Search Results (162)

Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating factor (PAF) pathway, a key mediator of inflammation. This study aimed to evaluate the effects of several commonly used cardiovascular and anti-inflammatory drug classes—including clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor blockers (ARBs), β-blockers, and analgesics—on platelet function via both the ADP and PAF pathways. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet aggregation in response to these two agonists in the absence and presence of graded concentrations of each of these drugs or of their usually prescribed combinations. The study identified differential drug effects on platelet aggregation, with some agents showing pathway-specific activity. Clopidogrel and NSAIDs demonstrated expected antiplatelet effects, while some (not all) antihypertensives exhibited additional anti-inflammatory potential. These findings highlight the relevance of evaluating pharmacological activity beyond traditional targets, particularly in relation to PAF-mediated inflammation and thrombosis. This dual-pathway analysis may contribute to a broader understanding of drug mechanisms and inform the development of more comprehensive therapeutic strategies for the prevention and treatment of cardiovascular, hypertension, and inflammation-driven diseases. Full article

Background/Objectives: Real-world evidence shows alarmingly suboptimal utilization of guideline directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). One of the barriers of GDMT implementation appears to be concerns about the potential development of drug-related adverse events (AEs), particularly in high-risk patients. This study aimed to evaluate whether advanced HFrEF (AHF) patients can be up-titrated safely and whether AHF predisposes individuals to the occurrence of putatively drug-related AEs. Methods: A total of 373 HFrEF patients with documented baseline, 2 months, and 12 months visits were analyzed for utilization and target dosages (TDs) of HF drugs. Successful up-titration and AEs were evaluated for different stages of HF reflected by N-terminal pro-B type natriuretic peptide (NT-proBNP) (<1000 pg/mL, 1000–2000 pg/mL, >2000 pg/mL). Results: A stepwise increase in HF medications was observed for all drug classes during follow-up. At 12 months, 73%, 75%, 62%, 86%, and 45% of patients received ≥90% of TDs of beta-blockers (BBs), renin–angiotensin system inhibitors (RASis), mineralocorticoid receptor antagonists (MRAs), sodium–glucose cotransporter-2 inhibitors (SGLT2 i), and triple-therapy, respectively. Predictors of successful up-titration in logistic regression were baseline HF drug TDs, estimated glomerular filtration rate (eGFR), and potassium, but not NT-proBNP or age. The development of AEs was rare, with hyperkalemia as the most common event (34% at 12 months). AEs were comparable in all stages of HF. However, the development of hyperkalemia was more frequent in patients with higher NT-proBNP and also accounted for most cases of incomplete up-titration. Conclusions: This study suggests that with dedicated protocols and frequent visits, GDMT can be successfully implemented across all stages of HFrEF, including patients with AHF. Full article

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

The coexistence of heart failure (HF) and chronic obstructive pulmonary disease (COPD) presents a significant clinical challenge due to the common risk factors, overlapping symptoms, and complex pathophysiological interactions and mechanisms. This comprehensive review explores the bidirectional relationship between HF and COPD, emphasizing their combined impact on morbidity, mortality, and quality of life. Epidemiological data reveal that up to one-third of patients with HF also have COPD, complicating diagnosis and leading to suboptimal treatment strategies. We discuss the pathways through which each disease exacerbates the other, the limitations of the current staging systems, the diagnostic tools needed to differentiate cardiac from pulmonary symptoms, and the treatment choices. Therapeutic management requires careful integration of pharmacologic and non-pharmacologic strategies, with attention paid to potential drug interactions. Evidence from clinical trials confirms that beta-blockers can be safely used in patients with COPD and highlights the importance of multidisciplinary, patient-centered care models. Prevention strategies, including smoking cessation, vaccination, and patient education, play a critical role in improving outcomes. Finally, we identify key research gaps and calls for more inclusive clinical guidelines to address the needs of patients with this overlapping syndrome. A coordinated, evidence-based approach is essential for optimizing care and improving the quality of life of patients facing the dual burden of HF and COPD. Full article

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Despite significant advances in pharmacological therapies, responses to treatment vary widely among patients. Growing evidence suggests that genetic factors play a crucial role in influencing individual responses to HF therapies. Genetic variations, including single-nucleotide polymorphisms (SNPs), gene expression profiles, and epigenetic modifications, have been shown to affect drug metabolism, receptor sensitivity, and the molecular pathways involved in HF progression. These genetic determinants may not only predict the efficacy of common therapeutic agents such as angiotensin-converting enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors, but also help identify patients at risk of adverse drug reactions. As personalized medicine continues to advance, a deeper understanding of the genetic basis of drug response in HF could enable more tailored treatment strategies, improving clinical outcomes and minimizing adverse effects. This review explores the current evidence on the genetic underpinnings of response to HF treatment and discusses its potential implications in clinical practice, highlighting current knowledge gaps. Full article

Background: Drug-drug interactions (DDIs) are a growing safety concern in dental care, particularly among patients with comorbidities and polypharmacy. However, real-world data (RWD) on the prevalence and severity of DDIs in dental settings remain scarce. Objectives: This study aimed to assess the frequency, severity, and clinical relevance of DDIs in dental patients and to identify age- and comorbidity-related risk patterns. Methods: This retrospective study analyzed a cohort of 105 dental patients, considering demographics, preexisting diseases, dental procedures, and prescribed medications. We examined drug-drug interactions (DDIs) employing the DrugBank Drug Interaction Checker, which yields DDI severity into major, moderate, or minor. Results: 45.7% of patients had preexisting diseases, with cardiovascular diseases most prevalent (19.0%). Higher prevalent dental diagnoses and procedures included apical lesions (47.6%) and tooth extractions (53.3%), suggesting frequent pharmacotherapy exposure. We identified 542 DDIs out of 1332 drug pairs and found 2.3% major, 25.0% moderate, and 13.4% minor, with 59.3% showing no interactions. Key high-risk DDIs included epinephrine with beta-blockers. Fifteen patients aged 31–60 years experienced the most major DDIs of 61.3%, patients ≥ 61 years faced 38.7%, and the 0–30 group had none, highlighting age-specific risks. The higher DDIs burden in the 31–60 age group may reflect better knowledge of the drugs they used and accurate reporting of them. Conclusions: Our retrospective study addresses the paucity of dental DDIs real-world data (RWD) studies, pleading for improved drug reconciliation, systematic screening, and age- and comorbidity-tailored strategies to enhance patient safety. Full article

Background/Objectives: Propranolol HCl (PPH), a nonselective beta-adrenergic receptor blocker, is employed as an anti-hypertensive, anti-anginal, anti-arrhythmic, and anti-migraine agent. Given its utility in chronic conditions, developing a sustained-release dosage form becomes imperative to optimize therapeutic outcomes while enhancing patient adherence and minimizing side effects. In this study, we employed a widely adopted matrix-based system to develop PPH sustained-release (PPH-SR) matrix tablets, ensuring the uniform dispersion of the drug within the polymeric matrix to regulate its release rate. Methods: Utilizing cellulose-based polymers, specifically HPMC K100M and ethyl cellulose (EC), as matrix formers, nine different formulations were prepared at varying drug-to-polymer ratios. We employed a wet granulation method, followed by compression of the dried granules, to fabricate round-shaped biconvex PPH-SR tablets. Results: Among these different formulations, formulation 2 (F2), comprising 40 mg PPH and 50 mg HPMC K100M (along with other excipients), showed excellent flowability, as evidenced by Carr’s index and angle of repose values of 12.50 and 28.50, respectively. Additionally, the mechanical properties of F2 tablets showed a hardness of 12.34 ± 0.91 KP, an average weight of 200.45 ± 1.87 mg, with a friability of 0.20%, and a content uniformity of 98.36%. Moreover, in vitro release characteristics of F2 tablets demonstrated a sustained-release behavior, with 94.3 ± 10.2% drug release over 24 h. A comparative analysis with marketed tablets yielded similarity and dissimilarity factors of 64 and 8, respectively. Furthermore, the release profile of F2 exhibited a high degree of linearity with the Korsmeyer–Peppas model (R² of 0.977), showcasing its reliability and predictability. Conclusions: In essence, this in-house developed PPH sustained-release formulation can improve patient adherence, reduce side effects, and improve therapeutic outcomes. These results align with our objective of enhancing the therapeutic efficacy of PPH and affirm the broader relevance of innovative formulation strategies in addressing the challenges of chronic disease management. Full article

Hypertension disorders of pregnancy affect almost 10% of pregnancies. Most hypertensive disorders associated with pregnancy, including chronic hypertension and gestational hypertension, often persist into the postpartum period. Thus, many breastfeeding mothers require ongoing antihypertensive treatment with antihypertensive medications while nursing. This highlights the importance of understanding the efficacy, safety, and potential adverse effects of antihypertensive therapy in breastfeeding mothers. Unfortunately, research in this area is limited, and references in clinical guidelines remain sparse. Our review aims to provide a comprehensive summary of the current knowledge on antihypertensive medications during breastfeeding, drawing from available research and evidence-based guidelines. This article discusses all groups of antihypertensive drugs, presenting societies’ recommendations and available clinical data. Based on the available literature, calcium channel blockers (extended-release nifedipine as the first choice) and beta-blockers (labetalol, metoprolol) appear to be the drugs of choice. Our review highlights the need for further research to evaluate the long-term safety of antihypertensive medications during breastfeeding, improve clinical guidelines, and ensure optimal treatment for nursing mothers. Full article

Hypertrophic cardiomyopathy (HCM) is often associated with left ventricular outflow tract (LVOT) obstruction, which affects a substantial proportion of patients. This obstruction results from a range of anatomical abnormalities involving both the valvular and subvalvular structures. Pharmacological therapies play a pivotal role in the management of LVOT obstruction, with a range of drug classes exhibiting distinct mechanisms of action. Beta-blockers, including atenolol and nadolol, are considered the first-line treatment due to their ability to reduce heart rate and myocardial contractility and enhance diastolic filling. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, are utilized as second-line agents when beta-blockers are ineffective or contraindicated. Disopyramid, a Class 1A antiarrhythmic agent, is employed for patients who do not respond to initial therapeutic interventions and can reduce LVOT gradients. Recent advancements in cardiac myosin modulators, such as Mavacamten and Aficamten, offer targeted therapies by modulating myosin–actin interactions to reduce LVOT gradients and improve symptoms, with promising results from clinical trials. Although gene therapy is still in its nascent stages, it has the potential to address the genetic basis of HCM by employing techniques such as genome editing, gene replacement, and the modulation of signaling pathways. For patients exhibiting severe symptoms or demonstrating unresponsiveness to medical treatment, invasive therapies, such as septal reduction therapy and alcohol septal ablation, are considered. Ultimately, the treatment and prevention of atrial fibrillation and sudden cardiac death are two key points of HCM management in both obstructive and non-obstructive forms. This review aims to provide an overview of current pharmacological and invasive strategies, as well as emerging therapies, in the management of HCM. Full article

Background/Objective: Cyclosporine A and other calcineurin inhibitors have been identified as prospective treatments for preventing Alzheimer’s disease. We previously found that calcineurin inhibitors elicit a unique behavioral profile in zebrafish larvae, characterized by increased activity, acoustic hyperexcitability, and reduced visually guided behaviors. Screening a large library of FDA-approved compounds using Z-LaP Tracker revealed that some heart medications produce a similar behavioral profile, suggesting these drugs may exert calcineurin-inhibitor-like effects relevant to prevent-ing or ameliorating Alzheimer’s disease. Methods: Screening a large library of FDA-approved drugs using Z-LaP Tracker, a neural network model, revealed a cluster of 65 drugs demonstrating a cyclosporine A-like behavioral profile. Fourteen of these drugs were heart medications, including angiotensin receptor blockers, beta blockers, al-pha-adrenergic receptor antagonists, and a statin. Results: Dual administration of the heart medications with cyclosporine A in Z-LaP Tracker revealed synergistic effects: lower doses of each heart medication could be delivered in conjunction with a lower dose of cyclosporine A to evoke a similar or larger behavioral effect than higher doses of each drug independently. Other studies have shown that many of these heart medica-tions drugs directly or indirectly inhibit the calcineurin–NFAT pathway, like cyclo-sporine A, providing a potential mechanism. Conclusions: Co-administering a low dose of cyclosporine A with select cardiac drugs could be a potentially effective treatment strategy for preventing Alzheimer’s disease occurrence and simultaneously treating cardiovascular dysfunction, while mitigating the side effects associated with higher doses of cyclosporine A. Given that heart disease precedes Alzheimer’s disease in many patients, physicians may be able to create a treatment regimen that addresses both con-ditions. Our results suggest that a calcineurin inhibitor combined with simvastatin, irbesartan, cilostazol, doxazosin, or nebivolol is the most promising candidate for future exploration. Full article

Background/Objectives: Colorectal cancer (CRC) is a significant global health issue with rising incidence and mortality rates. In oncology, drug repurposing has emerged as a promising therapeutic strategy in conjunction with conventional treatments. This study aimed to evaluate the potential of repurposing propranolol (PRO), a beta blocker, for the treatment of CRC cell lines (HCT-116 and HT-29), both as a monotherapy and in combination with capecitabine (CAP). Methods: Effects of mono- and combination therapies on viability, combination index, morphology, and cell death induction of CRC cells were assessed. Transcriptome analysis of HT-29 cells was performed using RNA sequencing. Metabolite profiling was conducted, and changes in biochemical parameters were evaluated using flow cytometry and biochemical analyses. Results: The combination index showed that HT-29 cells were the most responsive to the combined treatment, even with PIK3CA, B-RAF (V600E), and TP53 mutations. Moreover, ferroptosis was synergistically activated in the combined group of HT-29 in comparison to control. Furthermore, we observed an increase in OXPHOS metabolites, along with elevated intracellular and mitochondrial ROS, disruption of mitochondrial membrane potential, and greater levels of malondialdehyde (MDA) in the HT-29 combined group, which are the features of ferroptosis. Furthermore, ferroptosis induction was coupled with necroptosis, as indicated by RNA-sequencing data. Combination therapy inhibited cell migration and enhanced the immune response of HT-29 cells. Conclusions: These findings suggest that PRO is promising as a potential adjuvant therapy in combination with CAP for the treatment of CRC. Only HT-29 cells with the B-RAF (V600E) mutation showed promising findings in this study. Full article

One of the most serious consequences of cardiac arrest is asystole. It can occur in patients suffering from cardio-vascular diseases or during surgery following the use of certain drugs. The aim of this study was to identify the relationship between such use and the occurrence of cardiac arrest or asystole based on a review of literature identified in Science Direct, Web of Science and PubMed. Our findings confirm that a relationship exists between the use of certain drugs and the occurrence of asystole. Most drugs which induce asystole are used in cardiovascular disease, particularly beta-blockers, calcium L-channel blockers and potassium channel blockers. Medicine which can lead to asystole are drugs used, among others, for sedation during surgeries and intended for anesthesia; however, the relationship with asystole is not as clear as for the cardio-vascular drugs. Most patients who experience asystole during surgery after administration of the same drugs had other very serious health problems. Our findings are intended to support medical professionals in anticipating the possibility of asystole after drug administration. Full article

Background/Objectives: Beta adrenergic signaling has been implicated in cancer progression, leading to interest in repurposing beta blockers (BBs) as adjunctive anti-cancer agents. However, clinical findings are inconsistent. This systematic review and meta-analysis evaluates the association between BB use and survival outcomes in cancer patients. Methods: A systematic search of OVID Medline, EMBASE, and CENTRAL was conducted through 13 September 2023, for studies comparing survival outcomes in solid tumor patients using BBs versus non-users. Eligible studies reported hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), or cancer-specific survival (CSS). Perioperative studies and those without BB-specific HRs were excluded. Data extraction and quality assessment were performed in duplicate using ROBINS-I. A random-effects model was used, with heterogeneity assessed by the I² statistic. Results: Seventy-nine studies (492,381 patients) met the inclusion criteria; 2.5% were prospective. The most frequently studied cancers were breast (n = 33), ovarian (n = 30), and colorectal (n = 28). BB use was associated with improved PFS (HR 0.78, 95% CI: 0.66–0.92, I² = 79.8%), with significance maintained after excluding high-bias studies (HR 0.74, 95% CI: 0.61–0.91, I² = 36.6%). No significant associations were observed for OS (HR 0.99, 95% CI: 0.94–1.04, I² = 84.9%) or CSS (HR 0.95, 95% CI: 0.91–1.00, I² = 77.4%). Conclusions: BB use may be associated with longer PFS in cancer patients, but findings are limited by study design and heterogeneity; high-quality prospective studies are needed. Full article

Background and Clinical Significance: Congenital LQTS is a life-threatening condition, resulting from a mutation of the gene encoding the cardiac ion channels, which results in prolongation of the ventricular action potential. Genetic screening of family members in symptomatic and asymptomatic patients is crucial for the prevention of sudden cardiac death. There are a number of detected mutations of congenital LQTS, of which the three forms LQT1, LQT2, and LQT3 are the best described. In addition to the described ECG morphology, the key triggers and treatment approach are described. This emphasizes even more the importance of timely screening of these patients, and the decision for therapy. It should be emphasized that the phenotypic manifestations significantly depend on the affected genes. The guidelines in the treatment approach are very clear, although it should be emphasized that beta blockers are the first and basic treatment therapy. The therapeutic choice is narrowed especially if they are not effective. Case Presentation: This is a case report of a young woman diagnosed with LQTS who was confirmed to have KCNH2 mutations through genetic analysis. The same mutation was also confirmed in her children. Changes in the therapeutic approach are described, and the use of beta blockers, depending on the symptoms and drug tolerance. Especially in the postpartum period, due to reduced progesterone levels, in this case, the patient was implanted with a cardioverter defibrillator. Conclusions: It should be emphasized that timely recognition is essential for early diagnosis, regular control, timely initiation of treatment, and prevention of adverse events. Full article

Introduction: The International Classification of Orofacial Pain (ICOP) recognizes orofacial migraine (OFM) and neurovascular orofacial pain (NVOP) as migraine-related entities affecting the facial and oral regions. The diagnostic features of OFM and NVOP indicate that there are many similarities between the two. However, we recently demonstrated that NVOP and OFM are two distinct diagnostic entities, confirming the ICOP classification. It was the aim of the present study to examine whether OFM and NVOP differ in response to pharmacotherapy. Materials and Methods: The cohort was made up of 40 patients attending a tertiary orofacial pain clinic. When implementing ICOP criteria, an OFM diagnosis was made in 23 and an NVOP diagnosis in 17. Results: No statistically significant differences between NVOP versus OFM were observed in the global response to standard abortive therapy such as triptans, or NSAIDs. Similarly, no statistically significant differences were found following prophylactic therapy that included beta-blockers, anti-epileptic drugs, and tricyclic antidepressants. Up to 80% of patients responded favorably with ≥50% pain reduction. Conclusions: NVOP and OFM differ in diagnostic characteristics, demonstrating unique features, and were confirmed as two diagnostic entities. However, NVOP and OFM did not differ in their response to abortive or prophylactic treatments. Study limitations include the lack of starting data precluding a more precise pharmacological analysis. The small sample size limits any far reaching conclusions. This is particularly true regarding individual drug efficacy. We were unable to analyze drug and dose responses separately due to data constraints. Full article