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Question: Can previously reported, largely anecdotal associations between exposure to any of a comprehensive list of putative trigger drugs and the development of pemphigus be reproduced using population level data? Findings: In this series of observational, retrospective, case-control, pharmacovigilance analyses of the FDA Adverse Event Reporting System, the odds of reporting the adverse event pemphigus were significantly elevated among individuals exposed to 11/36 previously reported trigger drugs namely, gold sodium thiomalate, penicillamine, piroxicam, rifampin, hydroxychloroquine, imiquimod, hydrochlorothiazide, irbesartan, lisinopril, nivolumab, and nifedipine. Meaning: Environmental exposures such as drugs are relevant players in the pathogenesis of autoimmune diseases and clinicians who treat patients with autoimmune blistering diseases such as pemphigus should consider performing a detailed medication history leveraging this information regarding deleterious drug-disease interactions at initial evaluation as well as longitudinal monitoring of patients to better inform clinical care decisions. Importance: Pemphigus vulgaris (PV) is a rare, potentially fatal autoimmune disease with pathogenic contributions from both genetic as well as environmental factors, notably drug exposures. Despite anecdotal reports linking multiple drugs to PV, corroborating evidence from large datasets is missing. Objective: To examine the extent to which previously reported associations between a comprehensive list of 36 drugs implicated in PV pathogenesis could be replicated using population-level pharmacovigilance data. Design: Series of observational, retrospective, case-control, pharmacovigilance analyses (one analysis/drug, 36 total). Setting: Population based. Participants: Individuals who submitted a report of a drug-related adverse event to the FDA from Q4 of 2003 to Q2 of 2023. Exposure: Cases were identified by the presence of adverse events described by the MedDRA preferred term "pemphigus" (10034280) and then sorted based on exposure to each of the drugs of interest. Main outcomes and measures: Reporting Odds Ratios (RORs) quantifying the association between a given drug exposure and reports of pemphigus adverse events. Results: The analyses revealed statistically significant associations between reports of pemphigus and exposure to 11/36 previously reported drugs, two of which had particularly high RORs (>200) [gold sodium thiomalate (ROR, 266.0; 95% CI, 202.6-349.3) and hydroxychloroquine (ROR, 282.6; 95% CI, 261.0-306.1)], three had very strong RORs (14-45) [penicillamine (ROR, 30.5; 95% CI, 11.4-81.7), piroxicam (ROR, 14.8; 95% CI, 8.2-26.7), and imiquimod (ROR, 42.3; 95% CI, 26.2-68.3)], and six had modestly strong RORs (2-5) [rifampin (ROR, 2.8; 95% CI, 1.4-5.6), hydrochlorothiazide (ROR, 1.6; 95% CI, 1.2-2.1), irbesartan (ROR, 2.7; 95% CI, 1.6-4.4), lisinopril (ROR, 5.3; 95% CI, 4.5-6.2), nivolumab (ROR, 2.7; 95% CI, 1.8-4.1), and nifedipine (ROR, 3.0; 95% CI, 1.9-5.0)]. Associations for other previously reported drugs (25/36) were not detected. Conclusions and relevance: This study represents a comprehensive evaluation of suspected drug triggers of pemphigus using real-world data. The significant associations reported here provide empirical support for the hypothesis that certain drugs act as triggers for PV. Moreover, all of the drugs found to be associated with PV in this study harbor immunomodulatory capacity, suggesting that the ability to induce such perturbations, directly or indirectly, may be a critical factor connecting drug exposure to pemphigus pathogenesis. However, the absence of signals for other previously reported putative trigger drugs does not preclude their potential role in PV pathogenesis. Our findings reinforce the need for larger, more definitive studies to confirm these associations and to explore the mechanisms by which these drugs may contribute to PV development. Finally, these findings underscore the importance of considering environmental factors in the development and course of PV in genetically susceptible individuals. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase-4 inhibitors (DPP-4is) and drugs interfering with the renin-angiotensin-aldosterone system (RAAS) are frequently co-prescribed in type 2 diabetes management. Both drug classes have been independently associated with angioedema, raising concerns about potential interaction risks. This study aimed to evaluate the safety signals and interaction patterns for angioedema associated with DPP-4is alone and in combination with RAAS-interfering drugs. Methods: We conducted a comprehensive pharmacovigilance analysis using the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) database. Disproportionality analyses employing both frequentist (Reporting Odds Ratio, Proportional Reporting Ratio) and Bayesian approaches were performed. Drug-drug interactions were assessed using multiplicative drug-drug interaction model. Additionally, we reviewed published case reports of DPP-4i-associated angioedema. Results: Analysis of 29,163,222 reports identified 588 cases of DPP-4i-associated angioedema. Significant safety signals were detected for DPP-4i monotherapies, while combinations with RAAS-interfering drugs demonstrated stronger signals through both frequentist and Bayesian analyses. Significant interaction signals were observed for sitagliptin/irbesartan, sitagliptin/valsartan, linagliptin/valsartan and alogliptin/lisinopril combinations. Alogliptin/lisinopril and sitagliptin/irbesartan combinations showed the highest risk profiles. Angioedema occurred predominantly in elderly patients (> 65 years) and females. Sixteen case reports corroborated the findings from the database assessment. Clinical outcomes were comparable between monotherapy and combination therapy groups. Conclusion: This pharmacovigilance analysis reveals significant safety signals for angioedema with specific DPP-4i combinations with RAAS-interfering drugs, suggesting potential drug-drug interactions. These findings emphasize the need for careful patient monitoring, particularly in vulnerable populations, when prescribing these combinations. Further prospective studies are warranted to validate these findings and establish definitive causal relationships. [ABSTRACT FROM AUTHOR]

Novel derivatives of potential angiotensin converting enzyme (ACE-I) inhibitors (compounds 5a-e) were syn thesized by reacting homophthalic anhydride with methyl esters of L-amino acids (L-isoleucine, L-phenylalanine, L-tyrosine, L-methionine, and L-serine). This reaction resulted in yields of 85% for compound 5a, 83% for compound 5b, 84% for compound 5c, 80% for compound 5d, and 85% for compound 5e. All the synthesized compounds were characterized by 1D and 2D NMR methods. In silico ADME properties of compounds 5a-e conform to Lipinski’s drug rules. The in silico toxicological determination of the synthesized compounds sug gest that compound 5a exhibits significant potential for adverse effects, such as causing hormonal imbalances. In comparison, the remaining compounds 5b-c demonstrate a lower risk profile. In silico biological activities of compounds 5a-e in the active site of ACE-I were determined by docking, which were then compared to the FDA approved antihypertensive drugs enalalapril and lisinopril. Docking studies revealed that compound 5b (ΔGcomp = - 8.851 kcal/mol) possesses the greatest binding affinity in the Zn2+ binding site of ACE-I compared to those of lisinoprilat (ΔGcomp = - 8.066 kcal/mol) and enalapril (ΔGcomp = - 7.187 kcal/mol), strongly suggesting a great potential to be a lead candidate for novel antihypertensive drug development. [ABSTRACT FROM AUTHOR]

Subject matter experts from the U.S. Department of Veterans Affairs and Department of Defense updated the 2020 clinical practice guidelines for the management of headache. This article summarizes some of the important updates from the 2023 guideline particularly relevant to primary care, including recommendations for pharmacotherapy or invasive therapies for treatment and prevention of migraines and tension-type headaches, as well as for the use of nonpharmacologic interventions. Description: Headache medicine and therapeutics evidence have been rapidly expanding and evolving since the 2020 U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) clinical practice guideline (CPG) for the management of headache. Therefore, the CPG was revised in 2023, earlier than the standard 5-year cycle. This article reviews the 2023 CPG recommendations relevant to primary care clinicians for treatment and prevention of migraine and tension-type headache (TTH). Methods: Subject experts from the VA and the DoD developed 12 key questions, which guided a systematic search using predefined inclusion and exclusion criteria. After reviewing evidence from 5 databases published between 6 March 2019 and 16 August 2022, the work group considered the strength and quality of the evidence, patient preferences, and benefits versus harms on critical outcomes before making consensus recommendations. Recommendations: The revised CPG includes 52 recommendations on evaluation, pharmacotherapy, invasive interventions, and nonpharmacologic interventions for selected primary and secondary headache disorders. In addition to triptans and aspirin–acetaminophen–caffeine, newer calcitonin gene–related peptide (CGRP) inhibitors (gepants) are options for treatment of acute migraine. Medications to prevent episodic migraine (EM) include angiotensin-receptor blockers, lisinopril, magnesium, topiramate, valproate, memantine, the newer CGRP monoclonal antibodies, and atogepant. AbobotulinumtoxinA can be used for prevention of chronic migraine but not EM. Gabapentin is not recommended for prevention of EM. Ibuprofen (400 mg) and acetaminophen (1000 mg) can be used for treatment of TTH, and amitriptyline for prevention of chronic TTH. Physical therapy or aerobic exercise can be used in management of TTH and migraines. [ABSTRACT FROM AUTHOR]

Stability studies are crucial for pharmaceutical product registration, providing vital data to assess batch-to-batch consistency, monitor critical quality attributes, and ensure the product's quality, safety, and efficacy over its entire shelf life. Identifying potential issues such as potential out-of-specification (OOS) results and ensuring data quality is often facilitated by employing objective methods for trend analysis of stability data. The goal of the research was to explore the advantages of trend analysis in stability studies, highlighting its significance in forecasting OOS results and ensuring the consistent performance of pharmaceutical products within their estimated shelf life. To evaluate stability data and find the pattern of data that indicates change over time, stability studies for Lisinopril/Amlodipine tablets 20mg/10mg were subjected to trending analysis based on data from annual or routine stability studies. The trending analysis was performed to evaluate whether the data demonstrates increasing or decreasing trend (change of mean) for the stability indicating parameters over time or the data indicate no discernible change at all, as well as predicting potential OOS results during shelf life. Regression analysis as a statistical tool for trending analysis, is considered an appropriate approach to evaluating the stability data for a quantitative attribute.

Background: Over the last 20 years, pediatric hypertension (pHTN) prevalence in Western society has risen from 3.5 to 9% due to childhood overweight, obesity, and secondary kidney and cardiological conditions. Few studies have assessed commonly used antihypertensive medication lisinopril's (ACE-inhibitor) long-term efficacy and the long-term value of renin–angiotensin–aldosterone system (RAAS) biomarkers. Methods: This is a retrospective cohort study at Ghent University Hospital, Belgium, with 106 young patients (1–18 years) treated with lisinopril due to hypertension (HTN) and chronic kidney disease (CKD) assessed for treatment outcomes against clinical benchmarks over 10 years. Results: Lisinopril was mainly initiated for secondary hypertension or nephroprotection (89%) due to kidney causes. A starting dose across groups was lower than 0.07 mg/kg for 48% (n = 50). HTN patients without CKD achieved systolic blood pressure below the 95th percentile within 2 years, but efficacy declined after 2.5 years. CKD patients maintained a steady response, reaching systolic targets by 40 months and showing improved diastolic control over 70 months. Proteinuria reduction had a median urine protein creatinine ratio (UPCR) to 0.57 g/g at 6 months, with a reappearance of UPCR 2 g/g creatinine after 40 months. Aldosterone breakthrough occurred from 6 months onward in all groups. Over 70 months, aldosterone and aldosterone-renin-ratio (ARR) progression significantly differ between children with and without normal kidney function. Conclusions: Treatment efficacy for systolic blood pressure in hypertensive patients with abnormal kidney function diminishes after 2.5 years and for proteinuria in children after 3 years, highlighting the need for dosage recalibration according to guidelines and/or the need for alternative treatments. [ABSTRACT FROM AUTHOR]

Abstract Background The exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats. Methods Sixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters. Results Lisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2. Conclusion Notably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD.

Abstract 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.

Background Methods Results Conclusion Corneal fibrosis is a leading cause of blindness in mammalian species and may result in compromised performance in sports and daily functions. This study evaluated the safety and anti‐fibrotic effects of the FDA‐approved drugs, angiotensin‐converting enzyme inhibitor (ACE‐I) lisinopril and rho‐kinase inhibitor (ROCK‐I) fasudil, alone and in combination, on the canine cornea using an established in vitro model.To test the safety and efficacy of lisinopril and fasudil, primary canine corneal fibroblasts (CCFs) generated from donor corneas of healthy dogs (n = 20) were used. A series of dose‐dependent and time‐dependent assays with lisinopril (1–50 μM) and fasudil (1–10 nM) were performed. qRT‐PCR, immunofluorescence (IF) staining, cell viability assay, cell proliferation assay, LIVE/DEAD viability/cytotoxicity assay, TUNEL assay, and total cell count were performed.A 25‐μM lisinopril and 3‐nM fasudil dose were safe, nontoxic, and optimal for therapeutic evaluations in vitro. Treatments of lisinopril or fasudil, alone or in‐combination, to CCFs grown in the presence of TGF‐β1 (5 ng/mL) showed inhibition of myofibroblast formation based on phase‐contrast microscopy. The qRT‐PCR and IF studies showed a significant decrease in expression of profibrotic markers, including α‐smooth muscle actin (α‐SMA; p < .0001), fibronectin (FN; p = .0002), tenascin C (TNC; p < .0001), Collagen I (Col‐I; p < .0001), Collagen IIIA1 (Co‐IIIA1; p < .0001), and Collagen IV (Co‐lV; p < .0001).An ophthalmic formulation consisting of lisinopril and fasudil may offer a safe and effective method to treat canine corneal fibrosis. Additional studies evaluating safety and efficacy of this formulation in vivo are warranted. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a growing public health concern globally. The angiotensin-converting enzyme (ACE) is an enzyme that cleaves the carboxy-terminal His-Leu dipeptide from angiotensin I, yielding the potent vasopressor octapeptide, angiotensin II. ACE inhibitors are a primary treatment option for hypertension, heart failure, and myocardial infarction. However, the use of synthetic ACE inhibitors has been linked to a number of side effects. Therefore, the development of novel and safe ACE inhibitors is a need of time. Methods: This study used a computational screening of a library of known compounds with anti-inflammatory activities against the active site of ACE using the PyRx-Python 0.8 tool to find more potent ACE inhibitors with less or no side effects. The physicochemical properties of the anti-inflammatory compounds were obtained from the Life Chemicals website. Result: The five hits, specifically F3398-2114, F0193-0245, F0163-0089, F0193-0237, and F0302-0060, exhibited notable interactions within the ACE binding pocket and demonstrated greater binding energy compared to the control compound, Lisinopril. All of these compounds displayed favorable physicochemical characteristics and aligned to Lipinski's rule. Conclusion: The compounds F3398-2114, F0193-0245, F0163-0089, F0193-0237, and F0302-0060 have the potential to be used as ACE inhibitors; however, further experimental validation is required to optimize them as ACE inhibitors. [ABSTRACT FROM AUTHOR]

Background: The exact pathogenesis of Huntington's disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats. Methods: Sixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters. Results: Lisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2. Conclusion: Notably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD. Research highlights: Lisinopril alleviated the mitochondrial dysfunction and restored redox balance via Nrf2/TFAM signaling. Lisinopril downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6). Lisinopril upregulated the expression of ACE2/Ang1-7/MAS receptor axis of RAS. Lisinopril activated PI3K/Akt/CREB pathway and evoked the neurogenesis via its downstream product BDNF. Lisinopril could be a future neuroprotective treatment against Huntington disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hypertension is known to affect more than one billion people globally and is estimated to increase to 1.5 billion by 2025. It is considered one of the leading causes of death and cardiovascular disease worldwide. The safety of long-term antihypertensive use is also a concern. Through a narrative or literature review, this study evaluated antihypertensive agents based on the results of various literature searches. Researchers reviewed the safety and tolerability of five classes of antihypertensive agents such as Diuretics, Angiotensin-Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB), Beta-Blockers, and Calcium Channel Blockers (CCB). The use of ARB antihypertensive drugs like valsartan is well tolerated and safe. Moreover, the mortality rate associated with enalapril was 16% lower (95% CI 0.76-0.93; P < 0.001). Captopril and lisinopril of Angiotensin-converting Enzyme Inhibitors (ACEIs) have significant side effects (SEs) compared to any antihypertensive drug. Therefore, this study recommends using the ACEIs group, especially captopril and lisinopril, due to the minimal side effects produced compared to other antihypertensive drugs. In addition, the CCBs or Ca antagonists class like amlodipine is potentially well tolerated and safe as a first-line drug for hypertension treatment. [ABSTRACT FROM AUTHOR]

The article examines the ongoing challenges in diabetes management despite advancements in treatment and monitoring technology. Topics include the urgent need for effective decision-making tools for healthcare providers to support diabetes care, the significant role of Blood Glucose Monitoring (BGM) in diabetes management, and the limitations and accessibility issues surrounding Continuous Glucose Monitoring (CGM) that affect its adoption among individuals with diabetes.

Background: Rheumatic heart disease (RHD) is exacerbated by chronic inflammation that stimulates the release of proinflammatory cytokines, most notably transforming growth factor-beta 1 (TGF-β1), which promotes myofibroblast differentiation. This study aims to determine the optimal dosage of Lisinopril, an angiotensin-converting enzyme inhibitor, for mitigating the fibrotic changes associated with RHD. Methods: This in vitro, posttest-only control group study involved obtaining valvular interstitial cells from the heart valves of 25 male New Zealand rabbits (Oryctolagus cuniculus). Valvular interstitial cells were divided into 5 groups: a control group exposed to TGF-β1, and 4 experimental groups exposed to various Lisinopril doses (1 µM, 10 µM, and 100 µM) in addition to TGF-β1. The effect of Lisinopril on myofibroblast differentiation was assessed by measuring alpha-smooth muscle actin (αSMA) expression through immunocytochemical methods. Statistical significance was determined using an independent T-test with a P value of less than 0.050. Results: Independent T-tests conducted on 25 male Oryctolagus cuniculus demonstrated significantly lower αSMA expression in the groups treated with various Lisinopril doses (1 µM, 10 µM, and 100 µM) compared with the TGF-β1- induced control group (P<0.050). The most significant reduction in αSMA expression was observed in the group treated with the highest Lisinopril dose of 100 µM. Conclusion: Lisinopril demonstrates a significant ability to inhibit TGF-β1-induced myofibroblast differentiation in rabbit valve interstitial cells, with the 100 µM dose proving most effective. These results suggest that Lisinopril may have the potential to curb RHD progression, warranting further investigations in vivo. [ABSTRACT FROM AUTHOR]

Degree-based topological indices are very useful tools to model and characterize the molecular structure of drugs in order to predict their physicochemical properties without going into laborious and time-consuming laboratory experiments. These indices are numerical descriptors derived for the molecular structures using the principles of graph theory. Degree-based topological indices play a vital role in the QSPR analysis of heart attack drugs by providing molecular descriptors to predict their properties. The main goal of this paper is to compute six degree-based topological indices and a regression model for seven heart attack drugs. These drugs are nitroglycerin, clopidogrel, beta-blockers (metoprolol), ACE inhibitors (lisinopril), statins (atorvastatin), (ARBs) losartan, and beta-adrenergic blockers (propranolol). Regression analysis and degree-based indices correlate with various physicochemical properties related to drug activities, such as molecular weight, complexity, melting point, and boiling point. Correlations provide insights into how the molecular structure influences these properties, helping design and optimize new drugs. In the results, various statistical parameters are used to analyze heart attack drugs. [ABSTRACT FROM AUTHOR]

The article focuses on an 11-year-old boy presenting with slurred speech and involuntary movements, later diagnosed with a neurological disorder. Topics include his clinical symptoms such as dysarthria and abnormal involuntary movements, his physical exam findings including hyperreflexia and abnormal gait, and the absence of significant prior medical or family history.

Fluorometric method for detecting of five nitrogen-based drugs concentration based on inhibition of emission Eosin Y (EY). The selection of N-drugs comprised indapamide (INDP), clomipramine hydrochloride (CMI), promethazine hydrochloride (PMH), lisinopril (LSP), and trifluoperazine hydrochloride (TFPH). The Stern–Volmer style was plotted between relative emissions of EY vs. N-drugs concentration. The standard curves were linear over the concentration range of 5–50 µg mL−1 with R2 > 0.9, and the LOD for INDP, CMI, PMH, LSP, and TFPH were 2.07, 1.36, 3.02, 3.52, and 2.09 µmol·L−1, respectively. The binding constant K a p p for LSP was greater than other N-drugs. Furthermore, the suggested method was hence applied for the routine detection of the concentration of N-drugs in bulk and tablet or syrup dosage forms. FTIR analysis and the electron-mapping density provided the chemical affinity of N-drugs towards EY. [ABSTRACT FROM AUTHOR]

Background: A major side effect of some cancer drugs, including Doxorubicin, is cardiotoxicity. This study was designed to evaluate the cardioprotective role of ethanolic leaf extract of Gongronema latifolium (GL) compared to Lisinopril in doxorubicin-induced cardiotoxicity in rats. Methods: Forty Wistar rats of both sexes (150-200 g) were divided into 5 groups (n=8 each). Group 1 (control) took normal rat chow; Group 2 received 25 mg/kg Doxorubicin; Group 3 received Doxorubicin + GL (200 mg/kg orally); Group 4 received Doxorubicin + Lisinopril (10 mg/kg orally); and Group 5 received Doxorubicin + Lisinopril + GL. The regiment lasted for 28 days. Blood samples were collected from each animal via cardiac puncture for biochemical assays. Results: The results of the study showed a significant decrease in superoxide dismutase (SOD) concentration in the doxorubicin group as compared to the control group. Intervention with GL and Lisilopril caused a significant increase in SOD concentration. Total antioxidant capacity, catalase, SOD, and angiotensin-II levels were significantly decreased with a corresponding increase in malondialdehyde (MDA) in the Doxorubicin group. Treatment with GL and Lisinopril significantly reversed these changes by increasing the levels of TAC, SOD, CAT, and angiotensin-2 to normal while lowering the MDA levels to normal. Cardiac biomarkers, namely troponin and creatine kinase levels, were significantly increased in the doxorubicin group as compared to the normal control. However, the coadministration of GL and Lisinopril decreased the troponin and creatine kinase concentrations to normal levels. Conclusion: Gongronema Latifolium and Lisinopril provided better cardioprotective and antioxidant effects versus other agents against cardiotoxicity induced by Doxorubicin. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer survival but are associated with treatment-limiting hypertension, often attributed to endothelial cell (EC) dysfunction. Using phosphoproteomic profiling of VEGFRi-treated ECs, drugs were screened for mitigators of VEGFRi-induced EC dysfunction and validated in primary aortic ECs, mice, and canine cancer patients. VEGFRi treatment significantly raised systolic blood pressure (SBP) and increased markers of endothelial and renal dysfunction in mice and canine cancer patients. a-Adrenergic-antagonists were identified as drugs that most oppose the VEGFRi proteomic signature. Doxazosin, one such a-antagonist, prevented EC dysfunction in murine, canine, and human aortic ECs. In mice with sorafenib-induced-hypertension, doxazosin mitigated EC dysfunction but not hypertension or glomerular endotheliosis, while lisinopril mitigated hypertension and glomerular endotheliosis without impacting EC function. Hence, reversing EC dysfunction was insufficient to mitigate VEGFRi-induced-hypertension in this mouse model. Canine cancer patients with VEGFRi-induced-hypertension were randomized to doxazosin or lisinopril and both agents significantly decreased SBP. The canine clinical trial supports safety and efficacy of doxazosin and lisinopril as antihypertensives for VEGFRi-induced-hypertension and the potential of trials in canines with spontaneous cancer to accelerate translation. The overall findings demonstrate the utility of phosphoproteomics to identify EC-protective agents to mitigate cardio-oncology side effects. [ABSTRACT FROM AUTHOR]

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 Is 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 (R2) 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. [ABSTRACT FROM AUTHOR]

Introduction: Coingestion of cardiovascular drugs with angiotensin‐converting enzyme inhibitors (ACEIs) can be associated with refractory shock derangements complicated by vasopressor resistance, prompting the use of novel, unconventional, or uncommonly used agents. Case Report: A young adult male presented to the emergency department (ED) 10 h after ingesting lisinopril and amlodipine. On arrival, he was hypotensive with a blood pressure of 72/39 mmHg. In addition to crystalloid fluids, he was incrementally started on four vasopressors including norepinephrine, phenylephrine, epinephrine, and vasopressin without improvement in mean arterial pressure (MAP). He was then administered methylene blue, calcium gluconate, and hyperinsulinemic euglycemia therapy after discussion with medical toxicology. Shortly afterwards, he was started on an angiotensin II infusion with an improvement in MAP to a goal of > 65 mmHg. Conclusion: Despite evidence of efficacy in refractory vasodilatory shock secondary to sepsis, there is a paucity of data on the use of angiotensin II as an adjunctive vasopressor in drug‐induced shock. We report a case of successful use of angiotensin II in combined lisinopril and amlodipine overdose refractory to conventional vasopressor support. Combined overdose of ACEIs with calcium channel blockers (CCBs) has been shown to cause more significant hypotension and higher vasopressor requirements than overdose of CCBs alone. This may be due to the synergism between CCBs and ACEIs, where the normal homeostatic mechanism of the renin–angiotensin–aldosterone system (RAAS) activation in response to shock is now inhibited, leading to decreased compensatory vasoconstriction via angiotensin II and decreased endogenous catecholamine release. We hypothesize that angiotensin II may have been of particular benefit in this patient given the likelihood that reduced angiotensin II levels were contributing to his refractory shock. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic subdural hematoma (cSDH) is a common disease of growing significance due to the increasing use of antithrombotic drugs and population aging. There exists conflicting observational evidence that previous treatment with angiotensin-converting enzyme (ACE) inhibitors reduces the rate of cSDH recurrence. This study assesses the hypothesis that ACE inhibitors may affect recurrence rates by altering hematoma membrane formation. Methods: All patients with chronic subdural hematoma who were operated upon in a single university hospital between 2015 and 2020 were considered for inclusion. Hematomas were classified according to their structural appearance in computed tomography (CT) imaging into one of eight subtypes. Patients' own medication, prior to hospitalization for cSDH treatment, was noted, and the use of ACI-inhibitors was identified. Results: Of the included 398 patients, 142 (35.9%) were treated with ACE inhibitors before admission for cSDH treatment. Of these, 115 patients (81.0%) received ramipril, 13 received patients lisinopril (11.3%), and 11 patients (9.6%) received enalapril. Reflecting cardiovascular comorbidity, patients on ACE inhibitors were more often simultaneously treated with antithrombotics (63.4% vs. 42.6%; p ≤ 0.001). Hematomas with homogenous hypodense (OR 11.739, 95%CI 2.570 to 53.612; p = 0.001), homogenous isodense (OR 12.204, 95%CI 2.669 to 55.798; p < 0.001), and homogenous hyperdense (OR 9.472, 95%CI 1.718 to 52.217; p < 0.001) architectures, as well as the prior use of ACE inhibitors (OR 2.026, 95%CI 1.214 to 3.384; p = 0.007), were independently associated with cSDH recurrence. Conclusions: Once corrected for hematoma architecture, type of surgery, and use of antithrombotic medication, preoperative use of ACE inhibitors was associated with a twofold increase in the likelihood of hematoma recurrence. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the patterns and clinical significance of potential drug–drug interactions (pDDIs) in patients with diseases of the cardiovascular system. Methods: Electronic health records (EHRs), established in 2018–2023, were selected using the probability serial nested sampling method (n = 1030). Patients were aged 27 to 95 years (65.0% men). Primary diagnosis of COVID-19 was present in 17 EHRs (1.7%). Medscape Drug Interaction Checker was used to characterize pDDIs. The Mann–Whitney U test and chi-square test were used for statistical analysis. Results: Drug numbers per record ranged from 1 to 23 in T-List and from 1 to 20 in P-List. In T-List, 567 drug combinations resulted in 3781 pDDIs. In P-List, 584 drug combinations resulted in 5185 pDDIs. Polypharmacy was detected in 39.0% of records in T-List versus 65.9% in P-List (p-value < 0.05). The rates of serious and monitor-closely pDDIs due to 'aspirin + captopril' combinations were significantly higher in P-List than in T-List (p-value < 0.05). The rates of serious pDDIs due to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations were significantly lower in P-List compared with the corresponding rates in T-List (p-value < 0.05). Serious pDDIs due to administration of aspirin with fosinopril, perindopril, and ramipril were detected less frequently in T-List (p-value < 0.05). Conclusions: Obtained data may suggest better patient adherence to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations, which are potentially superior to the combinations of aspirin with fosinopril, perindopril, and ramipril. An abundance of high-order pDDIs in real-world clinical practice warrants the development of a decision support system aimed at reducing pharmacotherapy-associated risks while integrating patient pharmacokinetic, pharmacodynamic, and pharmacogenetic information. [ABSTRACT FROM AUTHOR]

COVID-19 causes more severe and frequently fatal disease in patients with preexisting comorbidities such as hypertension and heart disease. SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2), which is fundamental in maintaining arterial pressure through the renin-angiotensin system (RAS). Hypertensive patients commonly use medications such as angiotensin-converting enzyme inhibitors (ACEi), which can modulate the expression of ACE2 and, therefore, potentially impact the susceptibility and severity of SARS-CoV-2 infection. Here we assessed whether treatment of ACE2-humanized (K18-hACE2) mice with the ACEi Lisinopril affects lung ACE2 levels and the outcome of experimental COVID-19. K18-hACE2 mice were treated for 21 days with Lisinopril 10 mg/kg and were then infected with 105 PFU of SARS-CoV-2 (Wuhan strain). Body weight, clinical score, respiratory function, survival, lung ACE2 levels, viral load, lung histology, and cytokine (IL-6, IL-33, and TNF-a) levels were assessed. Mice treated with Lisinopril for 21 days showed increased levels of ACE2 in the lungs. Infection with SARS-CoV-2 led to massive decrease in lung ACE2 levels at 3 days post-infection (dpi) in treated and untreated animals, but Lisinopril-treated mice showed a fast recovery (5dpi) of ACE2 levels. Higher ACE2 levels in Lisinopril-treated mice led to remarkably higher lung viral loads at 3 and 6/7dpi. Lisinopril-treated mice showed decreased levels of the pro-inflammatory cytokines IL-6 and TNF-a in the serum and lungs at 6/7dpi. Marginal improvements in body weight, clinical score and survival were observed in Lisinopril-treated mice. No differences between treated and untreated infected mice were observed in respiratory function and lung histology. Lisinopril treatment showed both deleterious (higher viral loads) and beneficial (antiinflammatory and probably anti-constrictory and anti-coagulant) effects in experimental COVID-19. These effects seem to compensate each other, resulting in marginal beneficial effects in terms of outcome for Lisinopriltreated animals. [ABSTRACT FROM AUTHOR]

Angiotensin‐converting enzyme inhibitors are widely used in treating arterial hypertension, acting on the renin‐angiotensin‐aldosterone system and controlling blood pressure. We present a novel, greener, and faster methodology to assess the 1,2,4‐oxadiazol‐5‐one ring and perform molecular modifications to obtain angiotensin‐converting enzyme (ACE) inhibitors using this heterocyclic core. Molecular docking simulations indicate that the tested compounds exhibited an affinity for the ACE binding site, with scores comparable to the commercial inhibitor lisinopril. However, in vitro assays revealed that the compounds were ineffective in inhibiting ACE activity. The lack of inhibition may be related to the compounds' more apolar nature. These results emphasize the importance of integrating computational and experimental approaches in developing new drugs, providing valuable insights for planning future studies to optimize the activity of synthesized compounds. [ABSTRACT FROM AUTHOR]

The deterioration of mild steel in an acidic environment poses a significant challenge in various industries. The emergence of effective corrosion inhibitors has drawn attention to studies aimed at reducing the harmful consequences of corrosion. In this study, the corrosion inhibition efficiency of Prinivil in a 1M HCl solution through various electrochemical and gravimetric techniques has been investigated for the first time. The results demonstrated that the inhibition efficiency of Prinivil expanded from 61.37% at 50 ppm to 97.35% at 500 ppm concentration at 298 K. With a regression coefficient (R²) of 0.987, Kads value of 0.935 and Ea value of 43.024 kJ/mol at 500 ppm concentration of inhibitor, a strong affinity of Prinivil for adsorption onto the metal surface has been significantly found. Scanning electron microscopy (SEM) and contact angle measurement analyses further support the inhibitory behavior of Prinivil, demonstrating the production of a defensive layer on the surface of mild steel. Additionally, molecular dynamics (MD) and Monte Carlo simulations were employed to investigate the stability and interactions between Prinivil and the metallic surface (Fe (1 1 0)) at the atomic level. The computed results reveal strong adsorption of Prinivil upon the steel surface, confirming its viability as a corrosion inhibitor. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has published a list of priority pathogens that urgently require research to develop new antibiotics. The main aim of the current study is to identify potential marketed drugs that can be repurposed against bacterial infections. A pharmacovigilance‐based drug repurposing approach was used to identify potential drugs. OpenVigil 2.1 tool was used to query the FDA Adverse Event Reporting System database. The reporting odds ratio (ROR) < 1, ROR95CI upper bound <1, and no. of cases ≥30 were used for filtering and sorting of drugs. Sunburst plot was used to represent drugs in a hierarchical order using the Anatomical Therapeutic Chemical classification. Molecular docking and dynamics were performed using the Maestro and Desmond modules of Schrodinger 2023 software respectively. A total of 40 drugs with different classes were identified based on the pharmacovigilance approach which has antibacterial potential. The molecular docking results have shown energetically favored binding conformation of lisinopril against 3‐deoxy‐manno‐octulosonate cytidylyltransferase, UDP‐2,3‐diacylglucosamine hydrolase, and penicillin‐binding protein 3 (PBP3) of Pseudomonas aeruginosa; olmesartan, atorvastatin against lipoteichoic acids flippase LtaA and rosiglitazone and varenicline against d‐alanine ligase of Staphylococcus aureus; valsartan against peptidoglycan deacetylase (SpPgdA) and atorvastatin against CDP‐activated ribitol for teichoic acid precursors of Streptococcus pneumoniae. Further, molecular dynamic results have shown the stability of identified drugs in the active site of bacterial targets except lisinopril with PBP3. Lisinopril, olmesartan, atorvastatin, rosiglitazone, varenicline, and valsartan have been identified as potential drugs for repurposing against bacterial infection. [ABSTRACT FROM AUTHOR]

A method for quantification of antihypertensive drugs (lisinopril, indapamide, metoprolol, valsartan, and amlodipine) in human blood serum was developed using high-performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS). MeOH with added fexofenadine hydrochloride as an internal standard was used for sample preparation. The developed method was validated for the following parameters: selectivity, limit of quantitation, linearity, intra- and inter-run accuracy and precision, sample transfer, matrix effect, extraction effect, and sample stability. The analytical range of the method for all analytes was 1 – 1000 ng/mL, which made it possible to assess the patient adherence to treatment and conduct therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

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.