Treatment Of Arterial Hypertension Research Articles

Biopharmaceutical aspects of the development of transdermal forms of Lisinopril dihydrate

Abstract Prevention and treatment of arterial hypertension is of great importance. Improvement of existing medicines through the use of alternative routes of administration can enhance the pharmacotherapeutic characteristics of active pharmaceutical ingredients (APIs). Transdermal therapeutic systems (TTS) allow for delivery of a drug through intact skin into the systemic circulation, while minimizing side effects. The development of transdermal formulations of antihypertensive drugs, Lisinopril dihydrate in particular, has practical and scientific significance. Optimization of the algorithm for the development of transdermal drugs involves in vitro preformulation studies of the membrane permeability of APIs and the identification of factors that affect this process. The tests were performed by dialysis through a semipermeable hydrophilic membrane using a Valia-Chien diffusion device. The effect of the initial concentration of Lisinopril dihydrate on the flux rate I s was investigated. Different donor concentrations of Lisinopril dihydrate were tested at three levels, 10, 20 and 30 mg/ml, accordingly. It was noted that the permeation process of Lisinopril dihydrate under model conditions corresponds to zero-order kinetics and is characterized by a uniform speed. The correlation coefficient (R 2) for all the kinetic equations was 0.999. A linear dependence of the flux velocity of Lisinopril dihydrate on the initial concentration was indicated. The concentration of Lisinopril dihydrate in the donor solution of 30 mg/ml was found to be optimal for further stages of pharmaceutical development of the transdermal formulation. The studies of Lisinopril dihydrate permeability allow to give a positive assessment of the acceptability of this API for use in the transdermal formulation and the development of TTS.

Generalized Arterial Calcification of Infancy (GACI)

Generalized arterial calcification of infancy (GACI) is an ultra-rare autosomal recessive disorder associated with pathogenic variants in ENPP1, the major gene involved in this condition, and in ABCC6, which is involved in a small fraction of affected individuals. Loss-of-function pathogenic variants of ENPP1 and ABCC6 lead to perturbations in the PPi/Pi ratio, thereby promoting hydroxyapatite mineralization in peripheral tissues. GACI is initially characterized by an abnormal ectopic mineralization process in arteries and soft tissue. Nearly half of the patients die within the first 6 months of life from cardiovascular complications, hence the poor prognosis associated with an early diagnosis. In recent years, progress has been made in our understanding of the long-term natural history of GACI, the intricate symptoms due to vascular calcifications, the overmineralization of soft tissues, of hypophosphatemia designated as ARHR2, and of the consequences such as undermineralization of the skeleton, but also of the features possibly seen in pseudoxanthoma elasticum (PXE). Indeed, GACI, PXE, and ARHR2 share common pathophysiological pathways and clinical features beyond the vascular calcifications. Treatment options for severe forms of GACI are mostly based on symptomatic management, including the option of starting bisphosphonates early after birth, such as etidronate and pamidronate, analogues of PPi. Follow-up within an expert and coordinated multidisciplinary team includes treatment of arterial hypertension, calcitriol and phosphorus adjustments, hearing aids, and early detection of possible angioid streaks. It is hoped that ongoing basic and clinical research will lead to the development of effective therapies that specifically target the abnormal PPi regulation and the other mechanisms involved in this disorder.

P155 WHAT ARE THE SEX DIFFERENCES IN THE USE OF SINGLE-PILL COMBINATIONS IN THE TREATMENT OF ARTERIAL HYPERTENSION? RESULTS FROM HOME BLOOD PRESSURE MONITORING IN SLOVAKIA IN 2022

Arterial hypertension (AH) is the leading risk factor for cardiovascular morbidity and mortality for both, men and women. Aim of the trial: To evaluate the share of single-pill combinations (SPC) according to the gender of doctors and their patients. To evaluate the efficacy of the AH treatment with HBPM and education. Patients and Methods: This project was conducted from April to June 2022 at 178 general physician practices. We have enrolled consecutive adult patients willing to complete a questionnaire and take office BP and HBPM measurements. Results: 4375 pts with AH were enrolled (2089 women, 51,8%), mean age 61,1 ± 19,1 years. The mean office BP was higher in male (136,7 ± 10,9/ 81,9 ± 7,2 mmHg), vs female patients (135±7,2/ 80,2 ± 6,2 mmHg). Mean blood pressure at home (HBP) was also higher in males (134,1± 7,2/ 81,1± 6,3 mmHg). There were 72% (129) of female doctors, participating in the trial. The widest use of SPC was when male doctors treated male patients (70,7%). The lowest use of SPC was when female doctors treated female patients (52,1%). 44,6% of patients were treated with double SPC and 14,3% with triple. Dual SPC was the most preferred treatment when male patients were treated by male doctors (52,3%). Triple SPC strategy was used mostly when female doctors were giving care to male patients (16,8%). More patients reached optimal BP at home when treated by a male doctor (68%). Conclusion: Appropriate education of patients and their engagement via HBPM, led to 67% BP control. The preference for SPC by male doctors led to significantly better BP control at home, regardless of the gender of patients. By systematic rationalization of pharmacotherapy according to the 2023 ESH Guidelines, using SPC has the potential to improve adherence and increase the BP control rate in Slovakia to fulfill the initiative Charter 70/2023.

Therapeutical Approach to Arterial Hypertension - Current State of the Art.

Arterial hypertension (AH) is recognized as the most common illness within the group of cardiovascular diseases and the most massive chronic non-infectious disease in the world. The number of hypertensive patients worldwide has reached 1.28 billion, contributing to an increase in cardiovascular diseases and premature death globally. The high prevalence of hypertension emphasizes the importance of effectively treating this condition. Elevated blood pressure often leads to lethal complications (heart failure, stroke, renal disorders, etc.) if left untreated. Considering an increase in AH prevalence in the future, a successful therapeutical approach to this disease and its complications is essential. The goal of AH treatment is to maintain normotensive blood pressure through various approaches, including lifestyle changes, a well-balanced diet, increased physical activity, psychoeducation, and, when necessary, pharmacotherapy. The evolving pharmacotherapeutic landscape reflects the progress made in our understanding of hypertension and emphasizes the need for continuous innovation to meet the challenges posed by this prevalent global health concern. The journey toward more effective and tailored treatments for hypertension is ongoing, and the introduction of new medications plays a pivotal role in shaping the future of antihypertensive pharmacotherapy.

Peculiarities of approaches to the treatment of arterial hypertension in the Maldives in the practice of general practitioners from the point of view of evidence-based medicine

Background: Arterial Hypertension (AH), commonly known as high blood pressure, is a significant chronic condition affecting millions globally and is a primary cause of cardiovascular diseases (CVD). In the Maldives, the management of AH by general practitioners (GPs) is crucial due to its high prevalence and associated health complications. This study examines the approaches of GPs in treating AH, emphasizing evidence-based medicine (EBM) to ensure effective management and prevention strategies. Methods and Materials: The study involves a comprehensive review of current evidence-based methods used for AH management in the Maldives. It focuses on lifestyle modifications, dietary changes, increased physical activity, stress reduction techniques, and pharmacotherapy. Data were collected through clinical guidelines, patient records, and interviews with GPs to understand the practical application of these methods in Maldivian healthcare settings. Results: The findings indicate that lifestyle modifications, including healthier diets and increased physical activity, are critical in managing AH. Traditional Maldivian diets and community-based exercise programs play significant roles. Pharmacotherapy, involving antihypertensive medications, is essential but faces challenges such as limited access and patient adherence. GPs also highlighted the importance of stress reduction techniques and individualized treatment plans tailored to patient needs and cultural sensitivities. Conclusion: Effective management of AH in the Maldives requires a multifaceted approach combining evidence-based medical practices with local context sensitivity. GPs play a pivotal role in diagnosing, treating, and educating patients about AH. Addressing socioeconomic barriers, enhancing healthcare resources, and promoting cultural competence are essential for improving AH management and overall public health

Beta-blockers and their impact on metabolic processes

The aim of the study is to determine the effect of beta-blockers on lipid status, triglycerides and Body Mass Index (BMI) in patients using beta-blockers in the treatment of arterial hypertension. Our study included 120 patients at the Public Health Institution "Dom zdravlja" Živinice. The participants were monitored over a period of 3 years. Measurements were made after 12, 24 and 36 months of treatment. Patients were divided into two groups. The experimental group included 60 patients, who used beta-blockers in the treatment of arterial hypertension. The control group included 60 patients who used other antihypertensives as their first choice medication in the treatment of arterial hypertension. By monitoring cholesterol and triglyceride levels in patients using beta-blockers and other antihypertensive medications, and comparing these values within the group, no statistically significant difference in cholesterol and triglyceride levels was found in patients who used beta-blockers after 12, 24, and 36 months of treatment. There was also no statistically significant effect of therapy on the change in cholesterol and triglyceride values at observed time intervals, nor was there a statistically significant difference between these values. BMI monitoring showed a statistically significant difference between patients using beta-blockers and other antihypertensive drugs, with patients using beta-blockers having a higher BMI after 36 months of treatment. There was no statistically significant difference in BMI between patients using bisoprolol and carvedilol and patients using other beta-blockers, but patients using bisoprolol and carvedilol had lower BMI values. In studies conducted in recent years, it has been noted that many beta-blockers cause dose-dependent adverse metabolic effects on glucose and lipid metabolism, with the most adverse metabolic effects observed in patients treated with conventional non-selective beta-blockers. On the other hand, more favorable metabolic profile have drugs with β1 selective activity, such as atenolol and metoprolol, especially those with intrinsic sympathomimetic activity such as pindolol. In fact, with these beta-blockers, the adverse metabolic effects appear to be less prominent. In conclusion, beta-blockers do not lead to an increase in cholesterol and triglycerides, but they do lead to an increase in BMI in patients with arterial hypertension

Pulmonary hypertension associated with lung diseases.

Pulmonary hypertension (PH) associated with chronic lung disease (CLD) is both common and underrecognised. The presence of PH in the setting of lung disease has been consistently shown to be associated with worse outcomes. Recent epidemiological studies have advanced understanding of the heterogeneity of this patient population and shown that defining both the specific type of CLD as well as the severity of PH (i.e. deeper phenotyping) is necessary to inform natural history and prognosis. A systematic diagnostic approach to screening and confirmation of suspected PH in CLD is recommended. Numerous uncontrolled studies and one phase 3 randomised, controlled trial have suggested a benefit in treating PH in some patients with CLD, specifically those with fibrotic interstitial lung disease (ILD). However, other studies in diseases such as COPD-PH showed adverse outcomes with some therapies. Given the expanding list of approved pharmacological treatments for pulmonary arterial hypertension, developing a treatment algorithm for specific phenotypes of PH-CLD is required. This article will summarise existing data in COPD, ILD and other chronic lung diseases, and provide recommendations for classification of PH-CLD and approach to the diagnosis and management of these challenging patients.

Epicardial and liver fat implications in albuminuria: a retrospective study

BackgroundAlbuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status.MethodsA retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome.ResultsAfter a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]).ConclusionsIdentification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction.

Discovery and Optimization of Hsp110 and sGC Dual-Target Regulators for the Treatment of Pulmonary Arterial Hypertension.

Currently, bifunctional agents with vasodilation and ameliorated vascular remodeling effects provide more advantages for the treatment of pulmonary arterial hypertension (PAH). In this study, we first screened the hit 1 with heat shock protein 110 (Hsp110) inhibition effect from our in-house compound library with soluble guanylate cyclase (sGC) activity. Subsequently, a series of novel bisamide derivatives were designed and synthesized as Hsp110/sGC dual-target regulators based on hit 1. Among them, 17i exhibited optimal Hsp110 and sGC molecular activities as well as remarkable cell malignant phenotypes inhibitory and vasodilatory effects in vitro. Moreover, compared to riociguat, 17i showed superior efficacy in attenuating pulmonary vascular remodeling and right ventricular hypertrophy via Hsp110 suppression in hypoxia-induced PAH rat models (i.g.). Notably, our study successfully demonstrated that the simultaneous regulation of Hsp110 and sGC dual targets was a novel and feasible strategy for PAH therapy, providing a promising lead compound for anti-PAH drug discovery.

Mechanisms and treatment of pulmonary arterial hypertension.

Substantial progress has been made in the management of pulmonary arterial hypertension (PAH) in the past 25 years, but the disease remains life-limiting. Established therapies for PAH are mostly limited to symptomatic relief by correcting the imbalance of vasoactive factors. The tyrosine kinase inhibitor imatinib, the first predominantly non-vasodilatory drug to be tested in patients with PAH, improved exercise capacity and pulmonary haemodynamics compared with placebo but at the expense of adverse events such as subdural haematoma. Given that administration by inhalation might reduce the risk of systemic adverse effects, inhaled formulations of tyrosine kinase inhibitors are currently in clinical development. Other novel therapeutic approaches for PAH include suppression of activin receptor type IIA signalling with sotatercept, which has shown substantial efficacy in clinical trials and was approved for use in the USA in 2024, but the long-term safety of the drug remains unclear. Future advances in the management of PAH will focus on right ventricular function and involve deep phenotyping and the development of a personalized medicine approach. In this Review, we summarize the mechanisms underlying PAH, provide an overview of available PAH therapies and their limitations, describe the development of newer, predominantly non-vasodilatory drugs that are currently being tested in phase II or III clinical trials, and discuss future directions for PAH research.

Population pharmacokinetic modeling of sotatercept in healthy participants and patients with pulmonary arterial hypertension.

Sotatercept is a breakthrough, first-in-class biologic, that is FDA-approved for the treatment of pulmonary arterial hypertension (PAH). A population pharmacokinetic (PopPK) model was developed using data from two phase 1 studies in healthy participants, and two phase 2 studiesand one phase 3 study in participants with PAH. The pooled sotatercept PK data encompassed single intravenous (IV) or subcutaneous (SC) doses ranging from 0.01 to 3.0 mg/kg, as well as multiple SC doses ranging from 0.03 to 1.0 mg/kg, with PK samples collected up to a maximum of ~150 weeks following Q3W and Q4W dosing regimens. The final PopPK analysis included 350 participants, with 30 and 320 participants receiving sotatercept IV and SC, respectively. A two-compartment model with a first-order absorption rate constant and a linear disposition from central compartment well-described sotatercept PK. The estimated bioavailability is ~66%; bioavailability, clearance (CL), and central volume (VC) have low to moderate inter-individual variability. Time-varying body weight and baseline albumin concentration were statistically significant predictors of PK; CL and VC were predicted to increase with increasing body weight, while CL was predicted to decrease with increasing baseline albumin concentration. However, the magnitude of covariate effects is not predicted to meaningfully alter the disposition of sotatercept. Altogether, the PopPK modeling results demonstrate favorable PK characteristics (low to moderate variability and typical bioavailability), supporting sotatercept as a SC biological agent for the treatment of patients with PAH.

New and Emerging Therapeutic Drugs for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review.

Pulmonary arterial hypertension (PAH) is a serious, progressive, and potentially fatal lung disease characterized by a gradual increase in mean pulmonary arterial pressure to over 20 mmHg at rest. The pathogenesis of PAH is multifactorial. It involves dynamic obstruction of the pulmonary vasculature through vasoconstriction, structural obstruction due to adverse vascular remodeling, and pathological obstruction caused by vascular fibrosis and stiffening, which reduces compliance. PAH often presents with vague initial symptoms and is frequently diagnosed at an advanced stage. The increased pulmonary arterial pressure leads to vascular remodeling, eventually resulting in right ventricular hypertrophy and failure. PAH is a rare condition with a median life expectancy of three years, underscoring the need for effective treatment alternatives. Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat. Despite these advancements, current medications do not provide a permanent cure. This study presents an overview of current and emerging PAH therapies through a systematic literature review. It involved an analysis of nine studies and a review of 800 papers from reputable journals published between 2013 and June 2023. The research focused on drug effects on the six-minute walk distance (6-MWD) and associated side effects in randomized controlled trials. The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice.

Beta-blockers and their impact on blood pressure and heart rate

The aim of the study is to determine the impact of beta-blockers on blood pressure and heart rate in patients that use these drugs during treatment of arterial hypertension. The sample included 120 patients from the "Dom Zdravlja'' Živinice. Patients were monitored for 3 years. No statistically significant difference in the values of systolic and diastolic blood pressure as well as heart rate in patients using beta-blockers and other groups of antihypertensives was determined during monitoring period after 12, 24 and 36 months of treatment. Also, there was no statistically significant impact of the applied therapy on these values in the observed time intervals. In order to determine statistically significant difference between treatments, we compared their values sorted by time. No statistically significant difference was found in systolic blood pressure and heart rate between groups, but a statistically significant difference in diastolic blood pressure was found between groups after 12 and 36 months of therapy. No statistically significant difference was found in the values of systolic and diastolic blood pressure, as well as heart rate after 12, 24 and 36 months of treatment by comparing the same values within the group of beta-blockers (patients using bisoprolol and carvedilol and patients using other beta-blockers). Also, there was no statistically significant impact of the applied therapy on the change of these values during observed period. In order to determine statistically significant difference between the treatments, we compared their values sorted by time. There was no statistically significant difference in the values of systolic and diastolic blood pressure and heart rate between the groups. Also, the condition of patients who used beta-blockers in the treatment of hypertension did not require increasing the dose in order to achieve the required parameters. Therefore, in our research, haven't been proven the worse effect of beta-blockers on blood pressure and heart rate when compared to other antihypertensive drugs. Also, all drugs showed equal effectiveness within the group of beta-blockers.

Treatment of arterial hypertension in patients with chronic kidney disease from the perspective of the 2023 European recommendations

Treatment of arterial hypertension in patients with chronic kidney disease from the perspective of the 2023 European recommendations

Determinants of sleep disturbances in patients with pulmonary arterial hypertension

Abstract Introduction Pulmonary arterial hypertension (PAH) is a rare, chronic disease that leads to the development of a range of cardiopulmonary and cardiovascular symptoms. Studies indicate that sleep problems may contribute to the deterioration of function in patients with PAH. Identifying factors that are related to the occurrence of sleep disorders can help identify them, and will also allow you to take steps to minimize the risk of insomnia. Purpose The aim of this study was to determine the determinants affecting the incidence of sleep disorders among patients with pulmonary arterial hypertension. Material and methods The study included 89 patients with a diagnosis of pulmonary arterial hypertension (PAH) who are chronically treated and participate in the state program for Therapeutic Treatment of Pulmonary Arterial Hypertension by the National Health Service. The study used standardized tools: a self-administered survey questionnaire, as well as the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Results Patients had a mean PSQI score of M=8.7 (SD=4.64), indicating low sleep quality. Factors that had a significant impact on sleep disturbance were: old age (r=0.373), chest pain (r=0.307), weakness (r=0.296), fatigue (r=0.316), shortness of breath (r=0.242), MWT score 6 (r= -0.237), NT-proBNP (r=0, 517), social support (r=0.237), staying in a relationship (r= -0.21), arrhythmia (r=0.211), number of hospitalizations (r=0.33), male gender (r=0.257), WHO FC class (r=0.503). Conclusions In the study group of patients with PAH, sleep disorders are present in the majority. The progression of clinical symptoms and selected sociodemographic data significantly correlate with the occurrence of insomnia.

Contemporary Treatment of Pulmonary Arterial Hypertension: A U.S. Perspective.

Pulmonary arterial hypertension (PAH) is a complex fatal condition that requires aggressive treatment with close monitoring. Significant progress has been made over the last three decades in the treatment of PAH, but, despite this progress, survival has remained unacceptably low. In the quest to improve survival, therapeutic interventions play a central role. In the last few years, there have been remarkable attempts to identify novel treatments. Finally, we have had a breakthrough with the discovery of the fourth treatment pathway in PAH. Activin signaling inhibition distinguishes itself as a potential antiproliferative intervention as opposed to the traditional therapies, which mediate their effect primarily by vasodilatation. With this novel treatment pathway, we stand at an important milestone with an exciting future ahead and the natural question of when to use an activin signaling inhibitor for the treatment of PAH. In this state-of-the-art review, we focus on the placement of this novel agent in the PAH treatment paradigm, based on the available evidence, with special focus on the U.S. patient population. This review also provides an expert opinion of the current treatment algorithm in important subgroups of patients with comorbidities from the U.S. perspective.

Clinical Response to Pulmonary Arterial Hypertension Treatment Does Not Depend on Pulmonary Arterial Wedge Pressure: A Meta-Analysis Using Individual Participant Data from Randomized Clinical Trials.

Clinical Response to Pulmonary Arterial Hypertension Treatment Does Not Depend on Pulmonary Arterial Wedge Pressure: A Meta-Analysis Using Individual Participant Data from Randomized Clinical Trials.

Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag-treated PAH-CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH-CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety-eight selexipag-treated patients had follow-up information; 178 (26%) had PAH-CTD.The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years.There were 5% patients at low, 25% intermediate-low, 40% intermediate-high, and 30% high risk of 1-year mortality, according to the ESC/ERS 4-strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post-baseline. Over a median (Q1-Q3) selexipag exposure period of 8.6 (2.5-17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH-related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH-CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH-CTD by moving from escalating after years in response to clinical deteriorationto escalating sooner to prevent clinical deterioration.

Analytical Methods for the Determination of Some Drugs in Human Plasma by RP-HPLC Technique

ABSTRACT: An RP-HPLC method for the estimation of Bosentan in plasma was developed and validated in this regard. It is an important drug for the treatment of pulmonary arterial hypertension, whose plasma level monitoring is very essential. The composition of the mobile phase, flow rate, and detection wavelength of the RP-HPLC method were mainly optimized to provide high resolution and peak symmetry. The parameters for specificity, linearity, accuracy, precision, LOD, and LOQ, among others, were checked and proved to have good linearity within the concentration range with r² &gt; 0.999. The method described had excellent accuracy and precision. The validated method can be applied for clinical and pharmacokinetic use, acting as a reliable tool for Bosentan monitoring.

The Role of Immunohistochemistry in Managing Clinical Hypertension and Other Chronic Inflammatory Processes

Immunohistochemistry (IHC) is a pivotal technique in the visualization of specific proteins within tissue samples, leveraging antigen-antibody interactions to elucidate protein presence, distribution, and abundance. In clinical hypertension, IHC is instrumental in unraveling disease mechanisms, identifying biomarkers, and fostering targeted therapies. This review delves into IHC’s contributions to managing hypertension by examining its role in understanding the pathophysiology and identifying key proteins like those in the renin-angiotensin-aldosterone system. Elevated angiotensin II type 1 receptors in vascular walls, detected via IHC, correlate with hypertension and vascular remodeling. Additionally, IHC identifies inflammatory markers such as interleukin-6 and tumor necrosis factor-alpha, linking chronic inflammation to hypertension. The technique is vital for discovering biomarkers like endothelial nitric oxide synthase and vascular endothelial growth factor, essential for assessing endothelial function. IHC also detects oxidative stress markers, aiding in understanding oxidative mechanisms in hypertension. Evaluating antihypertensive therapies at a molecular level, IHC shows how interventions affect protein expression and vascular health, guiding therapeutic strategies. By revealing proteins differentially expressed in hypertensive tissues, IHC identifies new therapeutic targets, enhancing treatment efficacy. Furthermore, this review explores the application of IHC in other chronic inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease, highlighting its broader relevance in disease management. Recent advancements include the development of new drugs targeting specific molecular pathways, such as endothelin 1 receptor antagonists like aprocitentan, approved by the FDA in March 2024 for the treatment of resistant arterial hypertension. Overall, IHC significantly advances both research and clinical practice, promising improved health outcomes through continued methodological advancements.