Search Results (114)

Diabetic neuropathy (DN) remains a major clinical burden, characterized by progressive sensory dysfunction, pain, and impaired quality of life. Despite the available symptomatic treatments, there is a pressing need for disease-modifying therapies. In recent years, preclinical research has highlighted the potential of repurposed pharmacological agents, originally developed for other indications, to target key mechanisms of DN. This narrative review examines the main pathophysiological pathways involved in DN, including metabolic imbalance, oxidative stress, neuroinflammation, ion channel dysfunction, and mitochondrial impairment. A wide array of repurposed drugs—including antidiabetics (metformin, empagliflozin, gliclazide, semaglutide, and pioglitazone), antihypertensives (amlodipine, telmisartan, aliskiren, and rilmenidine), lipid-lowering agents (atorvastatin and alirocumab), anticonvulsants (topiramate and retigabine), antioxidant and neuroprotective agents (melatonin), and muscarinic receptor antagonists (pirenzepine, oxybutynin, and atropine)—have shown promising results in rodent models, reducing neuropathic pain behaviors and modulating underlying disease mechanisms. By bridging basic mechanistic insights with pharmacological interventions, this review aims to support translational progress toward mechanism-based therapies for DN. Full article

Background: Recent drug enforcement activities have possibly suggested the presence of some calcium channel blocker antihypertensives in association with cocaine. The seizure revealed the possibility that the two drugs might have been used together for some unknown reasons. Methods: Hence, this study aimed at investigating the nature and frequency of adverse drug reactions (ADRs) reported in association with the concomitant use of calcium channel blockers (CCBs) and cocaine, using data from the FDA Adverse Event Reporting System (FAERS). Results: After removing duplicate reports, a total of 67 cases involving concomitant use of cocaine and CCBs were analyzed and were stratified into three groups based on the CCB involved: verapamil (n = 19), diltiazem (n = 30), and amlodipine (n = 18). Logistic regression analysis identified “product use for unknown indication” (β = 0.33) as the strongest predictor of fatal outcomes. Age revealed a modest negative association with fatal outcome (β = −0.93, intercept = 4.07). Concomitant substance use was reported in over 84% of cases. Frequently co-used substances included opioids, benzodiazepines, antidepressants, antihistamines, and alcohol. Poly-drug use was most pronounced in the diltiazem group, which exhibited the highest burden of opioid and alcohol co-exposure. Conclusions: It is here suggested that clinicians should exercise caution when managing individuals who use cocaine, due to the potential for increased toxicity and lethality when CCBs are co-used, either as part of a prescribed treatment or if CCBs are present as adulterants in cocaine. Full article

This study reports the synthesis of activated carbon from dwarf elder, a lignocellulosic precursor, yielding a material with a high specific surface area (500.43 m²/g) and mesoporous structure (median pore radius: 3.88 nm). The physicochemical properties of the obtained carbon were characterized using field-emission scanning electron microscopy (FE-SEM), Brunauer–Emmett–Teller (BET) analysis, and Fourier-transform infrared spectroscopy (FTIR), confirming its suitability for aqueous-phase sorption applications. Batch experiments demonstrated carbon’s efficacy in adsorbing amlodipine besylate (AMB), a model pharmaceutical pollutant, with a maximum capacity of 325.9 mg/g under optimized conditions (pH 10.0, room temperature). Systematic evaluation of key parameters, such as initial AMB concentration, sorbent dosage, pH, and agitation speed revealed that sorption kinetics adhered to pseudo-second-order and Elovich model. The high efficiency of the synthesized carbon material, coupled with its low-cost and eco-friendly synthesis, positions it as a promising candidate for the scalable remediation of AMB and structurally related pharmaceuticals from contaminated water sources. Full article

Introduction: There are no clear predictors of high-sensitivity C-reactive protein (hsCRP) reductions following the use of antihypertensives and statins. Also, there are no clear data on the effect of BMI on hsCRP changes following the use of antihypertensives and statins. Therefore, we sought to identify predictors of significant hsCRP reduction after the use of rosuvastatin (RSV)/amlodipine (AML) and atorvastatin (ATV)/AML. Methods: We included 237 patients from 21 institutions in the Republic of Korea. Patients were randomly assigned to one of three treatment groups: RSV 10 mg/AML 5 mg; RSV 20 mg/AML 5 mg; or ATV 20 mg/AML 5 mg. Multivariate logistic regression analysis was performed to evaluate the predictors for hsCRP responders (hsCRP reduction ≥ 40% after 8 weeks). We also compared baseline hsCRP levels and their changes after 8 weeks between obese patients (n = 153) and nonobese patients (n = 84). Results: Baseline hsCRP ≥ 2 mg/dL and RSV 20 mg/AML 5 mg were independent predictors of hsCRP responders. Their median hsCRP % change rates were −53.11% and −40.0%, respectively. Normal weight, pre-obesity, and obesity were not independent predictors of hsCRP responders. The median hsCRP % reduction rates among normal weight, pre-obese, and obese patients were less than 40% in all groups, and the differences between each group were not significant (−20.0% vs. −33.33 vs. −23.08%, p = 0.289). Conclusions: In patients with ATV, RSV/AML polypill, baseline hsCRP ≥ 2 mg/dL, and baseline RSV 20 mg/AML 5 mg were independent predictors of a significant hsCRP reduction. BMI was not associated with hsCRP reduction (Clinical trial: NCT03951207). Full article

Background/Objectives: Diabetic foot infections (DFIs) are commonly associated with frequent hospitalizations, limb amputations, and premature death due to the profile of the bacteria infecting foot ulcers. DFIs are generally colonized by a polymicrobial net of bacteria that grows in biofilms, developing an increased antimicrobial resistance to multiple antibiotics. DFI treatment is a hurdle, and the need to develop new therapies that do not promote resistance is urgent. Therefore, the antibacterial efficacy of Nisin Z (antimicrobial peptide), a core–shell polycationic polyurea pharmadendrimer (PURE_G4OEI₄₈) (antimicrobial polymer), and amlodipine (antihypertensive drug) was evaluated against S. aureus and P. aeruginosa isolated from a DFI and previously characterized. Methods: The antibacterial activity was analyzed in vitro by determining the minimal inhibitory concentration (MIC) and in vivo in a Galleria mellonella model by assessing the larvae survival and health index. Results: The results indicate that Nisin Z exhibited antibacterial activity against S. aureus in vivo, allowing larvae full survival, and no antibacterial activity against P. aeruginosa. Nisin Z may have reduced the antibacterial effectiveness of both PURE_G4OEI₄₈ and amlodipine. PURE_G4OEI₄₈ significantly increased the survival of the larvae infected with P. aeruginosa, while amlodipine showed no activity against both bacteria in vivo. Conclusions: These findings suggest that both Nisin Z and PURE_G4OEI₄₈ could potentially be used individually as adjunct treatments for mild DFIs. However, further studies are needed to confirm these findings and assess the potential toxicity and efficacy of PURE_G4OEI₄₈ in more complex models. Full article

Background: Compounding is performed to adjust dosages and support medication for children. In Japan, tablets are crushed, diluted with lactose, and stored in bottles or sachets until use, but the stability and impact on dissolution of the ingredients after crushing have not been evaluated. Methods: Using a database established by the National Center for Child Health and Development in collaboration with 11 medical facilities, the status of tablet crushing was investigated. Commonly compounded drugs were selected as the target drugs. The selected drugs were sieved through a 500 μm mesh after crushing and diluted with lactose hydrate. The stability at 25 ± 2 °C/60 ± 5% relative humidity and the dissolution of the ingredients were evaluated after storing them for up to 120 days under the following conditions: (I) stored in a closed polycarbonate bottle (closed), (II) bottle opened once a day (in-use), or (III) stored in a laminated cellophane and polyethylene sachet (laminated). The changes in the ingredient content and dissolution behavior were evaluated in accordance with the Japanese Pharmacopoeia. Results: Five cardiovascular drugs (amlodipine besylate, carvedilol, propranolol hydrochloride, hydrochlorothiazide, and tadalafil) were selected as target drugs. No more than 10% change in ingredient content was observed for all five formulations compared to day 0. In addition, no related substances (impurities) were detected at more than 0.01%. There was no change in the dissolution rate of the samples after 120 days of storage under each storage condition. Conclusions: The five cardiovascular drugs commonly compounded for children in Japan maintained their pharmaceutical quality after compounding, even after long-term storage. Full article

Approximately 50% of Alzheimer’s disease (AD) patients develop psychotic symptoms, leading to a subtype known as psychosis in AD (AD + P), which is associated with accelerated cognitive decline compared to AD without psychosis. Currently, no FDA-approved medication specifically addresses AD + P. This study aims to improve psychosis predictions and identify potential therapeutic agents using the DeepBiomarker deep learning model by incorporating drug–target interactions. Electronic health records from the University of Pittsburgh Medical Center were analyzed to predict psychosis within three months of AD diagnosis. AD + P patients were classified as those with either a formal psychosis diagnosis or antipsychotic prescriptions post-AD diagnosis. Two approaches were employed as follows: (1) a drug-focused method using individual medications and (2) a target-focused method pooling medications by shared targets. The updated DeepBiomarker model achieved an area under the receiver operating curve (AUROC) above 0.90 for psychosis prediction. A drug-focused analysis identified gabapentin, amlodipine, levothyroxine, and others as potentially beneficial. A target-focused analysis highlighted significant proteins, including integrins, calcium channels, and tyrosine hydroxylase, confirming several medications linked to these targets. Integrating drug–target information into predictive models improves the identification of medications for AD + P risk reduction, offering a promising strategy for therapeutic development. Full article

Background/Objectives: Antimicrobial-resistant Staphylococcus aureus is a growing threat to human health for which alternative therapeutic options are needed. In this study, we aimed to evaluate the efficacy of amlodipine (AML) and imipramine (IMI) to treat S. aureus infection in the Galleria mellonella larval model by targeting efflux and biofilms, which are relevant contributors to antimicrobial resistance and virulence in S. aureus. Methods: In-house reared G. mellonella were used in virulence assays to determine the infective dose of two S. aureus strains differing in the expression of norA (gene encoding the native NorA efflux pump). Toxicology assays were conducted to determine the drugs’ LD₅₀ for G. mellonella. Drug efficacy assays were performed to evaluate the potential of amlodipine, imipramine and the control drugs ciprofloxacin (CIP) and enalapril (ENA) to clear S. aureus infection in G. mellonella. Results: Survival analysis defined the infective dose as 1 × 10⁷ CFU/larva for both strains. High LD₅₀ values were determined (CIP: >1000 mg/kg; AML: >640 mg/kg; IMI: 1141 mg/kg; ENA: >1280 mg/kg), revealing a high tolerance of G. mellonella to these drugs. AML at 15 mg/kg and IMI at 100 mg/kg increased the larvae survival by 20% (p = 0.04) and 11% (p = 0.11), respectively, also positively affecting health score indexes. In agreement with the literature, ciprofloxacin at >100 mg/kg promoted larvae survival by >73%. Conclusions: Amlodipine and imipramine show mild potential as new therapeutic options for managing S. aureus infections but are promising as new lead molecules. This study also reinforces G. mellonella as a sustainable, reliable model for drug evaluation. Full article

Background: Amlodipine has recently been incidentally reported with angioedema and is frequently prescribed with renin–angiotensin–aldosterone system inhibitors (RAAS-i) for hypertension management. While RAAS-i drugs are known to cause angioedema, the risk associated with amlodipine alone or in combination with RAAS-i drugs remains unclear. This study aimed to evaluate the association between amlodipine use and angioedema using pharmacovigilance data. Methods: We analyzed adverse event reports from the US FDA Adverse Event Reporting System using both frequentist and Bayesian approaches. Drug–drug interactions were assessed using multiplicative models. Additionally, we conducted a systematic review of published case reports of amlodipine-associated angioedema. Results: Among 29,661,136 reports, 2076 cases of angioedema were identified (1067 with amlodipine alone, 1009 with amlodipine–RAAS-i combinations). Significant safety signals were detected for amlodipine alone and in combination with aliskiren, specific ACE inhibitors (quinapril, benazepril, trandolapril, fosinopril, perindopril), and certain ARBs (candesartan, losartan). No significant interactions were observed between amlodipine and RAAS-i drugs except for the amlodipine–trandolapril combination. A review of published cases demonstrated definite causality in two cases and possible association in others, with most patients presenting with oropharyngeal/facial edema and achieving complete recovery following drug discontinuation and standard therapy. Conclusions: Our findings suggest a potentially increased risk of angioedema with amlodipine, both as monotherapy and in specific RAAS-i combinations. While these results should not discourage appropriate clinical use, they emphasize the importance of monitoring for angioedema, particularly during therapy initiation. The findings from this study need to be validated in prospective studies for further elucidation of the underlying mechanisms. Full article

Background: Drug-induced gingival enlargement is a commonly documented adverse effect in patients administered with calcium antagonist medications. Nifedipine is the medicine most frequently linked to instances of gingival enlargement; nevertheless, amlodipine, likewise a calcium antagonist, can elicit this adverse effect. This case report aims to detail a case of amlodipine-induced gingival hyperplasia, emphasizing the significance of a multidisciplinary approach and outlining its therapy across various surgical phases. Methods: A 48-year-old hypertensive patient using amlodipine therapy presents with aberrant gingival tissue growth in the upper arch. Intraoral examination reveals localized inflammation and tissue enlargement in the papillae areas of the upper arch gingiva, leading to partial covering of the dental crowns. The patient experienced painful sensations and episodes of spontaneous bleeding in the enlarged gingival tissue. Following an initial professional dental hygiene treatment, which included root planning in the upper quadrants, and in consultation with the referring cardiologist, it was determined to discontinue amlodipine and initiate a replacement therapy with olmesartan medoxomil. Fifteen days following the cessation of amlodipine, surgical excision of the thickened interdental gingival tissues in the anterior region was conducted to obtain biopsies for histological confirmation of the observed pathological condition. Results: Histopathological examination validated the diagnosis of drug-induced gingival enlargement, characterized by chorion fibrosis and significant lymphoplasmacytic infiltration. Specifically, parakeratotic and acanthotic characteristics were seen in the gingival epithelium. Adjacent to the inflammatory regions, fibrosis was noted, along with the presence of cytoid bodies, which are typically linked to pathological diseases driven by inflammatory processes. These histological characteristics were consistent with the diagnosis of drug-induced gingival enlargement. Conclusions: A multidisciplinary approach involving the treating physician, dentist, and hygienist, incorporating drug replacement and targeted oral hygiene sessions, is crucial for the management and resolution of calcium channel blocker-induced gingival enlargement. Full article

Introduction: This study assessed the therapeutic effectiveness of a single-pill combination (SPC) of olmesartan/amlodipine plus rosuvastatin for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in patients with hypertension and dyslipidemia. Methods: Adult patients with hypertension and dyslipidemia who were decided to be treated with the study drug were eligible. The primary endpoint was the proportion of patients who achieved BP, LDL-C and both BP and LDL-C treatment goals at weeks 24–48. Secondary endpoints were assessed at weeks 24–48 and included changes in BP and LDL-C levels from baseline; the proportion of patients who achieved treatment goals who were initially classified as uncontrolled at baseline; changes and percent changes in lipid parameters; changes in both BP and LDL-C levels among patients who reached treatment goals who were followed for more than 24 weeks; and the overall safety profile. Results: A total of 5476 patients were enrolled, and 4411 patients comprised the effectiveness evaluation set. The proportions of patients who reached the treatment goals for BP, LDL-C levels, and both BP and LDL-C levels were 67.93% [95% confidence interval (CI) 66.52–69.32], 80.19% [95% CI 78.85–81.49], and 58.07% [95% CI 56.43–59.7], respectively. Secondary endpoints showed statistically significant changes. Overall, the treatment was well tolerated. Conclusions: The treatment of patients with hypertension and dyslipidemia with the olmesartan/amlodipine plus rosuvastatin SPC was associated with significant decreases in SBP/DBP and LDL-C levels, and a high proportion of patients achieved the BP and LDL-C treatment goals. The finding of this study is worthwhile in that this study evaluated the effectiveness and safety in a broad patient population representative of those seen in everyday clinical practice. Full article

This study aimed to investigate the effect of antihypertensive drugs on reproductive function in Rattus norvegicus and demonstrate the potential role of oxidative stress in reproductive dysfunction. Rattus norvegicus were selected as the experimental animals and divided into the following groups: healthy (control group), clonidine (CL), rilmenidine (RLD), methyldopa (MTL), amlodipine (ALD), and ramipril (RML). Each individual in each group was marked from one to six. Doses of clonidine (0.075 mg/kg), rilmenidine (0.5 mg/kg), methyldopa (100 mg/kg), amlodipine (2 mg/kg), and ramipril (2 mg/kg) were administered orally via gavage to each Rattus norvegicus. Using blood obtained from Rattus norvegicus, the absorbance of the pink-colored complex formed by thiobarbituric acid (TBA) and malondialdehyde (MDA) was measured spectrophotometrically at the 532 nm wavelength. Blood samples were collected from the tail veins to analyze serum malondialdehyde (MDA) and total glutathione levels in the serum of all Rattus norvegicus. After sampling, two mature male Rattus norvegicus were introduced to every group of six female Rattus norvegicus and accommodated in a controlled laboratory environment for two months. Any female Rattus norvegicus that became pregnant during this time was transferred to a solitary cage within a controlled setting. Rattus norvegicus that did not become pregnant and did not give birth during this period were considered infertile. The results were compared among the groups. Total glutathione (tGSH) levels were determined using a spectrophotometer. According to our study, the increase in MDA levels observed was not statistically significant in the CL and RLD groups compared to that in the control group. MDA levels were significantly increased in the methyldopa, amlodipine, and RML groups. While total glutathione levels in the CL group were similar to those in the control group, the RLD, MTL, ALD, and RML groups showed a statistically significant decrease. While the animals in the CL and RLD groups were not infertile, infertility was apparent in the groups treated with MTL, ALD, and RML. Thus, it was determined that the antihypertensive drugs MTL, ALD, and RML had different effects on fertility, and that the use of such drugs could cause infertility by increasing oxidative stress and decreasing antioxidant levels. Full article

The process of manufacturing drug delivery systems (DDSs) by fused deposition modeling (FDM) with 3D printing requires the availability of a polymeric filament containing the drug of interest. This filament is fused in the printer heating system and used to print polymer/drug volumetric parts. Polymers with pH-dependent solubility are widely known in the literature for their controlled release and drug dissolution-enhancing properties, biocompatibility, and variety of release profiles. Given these characteristics, the study of pH-responsive 3D printing filaments appears as a potential alternative for the development of new 3D printing functional materials for healthcare area applications. In this sense, this work aimed at the preparation and characterization of pH-dependent filaments of the Eudragit E 100 copolymer (E100) containing the model drug Amlodipine (Aml) for potential application in the manufacturing of DDSs by 3D printing. The E100/Aml filaments with two distinct drug concentrations were produced by hot-melt extrusion at 105 °C. The posterior chemical protonation treatment of the filaments for 60 min provided a significant improvement in their flexibility. Microstructural analysis (SEM, XRD, FTIR, and DLS) and thermal studies by DSC proved the feasibility of producing the filaments by hot-melt extrusion without the degradation of their constituent materials. The in vitro dissolution profiles of the E100/Aml samples were evaluated in simulated gastric and intestinal fluids. The facilitated solubility of the polymer in an acidic medium (pH = 1.2) was preserved in the filament form, with rapid and reproducible drug release from the polymer matrix. The saturation of the drug concentration in the medium occurred after 30 min of testing for E100/Aml models. A customized 3D part with geometry and fill control was also printed from E100/Aml filaments as proof of concept. Full article

Background/Objectives: The etiology of diffuse gingival enlargement is multifactorial, and the definitive diagnosis may be challenging. To highlight the nuances of the differential diagnosis, we present two cases of generalized gingival overgrowth and discuss the diagnostic dilemmas. Case description: In the first case, an 82-year-old male with a medical history of hypertension and prostatitis had a chief complaint of symptomatic oral lesions of a 20-day duration, accompanied by fever and loss of appetite. The clinical examination revealed diffusely enlarged, hemorrhagic, and focally ulcerative upper and lower gingiva, ecchymoses on the buccal mucosa, as well as bilateral cervical lymphadenitis. The histopathologic and immunohistochemical findings combined with the hematologic examination led to a final diagnosis of acute myeloid leukemia, and the patient was referred to a specialized hematology/oncology unit for further management. The second case was a 74-year-old female with a medical history of breast cancer (successfully managed in the past), type II diabetes mellitus, and cardiovascular disease, taking various medications. An intraoral examination revealed diffusely enlarged, erythematous, and hemorrhagic upper and lower gingiva. An incisional biopsy showed hyperplastic granulation and fibrous connective tissue with a predominantly chronic inflammatory infiltrate. Considering the patient’s medical history and current medications, the clinical and microscopic findings were in support of the diagnosis of drug-induced gingival overgrowth associated with calcium channel blocker (amlodipine), partially controlled diabetes serving as an additional predisposing factor. Gingivectomy and periodontal scaling, along with substitution of the offending medication, were curative, and better diabetic control was recommended. Conclusions: Diffuse gingival overgrowth may be caused by a variety of diverse conditions, ranging from an exuberant response to local factors, potentially exacerbated by hormonal influences (e.g., puberty or pregnancy), to drug side effects to genetic, systemic, or even neoplastic diseases. A careful evaluation of the medical and drug history and clinicopathologic correlation is essential for accurate diagnosis and appropriate management. Full article

Background: Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. Methods: Raman and three near-infrared (NIR) process analysers were utilized to develop methods for API quantification. Four partial least squares (PLS) models were developed using measurements from three granulation batches, with an additional batch used to evaluate model predictability. Models performance was assessed using metrics such as root mean square error of prediction (RMSEP), root mean square error of cross-validation (RMSECV), residual prediction deviation (RPD), and others. Results: Off-line and at-line NIR models were identified as suitable for process control applications. Additionally, at-line Raman measurements effectively predicted the endpoint of the spraying phase. Conclusions: To the best of authors’ knowledge, this is the first study focused on monitoring API content during fluidized bed granulation (FBG) used for ASD preparation. The findings provide novel insights into the application of Raman and NIR process analysers with PLS modelling for monitoring and controlling ASD preparation processes. Full article