Search

Background: Antihypertensive drugs administered as fixed dose combination (FDC) therapy compared to separately administered combination therapy have been proposed to improve treatment compliance/adherence, and therefore the efficacy of blood pressure (BP) control treatment. Aim: The aim of this present study is to compare the blood pressure control, renal end-organ protection and medication compliance/adherence in patients receiving FDC and those receiving separately administered combinations of Lisinopril and Hydrochlorothiazide in treatment-naive hypertensive adult patients in a rural Nigerian community. Method: ology: This randomized two-arm prospective longitudinal 8-week parallel-group study was carried-out for 6-month at the Ajegunle Community between April 2018 and October 2018. Efficacy variables included the changes from baseline in mean sitting systolic BP (MSSBP) and mean sitting diastolic BP (MSDBP). Medication safety, compliance/adherence and renal end-organ protection were assessed. Results: The baseline characteristics of the two groups were similar. Prevalence of hypertension was found to be 32.9%. The mean blood pressure of all the participants was 165.6 ± 16.5 mmHg and 98.5 ± 11.5 mmHg for systolic BP and diastolic BP respectively, while the mean pulse rate of the participants was 85.0 ± 13.4 beats/min. At the 8-week end point, both regimens had achieved significant reductions from baseline in MSSBP (−33.18 and −37.16 mm Hg, respectively; both, P

An easy, sensitive and accurate spectrophotometric method has been developed for the determination of Lisinopril (LNP) in pure and tablet formulations based on derivatization reaction with 2-hydroxynaphthaldehyde (2HNA). The derivatization reaction was carried out in methanol solvent at pH-5.5 at 95±2C for 15 min. The linear calibration curve was obtained that obeyed the Beer’s law within the concentration range 5-50 µgmL-1 of LNP at 433 nm with a coefficient of determination R²=0.996. The recovery was in the range from 98.25-101.82 with molar absorptivity of drug 9×103 mole-1cm-1. The method was accurate and precise (intra-day variation 0.05-0.97% and inter-day 0.07-1.6%), with limit of detection (LOD) and limit of quantification (LOQ) 0.264 µgmL-1 and 0.8 µgmL-1, respectively. No interferences from the excipients were detected. The method was applied for the rapid analysis of LNP in pharmaceutical products.

Background: Non-communicable diseases are a growing burden in many African countries; cardiovascular disease is the main disease. Antihypertensive medicines (AHM) are a common treatment option but we know little about community use in most low- and medium-income countries (LMIC). We aimed to describe the use of antihypertensive medicines (AHM) in Ghana and Nigeria using a novel data source.Methods: We used data from mPharma-a health and pharmaceutical company which distributes pharmaceuticals to hospital and retail pharmacies. We extracted data using the anatomical therapeutic chemical (ATC) classification codes and calculated use in defined daily doses and explored patterns by class, medicines, dose, and originator or generic product.Results: AHM use differed between Ghana and Nigeria. The most used classes in Ghana were angiotensin receptor blockers (ARB) followed by calcium channel blockers (CCB) and angiotensin-converting-enzyme inhibitors (ACEi). The five most used products were 16 mg candesartan, 30 mg nifedipine, 10 mg lisinopril, 5 mg amlodipine and 50 mg losartan. In Nigeria ARB, CCB and diuretics were widely used; the top five products were 50 mg losartan, 10 mg lisinopril, 30 mg nifedipine, 40 mg furosemide, and 5 mg amlodipine. More originator products were used in Ghana than Nigeria.Conclusion: The differences between Ghana and Nigeria may result from a combination of medical, contextual and policy evidence and reflect factors related to clinical guidance (e.g. standard treatment guidelines), accessibility to prescribers and the role of community pharmacies, and structure of the health system and universal health coverage including funding for medicines. We show the feasibility of using novel data sources to gain insights on medicines use in the community. [ABSTRACT FROM AUTHOR]

Isolated angioedema of the small intestine is a rare adverse event in patients taking angiotensin-converting enzyme inhibitors. Here, we present a case of visceral angioedema in a 32-year-old woman who presented with left upper quadrant pain, nausea, vomiting, diarrhea, and characteristic radiographic signs of small bowel angio-edema, six months after starting lisinopril. Her symptoms improved within 48 hours of withholding the offending agent and with supportive care. We discuss the epidemiology, pathophysiology, diagnosis, and management of angiotensin-converting enzyme inhibitorinduced angioedema. [ABSTRACT FROM AUTHOR]

Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARBinduced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAEassociated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher’s exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phredscaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants. [ABSTRACT FROM AUTHOR]

Purpose: The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects. Methods: A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded. Results: Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80–1.25. A high-fat meal appeared to decrease the Cmax and AUC of lisinopril. No severe adverse events were observed. Conclusion: The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions. Trial registration: Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021). [ABSTRACT FROM AUTHOR]

Lisinopril dihydrate (LP) is an FDA approved drug used in the treatment of hypertension. When administered orally it is slowly and incompletely absorbed with a bioavailability of 25-30% only. The aim of the present study is to increase the bioavailability of LP by formulating into nano-spanlastic bio-adhesive gel for intranasal delivery. LP loaded nano-spanlastics (LPSp) were prepared by ethanol injection method according to 23 factorial designs using Design Expert® software, to explore the impact of different independent variables on Particle Size (PS) and Entrapment efficiency (EE%). The optimized LPSp was evaluated for PS, surface morphology, polydispersity index (PDI), zeta potential, EE% and in-vitro drug release. Further, the optimized LPSp was loaded into Carbopol gel base (1%) and evaluated for pH, percentage drug content, texture properties and rheology. The permeation and histopathological studies were carried out using goat nasal mucosa. The optimized LPSp possessed spherical shape with PS and EE% of 320±4.5 nm and 72±2.5% respectively. Drug release studies revealed that the drug enclosed in spanlastic dispersion showed higher drug release compared to niosome dispersion. The LPSp gels exhibited satisfactory results for pH, drug content, texture properties and rheology. The ex-vivo results showed that the permeation rate of LP loaded nanospanlastic bio-adhesive gel (LPSpG) increased when compared to that of LP loaded niosome gel (LPNiG). The results infer that encapsulating LP into vesicular carriers and formulating into a bio-adhesive gel augments its permeation and increases the residence time in nasal mucosa and therefore enhances its bioavailability. [ABSTRACT FROM AUTHOR]

Background: Tissue fillers are among the most popular cosmetic procedures performed and notably, cases of filler reactions after COVID‐19 vaccination have been reported. Objective: The objective was to determine the characteristics of patients with filler reaction after COVID‐19 vaccination and address several considerations that have to be taken into practice. Methods: A PRISMA compliant systematic search was conducted in Scopus, Web of Science, and PubMed/MEDLINE databases for articles published from inception up to October 21, 2021. Results: Out of 106 initially retrieved articles, four of them were included in our study, and a total number of 13 cases were analyzed. In this study, we found that all of the patients who developed delayed‐type reaction (DTR) following COVID‐19 vaccination were middle‐aged women without any known history of allergy to foods or drugs. All patients had a history of hyaluronic acid (HA) filler injection in their head and neck and demonstrated symptoms particularly swelling, from <1 day up to 10 days after the first or second doses of vaccines. Lisinopril, hyaluronidase, and corticosteroids seemed to have good results in management. Conclusion: Although rare, DTR to fillers after COVID‐19 vaccination can happen. Physicians should be aware of the pathogenesis and management of this phenomenon. [ABSTRACT FROM AUTHOR]

This is a case report of a 55-year-old woman with a past medical history of hypertension who presented to the emergency department with upper lip and cheek swelling isolated to the right side of her face. She was on lisinopril for several years and had never had an episode of swelling in the past. Her vital signs were stable. However, on reassessment, the patient's right sided swelling progressed to the entire upper lip and she complained of swelling in her submandibular space. Although no swelling was appreciated to the submandibular space on physical exam, and the patient still did not have any signs or symptoms of respiratory distress, the decision was made to use a fiberoptic laryngoscope to evaluate her airway. Fiberoptic laryngoscope showed noticeable laryngeal edema which did not improve after treatment, and the patient was admitted to the medical intensive care unit for close airway observation. This case highlights the use of fiberoptic laryngoscope by emergency physicians in the evaluation of patients with relatively benign appearing angioedema. Topics: ACE-I, angioedema, fiberoptic laryngoscope, laryngeal edema, tranexamic acid. [ABSTRACT FROM AUTHOR]

Background: Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. Here, we characterized the effect of the long-acting GLP-1R agonist semaglutide alone and in combination with an ACE inhibitor (lisinopril) in a model of hypertension-accelerated, advanced DKD facilitated by adeno-associated virus-mediated renin overexpression (ReninAAV) in uninephrectomized (UNx) female diabetic db/db mice. Methods: Female db/db mice received a single intravenous injection of ReninAAV 1 week prior to UNx. Six weeks post-nephrectomy, db/db UNx-ReninAAV mice were administered (q.d.) vehicle, semaglutide (30 nmol/kg, s.c.) or semaglutide (30 nmol/kg, s.c.) + lisinopril (30 mg/kg, p.o.) for 11 weeks. Endpoints included blood pressure, plasma/urine biochemistry, kidney histopathology and RNA sequencing. Results: Vehicle-dosed db/db UNx-ReninAAV mice developed hallmarks of DKD characterized by severe albuminuria and advanced glomerulosclerosis. Semaglutide robustly reduced hyperglycemia, hypertension and albuminuria concurrent with notable improvements in glomerulosclerosis severity, podocyte filtration slit density, urine/renal kidney injury molecule-1 (KIM-1) levels and gene expression markers of inflammation and fibrogenesis in db/db UNx-ReninAAV mice. Co-administration of lisinopril further ameliorated hypertension and glomerulosclerosis. Conclusions: Semaglutide improves disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Further benefits on renal outcomes were obtained by adjunctive antihypertensive standard of care. Collectively, our study supports the development of semaglutide for management of DKD. [ABSTRACT FROM AUTHOR]

A new, simple and rapid high-performance thin-layer chromatographic method was developed and validated for quantitative determination of hydrochlorothiazide and lisinopril. Both the drugs were chromatographed on silica gel 60 F254 HPTLC plate using chloroform: methanol: ethyl acetate: acetic acid (7:2:1.0:0.2; V/V/V/V) as the mobile phase. Hydrochlorothiazide and lisinopril were quantified by densitometric analysis at 218 nm. The method was found to give compact bands for hydrochlorothiazide and lisinopril at Rf 0.43 and 0.75, respectively. The linear regression analysis data for the calibration plots showed good linear relationship with r2 0.9990 and 0.9992 in the concentration range 200-1200 ng band-1 and 250-1500 ng band-1, for hydrochlorothiazide and lisinopril, respectively. The method was validated as per the International Conference on Harmonization guidelines Q2(R1). The minimum detectable amounts were found to be 50.16 ng and 37.93 ng, whereas the limits of quantitation were found to be 150.48 and 113.92 ng for hydrochlorothiazide and lisinopril, respectively. Statistical analysis of the data showed that the method was precise, accurate, reproducible, selective and specific for the analysis of hydrochlorothiazide and lisinopril. The method was successfully employed for the routine quantitative estimation of hydrochlorothiazide and lisinopril in pharmaceutical tablet formulations. [ABSTRACT FROM AUTHOR]

The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and platelets), and cardiac myocytes have the potential to damage vascular cells directly and cardiac myocytes, initiating mechanisms that induce apoptosis, inflammation, necrosis, and fibrosis of myocardial cells. In addition to reducing blood pressure, lisinopril, a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, increases the antioxidant defense in animals and humans. Recently, it has been shown that lisinopril can attenuate renal oxidative injury in the l-NAME-induced hypertensive rat and cause an impressive improvement in the antioxidant defense system of Wistar rats treated with doxorubicin. The potential effect of lisinopril on oxidative damage and fibrosis in human cardiomyocytes has not been previously investigated. Thus, the present study aims to investigate the effect of different doses of lisinopril on oxidative stress and fibrotic mediators in AC16 human cardiomyocytes, along with a 7-day presence in the culture medium. The results revealed that AC16 human cardiomyocytes exposed to lisinopril treatment significantly showed an upregulation of proteins involved in protecting against oxidative stress, such as catalase, SOD2, and thioredoxin, and a reduction of osteopontin and Galectin-3, critical proteins involved in cardiac fibrosis. Moreover, lisinopril treatment induced an increment in Sirtuin 1 and Sirtuin 6 protein expression. These findings demonstrated that, in AC16 human cardiomyocytes, lisinopril could protect against oxidative stress and fibrosis via the activation of Sirtuin 1 and Sirtuin 6 pathways. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced lung injury is a major dose-limiting toxicity for thoracic radiation therapy patients. In experimental models, treatment with angiotensin converting enzyme (ACE) inhibitors mitigates radiation pneumonitis; however, the mechanism of action is not well understood. Here, we evaluate the direct role of ACE inhibition on lung immune cells.Methods and Materials: ACE expression and activity were determined in the lung immune cell compartment of irradiated adult rats after either high dose fractionated radiation therapy to the right lung (5 fractions × 9 Gy) or a single dose of 13.5 Gy partial body irradiation. Mitigation of radiation-induced pneumonitis with the ACE-inhibitor lisinopril was evaluated in the 13.5 Gy rat partial body irradiation model. During pneumonitis, we characterized inflammation and immune cell content in the lungs and bronchoalveolar lavage fluid. In vitro mechanistic studies were performed using primary human monocytes and the human monocytic THP-1 cell line.Results: In both the partial body irradiation and fractionated radiation therapy models, radiation increased ACE activity in lung immune cells. Treatment with lisinopril improved survival during radiation pneumonitis (P = .0004). Lisinopril abrogated radiation-induced increases in bronchoalveolar lavage fluid monocyte chemoattractant protein 1 (chemokine ligand 2) and MIP-1a cytokine levels (P < .0001). Treatment with lisinopril reduced both ACE expression (P = .006) and frequency of CD45+ CD11b+ lung myeloid cells (P = .004). In vitro, radiation injury acutely increased ACE activity (P = .045) and reactive oxygen species (ROS) generation (P = .004) in human monocytes, whereas treatment with lisinopril blocked radiation-induced increases in both ACE and ROS. Radiation-induced ROS generation was blocked by pharmacologic inhibition of either NADPH oxidase 2 (P = .012) or the type 1 angiotensin receptor (P = .013).Conclusions: These data demonstrate radiation-induced ACE activation within the immune compartment promotes the pathogenesis of radiation pneumonitis, while ACE inhibition suppresses activation of proinflammatory immune cell subsets. Mechanistically, our in vitro data demonstrate radiation directly activates the ACE/type 1 angiotensin receptor pathway in immune cells and promotes generation of ROS via NADPH oxidase 2. [ABSTRACT FROM AUTHOR]

The article reports that Mr. J, age 73, has a 25-year history of generalized anxiety disorder and major depressive disorder. His medical history includes hypertension, hyperlipidemia, type 2 diabetes mellitus, hypothyroidism, osteoarthritis, insomnia, and allergic rhinitis. His last laboratory test results indicate his hemoglobin A1c, thyroidstimulating hormone.

Heart failure is a clinical syndrome, enormous problem caused by structural and functional defects in myocardium resulting in impairment of ventricular filling or the ejection of blood. ACE inhibitors (as Lisinopril) and Angiotensin II receptor blockers (as losartan) plays a central role in the pathogenesis of cardiovascular complications then improve the condition of the patients with heart failure. To compare the effect of Lisinopril and Losartan in Iraqi patients with left ventricular systolic dysfunction regarding to left ventricular systolic function, clinical feature and side effects of both Lisinopril and Losartan. Hundred patients were enrolled into the study; 50 patients were given Lisinopril and 50 patients were given Losartan for 26 weeks starting from September 2020 to March 2021. Patient's history, signs, symptoms, risk factors for cardiovascular diseases, possible causes(s) of left ventricular systolic dysfunction and side effects has been recorded in each patient at baseline and after 26 weeks of treatment initiation. In the current study, there was a significant improvement in the signs, symptoms, and Echo findings for the patients that given Lisinopril and others who take Losartan after 28 weeks, but the Lisinopril was produced better improvement and statically significant in most of signs, symptoms, and Echo findings than Losartan. Also, the incidence of adverse effect (cough, headache, dizziness and itching or skin rash) was lower with losartan when compared with Lisinopril while the other side effects were lower with Lisinopril. In conclusion, the study of these two drugs (Lisinopril and Losartan) provides distinct benefit in comparison with placebo or other standard treatment. Lisinopril was produced better improvement and statically significant in most of signs, symptoms and echocardiographic findings of the patients when compared with the improvement that was obtained from the use of Losartan but the incidence of some of adverse effects like cough, was significantly higher with Lisinopril than Losartan. [ABSTRACT FROM AUTHOR]

Background: Lisinopril-induced angioedema (LIA) is a rare but serious adverse drug event (ADE) with a published incidence of 0.1% to 0.7%. It is well known that ADEs are widely underreported; however, LIA is one of the most reported ADEs within the Veterans Health Administration (VHA). Objective: To estimate the effect of underreporting on the risk of LIA within VHA. Methods: The reported risk of LIA was calculated from reports submitted to the Veterans Affairs (VA) Adverse Drug Event Reporting System (VA ADERS) and the number of veterans prescribed lisinopril. To estimate underreporting, local chart review identified cases of LIA that were compared to reports submitted. The underreporting rate was then applied to the national reported risk. Results: Locally, 68 reports of LIA were submitted of the 21 262 patients prescribed lisinopril, for a reported risk of 0.32%. Nationwide, 14 289 reports of LIA were submitted of the 3 109 661 patients prescribed lisinopril, for a crude reported risk of 0.46%. Of the 324 patients identified for chart review, 240 patients were diagnosed with LIA, suggesting that at least 71.7% of cases were unreported. When this underreporting rate is extrapolated to the national reported risk, a better estimate of the risk of LIA within VHA could increase to 1.6%. Conclusion and Relevance: When estimating the effect of underreporting, the risk of LIA increases to approximately 1.6% or 1 in 63 patients. Because this ADE may affect more patients than previously understood, providers may wish to take LIA into consideration when prescribing lisinopril. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme 2 (ACE2) is the established cellular receptor for SARS-CoV-2. However, it is unclear whether ACE1 inhibitors (e.g., lisinopril) or angiotensin receptor blockers (e.g., losartan) alter tissue ACE2 expression. This study sought to determine whether lisinopril or losartan, as monotherapies or in combination, changes tissue levels of ACE2 in healthy male and female mice. Mice received lisinopril (10 mg/kg/day), losartan (10 mg/kg/day), or both for 21 days via drinking water. A control group received water without drug. The ACE2 protein index (ACE2 protein/total protein) was determined on the small intestine, lung, kidney, and brain. Oral lisinopril increased the ACE2 protein index across all tissues (p < 0.0001 vs. control). In contrast, the combination of lisinopril plus losartan did not increase ACE2 levels in any tissue (p = 0.89 vs. control) and even decreased tissue expression of the Ace2 gene (p < 0.001 vs. control). Tissue ACE2 remained elevated in the mice 21 days after cessation of lisinopril (p = 0.02). Plasma ACE2 did not correlate with the ACE2 protein index in any tissue. A sex difference was observed: kidney ACE2 levels were higher in male than in female mice (p < 0.0001). Oral lisinopril increases ACE2, the cellular receptor for SARS-CoV-2, in tissues that are relevant to the transmission and pathogenesis of COVID-19. Remarkably, the addition of losartan prevented lisinopril-induced increases in ACE2 across tissues. These results suggest that ACE inhibitors and angiotensin receptor blockers interact to determine tissue levels of ACE2. [ABSTRACT FROM AUTHOR]

The genetic bases and disparate responses to radiotherapy are poorly understood, especially for cardiotoxicity resulting from treatment of thoracic tumors. Preclinical animal models such as the Dahl salt-sensitive (SS) rat can serve as a surrogate model for salt-sensitive low renin hypertension, common to African Americans, where aldosterone contributes to hypertension-related alterations of peripheral vascular and renal vascular function. Brown Norway (BN) rats, in comparison, are a normotensive control group, while consomic SSBN6 with substitution of rat chromosome 6 (homologous to human chromosome 14) on an SS background manifests cardioprotection and mitochondrial preservation to SS rats after injury. In this study, 2 groups from each of the 3 rat strains had their hearts irradiated (8 Gy X 5 fractions). One irradiated group was treated with the ACE-inhibitor lisinopril, and a separate group in each strain served as nonirradiated controls. Radiation reduced cardiac end diastolic volume by 9-11% and increased thickness of the interventricular septum (11-16%) and left ventricular posterior wall (14-15%) in all 3 strains (5-10 rats/group) after 120 days. Lisinopril mitigated the increase in posterior wall thickness. Mitochondrial function was measured by the Seahorse Cell Mitochondrial Stress test in peripheral blood mononuclear cells (PBMC) at 90 days. Radiation did not alter mitochondrial respiration in PBMC from BN or SSBN6. However, maximal mitochondrial respiration and spare capacity were reduced by radiation in PBMC from SS rats (p=0.016 and 0.002 respectively, 9-10 rats/group) and this effect was mitigated by lisinopril (p=0.04 and 0.023 respectively, 9-10 rats/group). Taken together, these results indicate injury to the heart by radiation in all 3 strains of rats, although the SS rats had greater susceptibility for mitochondrial dysfunction. Lisinopril mitigated injury independent of genetic background. [ABSTRACT FROM AUTHOR]

Purpose: In aut-idem or generic substitution, discrepancies between summaries of product characteristics (SmPCs) referring to the same active substance (AS) may cause difficulties regarding informed consent and medical liability. The qualitative and quantitative characteristics of such discrepancies are insufficiently studied, impeding harmonization of same-substance SmPCs and compromising safe drug treatment. Methods: SmPCs of the one hundred most frequently prescribed ASs in Germany were analyzed for discrepancies in the presentation of indications (Inds) and contraindications (CInds). Inclusion and exclusion criteria of drugs/SmPCs were chosen according to the standards of the aut-idem substitution in Germany. Results: According to the study protocol, we identified 1486 drugs, of which 1426 SmPCs could be obtained. 41% respectively 65% of the ASs had same-substance SmPCs that differed from the respective reference SmPC in the number of listed Inds respectively CInds. The number of listed Inds/CInds varied considerably between same-substance SmPCs with maximum ranges in Inds of 7 in amoxicillin, and in CInds of 11 in lisinopril. Many ASs had large proportions (> 50%) of associated same-substance SmPCs that differed from the respective reference SmPC. A considerable proportion of ASs had same-substance SmPCs with formal and content-related differences other than the discrepancy in the number of Inds/CInds. Conclusion: This evaluation of same-substance SmPCs shows a clear lack of harmonization of same-substance SmPCs. Considering that generic substitution has become the rule and that physicians usually do not know which drug the patient receives in the pharmacy, these discrepancies raise several questions, that require a separate legal evaluation. [ABSTRACT FROM AUTHOR]

In this present work, we report structural and computational studies of 1,2,3‐triazole fused dicarboxylate derivative (TMND), which is investigated as an angiotensin‐converting enzyme (ACE) inhibitor for antihypertension treatment. The crystal structure of TMND is solved by single‐crystal XRD method and correlated with density functional B3LYP/6–311++ method. We performed Hirshfeld surface analysis to examine the strength of hydrogen bonds and to measure the intercontacts and enrichment ratio. The enrichment ratio of OH contact in TMND crystal validates (EOH = 1.20) that the OC and O═C bonds produce four weak hydrogen bonds of the type O...HC as evident in the supramolecular crystal packing. The enrichment ratio of CH contacts (ECH = 1.02) represent CH...π interactions with aromatic rings present in TMND crystal structure similar to XRD data. By using density functional theory (DFT/B3LYP/6–311++) method, frontier molecular orbital and molecular electrostatic potential map were computed and reactive regions were identified. In silico ACE inhibition nature of the TMND compound was evaluated using molecular docking method and followed by molecular dynamics simulation. Results reveals superior ACE inhibition ability of TMND compound over the native ligand and standard Food and Drug Administration approved antihypertensive drug lisinopril. Hence, it is concluded that our compound TMND could be considered for the antihypertensive drug design and development process. [ABSTRACT FROM AUTHOR]

Aim. To evaluate the single pill combination with lisinopril, amlodipine and indapamide ability in additional angioprotection achievement in patients with arterial hypertension and high pulse wave velocity (PWV) regardless on previous antihypertensive therapy (AHT).Material and methods. To the open non-randomized study duration 12 weeks 40 patients were included taking triple AHT during 6 months. All participants underwent ambulatory 24 hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), pulse wave velocity assessment, laboratory tests (HbA1c, serum uric acid, high sensitive C-reactive protein [hsCRP], serum uric acid).Results. We observed additional systolic BP (SBP) and diastolic BP (DBP) reduction by 16.9% and 22.11% on lisinopril, amlodipine and indapamide single pill combination. Lisinopril, amlodipine and indapamide single pill combination decreased 24 h mean SBP by 16.77%, and 24 h mean DBP -23.5% (ABPM data), PWV by 19.7%, augmentation index by 14.81%, central SBP by 11.9% (p

Introduction: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. Material and methods: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene–related peptide in the context of the COVID-19 pandemic. Results: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. Conclusions: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias. Resumen: Introducción: En los últimos meses han surgido dudas por parte de pacientes, médicos de familia y neurólogos sobre la posibilidad de que algunos de los fármacos que habitualmente se utilizan en cefaleas y neuralgias puedan facilitar o complicar la infección por el SARS-COV-2. Material y métodos: Hemos recabado información sobre el posicionamiento de sociedades científicas, así como de las distintas Agencias de Medicamentos (americana, europea y española) para poder esclarecer dudas respecto al uso de fármacos como lisinopril, candesartán, ibuprofeno, corticoides, carbamazepina, anticuerpos monoclonales contra el CGRP durante la pandemia por COVID-19. Resultados: Planteamos recomendaciones acerca del uso de fármacos habituales en el tratamiento de las cefaleas en el contexto de la pandemia por COVID-19, basándonos en las evidencias de las que disponemos en el momento actual. Conclusiones: Actualmente, no existe ningún argumento científico robusto para contraindicar formalmente ninguno de los tratamientos que se emplean en cefaleas y neuralgias.

Resumen: Introducción: En los últimos meses han surgido dudas por parte de pacientes, médicos de familia y neurólogos sobre la posibilidad de que algunos de los fármacos que habitualmente se utilizan en cefaleas y neuralgias puedan facilitar o complicar la infección por el SARS-CoV-2. Material y métodos: Hemos recabado información sobre el posicionamiento de sociedades científicas, así como de las distintas Agencias de Medicamentos (americana, europea y española) para poder esclarecer dudas respecto al uso de fármacos como lisinopril, candesartán, ibuprofeno, corticoides, carbamazepina, anticuerpos monoclonales contra el péptido relacionado con el gen de la calcitonina (CGRP) durante la pandemia por COVID-19. Resultados: Planteamos recomendaciones acerca del uso de fármacos habituales en el tratamiento de las cefaleas en el contexto de la pandemia por COVID-19, basándonos en las evidencias de las que disponemos en el momento actual. Conclusiones: Actualmente no existe ningún argumento científico robusto para contraindicar formalmente ninguno de los tratamientos que se emplean en cefaleas y neuralgias. Abstract: Introduction: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. Material and methods: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene–related peptide in the context of the COVID-19 pandemic. Results: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. Conclusions: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.

Abstract Background This study aimed to assess the pediatric lisinopril doses using an adult physiological based pharmacokinetic (PBPK) model. As the empirical rules of dose calculation cannot calculate gender-specific pediatric doses and ignores the age-related physiological differences. Methods A PBPK model of lisinopril for the healthy adult population was developed for oral (fed and fasting) and IV administration using PK-Sim MoBI® and was scaled down to a virtual pediatric population for prediction of lisinopril doses in neonates to infants, infants to toddler, children at pre-school age, children at school age and the adolescents. The pharmacokinetic parameters were predicted for the above groups at decremental doses of 20 mg, 10 mg, 5 mg, 2.5 mg, and 1.5 mg in order to accomplish doses producing the pharmacokinetic parameters, similar (or comparable) to that of the adult population. The above simulated pediatric doses were compared to the doses computed using the conventional four methods, such as Young’s rule, Clark’s rule, and weight-based and body surface area-based equations and the dose reported in different studies. Results Though the doses predicted for all subpopulations of children were comparable to those calculated by Young’s rule, yet the conventional methods overestimated the pediatric doses when compared to the respective PBPK-predicted doses. The findings of previous real time pharmacokinetic studies in pediatric patients supported the present simulated dose. Conclusion Thus, PBPK seems to have predictability potential for pediatric dose since it takes into consideration the physiological changes related to age and gender.

The important result of the revision of the European and Russian guidelines for the management of arterial hypertension was a conclusion about the need to use a double combination of antihypertensive drugs as the first stage of antihypertensive therapy. The review presents benefits of combined antihypertensive therapy, confirmed by the results of randomized clinical trials and meta-analysis. There are literature data suggesting one of the first line reasonable combinations is the combination of angiotensin converting enzyme inhibitors (ACEI) and thiazide-like diuretic. The article discusses the benefits of single-pill combinations before free ones, such as increase in patient adherence to long-term treatment, reduction in the cost of the drug and the number of tablets. As an example, a highly effective single-pill combination of one of the most used ACEI, lisinopril and indapamide sustained release, is considered, which has protective activity, vasodilator properties and metabolic neutrality. The article presents the data of the PIFAGOR IV study that indapamide is the most widely used diuretic in Russia, which is characterized by high antihypertensive efficacy, good tolerance, cardioprotective, nephroprotective and osteoprotective properties. The results of large-scale studies, which show the ability of lisinopril to retain target blood pressure level, antiproteinuric and cardioprotective activity, are also presented. This single-pill combination has a long additive effect, contributing to reliable daily monitoring of blood pressure. The authors expressed the opinion that the prescription of highly effective single-pill combinations will contribute to organ protection and reduce the risk of cardiovascular complications development.

A new, rapid and selective, HPLC method for simultaneous quantitative estimation of lisinopril and hydrochlorothiazide residues and sampling procedures from pharmaceutical manufacturing equipment surfaces were developed and validated. The sampling procedures have a good recovery (>80%). The limit of quantitation of the HPLC method - 0.155 µg/mL and 0.025 µg/mL for lisinopril and hydrochlorothiazide, respectively.

Arterial hypertension (AH) is one of the most significant modifiable risk factors that increase cardiovascular morbidity and mortality worldwide, including Russia. The complex of structural and functional changes in the heart that occurs during AH consists not only in the formation of left ventricular (LV) myocardial hypertrophy, but also in the myocardial stiffness increasing due to collagen formation and cardiomyocytes apoptosis. These abnormalities are substrate for diastolic function disturbances, electrical myocardial instability and ischemia. The article provides a clinical case of amlodipine/lisinopril single-pill combination (A/L SPC) use in real clinical practice in a patient with stage II grade 2 newly diagnosed AH and its effect on blood pressure and echocardiographic myocardial fibrosis markers, including speckle tracking parameters The high antihypertensive efficacy of A/L SPC, a favorable effect on blood pressure circadian rhythm, as well as pronounced target-organ protective properties, in particular the ability to reduce LV and left atrial stiffness, were demonstrated. So, we conclude that A/L SPC improve the elastic properties of the left heart.

Abstract Introduction Metoprolol succinate is a long-acting beta-blocker prescribed for the management of hypertension (HTN) and other cardiovascular diseases. Metabolomics, the study of end-stage metabolites of upstream biologic processes, yield insight into mechanisms of drug effectiveness and safety. Our aim was to determine metabolomic profiles associated with metoprolol effectiveness for the treatment of hypertension. Methods We performed a prospective pragmatic trial (NCT02293096) that enrolled patients between 30 and 80 years with uncontrolled HTN. Patients were started on metoprolol succinate at a dose based upon systolic blood pressure (SBP). Urine and blood pressure measurements were collected weekly. Individuals with a 10% decline in SBP or heart rate (HR) were considered responsive. Genotype for the CYP2D6 enzyme, the primary metabolic pathway for metoprolol, was evaluated for each subject. Unbiased metabolomic analyses were performed on urine samples using UPLC-QTOF mass spectrometry. Results Urinary metoprolol metabolite ratios are indicative of patient CYP2D6 genotypes. Patients taking metoprolol had significantly higher urinary levels of many gut microbiota-dependent metabolites including hydroxyhippuric acid, hippuric acid, and methyluric acid. Urinary metoprolol metabolite profiles of normal metabolizer (NM) patients more closely correlate to ultra-rapid metabolizer (UM) patients than NM patients. Metabolites did not predict either 10% SBP or HR decline. Conclusion In summary, urinary metabolites predict CYP2D6 genotype in hypertensive patients taking metoprolol. Metoprolol succinate therapy affects the microbiome-derived metabolites.

The genetic bases and disparate responses to radiotherapy are poorly understood, especially for cardiotoxicity resulting from treatment of thoracic tumors. Preclinical animal models such as the Dahl salt-sensitive (SS) rat can serve as a surrogate model for salt-sensitive low renin hypertension, common to African Americans, where aldosterone contributes to hypertension-related alterations of peripheral vascular and renal vascular function. Brown Norway (BN) rats, in comparison, are a normotensive control group, while consomic SSBN6 with substitution of rat chromosome 6 (homologous to human chromosome 14) on an SS background manifests cardioprotection and mitochondrial preservation to SS rats after injury. In this study, 2 groups from each of the 3 rat strains had their hearts irradiated (8 Gy X 5 fractions). One irradiated group was treated with the ACE-inhibitor lisinopril, and a separate group in each strain served as nonirradiated controls. Radiation reduced cardiac end diastolic volume by 9-11% and increased thickness of the interventricular septum (11-16%) and left ventricular posterior wall (14-15%) in all 3 strains (5-10 rats/group) after 120 days. Lisinopril mitigated the increase in posterior wall thickness. Mitochondrial function was measured by the Seahorse Cell Mitochondrial Stress test in peripheral blood mononuclear cells (PBMC) at 90 days. Radiation did not alter mitochondrial respiration in PBMC from BN or SSBN6. However, maximal mitochondrial respiration and spare capacity were reduced by radiation in PBMC from SS rats (p=0.016 and 0.002 respectively, 9-10 rats/group) and this effect was mitigated by lisinopril (p=0.04 and 0.023 respectively, 9-10 rats/group). Taken together, these results indicate injury to the heart by radiation in all 3 strains of rats, although the SS rats had greater susceptibility for mitochondrial dysfunction. Lisinopril mitigated injury independent of genetic background.

This systematic review provides a comprehensive comparison of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors in the management of chronic heart failure (CHF), with a focus on their long-term efficacy and safety profiles. By synthesizing evidence from randomized controlled trials (RCTs) and clinical studies, the review highlights the significant benefits of both drug classes in reducing mortality and hospital readmissions, and improving patient outcomes. Beta-blockers, such as bisoprolol and carvedilol, demonstrated superior efficacy in reducing sudden cardiac death, particularly in patients with heart failure with reduced ejection fraction (HFrEF). Angiotensin-converting enzyme (ACE) inhibitors, including enalapril and lisinopril, effectively lowered overall cardiovascular mortality by targeting the renin-angiotensin-aldosterone system (RAAS) and preventing further cardiac remodeling. The findings of this review underscore the importance of utilizing these therapies, either alone or in combination, for optimal heart failure management. Combining beta-blockers and ACE inhibitors, or integrating them with newer agents such as angiotensin receptor-neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs), provides an additive benefit, improving long-term survival and reducing heart failure-related hospitalizations. The review also identifies gaps in the current literature, suggesting that future research should focus on personalized treatment approaches, longer follow-up periods, and exploring novel therapeutic combinations for diverse heart failure populations. This evidence reinforces the role of beta-blockers and ACE inhibitors as foundational therapies in CHF and offers actionable insights for clinicians to enhance patient care., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hassan et al.)

A 47-year-old woman presents to our clinic with a chief complaint of rhinorrhea; she had chronic hypertension managed with four antihypertensive drugs, including an ACE inhibitor. While dry cough is a well-known side effect associated with ACE inhibitors, this case highlights a common chief complaint yet less recognized side effect of ACE inhibitors and further emphasizes the idea that overall, angiotensin receptor blockers may be a better drug of choice in hypertension due to their favorable side effect profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Amudzi, Samale and Vela-Parada.)

The objective was to investigate the effect of co-administration of hydrochlorothiazide and lisinopril as fixed dose combination on their intestinal absorption. The scope was extended to enhance intestinal absorption of both drugs. In situ rabbit intestinal absorption through the duodenum and jejuno-ileum was used to monitor membrane permeability of both drugs when perfused alone or in combination. Niosomes containing glycerols (glyceroniosomes) were loaded with both drugs. Glyceroniosomes comprised Span 60 or Tween 40 in combination with cholesterol and glycerol were prepared by bath sonication. Glyceroniosomes were characterized with respect to vesicle size, drug entrapment efficiency and were examined using transmission electron microscope (TEM). The prepared vesicles were nanosized spherical vesicles with average size of 202.4 nm and 108.8 nm for span free and span containing glyceroniosomes, respectively. The recorded Zeta potential values suggested good stability of the prepared formulations. Intestinal absorption studies reflected incomplete absorption of hydrocholothiazide and lisinopril correlating with their categorization as class IV and III drugs, respectively. Co-perfusion of both drugs reduced the intestinal absorption of lisinopril. Simultaneous encapsulation in glyceroniosomes enhanced the intestinal absorption of both drugs. Tween based systems were more efficient. The study introduced glyceroniosomes as carriers of simultaneous delivery of hydrochlorothiazide and lisinopril., (© 2024. The Author(s).)