OBJECTIVE: Intravenous diltiazem has experienced numerous supply shortages over the past few years. The purpose of this study was to compare the safety and efficacy of a traditional diltiazem intravenous bolus and continuous infusion protocol to a diltiazem intravenous bolus and oral maintenance protocol for acute rate control in the emergency department.
METHODS: Patients who received intravenous diltiazem in the emergency department between January 1, 2018 and May 31, 2019 were screened. Patients were included if they received the diltiazem intravenous bolus and continuous infusion protocol (IV + infusion group) or the hybrid diltiazem intravenous bolus and oral maintenance protocol (IV + PO group). The primary outcome was the proportion of patients with rate control, without need for additional rate control agents or additional boluses during the maintenance phase.
RESULTS: A total of 106 patients were matched with 53 patients in each group. For the primary outcome of rate control at four hours, 62.3% of patients in the intravenous bolus + infusion group versus 75.5% of patients in the IV bolus + PO group (p = 0.142) achieved rate control. There was no difference in rates of hypotension or bradycardia between groups.
CONCLUSIONS: Results of this study demonstrated no difference in acute rate control when using a hybrid IV and oral diltiazem protocol, compared to a traditional IV bolus and infusion strategy. This information supports the further use of a hybrid diltiazem IV and oral protocol, which provides increased flexibility during shortages of either medication.

暂无摘要。

Since 3D printing technology is an emerging field in pharmaceutical technology, the present study aimed at the development of a mixed-mode liquid chromatographic method for the separation and determination of hydrochlorothiazide, diltiazem, and propranolol to investigate their in-vitro release performance from 3D printed tablets. Due to the unique properties of the mixed-mode stationary phase, the three drugs were separated in less than 8 min under isocratic elution. Method development was accomplished following the Analytical Quality by Design principles and was evaluated using risk assessment and multivariate analysis. The influences of critical method parameters on critical method attributes (were screened using a 2-level fractional factorial design and subsequently optimized through a central composite design. The method operable design region was approved by the establishment of a robust zone using Monte Carlo simulation and capability analysis. The validation of the HPLC method was performed based on the total error concept. The relative bias was varied between ─ 11.6 % and 10.5 % and the RSD values for repeatability and intermediate precision were below 4.4 % in all cases. The limits of detection (LOD) ranged between 0.17 - 0.90 μg/mL and were adequate for the specific application. The developed method was successfully applied to the analysis of the studied drugs in in-vitro drug release samples obtained from 3D-printed tablets combining the above-mentioned active pharmaceutical ingredients (APIs).

BACKGROUND: Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear.
OBJECTIVE: The purpose of this study was to investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil.
METHODS: We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011, to December 31, 2019. We used a cohort design to estimate hazard ratios for ischemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality, comparing DOACs + amiodarone/diltiazem/verapamil users and DOACs + beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window vs referent window within an individual also was conducted.
RESULTS: Of 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs + amiodarone/diltiazem/verapamil users vs DOACs + beta-blocker users in the cohort design. However, in the case-crossover design, we observed an odds ratio (OR) of 2.09 (99% confidence interval [CI] 1.37-3.18) for all-cause mortality associated with initiation of a DOAC while taking amiodarone, which was greater than that observed for DOAC monotherapy (OR 1.30; 99% CI 1.25-1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem.
CONCLUSIONS: Our study showed no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem, or verapamil. Elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken.

BACKGROUND: Postoperative pain remains the greatest problem after hemorrhoidectomy. Pain is hypothesized to arise from bacterial infection, sphincter spasm, and local inflammation.
OBJECTIVE: This trial was conducted to assess the effects of metronidazole, diltiazem, and lidocaine on posthemorrhoidectomy pain.
METHODS: A double-blinded randomized controlled factorial trial.
METHODS: This multicenter trial was conducted in Auckland, New Zealand.
METHODS: A total of 192 participants were randomly assigned (1:1:1:1) into 4 parallel arms.
METHODS: Participants were randomly assigned into 1 of 4 groups receiving topical treatment with 10% metronidazole, 10% metronidazole + 2% diltiazem, 10% metronidazole + 4% lidocaine, or 10% metronidazole + 2% diltiazem + 4% lidocaine. Participants were instructed to apply treatment to the anal verge 3 times daily for 7 days.
METHODS: The primary outcome was pain on the visual analog scale on day 4. The secondary outcomes included analgesia usage, pain during bowel movement, and functional recovery index.
RESULTS: There was no significant difference in the pain and recovery scores when diltiazem or lidocaine was added to metronidazole (score difference between presence and absence of diltiazem in the formulation: -3.69; 95% CI, -13.3 to 5.94; p = 0.46; between presence and absence of lidocaine: -5.67; 95% CI, -15.5 to 3.80; p = 0.24). The combination of metronidazole + diltiazem + lidocaine did not further reduce pain. Secondary analysis revealed a significant difference between the best (metronidazole + lidocaine) and worst (metronidazole + diltiazem + lidocaine) groups in both pain and functional recovery scores. There were no significant differences in analgesic usage, complications, or return to work between the groups. No clinically important adverse events were reported. The adverse event rate did not change in the intervention groups.
CONCLUSIONS: Topical metronidazole was used in the control group rather than a pure placebo.
CONCLUSIONS: There was no significant difference in pain when topical diltiazem, lidocaine, or both were added to topical metronidazole. See Video Abstract .
BACKGROUND: NCT04276298.
UNASSIGNED: ANTECEDENTES:El dolor postoperatorio sigue siendo el mayor problema tras hemorroidectomía. La hipótesis es que el dolor se debe a infección bacteriana, el espasmo esfínteriano e inflamación local.OBJETIVO:Se realizó un ensayo factorial aleatorizado y controlado para evaluar los efectos del metronidazol, el diltiazem y la lidocaína en el dolor posthemorroidectomía.DISEÑO:Ensayo factorial controlado aleatorizado doble ciego.ESCENARIO:Se realizó un ensayo multicéntrico en Auckland, Nueva Zelanda.PACIENTES:Se aleatorizó a 192 participantes (1:1:1:1) en cuatro brazos paralelos.INTERVENCIONES:Los participantes se asignaron aleatoriamente a uno de los cuatro grupos que recibieron tratamiento tópico con metronidazol al 10% (M), metronidazol al 10% + diltiazem al 2% (MD), metronidazol al 10% + lidocaína al 4% (ML), o metronidazol al 10% + diltiazem al 2% + lidocaína al 4% (MDL). Se indicó a los participantes que lo aplicaran en el margen anal 3 veces al día durante 7 días.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el dolor en la escala analógica visual en el día 4. Los resultados secundarios incluyeron el uso de analgesia, el dolor al defecar y el índice de recuperación funcional.RESULTADOS:No hubo diferencias significativas en las puntuaciones de dolor y recuperación cuando se añadió diltiazem o lidocaína al metronidazol (diferencia de puntuación entre la presencia y la ausencia de D en la formulación: -3.69; IC del 95%: -13.3; 5.94; p = 0.46; entre la presencia y la ausencia de L: -5.67; IC del 95%: -15.5; 3.80; p = 0.24). La combinación de MDL no redujo más el dolor. El análisis secundario reveló una diferencia significativa entre los grupos mejor (ML) y peor (MDL) tanto en las puntuaciones de dolor como en las de recuperación funcional. No hubo diferencias significativas en el uso de analgésicos, las complicaciones o la reincorporación al trabajo entre los grupos. No se notificaron eventos adversos clínicamente importantes. La tasa de eventosadversos no cambió en los grupos de intervención.LIMITACIONES:Se utilizó metronidazol tópico en el grupo de control, en lugar de un placebo puro.CONCLUSIONES:No hubo diferencias significativas en el dolor cuando se añadió diltiazem tópico o lidocaína, o ambos, al metronidazol tópico. ( Traducción-Dr. Jorge Silva Velazco )Identificador de registro del ensayo clínico:NCT04276298.

This study introduces a practical and cost-effective method for tracking diltiazem (DLZ) analytically. It utilizes a fluorimetric approach that relies on the modulation of fluorescence intensity of a dye called erythrosine B. Through a one-pot experiment performed in an acidic environment, a complex is rapidly formed between DLZ and erythrosine B. By observing the decrease in erythrosine B emission, a linear calibration plot is established, enabling the detection and quantification of DLZ concentrations ranging from 40 to 850 ng/ml. The estimated limits of detection and quantitation were 10.5 and 32.1 ng/ml, respectively. The variables affecting the DLZ-dye complex system were carefully adjusted. The validity of the approach was confirmed through a thorough evaluation based on the criteria set by ICH guidelines. The accuracy and precision of the methodology were evaluated, and the standard deviation and relative standard deviation were below 2. The strategy was successfully employed to analyze DLZ in tablets and capsules, and no significant variation between the proposed and reported methods as the values of the estimated t-test and F-test at five determinations were below 2.306 and 6.338, respectively. Notably, the method adheres to the principle of green chemistry by utilizing distilled water as the dispersing medium.

暂无摘要。

UNASSIGNED: The prehospital treatment for stable patients with atrial fibrillation with rapid ventricular response is rate-controlling agents such as calcium channel blockers, often diltiazem given as a bolus. At our agency we encourage the use of a bolus given via the infusion pump over two to four minutes immediately followed by a maintenance infusion, given concerns of recurrent tachycardia or hypotension secondary to rapid bolus administration. We examined if administering a bolus and infusion via an infusion pump shows better heart rate (HR) control at arrival to the emergency department (ED) compared with administration of a bolus only, while maintaining hemodynamic stability during transport. We also analyzed if a patient received a second bolus within 60 min of arrival to the ED.
UNASSIGNED: We used a retrospective propensity-matched cohort of prehospital patients with atrial fibrillation for whom diltiazem was administered, from 1/1/2018 to 12/31/2021, in our system of 10 New Jersey paramedic units. We analyzed the age, gender, and initial HR and used it to match groups. We analyzed the mode and time of administration, dosage of the bolus, and presence of hypotension prehospitally.
UNASSIGNED: The matched groups contained 145 patients who received a prehospital diltiazem bolus only (BO) and 146 patients who received a diltiazem bolus and infusion (BI). There was no significant difference between the mean change in HR from initial paramedic arrival to ED arrival between the two groups (BO 38 vs. BI 34, p = 0.16). There was no significant difference in the need for a second bolus within the first 60 min of arrival to the ED (BO 9.7% vs. BI 11.6%, p = 0.30). Patients in the BO group were more likely to experience prehospital hypotension then in the BI group (BO 17.2% vs BI 8.2%, p = 0.01), despite receiving smaller initial bolus doses (BO 14.2 mg vs. BI 17.4 mg, p < 0.001).
UNASSIGNED: Our results show no significant differences in HR control or need for repeat bolus at the ED with the use of a diltiazem infusion following a diltiazem bolus. However, even when administering larger boluses, the use of an infusion pump resulted in less hypotension.

This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate, focusing on rate control efficacy and hemodynamic adverse events. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, electronic searches were conducted in Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) until February 20, 2024. The primary outcome was achieving ventricular rate control < 110/min. Secondary outcomes included new hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (heart rate < 60/min). Nineteen studies (three randomized controlled trials and 16 observational studies) were included in this meta-analysis. Pooled analysis showed intravenous metoprolol resulted in a 39% lower rate control attainment compared to diltiazem (OR: 0.61; 95% CI: 0.44 to 0.84; p = 0.002). There were no significant differences in bradycardia (OR: 0.51; 95% CI: 0.22 to 1.22; p = 0.13) or hypotension risk (OR: 1.08; 95% CI: 0.72 to 1.61; p = 0.72) between the two groups. Intravenous diltiazem demonstrated superior rate control efficacy compared to metoprolol in AF patients with rapid ventricular rate. However, no significant differences were observed in safety outcomes, namely, bradycardia and hypotension.

This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP\'s carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP\'s potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.