Effectiveness of herbs taken concurrently with antihypertensive drugs in managing hypertension and lipid outcomes. A systematic review and meta-analysis.

PURPOSE: Hypertension is the primary cause of mortality. Hence globally, there is a growing interest in complementing antihypertensive drugs with herbs to alleviate blood pressure among hypertensive patients. Thus, this review aimed to evaluate the effectiveness of complementing drugs with herbs on blood pressure and lipid profile outcomes, the associated factors and the types of complementary herbs alongside their consumption regimes. METHODS: This review is registered in PROSPERO on the National Institute of Health Database with an ID: CRD42021270481. Using the PICOS (population, intervention, comparison, outcome, study type) mnemonic formula and search strategy, we searched (January 2010 to February 2024) five electronic databases including Pubmed, Scopus, Web of Science, CINAHL (Cumulative Index for Nursing and Allied Health Literature) and Psychology & Behavioral Sciences Collection (PBSC). The inclusion criteria of the review were that all included papers had to be randomised control trials in English among hypertensive adults who complemented antihypertensive drugs with herbs. A Cochrane risk of bias assessment as well as a meta-analysis and narrative synthesis were conducted to answer the objectives. RESULTS: Twenty-five randomised controlled trials involving 1996 participants from 14 countries were included. The risk of bias among included articles was assessed and presented using the Cochrane risk of bias tool and the graphs were generated. The effects of complementing antihypertensive drugs with different herb regimes on blood pressure and lipid profile outcomes were compared to those solely on antihypertensive drugs and placebo via a random model effects meta-analysis using the Revman manager. Systolic blood pressure (SBP) and triglycerides gave a significant reduction in favour of the intervention group which complemented herbs. The overall pooled systolic blood pressure showed a reduction of (SMD=0.81, 95 % CI 0.14-1.47, p < 0.02, p for heterogeneity=0.00001, I2 =97 %) while triglycerides were (SMD=0.73, 95 % CI 0.17-1.28, p < 0.01, p for heterogeneity=0.00001, I2 =85 %). However, diastolic blood pressure, total cholesterol, HDL and LDL did not exert significant outcomes. CONCLUSION: The complemented herbs with antihypertensive drugs did show improvement in overall blood pressure management in the majority of the studies compared to the placebo group. Blood pressure and lipid profiles are the health outcomes that enable access to complementing herbs in controlling high blood pressure. Some limitations of this review are attributed to performance, detection and attrition bias in a few included articles alongside the presence of a high heterogeneity overall.

Captopril's influence on Danio rerio embryonic development: Unveiling significant toxic outcomes at environmentally relevant concentrations.

Anticipating a global increase in cardiovascular diseases, there is an expected surge in the use of angiotensin-converting enzyme inhibitors, notably captopril (CAP). This heightened usage raises significant environmental apprehensions, mainly due to limited knowledge regarding CAP's toxic effects on aquatic species. In response to these concerns, the current study aimed to tackle this knowledge gap by evaluating the potential influence of nominal concentrations of CAP (0.2-2000 µg/L) on the embryonic development of Danio rerio. The findings revealed that CAP at all concentrations, even at concentrations considered environmentally significant (0.2 and 2 µg/L), induced various malformations in the embryos, ultimately leading to their mortality. Main malformations included pericardial edema, craniofacial malformation, scoliosis, tail deformation, and yolk sac deformation. In addition, CAP significantly altered the antioxidant activity of superoxide dismutase and catalase across all concentrations. Simultaneously, it elevated lipid peroxidation levels, hydroperoxides, and carbonylic proteins in the embryos, eliciting a substantial oxidative stress response. Likewise, CAP, at all concentrations, exerted significant modulatory effects on the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3), organogenesis (tbx2a, tbx2b, and irx3b), and ion exchange (slc12a1 and kcnj1) in Danio rerio embryos. Both augmentation and reduction in the expression levels of these genes characterized this modulation. The Pearson correlation analysis indicated a close association between oxidative damage biomarkers and the expression patterns of all examined genes with the elevated incidence of malformations and mortality in the embryos. In summary, it can be deduced that CAP poses a threat to aquatic species. Nevertheless, further research is imperative to enhance our understanding of the environmental implications of this pharmaceutical compound.

Calcium channel blockers may reduce the development of long COVID in females.

With the rising numbers of patients infected with severe acute respiratory syndrome coronavirus 2, long coronavirus disease 2019 (COVID-19)-a sequelae of COVID-19-has become a major problem. Different sexes and age groups develop different long COVID symptoms, and the risk factors for long COVID remain unclear. Therefore, we performed subgroup analyses of patients with COVID-19, classifying them into different groups. In this multicenter cohort study, using an original questionnaire, we examined patients (≥18 years old) diagnosed with COVID-19 from November 2020 to March 2022 and hospitalized at participating medical facilities. In total, 1066 patients were registered (361 female, 620 male). Hypertension was the most common comorbidity (n = 344; 32.5%). Females with hypertension were significantly less likely to develop long COVID symptoms than those without hypertension (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27-0.98; p = 0.043). In females, Ca channel blocker administration, rather than having hypertension, was significantly associated with reductions in the frequency of alopecia (OR 0.14, 95% CI 0.03-0.67, p = 0.015), memory impairment (OR 0.14, 95% CI 0.02-0.82, p = 0.029), sleeping disorders (OR 0.17, 95% CI 0.04-0.67, p = 0.012), tinnitus (OR 0.23, 95% CI 0.05-0.98, p = 0.047), sputum (OR 0.31, 95% CI 0.10-0.92, p = 0.035), and fever (OR 0.33, 95% CI 0.12-0.93, p = 0.036). Several long COVID symptoms, including alopecia, were significantly negatively associated with Ca channel-blocker administration in female patients with long COVID. Calcium channel blockers may reduce the development of long COVID in females.

Relationship between antihypertensive drug use and number of people with high blood pressure in FY 2018: a descriptive epidemiological study based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan open data.

BACKGROUND: In most countries barring Japan, antihypertensive drug use has been reported using the defined daily doses/1000 inhabitants/day (DID). Although DID has been shown to allow for the assessment of the number of patients treated with a particular drug, the relationship between DID and the number of patients with hypertension has not been clarified. This study aimed to clarify the relationship between antihypertensive drug use and the number of people with high blood pressure based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open data. METHODS: DID was calculated by extracting the use of oral antihypertensive drugs from outpatient prescriptions in the NDB Open Data in FY 2018. The number of people with high blood pressure was calculated using the number of enrollees in each sex-age group for systolic and diastolic blood pressure in the 40-74 years age group. The correlation between the DID of antihypertensive drugs and the number of people with high blood pressure by sex and age class was evaluated using Spearman's rank correlation coefficient. RESULTS: The use of antihypertensive drugs increased with age in both men and women. Furthermore, in both sexes, dihydropyridine derivatives, calcium antagonists, and angiotensin II receptor blockers were the main drugs used from the age of 20 years onward. In addition, a very strong positive correlation was found between the number of people with high systolic blood pressure and DID in both sexes (men: r = 1, P < 0.05; women: r = 1, P < 0.05). In contrast, there was no significant correlation between the number of people with high diastolic blood pressure and DID in both sexes (men: r = - 0.214, P > 0.05; women: r = 0.393, P > 0.05). CONCLUSIONS: To our knowledge, this study is the first to investigate the use of oral antihypertensive drugs in outpatient settings in Japan. In addition, the DID of antihypertensive drugs can be used as an alternative indicator of the number of people with high systolic blood pressure.

Antihypertensive drugs may not delay the symptom progression of Parkinson's disease: A 2-year follow-up study.

Background: Parkinson's disease (PD) is one of the most common neurodegenerative disease, and half of PD patients have hypertension as well. The effect of antihypertensive drugs on the progression of PD has been less studied. The focus of this study was on the changes in dopamine transporter (DAT) levels to assess the effect of antihypertensive drugs on the progression of PD. Methods: Data from 321 drug-naïve patients from the Parkinson's Disease Progression Marker Initiative (PPMI) were collected over a 2-year period. Patients were divided into the PD with arterial hypertension (AH) group (102 cases) with antihypertensive drugs, the PD with other cardiovascular risk factors (CVRFs) group (60 cases) with antidiabetic and/or lipid-lowering drugs, and the pure PD group (159 cases) without CVRFs. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Hoehn-Yahr (H&Y) stage were used to assess progression. DAT semiquantitative values were used to evaluate damage to dopaminergic neurons in the substantia nigra, including the contralateral and ipsilateral count density ratio and asymmetry index. Results: There were no significant differences among the three groups in MDS-UPDRS score and H&Y stage. Changes in DAT levels among the three groups were without distinct differences in the first year and second year. In each group, DAT decreased more in the first year than in the second year. There was no decrease in DAT uptake in the PD with AH group compared with the other groups during the follow-up period. Conclusions: There is no evidence that antihypertensive drugs can delay PD progression within 2 years.

Long-Term Physical Activity Effectively Reduces the Consumption of Antihypertensive Drugs: A Randomized Controlled Trial.

BACKGROUND: Although physical activity (PA) has been shown to enhance hypertension control, the impact of exercise on the potential decrease of the use of antihypertensive medications remains inadequately researched. AIM: The aim was to assess the impact of a two-year PA on the medication requirements of individuals with hypertension. METHODS: A clinical trial was conducted, involving 130 participants with essential hypertension who took at least one antihypertensive medication. Participants were randomly assigned to either a control group (CG n = 65) or an experimental group (EG n = 65) that underwent a 24-month supervised PA program based on a combination of aerobic and resistance training. The antihypertensive drug load for each participant was determined by adding the ratios of the prescribed daily dose (PDD) to the defined daily dose (DDD) for all antihypertensive medications taken by the participants. The outcome measures were evaluated at 0, 6, 12, 18, and 24 months. RESULTS: A total of 76 participants completed the 24-month assessment, and RM-ANOVA revealed a significantly lower antihypertensive drug load in the EG compared to the CG at 18 (p < 0.017) and 24 months (p < 0.003). CONCLUSION: A long-term PA program can decrease the antihypertensive drug load in older adults with essential hypertension. The trend of improvement regarding the EG drug load intake and the trend of CG drug load increase, although not significant over time, results in a significant difference between the groups at 18 months and an even greater difference at 24 months. This trend certifies the protective value of PA against the aging process and its related health risk factors.

Impact of COVID-19 epidemic on antihypertensive drug treatment disruptions: results from a nationwide interrupted time-series analysis.

Background: The COVID-19 epidemic has disrupted care and access to care in many ways. It was accompanied by an excess of cardiovascular drug treatment discontinuations. We sought to investigate a deeper potential impact of the COVID-19 epidemic on antihypertensive drug treatment disruptions by assessing whether the epidemic induced some changes in the characteristics of disruptions in terms of duration, treatment outcome, and patient characteristics. Methods: From March 2018 to February 2021, a repeated cohort analysis was performed using French national health insurance databases. The impact of the epidemic on treatment discontinuations and resumption of antihypertensive medications was assessed using preformed interrupted time series analyses either on a quarterly basis. Results: Among all adult patients on antihypertensive medication, we identified 2,318,844 (18.7%) who discontinued their antihypertensive treatment during the first blocking period in France. No differences were observed between periods in the characteristics of patients who interrupted their treatment or in the duration of treatment disruptions. The COVID-19 epidemic was not accompanied by a change in the proportion of patients who fully resumed treatment after a disruption, neither in level nor in trend/slope [change in level: 2.66 (-0.11; 5.42); change in slope: -0.67 (-1.54; 0.20)]. Results were similar for the proportion of patients who permanently discontinued treatment within 1 year of disruption [level change: -0.21 (-2.08; 1.65); slope change: 0.24 (-0.40; 0.87)]. Conclusion: This study showed that, although it led to an increase in cardiovascular drug disruptions, the COVID-19 epidemic did not change the characteristics of these. First, disruptions were not prolonged, and post-disruption treatment outcomes remained unchanged. Second, patients who experienced antihypertensive drug disruptions during the COVID-19 outbreak were essentially similar to those who experienced disruptions before it.

Univariate versus multivariate spectrophotometric data analysis of triamterene and xipamide; a quantitative and qualitative greenly profiled comparative study.

Triamterene (TRI) and xipamide (XIP) mixture is used as a binary medication of antihypertension which is considered as a major cause of premature death worldwide. The purpose of this research is the quantitative and qualitative analysis of this binary mixture by green univariate and multivariate spectrophotometric methods. Univariate methods were zero order absorption spectra method (D0) and Fourier self-deconvolution (FSD), as TRI was directly determined by D0 at 367.0 nm in the range (2.00-10.00 µg/mL), where XIP show no interference. While XIP was determined by FSD at 261.0 nm in the range (2.00-8.00 µg/mL), where TRI show zero crossing. Multivariate methods were Partial Least Squares, Principal Component Regression, Artificial Neural Networks, and Multivariate Curve Resolution-Alternating Least Squares. A training set of 25 mixtures with different quantities of the tested components was used to construct and evaluate them, 3 latent variables were displayed using an experimental design. A set of 18 synthetic mixtures with concentrations ranging from (3.00-7.00 µg/mL) for TRI and (2.00-6.00 µg/mL) for XIP, were used to construct the calibration models. A collection of seven synthetic mixtures with various quantities was applied to build the validation models. All the proposed approaches quantitative analyses were evaluated using recoveries as a percentage, root mean square error of prediction, and standard error of prediction. Strong multivariate statistical tools were presented by these models, and they were used to analyze the combined dosage form available on the Egyptian market. The proposed techniques were evaluated in accordance with ICH recommendations, where they are capable of overcoming challenges including spectral overlaps and collinearity. When the suggested approaches and the published one were statistically compared, there was no discernible difference between them. The green analytical method index and eco-scale tools were applied for assessment of the established models greenness. The suggested techniques can be used in product testing laboratories for standard pharmaceutical analysis of the substances being studied.

Causal effects of hypertension on risk of erectile dysfunction: A two-sample Mendelian randomization study.

Background: Erection dysfunction has been associated with hypertension in several epidemiological and observational studies. But the causal association between hypertension and erectile dysfunction requires further investigation. Methods: A two-sample Mendelian randomization (MR) was conducted to analyze the causal effect of hypertension on risk of erection dysfunction. Large-scale publicly available genome-wide association study data were used to estimate the putative causality between hypertension and risk of erectile dysfunction. A total of 67 independent single nucleotide polymorphisms were selected as instrumental variables. Inverse-variant weighted, maximum likelihood, weighted median, penalized weighted median, and MR-PRESSO approaches were utilized in MR analyses. Heterogeneity test, horizontal pleiotropy test, and leave-one-out method were used to prove the stability of the results. Results: In total, all P values were less than 0.05, demonstrating a positive causal link between hypertension and risk of erectile dysfunction in multiple MR methods, such as inverse-variant weighted (random and fixed effect) (OR 3.8315, 95% CI 2.3004-6.3817, P = 0.0085), maximum likelihood (OR 3.8877, 95% CI 2.3224-6.5081, P = 0.0085), weighted median (OR 4.9720, 95% CI 2.3645-10.4550, P = 0.0309), penalized weighted median (OR 4.9760, 95% CI 2.3201-10.6721, P = 0.0355), and MR-PRESSO (OR 3.6185, 95% CI 2.2387-5.8488, P = 0.0092). Sensitivity analysis detected no evidence of heterogeneity, pleiotropy, or outlier single nucleotide polymorphisms. Conclusion: The study revealed a positive causal link between the presence of hypertension and the risk of erectile dysfunction. More attention should be paid during the management of hypertension with the purpose of preventing erectile dysfunction or improving erectile function.

The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial.

Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union's Horizon 2020 programme. Trial registration: NCT03082014.

Significant Correlates of Nocturnal Hypertension in Patients With Hypertension Who Are Treated With Antihypertensive Drugs.

BACKGROUND: Nocturnal hypertension assessed by a home blood pressure monitoring (HBPM) device is associated with an increased risk of cardiovascular events. However, it is still difficult to assess nighttime blood pressure (BP) frequently. The purpose of this cross-sectional study was to identify significant correlates of nocturnal hypertension assessed by an HBPM device in patients with hypertension who are treated with antihypertensive drugs. METHODS: We measured nighttime BP, morning BP, and evening BP by an HBPM device for 7 consecutive days in 365 medicated patients with hypertension. RESULTS: Of the 365 subjects, 138 (37.8%) had nocturnal hypertension defined as a mean nighttime systolic BP of ≥ 120 mm Hg. Receiver operating characteristic curve analyses showed that the diagnostic accuracy of morning systolic BP for subjects with nocturnal hypertension was significantly superior to that of evening systolic BP (P = 0.04) and that of office systolic BP (P < 0.001). Multivariate analysis revealed that morning systolic BP of 125-<135 mm Hg (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.13-4.58; P = 0.02), morning systolic BP of ≥ 135 mm Hg (OR, 16.4; 95% CI, 8.20-32.7; P < 0.001), and a history of cerebrovascular disease (OR, 3.99; 95% CI, 1.75-9.13; P = 0.001) were significantly associated with a higher risk of nocturnal hypertension and that bedtime dosing of antihypertensive drugs was significantly associated with a lower risk of nocturnal hypertension (OR, 0.56; 95% CI, 0.32-0.97; P = 0.04). CONCLUSIONS: Morning systolic BP of ≥ 125 mm Hg, a history of cerebrovascular disease, and bedtime dosing were significant correlates of nocturnal hypertension in medicated patients with hypertension, and may help detect this risky BP condition. CLINICAL TRIALS REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000019173).

Assessment of the genotoxic effects of antihypertensive drug active ingredient indapamide in human lymphocytes.

Hypertension is the most common cardiovascular disease and is also known as high blood pressure. The large majority of hypertensive patients need long-term administration of antihypertensive agents. Indapamide is an orally administered diuretic antihypertensive drug. The present work aimed to assess the possible genotoxic effects of indapamide using four different assays: chromosomal aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet. Lymphocytes from three different donors were exposed to 18.75, 37.50, 75.00, and 100.00 µg/ml indapamide. Additionally, a negative, a positive (mitomycin C = MMC, 0.20 µg/ml), and a solvent control (5.4 µl/ml methanol) were also applied. As a result, it was seen that indapamide did not cause a significant change in CAs and MN frequencies compared to the control. It caused significant damage only at the highest concentration in the comet assay. Similarly, while it did not affect the number of SCEs in the 24-h treatment, it increased the SCE frequency at the two highest concentrations in the 48-h. Mitotic index (MI) decreased at almost all concentrations. Considering all these results, this study revealed that indapamide did not have a significant genotoxic effect in these conditions. To the best of our knowledge, this is the first investigation about the genotoxic effect of indapamide in human lymphocytes in vitro.

Narrative update of clinical trials with antihypertensive drugs in children and adolescents.

Introduction: To date, our knowledge on antihypertensive pharmacological treatment in children and adolescents is still limited because there are few randomized clinical trials (CTs), hampering appropriate management. The objective was to perform a narrative review of the most relevant aspects of clinical trials carried out in primary and secondary hypertension. Methods: Studies published in PubMed with the following descriptors: clinical trial, antihypertensive drug, children, adolescents were selected. A previous Cochrane review of 21 randomized CTs pointed out the difficulty that statistical analysis could not assess heterogeneity because there were not enough data. A more recent meta-analysis, that applied more stringent inclusion criteria and selected 13 CTs, also concluded that heterogeneity, small sample size, and short follow-up time, as well as the absence of studies comparing drugs of different classes, limit the utility. Results: In the presented narrative review, including 30 studies, there is a paucity of CTs focusing only on children with primary or secondary, mainly renoparenchymal, hypertension. In trials on angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics, a significant reduction of both SBP and DBP in mixed cohorts of children with primary and secondary hypertension was achieved. However, few studies assessed the effect of antihypertensive drugs on hypertensive organ damage. Conclusions: Given the increasing prevalence and undertreatment of hypertension in this age group, innovative solutions including new design, such as 'n-of-1', and optimizing the use of digital health technologies could provide more precise and faster information about the efficacy of each antihypertensive drug class and the potential benefits according to patient characteristics.

A comparative study of antihypertensive drugs prediction models for the elderly based on machine learning algorithms.

Background: Globally, blood pressure management strategies were ineffective, and a low percentage of patients receiving hypertension treatment had their blood pressure controlled. In this study, we aimed to build a medication prediction model by correlating patient attributes with medications to help physicians quickly and rationally match appropriate medications. Methods: We collected clinical data from elderly hypertensive patients during hospitalization and combined statistical methods and machine learning (ML) algorithms to filter out typical indicators. We constructed five ML models to evaluate all datasets using 5-fold cross-validation. Include random forest (RF), support vector machine (SVM), light gradient boosting machine (LightGBM), artificial neural network (ANN), and naive Bayes (NB) models. And the performance of the models was evaluated using the micro-F1 score. Results: Our experiments showed that by statistical methods and ML algorithms for feature selection, we finally selected Age, SBP, DBP, Lymph, RBC, HCT, MCHC, PLT, AST, TBIL, Cr, UA, Urea, K, Na, Ga, TP, GLU, TC, TG, γ-GT, Gender, HTN CAD, and RI as feature metrics of the models. LightGBM had the best prediction performance with the micro-F1 of 78.45%, which was higher than the other four models. Conclusion: LightGBM model has good results in predicting antihypertensive medication regimens, and the model can be beneficial in improving the personalization of hypertension treatment.

Development and Comprehensive Characteristics of Thermosensitive Liquid Suppositories of Metoprolol Based on Poly(lactide-co-glycolide) Nanoparticles.

Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children.

Design, Formulation, and Characterization of Valsartan Nanoethosomes for Improving Their Bioavailability.

The objective of this study was to formulate and evaluate valsartan (VLT) ethosomes to prepare an optimized formula of VLT-entrapped ethosomes that could be incorporated into a sustained release transdermal gel dosage form. The formulation of the prepared ethosomal gel was investigated and subjected to in vitro drug release studies, ex vivo test, and in vivo studies to assess the effectiveness of ethosomal formulation in enhancing the bioavailability of VLT as a poorly soluble drug and in controlling its release from the transdermal gel dosage form. The acquired results are as follows: Dependent responses were particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized VLT-ETHs had a nanometric diameter (45.8 ± 0.5 nm), a negative surface charge (-51.4 ± 6.3 mV), and a high drug encapsulation (94.24 ± 0.2). The prepared VLT ethosomal gel (VLT-ethogel) showed a high peak plasma concentration and enhanced bioavailability in rats compared with the oral solution of valsartan presented in the higher AUC (0-∞). The AUC (0-∞) with oral treatment was 7.0 ± 2.94 (µg.h/mL), but the AUC (0-∞) with topical application of the VAL nanoethosomal gel was 137.2 ± 49.88 (µg.h/mL), providing the sustained release pattern of VLT from the tested ethosomal gel.

Antihypertensive drug prescription trends for pregnant women with hypertension in acute hospitals in Japan.

Hypertensive disorders of pregnancy cause maternal organ damage. Therefore, appropriate management with antihypertensive medication is required from the first trimester. We aimed to clarify the antihypertensive drug prescription trends in pregnant women with hypertension in Japan. The administrative data of pregnant outpatients aged 16-49 years who visited acute hospitals between 2013 and 2020 were included. The annual antihypertensive drug prescription trends were evaluated based on their prescription proportions. The most prescribed drug in 2020 was nifedipine, followed by methyldopa and amlodipine. The proportion of nifedipine prescriptions significantly increased from 33.5 to 40.8% during the study period, whereas that of methyldopa significantly decreased from 16.6 to 11.6%. There was no change in the prescription trend of amlodipine. Dihydropyridine calcium channel blockers were the most commonly prescribed drug for pregnant women with hypertension.

Antihypertensive Drugs and Cancer Risk.

Hypertension is the most prevalent comorbidity in cancer patients. Consequently, many cancer patients are prescribed antihypertensive drugs before cancer diagnosis or during cancer treatment. However, whether antihypertensive drugs affect the incidence, treatment efficacy, or prognosis of cancer remains unanswered. For instance, renin-angiotensin and ß-adrenergic signaling may be involved not only in blood pressure elevation but also in cell proliferation, angiogenesis, and tissue invasion. Therefore, the inhibition of these pathways may have beneficial effects on cancer prevention or treatment. In this article, we reviewed several studies regarding antihypertensive drugs and cancer. In particular, we focused on the results of clinical trials to evaluate whether the use of antihypertensive drugs affects future cancer risk and prognosis. Unfortunately, the results are somewhat inconsistent, and evidence demonstrating the effect of antihypertensive drugs remains limited. We indicate that the heterogeneity in the study designs makes it difficult to clarify the causal relationship between antihypertensive drugs and cancer. We also propose that additional experimental studies, including research with induced pluripotent cells derived from cancer patients, single-cell analyses of cancer cell clusters, and clinical studies using artificial intelligence electronic health record systems, might be helpful to reveal the precise association between antihypertensive drugs and cancer risk.

Cardiovascular risk in patients receiving antihypertensive drug treatment from the perspective of endothelial function.

Blood-pressure-lowering therapy with antihypertensive drugs can reduce the risk of cardiovascular morbidity and mortality in patients with hypertension. However, patients treated with antihypertensive drugs generally have a worse prognosis than untreated individuals. Consistent with the results obtained from epidemiological studies, a clinical study showed that endothelial function was impaired more in treated patients with hypertension than in untreated individuals with the same blood pressure level, suggesting that blood-pressure-lowering therapy with currently available antihypertensive drugs cannot restore endothelial function to the level of that in untreated individuals. Several mechanisms of endothelial dysfunction in treated patients are postulated: irreversible damage to the endothelium caused by higher cumulative elevated blood pressure exposure over time; the persistence of the primary causes of hypertension even after the initiation of antihypertensive drug treatment, including an activated renin-angiotensin-aldosterone system, oxidative stress, and inflammation; and higher global cardiovascular risk related not only to conventional cardiovascular risk factors but also to undetectable nonconventional risk factors. Lifestyle modifications/nonpharmacological interventions should be strongly recommended for both untreated and treated individuals with hypertension. Lifestyle modifications/nonpharmacological interventions may directly correct the primary causes of hypertension, which can improve endothelial function and consequently reduce cardiovascular risk regardless of the use or nonuse of antihypertensive drugs.

Antihypertensive Drug Combinations Modify Cisplatin-induced Acute Kidney Injury.

BACKGROUND/AIM: There is limited evidence about the nephrotoxicity of calcium channel blockers (CCBs) and renin-angiotensin system (RAS) inhibitors with concomitant cisplatin (CDDP). We investigated whether combinations of antihypertensive drugs are associated with CDDP-related acute kidney injury (AKI) using the Japanese Adverse Drug Event Report database. PATIENTS AND METHODS: We analysed 544,864 reports in the database from 2004 to 2020. A reporting odds ratio (ROR) and confidence interval (CI) with adjustment for potential confounding factors was calculated for AKI for each drug and the combined use of the drugs and CDDP. RESULTS: CDDP, CCBs, and RAS inhibitors were all detected signals for AKI. The ROR in cases with concomitant use of CCBs, RAS inhibitors, and CDDP (adjusted ROR 7.28; 95% CI=5.56-9.54) was higher than that in cases with use of each drug. CONCLUSION: AKI may require more attention when patients receiving CDDP take CCBs and RAS inhibitors together.