbar. Conclusiones: el tratamiento con atenolol fue eficaz en reducir la incidencia de hipertensión perioperatoria.

Limited studies have attempted to evaluate pharmaceutical removal during the sidestream partial nitritation (PN) process. In this work, atenolol biodegradation by PN cultures was investigated by maintaining ammonium and pH at different levels. For the first time, free nitrous acid (FNA), other than ammonium, pH, and free ammonia, was demonstrated to inhibit atenolol removal, with biodegradation efficiencies of ∼98, ∼67, and ∼28% within 6 days at average FNA levels of 0, 0.03, and 0.19 mg-N L

Adherence to therapy is the key to a successful therapeutic intervention, especially in cardiovascular diseases in which a lack of adherence may have serious consequences in terms morbidity and/or mortality. In this context, hair analysis can be an excellent tool to monitor adherence to therapy. Indeed, drugs present in blood are incorporated into the hair matrix, where drugs and metabolites can stay unaltered for a long time protected from metabolism and degradation. In the present study, a simple, specific, and sensitive ultra-high performance liquid-chromatography-tandem mass spectrometry (UHPLC-MS/MS) method set up to determine in human hair seven beta-blockers (viz., metoprolol, sotalol, labetalol, atenolol, nebivolol, bisoprolol, and nadolol) and two calcium-channel blockers (lercanidipine and amlodipine), which are widely prescribed to treat medium-to-severe hypertensive conditions. The optimized method was successfully validated in terms of accuracy, repeatability, reproducibility, matrix effect and extraction recovery. Moreover, the applicability of the method was evaluated by analyzing 34 real samples of hair obtained from patients under long-term therapy with calcium channel blockers and beta-blockers.

The pollution of the surface waters by pharmaceuticals and personal care products (PPCPs) has attracted worldwide attention, but data regarding their occurrence and potential risks for the aquatic biota on tropical coastal rivers of South America are still scarce. In this context, the occurrence and the preliminary ecological risk assessment of eleven pharmaceuticals of various therapeutic classes (including cocaine and its primary metabolite, benzoylecgonine) were investigated, for the first time, in five rivers of São Paulo, southeast Brazil, covering a coastline of about 140 km, namely Perequê River, Itinga River, Mongaguá River, Itanhaém River and Guaraú River. Although these five rivers are born in well-preserved areas of the Atlantic rainforest biome, on its way to sea and when they cross the urban perimeter, they receive untreated sewage discharges containing a complex mixture of contaminants. In addition, a "persistence, bioaccumulation and toxicity" (PBT) approach allowed to pre-select the priority PPCPs to be monitored in this coastline. Identification of several PPCPs in the samples was done using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Ten PPCPs were successfully quantified in all five rivers, namely caffeine (9.00-560.00 ng/L), acetaminophen (LOQ-22.24 ng/L), benzoylecgonine (0.30-14.93 ng/L), atenolol (0.12-13.22 ng/L), losartan (0.10-8.42 ng/L), diclofenac (0.76-3.93 ng/L), cocaine (0.05-3.22 ng/L), furosemide (LOQ-3.16), carbamazepine (0.04-0.50 ng/L) and orphenadrine (LOQ-0.14 ng/L). From an ecological risk perspective, caffeine, acetaminophen and losartan can be considered as priority PPCPs because they showed low to moderate risks to algae, crustacean and fishes. However, using the PBT approach, carbamazepine and orphenadrine were also classified as priority compounds, followed by furosemide, acetaminophen, cocaine and losartan (all in second position) and caffeine, atenolol, diclofenac and benzoylecgonine (all in third position). This study provides valuable information to reinforce the importance of continuous monitoring of the coastal rivers of South America (containing PPCPs and illicit drugs) whose diffuse loads flow continuously into the marine ecosystems. Furthermore, ecotoxicological studies (especially with tropical marine organisms) to assess the long-term toxicity of these bioactive compounds are urgent.

The concentrations and distribution of β-blockers, lipid regulators, and psychiatric and cancer drugs in the influent and effluent of the municipal wastewater treatment plant (WWTP) and the effluent of 16 hospitals that discharge into the wastewater treatment plant mentioned in this study at two sampling dates in summer and winter were examined. The pharmaceutical contribution of hospitals to municipal wastewater was determined. The removal of target pharmaceuticals was evaluated in a WWTP consisting of conventional biological treatment using activated sludge. Additionally, the potential environmental risk for the aquatic receiving environments (salt lake) was assessed. Beta-blockers and psychiatric drugs were detected in high concentrations in the wastewater samples. Atenolol (919 ng/L) from β-blockers and carbamazepine (7008 ng/L) from psychiatric pharmaceuticals were detected at the highest concentrations in hospital wastewater. The total pharmaceutical concentration determined at the WWTP influent and effluent was between 335 and 737 ng/L in summer and between 174 and 226 ng/L in winter. The concentrations detected in hospital effluents are higher than the concentrations detected in WWTP. The total pharmaceutical contributions from hospitals to the WWTP in summer and winter were determined to be 2% and 4%, respectively. Total pharmaceutical removal in the WWTP ranged from 23 to 54%. According to the risk ratios, atenolol could pose a high risk (risk quotient10) for fish in summer and winter. There are different reasons for the increase in pharmaceutical consumption in recent years. One of these reasons is the COVID-19 pandemic, which has been going on for 2 years. In particular, hospitals were operated at full capacity during the pandemic, and the occurrence and concentration of pharmaceuticals used for the therapy of COVID-19 patients has increased in hospital effluent. Pandemic conditions have increased the tendency of people to use psychiatric drugs. It is thought that beta-blocker consumption has increased due to cardiovascular diseases caused by COVID-19. Therefore, the environmental risk of pharmaceuticals for aquatic organisms in hospital effluent should be monitored and evaluated.

The histidine-modified zeolitic imidazolate framework [His-ZIF-67] was prepared with the histidine, 2-methylimidazole, and Co

The worldwide occurrence of pharmaceuticals and personal care products (PPCPs) in aquatic ecosystems is reason for concern, since these emerging micro pollutants, includes a large and diverse group of organic compounds, with continuous input, high environmental persistence and potential threat to biota and human health. The aim of this study was to evaluate, for the first time, the occurrence of twenty-seven PPCPs of various therapeutic classes (including cocaine and its primary metabolite, benzoylecgonine), in the coastal waters of Santa Catarina, southern Brazil. Water samples were taken in November 2020, during the low tide periods, at eight sampling points located along the coast of Santa Catarina, covering its entire geographical extension. Sampling was carried out in triplicate and at different depths of the water column. Nine compounds were detected through liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS): caffeine (12.58-119.80 ng/L), diclofenac (1.398-7.920 ng/L), losartan (0.432-3.200 ng/L), cocaine (0.0248-0.1686 ng/L) and benzoylecgonine (0.0146-1.094 ng/L) were quantified in 100% of the samples; carbamazepine (0.0242-0.2720 ng/L) was quantified in 75% of the samples; acetaminophen (0.212-10.040 ng/L) was quantified in 60% of the samples; and both atenolol (1.13-2.50 ng/L) and orphenadrine (0.073-0.0886 ng/L) were quantified in 25% of the samples. The other PPCPs were below the limit of detection (LOD). The highest occurrence of these compounds was detected in the northern and central coastal region of Santa Catarina, namely in Penha and Palhoça cities. The sources of these compounds may be associated with areas with high population density, awaited by tourism, with consequent production of sanitary sewage and solid waste. The ecological risk assessment of these substances in the aquatic ecosystems showed that 67% and 77% of the compounds respectively presented no ecological risk, acute and chronic, but 44% presented low to moderate risks for acute and chronic effects in the three trophic levels evaluated. The occurrence of these chemical compounds can imply deleterious effects on the environmental health of Santa Catarina coastal zone, and therefore deserve more acute and directed attention.

The objective of the present study was formulation and evaluation of pulsatile release tablets of Atenolol. A tablet system consisting of cores which was coated with layers of swelling and rupturable coatings. Cores containing Atenolol as model drug were prepared by direct compression with appropriate ratios of lactose and microcrystalline cellulose and then coated sequentially with different ratios of an inner swelling layer containing HPMC and an outer rupturable layer of Ethyl Cellulose. The effect of level of swelling layer and rupturable coating was investigated. The different formulation press coated by using different weight ratios of Hydroxy Propyl Methyl Cellulose (HPMC) / Ethyl Cellulose (EC) / both HPMC and EC. The optimum result was achieved in formulation containing HPMC: EC weight ratios. The F3 batch achieved a highest burst release after the lag time which is applicable pulsatile drug delivery system of Atenolol.

Emerging contaminants in wastewater pose a greater threat to the environment and the organism in water bodies. The emerging contaminant Atenolol (ATL) belongs to a class of drugs known as beta-blockers. Even micro-level of these contaminants may harm the environment adversely. Hence removal of Atenolol and other emerging contaminants is given prime focus. In this study, modelling of Advanced Oxidation Process (AOP) as the treatment techniques for the removal of Atenolol was performed. Based on literature review, the input parameters for this study were chosen and includes Initial concentration of Atenolol (10–30 mg/L), pH range (7–11), TiO2 Catalyst Concentration (500–1000 mg/L) and Reaction Time (40–120 min). Further the two types of radiation (UV and Visible light radiations) were considered and the process modelled using MINITAB, regression equations and Pareto charts were obtained. In this study, the optimum experimental conditions for maximum removal of ATL was obtained for UV/ TiO2 and Visible light/ TiO2.

Enantioseparation of three β-blockers, i.e., atenolol, metoprolol and propranolol, was studied on amylose tris(3-chloro-5-methylphenylcarbamate) immobilized chiral stationary phase using supercritical fluid chromatography (SFC). The effect of organic modifiers (methanol, isopropanol and their mixture), column temperature and back pressure on chiral separation of β-blockers was evaluated. Optimum chromatographic separation with respect to resolution, retention, and analysis time was achieved using a mixture of CO2 and 0.1% isopropyl amine in isopropanol: methanol (50:50, V/V), in 75:25 (V/V) ratio. Under the optimized conditions, the resolution factors (Rs) and separation factors (α) were greater than 3.0 and 1.5, respectively. Further, with increase in temperature (25–45 °C) and pressure (100–150 bars) there was corresponding decrease in retention factors (k), α and Rs. However, a reverse trend (α and Rs) was observed for atenolol with increase in temperature. The thermodynamic data from van't Hoff plots revealed that the enantioseparation was enthalpy driven for metoprolol and propranolol while entropy driven for atenolol. To understand the mechanism of chiral recognition and the elution behavior of the enantiomers, molecular docking studies were performed. The binding energies obtained from simulation studies were in good agreement with the elution order found experimentally and also with the free energy values. The method was validated in the concentration range of 0.5–10 μg/mL for all the enantiomers. The limit of detection and limit of quantitation ranged from 0.126 to 0.137 μg/mL and 0.376–0.414 μg/mL, respectively. The method was used successfully to analyze these drugs in pharmaceutical preparations., Graphical abstract Image 1, Highlights • Simultaneous enantioseparation of three β-blockers in a single analysis using chiral SFC • Separation efficiency was mainly dependent on the nature and composition of mobile phase • van't Hoff plots revealed enthalpy driven process for metoprolol and propranolol and entropy driven for atenolol • Binding energies from molecular docking study were in good agreement with the elution order • The results suggested hydrogen bonding and hydrophobic interactions, as the dominant interaction modes.

Finally in the project work Atenolol is an anti-hypertensive drug. It has been formulated into fast dissolving tablets by direct compression method by using the Excipients like lactose, sucrose magnesium stearate, sodium lauryl and sulphate and many type super disintegrates such as crosscarmellose and sodium starch glycolate and the prepared by the tablets were evaluated for the pre-compression parameter such as angle of repose, bulk density, tapped density, % index, Hausners ratio, partition coefficients, melting points, UV spectroscopy, % assay, TLC, loss on drying and post compression parameter such as thickness, hardness, friability, drugs contents, weight variation, water absorbance ratio, Invitro disintegrating time , Invitro dissolution studies. All the parameter shows good results. FDTs are prepared by direct compression method are results found to be that the among of nine formulation as the F9 to be best as its shows 87.10% (direct compression method) maximum drug release respectively. The stability testing of manufactured tablets have being at 400 c having 75% relativity humidity for 1month and found to be stable. Prepared fast dissolving tablets of Atenolol 10 mg was found to be under fasting federal condition.

Atenolol was examined as a copper corrosion inhibitor in 1M nitric acid solution using the mass loss technique and quantum chemical studies, based on density functional theory (DFT) at the B3LYP level with the base 6-311G (d,p). The inhibitory efficiency of the molecule increases with increasing concentration and temperature. The adsorption of the molecule on the copper surface follows the modified Langmuir model. The thermodynamic quantities of adsorption and activation were determined and discussed. The calculated quantum chemical parameters related to the inhibition efficiency are the energy of the highest occupied molecular orbital E(HOMO), the energy of the lowest unoccupied molecular orbital E(LUMO), the HOMO-LUMO energy gap, the hardness (η), softness (S), dipole moment (μ), electron affinity (A), ionization energy (I), absolute electronegativity (χ),absolute electronegativity (χ), fraction (ΔN) of electrons transferred from Atenolol to copper and electrophilicity index(ω). The local reactivity was analyzed through the condensed Fukui function and condensed softness indices to determine the nucleophilic and electrophilic attack sites. There is good agreement between the experimental and theoretical results.

OBJECTIVE To investigate associations between short-term treatment with a previously described compounded transdermal formulation of atenolol and heart rate in cats. ANIMALS 11 healthy adult cats. PROCEDURES Cats received the atenolol gel formulation (gradually increased from 12.5 mg/cat, q 24 h to 25 mg/cat, q 12 h) by application to the pinnae at home over a 10-day period in a prospective, experimental study. On day 10, cats were hospitalized for measurement of serum atenolol concentrations 3, 6, and 12 hours after the morning treatment. Mean heart rate measured at the 3- and 6-hour time points was compared with a baseline value (measured at enrollment). RESULTS All cats completed the study; 4 were excluded from analyses after an apparent formulation error was detected in 1 batch. Two cats had minor adverse effects (localized erythema of the pinna). Five of 7 cats had serum atenolol concentrations ≥ 260 ng/mL (considered therapeutic) at ≥ 1 time point. Heart rate had a strong negative correlation (r =–0.87) with serum atenolol concentration. A 90-day drug stability investigation of 4 formulations (identical to the intended study treatment except for pH [range, 6.5 to 7.7]) revealed an apparent decrease in atenolol concentration at a pH of 7.7. CONCLUSIONS AND CLINICAL RELEVANCE Topical administration of the formulation as described resulted in targeted serum atenolol concentrations in most cats, with attendant HR reduction. Validation of these preliminary results in a larger sample and investigation of the treatment in cats with structural heart disease is needed. Verification of appropriate pH (target, 7.0) is likely essential for the compound's stability.

Hypertension is responsible for many morbidities and increasing mortality in India. A lot needs to be done to find safe and yet effective treatment of hypertension. Ayurveda has no direct reference of blood pressure or hypertension in its classics, but various conditions mentioned in classical texts resembles hypertension. A poly herbal combination of ten Ayurvedic herbs called “Shamak Yoga” was in use in Pakwasa hospital, Nagpur for more than twenty five years for management of hypertension along with anxiety, palpitation and insomnia. Objective- To evaluate the effect of Shamak Yoga (SY) on essential hypertension in comparison of Atenolol. Material and Methods – thirty four clinically freshly diagnosed patients of hypertension were randomly divided in two groups. Control group was treated with Tablet Atenolol 50 mg once a day orally and experimental group was treated with SY 2 gm orally twice a day with plain water for 4 weeks. Subjective criteria and objective criteria were observed and recorded; data was analyzed statistically. Results - SY was found comparable and statistically significant effective with Atenolol for systolic and diastolic blood pressure in mild hypertensive patients. SY is most effective on symptoms like headache, giddiness, fatigue, dizziness, sleeplessness, body ache and palpitation.

Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUCiris-ciliary body than AUCaqueous humor, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.

The aim of this study is to investigate the atenolol (ATL) degradation in aqueous suspension using commercial ZnO photocatalysts under solar irradiation. Effects of various operating parameters suc...

BACKGROUND Bleeding during functional endoscopy sinus surgery (FESS) remains a main consideration. Even a small amount of blood may disturb the endoscopic view, increasing the likelihood of complications. So, we decided to compare the effects of clonidine and atenolol as oral premedication for hypotensive anaesthesia in patients undergoing FESS under general anaesthesia. The purpose of this study was to analyse and compare the efficacy of oral atenolol versus oral clonidine as premedication under general anaesthesia for induced hypotension in patients undergoing a functional endoscopic sinus surgery. METHODS The study included total 100 patients of age (18 – 60 years) [American Society of Anaesthesiologists (ASA grade I and II)] who were randomly divided into two groups of 50 each. Group - A (n = 50), a non-labelled clonidine tablet PO was given to the patients in the clonidine group in the dose of 2 mcg/kg at 7 pm the day before surgery and 4 mcg/kg two hours before surgery. Group - B (n = 50), a non-labelled atenolol 25 mg tablet was given PO to the patients in the atenolol group at 7 pm the day before surgery and also 2 hours before surgery. Induction and maintenance of general anaesthesia was performed by the same standard protocol for both groups. Hemodynamic effects [heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), quality of surgical field, intraoperative complications, and post anaesthetic discharge score system (PADSS)] were recorded and statistically analysed. RESULTS The hemodynamic stability and good quality surgical field was obtained in both the groups. The lesser incidence of intraoperative complications recorded with atenolol gives it a more favourable profile when compared to clonidine. CONCLUSIONS We conclude that both oral clonidine and atenolol premedication provides superior and predictable perioperative hemodynamic control, reduces the requirement of hypotensive agents, and produces acceptable recovery characteristics. The lesser incidence of intraoperative complications recorded with atenolol gives it a more favourable profile when compared to clonidine. KEYWORDS Atenolol, Clonidine, Functional Endoscopic Sinus Surgery (FESS)

The incidence of chronic kidney disease is escalating; cardiorenal syndrome (CRS) type 4 is gaining a major health concern causing significant morbidity and mortality, putting major burdens on the healthcare system. This study was designed to compare the cardioprotective effects of carvedilol versus atenolol against CRS type 4 induced by subtotal 5/6 nephrectomy in rats and to explore the underlying mechanisms. Immediately after surgery, carvedilol (20 mg/kg/day) or atenolol (20 mg/kg/day) was added to drinking water for 10 weeks. Carvedilol was more effective than atenolol in improving kidney functions, decreasing elevated blood pressures, attenuating cardiac hypertrophy, reducing serum brain natriuretic peptide, and diminished cardiac fibrous tissue deposition. However, carvedilol was equivalent to atenolol in modulating β1-adrenergic receptors (β1ARs) and cardiac diacylglycerol (DAG) signaling, but carvedilol was superior in modulating β-arrestin2, phosphatidyl inositol 4,5 bisphosphates (PIP2), and caspase 3 levels. Carvedilol has superior cardioprotective effects than atenolol in a rat model of CRS type 4. These protective effects are mediated through modulating cardiac β1ARs/β-arrestin2/PIP2/DAG as well as abating cardiac apoptotic signaling pathways (caspase3/pS473 protein kinase B (Akt)).

The pharmaceutically active compound atenolol, a kind of β-blockers, may result in adverse effects both for human health and ecosystems if it is excreted to the surface water resources. To effectively remove atenolol in the environment, both direct and indirect photodegradation, driven by sunlight play an important role. Among indirect photodegradation, singlet oxygen (1O2), as a pivotal reactive species, is likely to determine the fates of atenolol. Nevertheless, the kinetic information on the reaction of atenolol with singlet oxygen has not been well investigated and the reaction rate constant is still ambiguous. Herein, the reaction rate constant of atenolol with singlet oxygen is investigated directly through observing the decay of the 1O2 phosphorescence at 1270 nm. It is determined that the reaction rate constant between atenolol and 1O2 is 7.0×105 (mol/L)−1·s−1 in D2O, 8.0×106 (mol/L)−1·s−1 in acetonitrile, and 8.4×105 (mol/L)−1·s−1 in EtOH, respectively. Furthermore, the solvent effects on the title reaction were also investigated. It is revealed that the solvents with strong polarity and weak hydrogen donating ability are suitable to achieve high rate constant values. These kinetics information on the reaction of atenolol with singlet oxygen may provide fundamental knowledge to the indirect photodegradation of β-blockers.

Takotsubo syndrome (TS) is a rare but dangerous disease that can be fatal. The pathogenesis of TS is not well understood because there is no animal model of TS that fully mimics TS. It has now been documented that stress exposure (24 h) of rats induced the state which is similar TS in human: contracture damage of myofibrils, elevation of the serum creatine kinase MB level, increased 99mTc-pyrophosphate (99mTc-PYP) accumulation in the heart, QTc interval prolongation, and contractility dysfunction of the heart. Immobilization stress resulted in an increase in coronary blood flow. Emotional stress increased the serum catecholamine level. Blockade of β1-adrenergic receptor (AR) prevented stress-induced cardiac injury (SICI). Blockade of β2-AR aggravated stress-induced cardiac injury. Stimulation of β2-AR increased cardiac tolerance to stress. Inhibition of β3-AR, α1-AR had no effect on SICI. Blockade of peripheral muscarinic receptors or α2-AR aggravated SICI. Pretreatment with the selective β1-AR antagonist atenolol attenuates stress-induced cardiac contractility dysfunction, but recovery of cardiac contractility is not complete. There is indirect evidence that circulating catecholamines play an important role in SICI. Consequently, the activation of β1-AR plays a significant role in SICI. However, there are other receptors which are also involved in SICI and require further investigation.

Hypertension (HTN) in pregnancy is defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg. Based on the values, it is classified as non-severe (< 160/110 mmHg) and severe (≥ 160/110 mmHg). Before starting treatment in non-severe HTN, white- coat HTN should be ruled out. If outpatient management is possible, pharmacological initiation is suggested with sustained high values, avoiding < 120/80 mmHg. Safe drugs during pregnancy are methyldopa, labetalol, and nifedipine-retard. The use of nifedipine-XL or amlodipine can be considered with a lower level of evidence of safety. Diuretics, atenolol, and other beta-blockers for antihypertensive purposes is not recommended in this period. Renin-angiotensin-aldosterone system inhibitors are strictly contraindicated. In postpartum and breastfeeding, the same therapeutic regimen used during pregnancy can be maintained, trying early withdrawal of methyldopa. During puerperium, amlodipine and enalapril are safe, with minimal excretion in breast milk.

In order to improve stability and antibacterial property, a novel super-hydrophilic partially reduced graphene oxide membrane was prepared by interfacial polymerization of piperazine and partially reduced graphene oxide as aqueous solution and trimesoyl chloride as organic solution. Fourier transform infrared spectroscopy, scanning electron microscope, and contact angle measurement were conducted to probe the morphology and properties of the membranes. The modified membrane possessed super-hydrophilicity, improved durability and swelling resistance. The optimized membrane had a molecular weight cut off of about 674 Da and possessed a pure water permeability of 49.86 L·m−2·h−1·MPa−1. The retention order of salts was Na2SO4 > MgSO4 > MgCl2 > Na2CO3 > CaCl2 > NaCl, while the rejection for four kinds of pharmaceuticals followed the order of ibuprofen (92%) > carbamazepine (87%) > amlodipine (80%) > atenolol (76%), indicating that the negatively charged membrane could improve the retention performance by the electrostatic repulsive effect. Moreover, the enhanced antibacterial performance of membrane attributed to the dual effects of the super-hydrophilicity and the tea polyphenols antibacterial material loading, which may alter the charge distribution on and within the membrane, leading to loss of cell viability.

This is a case study of a 25-year-old female, Ashkenazy Jewish, previously healthy, presented with a complaint of weakness. Her sugar level on the glucometer was 50 mg% and she felt better after ingestion of a small amount of sugar. Two weeks earlier, while traveling in Peru, she developed thyrotoxicosis and began taking Mercaptizol 30 mg a day and Atenolol 100 mg. She didn't drink iodine (iodinated preparations for water purification) while traveling and had no pain or fever. Her physical examination showed no goiter or exophthalmos. While I saw her she was already euthyroid and felt quite good except for fatigue. In the literature, we found a few case reports of Mercaptizol and PTU-induced insulin autoantibodies which cause symptomatic hypoglycemia. Most cases were described in the Asian population (especially Japanese people) and resolved a few weeks after stopping intake of the drug. In our patient, the hypoglycemia resolved after only one episode and discontinuation of Mercaptizol. Insulin antibodies were negative, and insulin levels (C-peptide) were relatively high. My conclusion is that physicians should be aware of Mercaptizol and PTU-induced hypoglycemia which can be life-threatening.

Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trials. Hypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rate. Beta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic properties. This position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failure. Analogous differences in beta-blocker efficacy is also likely in hypertension. Beta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blocker first choices in clinical practice. Thus, beta-blockers should be regarded as relevant first choices for hypertension in clinical practice, particularly if characterised by a long half-life, highly selective beta-1 blocking activity and no intrinsic agonist properties.SUMMARYBeta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trialsHypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rateBeta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic propertiesThis position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failureAnalogous differences in beta-blocker efficacy is also likely in hypertensionBeta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blockers first choices in clinical practiceThese observations, in totality, inform our opinion that beta-blockers are relevant first choices for hypertension in clinical practice and this fact needs highlightingFurther, these arguments suggest European hypertension guideline downgrading of beta-blockers is not justified.

Atenolol is a β-blocker considered to be an emerging contaminant due to its potential risk to aquatic ecosystems and human health. The removal of atenolol from water was studied using pumice stone, an amorphous, porous, and low-cost adsorbent. The adsorption process was evaluated in ultrapure water by kinetic, pH, and isotherm batch assays; the matrix effect of wastewater and desorption using ultrapure water were evaluated as well. The adsorption of atenolol in pumice stone adjusted to the pseudo-second-order kinetic model showed fast adsorption in the first 2 h and reached final equilibrium after 48 h. The highest removal in ultrapure water was at pH 7.0. The maximum experimental adsorption capacity obtained for ultrapure water and actual wastewater ranged from 0.632 to 0.154 mg/g, respectively. The equilibrium adsorption experiments showed S-shaped isotherms following the Freundlich model and an increase in adsorption capacity as equilibrium concentration increased. Desorption was up to 55%, demonstrating the potential regeneration of the adsorbent, even on site, using ultrapure water. Furthermore, the results for atenolol, a cationic substance (pKa 9.6), suggest the application of negatively charged pumice as an adsorbent for similar substances of concern.

Aim The mechanism underlying the stiffness of the aorta and iliofemoral artery that is required to maintain blood pressure (BP) is unclear. A new stiffness index of the aorta (aBeta) and iliac-femoral arteries (ifBeta) was defined by applying the cardio-ankle vascular index (CAVI). We compared changes in stiffness of the two arteries in response to reduced BP, due to the non-selective α adrenergic blocker phentolamine and the β1 adrenergic blocker atenolol, in rabbits. Methods Pressure waves at the origin (oA) and distal ends of the aorta (dA) and the distal end of the left femoral artery (fA) were recorded simultaneously using three pressure sensors in 25 anesthetized rabbits. Phentolamine (50 µg/kg/min) and atenolol (10 mg/kg/min) were infused for 2 min. The pulse wave velocity (PWV) in each artery was determined; aBeta, ifBeta, and whole Beta (aifBeta) were calculated by the following formula; Beta=2ρ/PP×ln(SBP/DBP)×PWV2 (ρ: blood density; SBP, SBP, and PP: systolic, diastolic, and pulse pressures, respectively). Results SBP and DBP at oA, dA, and fA decreased by the administration of phentolamine and atenolol, with and without decreased total peripheral vascular resistance. After phentramine infusion, cardiac output (CO), aBeta, and aifBeta increased, while ifBeta decreased. After infusion of atenolol, CO decreased, while aBeta, ifBeta, and aifBeta remained unchanged. Conclusion The contradictory reactions of aBeta and ifBeta to phentolamine suggest that the stiffness of the aorta and ilio-femoral artery is regulated separately during decreased BP induced by phentolamine, but not by atenolol.

Interaction of atenolol (Atn) and metoprolol (Met) beta-blocker drugs with human serum albumin (HSA) at pH 7.4 was investigated by UV–Vis spectroscopy and molecular modeling methods. In addition, the binding interaction information of Atn and Met with HSA practicaly of binding constant (Kb) were determined by the UV–Vis absorption titration at body actual temperature (310.15 K), and were found to be 9.5 × 103, 1.4 × 104, and 2.3 × 104 M–1 for Atn, Met, and Atn + Met, respectively. The results indicated that addition of Atn in many concentrations causes decrease, while addition of Met and Met + Atn leads to an increase in absorption upon complexation with HSA. The binding mechanisms of two target drugs are different from each other, as indicated by spectroscopic analysis. The results show that interactions in all systems are exothermic with negative entropy, which lead to more spontaneous reaction at lower temperatures. Molecular dynamics simulation calculations show that the number of interactive residues between Met and protein is less than the number of interactive residues between Atn and protein.

Background The implications of removing the adjustment for Black race in equations to eGFR on the prevalence of CKD and management strategies are incompletely understood. Methods We estimated changes in CKD prevalence and the potential effect on therapeutic drug prescriptions and prediction of kidney failure if race adjustment were removed from the CKD-EPI GFR estimating equation. We used cross-sectional and longitudinal data from adults aged ≥18 years in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2016, and the Veterans Affairs (VA) Health Care System in 2015. In the VA cohort, we assessed use of common medications that require dose adjustment on the basis of kidney function, and compared the prognostic accuracy of the Kidney Failure Risk Equation with versus without race adjustment of eGFR. Results The prevalence of CKD among Black adults increased from 5.2% to 10.6% in NHANES, and from 12.4% to 21.6% in the VA cohort after eliminating race adjustment. Among Black veterans, 41.0% of gabapentin users, 33.5% of ciprofloxacin users, 24.0% of metformin users, 6.9% of atenolol users, 6.6% of rosuvastatin users, and 5.8% of tramadol users were reclassified to a lower eGFR for which dose adjustment or discontinuation is recommended. Without race adjustment of eGFR, discrimination of the Kidney Failure Risk Equation among Black adults remained high and calibration was marginally improved overall, with better calibration at higher levels of predicted risk. Conclusions Removal of race adjustment from CKD-EPI eGFR would double the estimated prevalence of CKD among Black adults in the United States. Such a change is likely to affect a sizeable number of drug-dosing decisions. It may also improve the accuracy of kidney failure risk prediction among higher-risk Black adults.

The medicinal application of sandpaper leaves in the management of hypertension has been reported with very little knowledge on the variety with better anti-hypertensive properties. Hence, this study seeks to compare phenolic content and the effect of some varieties of sand paper leaves (Ficus spp.), namely, Ficus exasperata (FE), Ficus asperifolia (FA), Ficus mucuso (FM) and Ficus capensis (FC) on the systolic and diastolic bood pressures (SBP and DBP), angiotensin-1-converting enzyme (ACE), and arginase activities and antioxidant status in L-NAME induced hypertensive rats. The animals were divided into eleven groups (n = 6): normotensive control rats, hypertensive rats, hypertensive rats treated with atenolol (10 mg/kg/day), hypertensive rats treated with 2.5% and 5% FE, FA, FM, and FC extract inclusive diet respectively. There was a significant rise (p < 0.05) in the systolic and diastolic blood pressures, ACE and arginase activities, and antioxidant status in the hypertensive rats. However, there were reductions in the SBP, DBP, ACE, and arginase activities and increase in the antioxidant status of the rats fed with the Ficus leaves. FM had the highest phenolic (91.09 mg/100 g) and flavonoid content (43.35 mg/100 g). FA showed the best anti-oxidant property, while FC showed the strongest inhibition of ACE and arginase activities.

Atenolol is a beta-blocker that is cardioselective, meaning it only affects beta receptors. It is used to treat angina pectoris and high blood pressure. The HPLC and Capillary Zone Electrophoresis analytical technique was developed for the purpose of detecting and quantifying Atenolol in human plasma, according to the study paper you're reading right now. The internal standard and atenolol were recovered from the solution after being extracted from plasma using the Liquid-Liquid Extraction method. A mobile phase of 10mM sodium hydrogen phosphate, 7.3mM Sodium Lauryl sulphate (pH=3), methanol, and acetonitrile (40:57:3, v:v:v) is used, with a flow rate of 1.0ml/min. A fluorescence detector was used to detect the isolated materials, which had an excitation wavelength of 229 nm and an emission wavelength of 298 nm. With this in view, Atenolol's and the internal norm's survival times are observed to be 5.4 and 8.3 minutes, respectively. The linear correlation coefficient (R20.9992) was found in the Atenolol calibration curve. The recovery rate for atenolol and an internal norm was estimated to be between 76 and 87 percent. Solid-phase extraction was performed on an uncoated silica capillary with a diameter of 58.5 cm 75 m, and detection was performed at 194 nm in the Capillary Zone Electrophoresis procedure. For an electrolyte solution containing 50mM H3BO3 and 50mM Na2B4O7 (50:50 V/V), atenolol was determined to be present in the solution in less than 3 minutes. Energized with a voltage of 25kV and injected with a hydrodynamic configuration for 4S. Under various conditions, this method was used to assess the stability and capability of measuring Atenolol in human plasma.

The use of recycled glass as a substrate for constructed wetlands was assessed through two studies. The first study examined the dissipation of atenolol, carbamazepine, and sulfamethoxazole in mesocosm-modeled wetlands using glass or limestone gravel as substrates, with or without cattails (Typha spp.). Following pseudo-first-order kinetics, atenolol dissipated the fastest from the water surface of the mesocosms (t1/2~1 day), followed by sulfamethoxazole (t1/2~14 days), and carbamazepine (t1/2~48 days), with no significant differences across treatments. Increased half-lives were observed at greater depth, likely due to light screening. A Monte Carlo sensitivity analysis diagnosed sunlight absorption rates and second-order hydroxyl-mediated indirect photolysis rates to be the main sources of uncertainty in our dissipation rate estimates, compared to our observed rates. The second study examined in situ pharmaceutical removal in tertiary pilot-scale subsurface filters made of crushed recycled glass or sand in a wastewater treatment facility in Manitoba, Canada. Glass and sand showed no significant differences for pharmaceutical removals; atenolol and metoprolol were removed below limits of detection, while carbamazepine and sulfamethoxazole persisted over a retention time of 24 h. Overall, recycled glass performed similarly to traditional substrates for wetland-based wastewater treatment.

Background. The urgent issue of hypertension is determined by its high population incidence, significant burden of the disease, risk of disability and impact on life expectancy. Rational combinations of drugs of different pharmacological groups in case of ineffectiveness of monotherapy to achieve the clinical effect of pharmacotherapy are clearly recommended in the world and national recommendations for diagnosis and treatment of hypertension. Therefore, innovative pharmaceutical development of a combination of antihypertensive drugs and creation of domestic drugs with antihypertensive action is an urgent task of contemporary pharmacy. Objective. The aim of this study was to perform the quality control measurements and evaluation of dissolution tests for different brands of valsartan and atenolol tablets available in Ukraine. Methods. The concentrations of valsartan and atenolol in samples (drug content and dissolution study) were determined by the proposed HPLC method. Results. The results of the tests conducted for evaluation of the tablets were found to be in acceptable limits for all the selected brands. The correlation coefficient (R2) was 0.9991 and the regression equation was y=61.39x+0.3117. It has been established that the equivalence of dissolution profiles for all recommended dissolution media is observed (рН 1.2, 4.5, and 6.8) for the studied drugs. In all three dissolution media, the release rates of valsartan and atenolol of all dosage forms are more than 85% in 15 min. The dissolution profile of all the selected brands was within the standard limits and was acceptable. Conclusions. Analytical method development is an integral part of the quality control measurements and evaluation of dissolution tests. Our previously developed HPLC method is essential for quality control of a large number of samples in short time intervals. Therefore, the method developed by our group is suitable for a routine quality control analysis of any pharmaceutical preparation containing two tested drugs with the suggested chromatographic method advantages for checking quality during dissolution studies of their dosage forms.

In this work, enantiomeric separation of a drug combination of two chiral drugs, namely, atenolol and chlorthalidone, is described. Prior investigation of the effect of different variables on the resolution of the enantiomers' peaks and the total run time represented by the retention time of the last eluted peak was conducted using face-centered composite design. Twenty-two experiments were carried out by varying the chiral stationary phase type as a categorical factor and mobile phase composition including the percentage of ethanol and percentage of diethylamine as continuous factors. According to the optimization process, a mobile phase consisting of hexane:ethanol:DEA:TFA (60:40:0.2:0.1%, v/v/v/v) pumped at flow rate 1 ml min-1 onto Lux-Cellulose 2 stationary phase was applied for the chiral separation and quantification of the drug combination at 230 nm. Application of the developed method to the pharmaceutical formulation of this combination was successfully performed, and satisfactory percentage of recoveries was obtained. The method was also fully validated following International Conference on Harmonization (ICH) guidelines. This method could be of high value and relevance for application in quality control laboratories.

Considering that the treatments adopted by the pharmaceutical industry to remedy their effluents have limitations concerning the efficient degradation of drugs, it is necessary to search for more efficient alternatives. The use of advanced oxidation processes (AOPs) has been showing satisfactory results with regard to the degradation of these persistent substances. In this context, the present work studied the efficiency of the different AOPs for treating an aqueous mixture composed of the drugs atenolol and propranolol. It was observed that the photoperoxidation and photo-Fenton processes were the most efficient for the proposed. The photoperoxidation/UV-C radiation is the best result, with degradations of 94.76% and 100% for the λ of 215 and 280 nm, respectively. For the photo-Fenton process, degradations of 97.53 and 99.26% (UV-C) and 84.60 and 65.72% (LED) were obtained for the two λ mentioned, respectively. The degradation kinetics showed good adjustments to the modified pseudo-first-order models, with 0.92 ≤ R2 ≤ 0.99, for both processes. The toxicity tests carried out with watercress, carrot, and thyme seeds showed that the solutions before and after the tested processes did not present any significant difference in toxicity. These results are in agreement with the HPLC analysis, which verified only the formation of a small peak for each process, with 100% degradation of the drugs.

Objective: In the present scenario high rate of mortality is mainly because of cardiovascular diseases globally. Hence, there is need for extensive research for effective treatment of these cardiovascular diseases. The present study was carried out with aim to evaluate the combined cardioprotective effect of standardized extract of Tinospora cordifolia extract (TCE) with atenolol (AT) and propranolol (PP) in isoproterenol (ISO) induced cardiac necrosis in rats. Methods: Myocardial infarction (MI) or cardiac necrosis was induced by subcutaneous administration of ISO for two days consecutively at an interval of 24 h. Rats were pre-administered with test drugs for 21 days followed by ISO was administration on 20 and 21st day. 24 h after final ISO administration mean arterial blood pressure (MAB), Heart rate (HR), electrocardiogram (ECG), heart bio-marker enzyme and histopathological study of cardiac tissue were evaluated from control and experimental groups and analyzed statistically by one-way ANOVA followed by Tukeys’s test. Results: Rats administered with ISO showed significant changes in ECG, HR, MAB, heart bio-marker enzyme, antioxidant parameters and histopathology of heart. The activities of biomarkers have reduced in serum and there is increase antioxidants in heart tissue of drug treated animals. Similarly, ECG, MAB and HR were restored to normalcy in drug treated animals. Conclusion: It may be concluded that the herb-drug combinations i.e TCE (500 mg/kg) + AT (10 mg/kg) and TCE (500 mg/kg) + PP (10 mg/kg) have shown increased cardioprotective activity than they were used alone.

Evidence for the effectiveness and safety of the third-generation beta-blockers other than atenolol in hypertension remains scarce. We assessed the effectiveness and safety of beta-blockers as first-line treatment for hypertension using three databases in the United States: two administrative claim databases and one electronic health record-based database from 2001 to 2018. In each database, comparative effectiveness of beta-blockers for the risks of acute myocardial infarction, stroke, and hospitalization for heart failure was assessed, using large-scale propensity adjustment and empirical calibration. Estimates were combined across databases using random-effects meta-analyses. Overall, 118,133 and 267,891 patients initiated third-generation beta-blockers (carvedilol and nebivolol) or atenolol, respectively. The pooled hazard ratios of acute myocardial infarction, stroke, hospitalization for heart failure, and most metabolic complications were not different between the third-generation beta-blockers versus atenolol after propensity score matching and empirical calibration (hazard ratio 1.07, 95% CI 0.74 to 1.55 for acute myocardial infarction; hazard ratio 1.06, 95% CI 0.87 to 1.31 for stroke; hazard ratio 1.46, 95% CI 0.99 to 2.24 for hospitalized heart failure). Third-generation beta-blockers were associated with significantly higher risk of stroke than angiotensin-converting enzyme inhibitors (hazard ratio 1.29, 95% CI 1.03 to 1.72), and thiazide diuretics (hazard ratio 1.56, 95% CI 1.17 to 2.20). In conclusion, this study found many patients with first-line beta-blocker monotherapy for hypertension and no statistically significant differences in the effectiveness and safety comparing atenolol with third-generation beta-blockers. Patients on third-generation beta-blockers had a higher risk of stroke than those on angiotensin-converting enzyme inhibitors and thiazide diuretics.

Rational & Objective Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether β-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis. Study Design Retrospective cohort study. Setting & Participants Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included. Exposures Patients were considered treated with β-blockers if they had a quantity of drug dispensed covering the dialysis transition date. Outcomes All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis. Analytical Approach Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between β-blocker use and study outcomes. Results 3,503 patients were included in the study. There were 2,115 (60.4%) patients using β-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any β-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization. Limitations The observational nature of our study could not fully account for residual confounding. Conclusions Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Herein, a novel molecularly imprinted polymer was synthesized on silica nanoparticles via surface imprinting approach for rapid, sensitive and selective detection of atenolol in artificial urine samples. For this purpose, silica nanoparticles were firstly modified with methacryloxy group for surface initiated polymerization and then, polymerization was carried out in the presence of 2-hydroxyethyl methacrylate (functional monomer), ethylene glycol dimethacrylate (cross-linker), azobisisobutyronitrile (initiator), atenolol (template) and acetonitrile (porogen). The surface characterization of imprinted nanoparticles indicated that a thin polymer layer was grafted on the silica nanoparticles. The rebinding properties of the imprinted nanoparticles were investigated in detail and the results revealed that the imprinted nanoparticles had high adsorption capacity (32.06 mg/g), fast adsorption kinetics (15 min for equilibration), high imprinting factor (4.14) towards atenolol and good regeneration ability. The imprinted nanoparticles were also used as selective sorbent for selective extraction and determination of atenolol in artificial urine samples. The results showed that the proposed method good recovery percentages (98.6 %-100.1%) with low standard deviations (less than 4.4%). It is believed that the atenolol-imprinted silica nanoparticles can be used as an alternative sorbent for selective quantification of atenolol in artificial urine samples.

Atenolol is beta blocker absorbed through GIT use for heart diseases. Single tablets, floating tablets and sustained released formulations studied are insufficient to produce effective dose to enhance bioavailability and effectiveness. Our study is focused on development of capsule dosage form containing immediate release (IR) and floating extended release (ER) tablets for monitoring release of atenolol in single dosage form. Two different tablets for IR and ER were prepared in three different combinations (Batch). Pre-formulation and post formulation parameters found to be within acceptable limits of formulation. Release behavior of individual tablets and capsule containing two tablets were studied. Among the batches, capsules containing smaller amount of atenolol in IR and large amount of Atenolol in ER (batch II) showed impressive drug release pattern. This formulation was stable even after a month and achieved optimum release behavior of immediate release and sustained release. This study could be used for effective treatment for different heart complications and reduce toxicity due to high plasma concentration in increased dose frequency.

Objective: analyzing the acquisition and monthly costs for patients on modern fixed-dose antihypertensive combinations in three regions of the Far Eastern Federal District.Material and methods. Intra-group analysis of retail of antihypertensive drugs for 2019 in drugstores of the Khabarovsk Region, Sakhalin Region, Amur Region (n=100) was carried out. The calculation of the monthly cost of therapy was performed and total sales indicators were identified. Statistical analysis: dispersion analysis, Spearman's rank correlation coefficient, Kruskal–Wallis test.Results. The maximum demand in patients among combinations of -blockers in the price range of 100-500 rubles: atenolol+chlortalidone; bisoprolol+amlodipine. In the grope of combinations of angiotensin-converting enzyme inhibitors with diuretics/calcium channel blockers, the most often acquired were: perindopril/ramipril+indapamide/amlodipine, enalapril+hydrochlorothiazide – in the price segment of 500–1000 rubles. Preferences for the use of combinations of angiotensin II receptor blockers+diuretic/calcium channel blockers: valsartan+amlodipine with a monthly cost of therapy of 300–500 rubles; losartan+hydrochlorothiazide – 100–500 rubles and azilsartan+chlortalidonee – 500–1000 rubles. The most popular three-component drugs were valsartan+amlodipine+hydrochlorothiazide, perindopril+amlodipine+indapamide with a monthly cost over 500 rubles. Differences in the acquisition structure of fixed-dose antihypertensive combinations between regions were statistically significant.Conclusion. The share of sales of combined antihypertensive drugs remains insignificant. The main selection criteria within an international nonproprietary name are affordability or trust in a brand. The presence of a reliable correlation of the acquisition structure with the region proves the influence of regional preferences of specialists in drug prescribing.

Pharmaceutically active compounds (PhACs) released into the environment have an adverse impact on the soil and water ecosystem as well as human health. Sorption of PhACs by soils and its potential modification through introduced DOM in the applied animal manure or treated wastewater (TWW) determines the mobility and environmental relevance of PhACs. Sulfadiazine, caffeine and atenolol were selected as target PhACs to investigate their sorption behaviors by five selected arable soils in the absence and presence of pig manure DOM. Sulfadiazine was least sorbed, followed by caffeine and atenolol according to the Freundlich sorption isotherm fit (soil average Kf [μg(1−n) mLn g−1] 4.07, 9.06, 18.92, respectively). The addition of manure DOM (31.34 mg C L−1) decreased the sorption of sulfadiazine and especially of caffeine and atenolol (average Kf 3.04, 6.17, 5.79, respectively). Freundlich sorption isotherms of the PhACs became more nonlinear in the presence of manure DOM (Freundlich exponent n changed from 0.74–1.40 to 0.62–1.12), implying more heterogeneous sorption of PhACs in soil–DOM binary systems. Sorption competition of DOM molecules with sulfadiazine and caffeine mostly contributed to their decreased soil sorption when DOM was present. In contrast, the formation of DOM–atenolol associates in the solution phase caused the largely decreased soil sorption of atenolol in the presence of DOM. It is suggested that DOM concentration (e.g., ≥ 60 mg C L−1) and its interaction with PhACs should be taken into consideration when assessing the environmental impact of land application of animal manure or irrigation with TWW.

Hypertension in pregnancy is currently defined as a systolic blood pressure (BP) of 140 mmHg or more, or a diastolic BP of 90 mmHg or more. This level of BP warrants antihypertensive therapy. Treating to a target BP of 135/85 mmHg halves the risk of severe hypertension that is itself associated with adverse maternal and perinatal outcomes, similar in magnitude to preeclampsia. While based on the results of the Control of Hypertension in Pregnancy Study (CHIPS) trial, this finding is consistent with all antihypertensive trials to date. Also, in the CHIPS trial, “tight” BP control also halved the risk of progression to thrombocytopenia and elevated liver enzymes for the mother, without adverse effects for the fetus or newborn. This was true regardless of the gestational age at which BP control was instituted. While methyldopa, labetalol, and nifedipine are the most commonly-recommended oral antihypertensives, it is not clear that one antihypertensive agent has advantages over the others for treatment of non-severe hypertension in pregnancy. No antihypertensives, including renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to be teratogenic, although there may be an increase in malformations associated with the underlying condition of chronic hypertension. Atenolol and RAAS inhibitors should not be used once pregnancy is diagnosed, based on fetotoxicity. At present, BP treatment targets used in clinic are the same as those used at home as the differences are quite variable among hypertensive women. For treatment of acute severe hypertension, the most commonly-recommended antihypertensives are oral nifedipine, IV labetalol, and IV hydralazine, although oral agents have also been shown to be effective in the majority of women; while concerns raised about IV hydralazine-induced maternal hypotension and its consequences have not been confirmed, this medication may be an inferior antihypertensive to oral nifedipine. While treatment recommendations are based on evidence, women should be engaged in decision-making, as their values may alter target BP and antihypertensive choice. Future work will clarify the optimal target BP based on home BP measurements; whether BP targets should be lowered further if the definition of hypertension is based on a lower BP; which, if any, antihypertensive medication for non-severe hypertension is better with regards to maternal and perinatal outcomes; and whether factors beyond BP level (such as variability, race, and other physiological variables) should inform antihypertensive therapy in pregnancy.

This study is on photocatalytic degradation of pharmaceutical residues of atenolol (ATL) and acetaminophen (ACT) present in secondary effluent under visible light irradiation stimulated by Ag doped ZnO (Ag-ZnO) photocatalyst. Lawsonia inermis leaf extract was used for reduction of Zinc sulphate to ZnO nanoparticles (NPs). Further, ZnO NPs were doped with Ag and characterized by XRD, FT-IR, SEM-EDX, surface area analyzer, UV-Vis, and photoluminescence spectrometry to analyze the structure, morphology, chemical composition, and optical property. FT-IR analysis revealed major functional groups such as OH, C=O, and SEM analysis depicted the polyhedron shape of the NPs with size range of 100 nm. Ag-ZnO NPs were used in the photocatalytic degradation of ATL and ACT, and its removal was evaluated by varying initial contaminant concentration, catalyst dosage, and initial pH. Findings indicate that Ag-ZnO NPs demonstrated relative narrow bandgap and efficient charge separation that resulted in enhanced photocatalytic activity under visible light illumination. The photocatalytic degradation of ATL and ACT fitted well with pseudo-first-order kinetic model. Further, it was found that under optimal conditions of 5 mg/L of contaminants, pH of 8.5, and catalyst dose of 1 g/L, degradation efficiency of 70.2% (ATL) and 90.8% (ACT) was achieved for a reaction time of 120 min. More than 60% reduction in TOC was observed for both contaminants and OH• pathway was found to be the major removal process. Ag-ZnO photocatalyst showed good recycling performance, and these findings indicate that it could be cost effectively employed for removing emerging contaminants under visible light radiation. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-13532-2.

Amongst a wide range of biological macromolecules, saccharides exhibit the potential to be specifically recognized by cell-surface receptors and hence can be utilized as ligands in targeted drug delivery. The current study aims to use saccharides viz. Galactose, Pectin and Chitosan to improve targeting of Atenolol by oxalyl chloride mediated grafting. Conjugates were engineered by grafting Atenolol, a cardiovascular agent with the modified saccharide units. The conjugates were characterized by FTIR, DSC and 1H NMR study. Drug release analysis and cellular uptake study was carried out using H9c2 cell lines which represent that concentration of drug in cells treated with all atenolol-saccharide conjugates is enhanced by almost two-folds in comparison with cells treated with atenolol solution. Thus cell line study confers the evidence of selective cardiac delivery. No significant cytotoxicity was observed in case of all synthesized conjugates in the Brine shrimp lethality bioassay. Possible binding of the developed conjugates with the GLUT-4 receptors was assessed by in silico analysis using homology model developed by Swiss Model server. Hence it was concluded that the application of these conjugates with saccharides in selective cardiovascular drug delivery can be a promising approach to increase bioavailability, minimize drug loss by degradation and prevent harmful side effects by increasing specific cell targeting.

Tazeen Husain, Muhammad Harris Shoaib, Farrukh Rafiq Ahmed, Rabia Ismail Yousuf, Sadaf Farooqi, Fahad Siddiqui, Muhammad Suleman Imtiaz, Madiha Maboos, Sabahat Jabeen Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, PakistanCorrespondence: Muhammad Harris Shoaib; Farrukh Rafiq AhmedDepartment of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, PakistanEmail harrisshoaib2000@yahoo.com; farrukh.ahmed@uok.edu.pkPurpose: This study systematically investigated the potential of four model drugs (verapamil HCl, flurbiprofen, atenolol, and furosemide), each belonging to a different class of Biopharmaceutics Classification Systems (BCS) to be developed into oral modified release dosage forms after loading with halloysite nanotubes (HNTs).Methods: The drugs were studied for their loading (mass gain %) by varying solvent system, method, pH, and ratios of loading into the nanotubes using D-optimal split-plot design with the help of Design Expert software. Drug-loaded halloysites were characterized by XRD, DTA, FTIR, SEM, and HPLC-UV-based assay procedures. Dissolution studies were also performed in dissolution media with pH 1.2, 4.5, and 6.8. Moreover, the optimized samples were evaluated under stress stability conditions for determining prospects for the development of oral dosage forms.Results: As confirmed with the results of XRD and DTA, the drugs were found to be converted into amorphous form after loading with halloysite (HNTs). The drugs were loaded in the range of ∼ 7– 9% for the four drugs, with agitation providing satisfactory and equivalent loading as compared to vacuum plus agitation based reported methods. FTIR results revealed either only weak electrostatic (verapamil HCl and flurbiprofen) or no interaction with the surface structure of the HNTs. The dissolution profiling depicted significantly retarded release of drugs with Fickian diffusion from a polydisperse system as a model that suits well for the development of oral dosage forms. HPLC-UV-based assay indicated that except furosemide (BCS class IV), the other three drugs are quite suitable for development for oral dosage forms.Conclusion: The four drugs investigated undergo phase transformation with HNTs. While agitation is an optimum method for loading drugs with various physicochemical attributes into HNTs; solvent system, loading ratios and pH play an important role in the loading efficiency respective to the drug properties. The study supports the capability of developing HNT-based modified release oral dosage forms for drugs with high solubility.Keywords: halloysite nanotubes, HNT, biopharmaceutics classification system, drug release kinetics, verapamil HCl, flurbiprofen, atenolol, furosemide, XRD, DTA, FTIR, SEM

AIMS To investigate the statistical association between hypoglycaemia and β-blocker use and to define what patient and drug characteristics could potentially increase the risk for its occurrence. METHODS We investigated the relationship between pharmacological parameters of β-blockers and the occurrence of hypoglycaemia by conducting a case/non case analysis using the Food and Drug Administration Adverse Event Reporting System database. Pharmacological properties that could represent a predictive factor for hypoglycaemia were analysed through a multilinear binary logistic regression (null hypothesis rejected for values of P < .05). We also performed a systematic review of clinical studies on this association. RESULTS Of 83 954 selected reports, 1465 cases (1.75%) of hypoglycaemia were identified. The association was found statistically significant for nadolol (reporting odds ratio [95% confidence interval]: 6.98 [5.40-9.03]), celiprolol (2.35 [1.35-4.10]), propranolol (2.14 [1.87-2.46]) and bisoprolol (1.42 [1.25-1.61]). Paediatric cases (n = 310) showed a positive association with hypoglycaemia for long half-life drugs (odds ratio [95% confidence interval]: 2.232 [1.398-3.563]) and a negative association for β1-selectivity (0.644 [0.414-0.999]). Seven papers were included in the systematic review. Because of great heterogeneity in study design and demographics, hypoglycaemia incidence rates varied greatly among studies, occurring in 1.73% of the cases for propranolol treatment (n total participants = 575), 6.6% for atenolol (n = 30) and 10% for carvedilol (n = 20). CONCLUSION Nadolol appears to be the β-blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half-life and nonselective β-blockers seem to increase the risk for its occurrence.

β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of traditional β-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor β (TGF-β), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional β-blockers must not be carried forward to third-generation β-blockers.