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Indian Heart Journal Jun 2024The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with...
Comparison of the efficacy, safety, and tolerability of the FDC of telmisartan + bisoprolol with telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: A double-blind, multicentric, phase-III clinical study.
AIM
The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension.
METHODOLOGY
The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician.
RESULTS
Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A.
CONCLUSION
Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension.
TRIAL REGISTRY NAME
Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.
PubMed: 38871219
DOI: 10.1016/j.ihj.2024.06.002 -
Frontiers in Neuroscience 2023To study whether a Poincaré plot can help predict the curative effect of metoprolol for postural orthostatic tachycardia syndrome (POTS) in children.
PURPOSE
To study whether a Poincaré plot can help predict the curative effect of metoprolol for postural orthostatic tachycardia syndrome (POTS) in children.
METHODS
Pediatric patients with POTS who were administered metoprolol were retrospectively included. The collected data included general data (sex, age, height, weight, and body mass index), the manifestations and treatment (baseline orthostatic intolerance symptom score and course of metoprolol treatment), vital signs (supine heart rate [HR], supine blood pressure, and increased HR during the standing test), HR variability indexes (standard deviation of normal-to-normal intervals [SDNN]; standard deviation of the averages of normal-to-normal intervals [SDANN]; mean standard deviation of the NN intervals for each 5-min segment [SDNNI]; root mean square of the successive differences [rMSSD]; percentage of adjacent NN intervals that differ by >50 ms [pNN50]; triangular index; ultra-low [ULF], very low [VLF], low [LF], and high frequency [HF]; total power [TP]; and LF/HF ratio), and graphical parameters of the Poincaré plot (longitudinal axis [L], transverse axis [T], and L/T). Receiver operator characteristic curves were used to calculate the predictive function of the indexes with significant differences between patients who responded and those who did not. The index combination with the highest predictive value was obtained through series-parallel analysis.
RESULTS
Overall, 40 responders and 23 non-responders were included. The L and T in the Poincaré plots and rMSSD, pNN50, HF, and TP of the HR variability data were significantly lower in participants who responded to metoprolol than in participants who did not ( < 0.001). The L/T of participants who responded to metoprolol was greater than that of non-responders ( < 0.001). Moreover, we noted a strong correlation between every two indexes among L, T, rMSSD, pNN50, HF, TP, and L/T ( < 0.05). T < 573.9 ms combined with L/T > 2.9 had the best performance for predicting the effectiveness of metoprolol, with a sensitivity of 85.0%, specificity of 82.6%, and accuracy of 84.1%.
CONCLUSION
In the Poincaré plot, a T < 573.9 ms combined with an L/T > 2.9 helps predict good outcomes of using metoprolol to treat pediatric POTS.
PubMed: 38033543
DOI: 10.3389/fnins.2023.1280172 -
Naunyn-Schmiedeberg's Archives of... Jul 2024The aim of the research was to evaluate the influence of antagonists of specific beta-adrenergic receptor subtypes on bowel motility following abdominal surgery in rat...
The aim of the research was to evaluate the influence of antagonists of specific beta-adrenergic receptor subtypes on bowel motility following abdominal surgery in rat model of postoperative ileus. Bowel motility was measured by the intestinal transit of Evans blue introduced via orogastric tube after surgical procedures of skin incision, laparotomy and laparotomy with gut manipulation. Male rats were given individual adrenergic receptor subtypes antagonists intraperitoneally, and the influence of administered agents on intestinal transit of Evans blue was then evaluated. No statistically significant differences in the length of intestine in tested rats were observed. Propranolol administered prior to surgical procedure has shown protective effect on Evans blue migration in rats undergoing laparotomy and gut manipulation. Intestinal dye transit for propranolol doses of 10, 30 and 45 mg/kg was 18.00 ± 1.88c m, 23.75 ± 1.71 cm and 22.5 ± 2.43 cm, respectively, and for last two doses, statistically significant increase of dye passage was noted, compared to Evans blue transit of 11.00 ± 2.43 cm in the control group. No acceleration of dye migration was seen following administration of beta1-, beta2- and beta3-selective adrenergic receptor antagonist metoprolol, ICI 118.551 and SR58894A, respectively. Our research confirmed that propranolol at high doses, as seen by other researchers, improved bowel motility in early phase of postoperative ileus. That slight acceleration of intestinal dye transit after surgery with gut manipulation is rather connected with membrane-stabilizing action, than the receptor blocking effect, as this effect was not observed after the application of selective antagonists of respective subtypes of beta-adrenergic receptor.
Topics: Animals; Ileus; Male; Propranolol; Postoperative Complications; Adrenergic beta-Antagonists; Rats; Receptors, Adrenergic, beta; Rats, Wistar; Gastrointestinal Motility; Gastrointestinal Transit; Evans Blue
PubMed: 38157026
DOI: 10.1007/s00210-023-02918-3 -
CPT: Pharmacometrics & Systems... Jun 2024The first-generation tyrosine kinase inhibitor imatinib has revolutionized the development of targeted cancer therapy and remains among the frontline treatments, for...
The first-generation tyrosine kinase inhibitor imatinib has revolutionized the development of targeted cancer therapy and remains among the frontline treatments, for example, against chronic myeloid leukemia. As a substrate of cytochrome P450 (CYP) 2C8, CYP3A4, and various transporters, imatinib is highly susceptible to drug-drug interactions (DDIs) when co-administered with corresponding perpetrator drugs. Additionally, imatinib and its main metabolite N-desmethyl imatinib (NDMI) act as inhibitors of CYP2C8, CYP2D6, and CYP3A4 affecting their own metabolism as well as the exposure of co-medications. This work presents the development of a parent-metabolite whole-body physiologically based pharmacokinetic (PBPK) model for imatinib and NDMI used for the investigation and prediction of different DDI scenarios centered around imatinib as both a victim and perpetrator drug. Model development was performed in PK-Sim® using a total of 60 plasma concentration-time profiles of imatinib and NDMI in healthy subjects and cancer patients. Metabolism of both compounds was integrated via CYP2C8 and CYP3A4, with imatinib additionally transported via P-glycoprotein. The subsequently developed DDI network demonstrated good predictive performance. DDIs involving imatinib and NDMI were simulated with perpetrator drugs rifampicin, ketoconazole, and gemfibrozil as well as victim drugs simvastatin and metoprolol. Overall, 12/12 predicted DDI area under the curve determined between first and last plasma concentration measurements (AUC) ratios and 12/12 predicted DDI maximum plasma concentration (C) ratios were within twofold of the respective observed ratios. Potential applications of the final model include model-informed drug development or the support of model-informed precision dosing.
Topics: Humans; Imatinib Mesylate; Drug Interactions; Models, Biological; Cytochrome P-450 CYP3A; Antineoplastic Agents; Male; Computer Simulation; Adult; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Female; Cytochrome P-450 CYP2C8; Ketoconazole; Middle Aged; Rifampin
PubMed: 38482980
DOI: 10.1002/psp4.13127 -
Marine Pollution Bulletin Mar 2024Pharmaceutical compounds are micropollutants of emerging concern, as well as other classes of chemicals such as UV filters and artificial sweeteners. They enter marine...
Pharmaceutical compounds are micropollutants of emerging concern, as well as other classes of chemicals such as UV filters and artificial sweeteners. They enter marine environments via wastewater treatment plants, aquaculture runoff, hospital effluents, and shipping activities. While many studies have investigated the presence and distribution of these pollutants in numerous coastal areas, our study is the first to focus on their occurrence, spatial distribution, and vertical distribution in the sea surface microlayer (SML) and the near-surface layer of marine environments. We analyzed 62 pharmaceutical compounds, one UV filter, and six artificial sweeteners from the SML to the corresponding underlying water (0 cm, 20 cm, 50 cm, 100 cm, and 150 cm) at four stations in the southern North Sea. One station is the enclosed Jade Bay, one is the Weser estuary at Bremerhaven, and the other two stations (NS_7 and NS_8) are in the open German Bight. Jade Bay receives pollutants from surrounding wastewater treatment plants, while the Weser estuary receives pollutants from cities like Bremerhaven, which has dense populations and industrial activities. Concentrations of pharmaceutical compounds were higher in the upper water layers (from the SML to 20 cm). Eleven pharmaceutical compounds (caffeine, carbamazepine, gemfibrozil, ibuprofen, metoprolol, salicylic acid, clarithromycin, novobiocin, clindamycin, trimethoprim, and tylosin) were detected in >95 % of our samples. One UV filter (benzophenone-4) was found in 83 % and three artificial sweeteners (acesulfame, saccharin, and sucralose) in 100 % of all our samples. All artificial sweeteners posed high risks to the freshwater invertebrate Daphnia magna. Understanding the spatial and vertical distribution of pharmaceuticals and other micropollutants in marine environments may be essential in assessing their dispersal and detection in other aquatic environments.
Topics: North Sea; Water Pollutants, Chemical; Sweetening Agents; Water; Risk Assessment; Pharmaceutical Preparations; Environmental Monitoring
PubMed: 38309177
DOI: 10.1016/j.marpolbul.2024.116099 -
World Journal of Clinical Cases Dec 2023Lyophilized recombinant brain natriuretic peptide (BNP) is an exogenous peptide synthesized by artificial recombination technology, with a similar structure and similar...
Lyophilized recombinant brain natriuretic peptide (BNP) is an exogenous peptide synthesized by artificial recombination technology, with a similar structure and similar physiological effects with the endogenous natriuretic peptide secreted by the human body. It's main mechanism of action is to increase cyclic guanosine monophosphate by binding with its corresponding receptor in the body, regulating, thus, the imbalance of the vascular system and cardiac hemodynamics, improving the heart's pumping capacity, and inhibiting sympathetic excitability and myocardial remodeling. Moreover, it can promote mitochondrial metabolism and enhance the use of adenosine triphosphate in cardiomyocytes. In the present study, 102 chronic heart failure (HF) patients were randomly assigned to a control and an observation group consisting of 51 patients each. Patients of the control group were treated with standard HF therapy for 3 d including oral metoprolol tartrate tablets, spironolactone, and olmesartanate while patients of the observation group were administered the recombinant human BNP injection for the same time-period, plus the standard HF therapy. The recombinant human BNP group (observation group) demonstrated better physical, emotional, social, and economic scores, as well as cardiac and inflammatory biomarkers such as serum hypersensitive C-reactive protein, N-terminal pro BNP and troponin I levels, compared to the control group. Moreover, cardiac function was also improved, as left ventricular ejection fraction and stroke volume were significantly higher in the observation group than in the control group. Interestingly, adverse reactions were not different between the 2 groups. However, these results are not generalizable and the need of large multicenter randomized controlled trials examining the safety and efficacy of recombinant human BNP in HF patients is of major importance.
PubMed: 38188212
DOI: 10.12998/wjcc.v11.i36.8603 -
Frontiers in Medicine 2024BRASH syndrome is a vicious cycle of hyperkalemia and bradycardia and is an under-recognized life-threatening clinical diagnosis. It is usually initiated by hypovolemia...
BRASH syndrome is a vicious cycle of hyperkalemia and bradycardia and is an under-recognized life-threatening clinical diagnosis. It is usually initiated by hypovolemia or hyperkalemia. We report here on the case of a 92-year-old man with hypertension and heart failure who presented to the emergency department with weakness following diarrhea. He was on amlodipine, benazepril, metoprolol, furosemide and spironolactone. The patient's blood pressure was 88/53 mmHg and the serum creatinine was 241 μmol/L. Within 2 h, the patient's heart rate decreased from 58 beats per minute to 26 beats per minute, and serum potassium levels gradually increased from 6.07 mmol/L to 7.3 mmol/L. The electrocardiogram showed a junctional escape rhythm with accidental sinus capture. The diagnosis of BRASH syndrome was made based on clinical symptoms, a biochemical profile and the results of an electrocardiogram. The patient was rapidly stabilized with the administration of intravenous calcium gluconate, dextrose and insulin, 5% sodium bicarbonate, 0.9% sodium chloride, furosemide, and oral zirconium cyclosilicate. Sinus rhythm at a heart rate of 75 bpm was detected 5 h later, along with normal serum potassium levels. After 2 weeks, kidney function returned to normal. Clinicians should be alert to patients with hyperkalemia and maintain a high index of suspicion for BRASH syndrome. Timely diagnosis and comprehensive intervention are critical for better outcomes in managing patients with BRASH.
PubMed: 38873207
DOI: 10.3389/fmed.2024.1405494 -
Indian Journal of Critical Care... Dec 2023High-alert medications (HAMs) potentiate heightened risk of causing patient harm ranging from 0.24 to 89.6 errors per 100 prescriptions. High-alert medications are...
BACKGROUND
High-alert medications (HAMs) potentiate heightened risk of causing patient harm ranging from 0.24 to 89.6 errors per 100 prescriptions. High-alert medications are crucially utilized in the intensive care settings (ICUs) due to their excellent potential in delivering therapeutic efficacy, yet these medications could cause severe harm if used inappropriately. Despite the cautious use of these medications, medication safety issues persist, which compromises patient safety.
METHODS
A prospective interventional study was conducted in ICUs for a period of 6 months. The HAMs were adopted from the Institute for Safe Medication Practices (ISMP) list of HAMs that were used. A suitably designed medication error assessment form was used to capture the necessary data, including demographics, medications, medication error, and the contributing factors. The National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) index was used to categorize the medication errors (MEs). The error rate was calculated using error rate formula. Continuous variables were expressed as mean ± standard deviation, whereas categorical variables were presented in frequencies and percentages.
RESULTS
A total of 165 patients were enrolled during the study period, with 98 (59.4%) being male and 67 (40.6%) female. The majority [54 (32.73%)] of the study participants belonged to the 61-70 age range. A total of 204 MEs were reported, of which [92 (41.5%)] errors were prescribing errors, followed by documentation errors [69 (33.82%)] and administration errors [43 (21.08%)]. The baseline medication error rate was noted to be 160.12/1,000 patient days. Potassium chloride, tramadol, propranolol, aspirin, insulin, and metoprolol were identified as the most common HAMs to cause errors. According to NCC MERP classification, 41.18% were categorized as category B, followed by category C (35.78%). An overall of 666 contributing factors (CFs) were identified for 204 errors. Stress (24.32%) was the most common factor that contributed to the MEs, followed by workload (21.47%).
CONCLUSION
While great strides have been adopted in error prevention, yet the goal of making HAM errors "never" event has not been achieved. Thus, an active surveillance by a clinical pharmacist could support the healthcare team in promoting patient care.
HOW TO CITE THIS ARTICLE
Aradhya PJ, Ravi R, Subhash Chandra BJ, Ramesh M, Chalasani SH. Assessment of Medication Safety Incidents Associated with High-alert Medications Use in Intensive Care Setting: A Clinical Pharmacist Approach. Indian J Crit Care Med 2023;27(12):917-922.
PubMed: 38074962
DOI: 10.5005/jp-journals-10071-24588 -
Brazilian Journal of Anesthesiology... 2024Respiratory responses to extubation can cause serious postoperative complications. Beta-blockers, such as metoprolol, can interfere with the cough pathway. However,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Respiratory responses to extubation can cause serious postoperative complications. Beta-blockers, such as metoprolol, can interfere with the cough pathway. However, whether metoprolol can effectively control respiratory reflexes during extubation remains unclear. The objective of this study is to evaluate the efficacy of intravenous metoprolol in attenuating respiratory responses to tracheal extubation.
METHODS
Randomized, double-blinded, placebo-controlled trial.
SETTING
Tertiary referral center located in Brasília, Brazil. Recruitment: June 2021 to December 2021.
SAMPLE
222 patients of both sexes with an American Society of Anesthesiologists (ASA) physical status I-III aged 18-80 years. Patients were randomly assigned to receive intravenous metoprolol 5 mg IV or placebo at the end of surgery. The primary outcome was the proportion of patients who developed bucking secondary to endotracheal tube stimulation of the tracheal mucosa during extubation. Secondary outcomes included coughing, bronchospasm, laryngospasm, Mean Blood Pressure (MAP), and Heart Rate (HR) levels.
RESULTS
Two hundred and seven participants were included in the final analysis: 102 in the metoprolol group and 105 in the placebo group. Patients who received metoprolol had a significantly lower risk of bucking (43.1% vs. 64.8%, Relative Risk [RR = 0.66], 95% Confidence Interval [95% CI 0.51-0.87], p = 0.003). In the metoprolol group, 6 (5.9%) patients had moderate/severe coughing compared with 33 (31.4%) in the placebo group (RR = 0.19; 95% CI 0.08-0.43, p < 0.001).
CONCLUSION
Metoprolol reduced the risk of bucking at extubation in patients undergoing general anesthesia compared to placebo.
Topics: Male; Female; Humans; Metoprolol; Airway Extubation; Heart Rate; Arterial Pressure; Intubation, Intratracheal; Double-Blind Method
PubMed: 37541486
DOI: 10.1016/j.bjane.2023.07.012 -
Journal of Pharmaceutical Sciences Jun 2024Drug release plays a crucial role in drug delivery. While current formulation approaches are capable of coarse-tuning the release profile, their precision and...
Drug release plays a crucial role in drug delivery. While current formulation approaches are capable of coarse-tuning the release profile, their precision and reproducibility are limited by the physicochemical properties of the excipients and active pharmaceutical ingredient (API). Innovative and advanced approaches are urgently needed, especially for site-specific targeting of drugs and to address their pharmacological requirements for optimal therapy. The 5 × 5 × 0.6 mm piezoelectric micropump developed by Fraunhofer EMFT was designed to enable precise drug delivery in a low volume format. In this study, we investigated the ability of the micropump to deliver solutions of highly soluble APIs using a wide range of customized pump profiles. Additionally, we examined the ability of the micropump to deliver suspensions containing various defined particle sizes. While results for suspensions indicate that pumping performance is highly dependent on the size and concentration of the suspended particles, results with API solutions demonstrate high precision and reproducibility of release, coupled with maximum flexibility in the release profile of the API. The piezoelectric micropump thus lays the cornerstone in the development of a wide range of innovative drug delivery profiles, enabling customized release profiles to be programmed and thus paving the way to fully personalized medicine.
Topics: Drug Delivery Systems; Silicon; Equipment Design; Particle Size; Drug Liberation; Reproducibility of Results; Pharmaceutical Preparations; Excipients
PubMed: 38232804
DOI: 10.1016/j.xphs.2024.01.003