A Brief Review of a Common Clinical Question: Intravenous Diltiazem or Metoprolol for Atrial Fibrillation with Rapid Ventricular Response?

Two classes of rate controlling medications—beta blockers (BBs) and non- dihydropyridine calcium channel blockers (CCBs)—are given to patients who present with atrial fibrillation (AF) with rapid ventricular response (RVR). Both are Class I recommendations from the American Heart Association (AHA), American College of Cardiology (ACC), and Heart Rhythm Society (HRS) for the management of AF with RVR. Multiple studies support the view that diltiazem is more effective than metoprolol, even though data from the AFFIRM trial suggests BBs are more frequently used. CCBs are generally avoided in AF with RVR patients who have concomitant heart failure with reduced ejection fraction (HFrEF) for concern of triggering decompensation. However, some recent studies indicate this idea may be unfounded. The aim of this article is to compare the efficacy of diltiazem and metoprolol for rate control in AF with RVR and examine the use of diltiazem in patients with both AF with RVR and HFrEF.

The effects of diltiazem in renal transplantation patients treated with cyclosporine A

Objective： To investigate the effects of diltiazem and cyclosporine A （CsA） combination therapy on protecting the kidney, promoting graft functioning and improving post-transplanted kidney recovery. Methods： The blood con- centrations of CsA, the condition of the post-transplant kidney, the rate of acute rejection （AR）, as well as hepatic and renal toxicity in 636 cases of renal transplant recipients were determined after being treated by CsA, with or without diltiazem. Results： Compared with the control group which received CsA, mycophenolate mofetil （MMF） and prednisolone （Pred） but lacked diltiazem, the group receiving these agents together with diltiazem required reduced dosage of CsA （P 〈 0.01）, while blood concentrations of CsA were significantly increased （P 〈 0.01）; the recovery time of graft function was reduced from （6.2± 1.5） d to （3.9± 1.4） d （P 〈 0.01）, and the rate of AR was decreased from 13.2% to 7.9% （P 〈 0.01）. Conclusion： In renal transplantation patients treated with CsA and diltiazem, blood concentrations of CsA were increased while the dosage was decreased. This efficient combination therapy reduced patients economic burden, at the same time retained kidney function, promoted graft function recovery and decreased hepatic and renal toxicity and the rate of AR.

Validated gradient stability indicating HPLC method for determining Diltiazem Hydrochloride and related substances in bulk drug and novel tablet formulation

A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride(DTZ) together with its six related substances(Diltiazem sulphoxide,Imp-A,Imp-B,Imp-D,Imp-E,and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house.Efficient chromatographic separation was achieved on a Hypersil BDS C18(150 mm*4.6 mm,5.0 μm) with mobile phase containing 0.2% Triethylamine(TEA) in gradient combination with acetonitrile(ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm.In the developed method,the resolution of DTZ from any pair of impurities was found to be greater than 2.0.The test solution and related substances were found to be stable in the diluent for 24 h.The developed method resolved the drug from its known impurities,stated above,and also from additional impurities generated when the formulation was subjected to forced degradation;the mass balance was found close to 99.9%.Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities.The LOD for DTZ and the known impurities was at a level below 0.02%.The method has shown good,consistent recoveries for DTZ(99.8-101.2%) and also for its six known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and stability-indicating.

Rhabdomyolysis induced by simvastatin-diltiazem interaction in unrecognized hypothyriodism

Simvastatin,a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,is widely prescribed to patients with hypercholesteremia and its muscular toxicity has been widely reported.The metabolism of simvastatin depends on the enzymic activity of cytochrome P450 3A4 （CYP3A4） and inhibitors of CYP3A4 can result in clinical events by interacting with simvastatin.Diltiazem is a moderate inhibitor of CYP3A4,which is known to increase the serum concentration of simvastatin.Here we report a patient with unrecognized hypothyroidism who had been stable for more than one year on low-dose simvastatin therapy of hypercholesteremia and rhabdomyolysis occurred with the addition of diltiazem.This is one of scanty reports of rhabdomyolysis induced by simvastatindiltiazem drug interaction,especially in hypothyroid patient.This case reminds the clinicians that although diltiazem as a moderate CYP3A4 inhibitor can be used cautiously with small doses of CYP3A4-dependent statius （eg,simvastatin）,these two commonly used drugs should be avoided in hypothyroid patient.

Preparation and evaluation of sustained-release diltiazem hydrochloride pellets

In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with Eudragit
NE30D were similar to Herbesser
,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesser
was 98.5
36.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.

Quality of compounded topical 2% diltiazem hydrochloride formulations for anal fissure

AIM:To investigate the quality of topical 2%diltiazem formulations extemporaneously compounded by retail pharmacies openly offering drug-compounding services.METHODS:A participating healthcare professional wrote 12 prescriptions for compounded 2%diltiazem cream,with 2 refills allowed per prescription.The 12sets of prescriptions were filled,at intervals of 1-2 wk between refills,at 12 different independent retail pharmacies that openly offer drug-compounding services in a major metropolitan region.The 36 resultant preparations,provided as jars or tubes,were shipped,as soon as each was filled,at ambient temperature to the study core laboratory for high-performance liquid chromatography(HPLC)analysis,within 10 d of receipt.For the HPLC analysis,8 different samples of the topical diltiazem,each approximately 1 g in weight,were taken from prespecified locations within each container.To initiate the HPLC analysis,each sample was transferredto a 100 mL volumetric flask,to which methanol was added.The HPLC analysis was conducted in accordance with the laboratory-validated method for diltiazem in cream,ointment,and gel formulations.The main outcome measures were potency(percentage of label claim)and content uniformity of the compounded topical 2%diltiazem formulations.RESULTS:Of the 36 prescriptions filled,30 were packaged in jars and 6 were packaged as tubes.The prescriptions were specifically for cream formulations,but6 of the 12 pharmacies compounded 2%diltiazem as an ointment;for another pharmacy,which had inadequate labeling,the dosage form was unknown.The United States Pharmacopoeia(USP)standard for potency is 90%-115%of label claim.Of the 36 preparations,5(13.89%)were suprapotent and 13(36.11%)were subpotent.The suprapotent prescriptions ranged in potency from 117.2%to 128.5%of label claim,and the subpotent prescriptions ranged in potency from34.8%to 89.8%of label claim.Fourteen(38.9%)preparations lacked content uniformity according to the USP standard of 90%-110%potency and<6%relative standard deviation.Of the 30 formulations packaged in jars,12(40%)lacked content uniformity,while of the6 formulations packaged in tubes,2(33.3%)lacked content uniformity.Nine of the 12 pharmacies(75%)failed USP potency or content-uniformity specifications for at least 1 of the 3 prescription fills.For 5 of the 12pharmacies(41.7%),the mean potency across all three prescription fills was<90%of label claim.CONCLUSION:Patients prescribed topical 2%diltiazem for treatment of anal fissure frequently receive compounded formulations that are misbranded with respect to potency and that lack content uniformity.

Quality of life in patients with chronic anal fissure after topical treatment with diltiazem

AIM: To assess the physical and mental health of fissure patients before and after topical treatment with diltiazem. METHODS: Consecutive patients were enrolled prospectively into the study. Quality of life was measured with the short-forum 36 health survey (SF-36) before and after 6-wk treatment with diltiazem. Patients scored symptoms of pain, bleeding, and irritation using numeral rating scales at the initial and follow-up visits. Fissure healing was assessed and side effects were noted. RESULTS: Fissures healed in 21 of 30 (70%) patients. There were significant reductions in the scores of pain, bleeding, and irritation after 1 wk of treatment, respectively. Four patients experienced perianal itching and one patient reported headache. When measured at baseline, pain and irritation showed a negative impact on two of the eight subscales on the SF-36, respectively (bodily pain and social functioning for pain; vitality and mental health for irritation). Repeating the SF-36 showed an improvement in bodily pain (P = 0.001). Patients whose fissures healed reported an improvement in bodily pain, health-perception, vitality, and mental health (P < 0.05). CONCLUSION: Successful treatment of chronic anal fissure with topical diltiazem leads to improvement in health-related quality of life.

Effect of diltiazem and lidocaine on arterial pressure or heart rate and the quality of extubation in patients undergoing uvulopalatopharyngoplasty

Objective：To evaluate the effect of diltiazem and lidocaine on arterial pressure or heart rate and the quality of extubation in patients undergoing uvulopalatopharyngoplasty. Methods： Sixty patients were randomly divided into 4 groups： In the control group patients were given saline; in the lidocaine group patients were given 1.0 mg/kg lidocaine ; in the diltiazem group patients were given 0. 2 mg/kg diltiazem; and in the lidocaine plus diltiazem group patients were given 1.0 mg/kg lidocaine and 0. 2 mg/kg diltiazem. These drugs were given 2 rain before tracheal extuhation. Values for SBP, DBP, and HR were recorded, on arriving at the operating room, immediately at the end of the surgery, at the time of injection of the study drugs, at tracheal extubation, at 1 min and 5 min after extubation. The quality of extubation according to the Sebel＇s grading scale were compared among the 4 groups. Results：During extubation in the control group HR, SBP and DBP increased significantly when compared to baseline levels. Both lidocaine （1.0 mg/kg） and diltiazem （0. 2 mg/kg） successfully alleviated these increases. The suppressive effect of diltiazem was greater than that of lidocaine. The combinative use of the two drugs minimized the increases. The administration of lidocaine significantly suppressed bucking or coughing compared with the other groups. Conclusions： The pressor responses and tachycardia occurring in patients with uvulopalatopharyngoplasty during emergence from anesthesia and tracheal extubation, can be easily blocked by a bolus dose of 1.0 mg/kg lidocaine, 0. 2 mg/kg diltiazem or the comhinative use of the two drugs. And the concurrent use of lidocaine and diltiazem alleviated the hemodynamic changes more obviously.

Design and in vitro evaluation of controlled release alginate beads of diltiazem hydrochloride

Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compliance by prolonging dosing intervals.The major drawback of orally administered drug like diltiazem as a calcium channel blocker for the treatment of angina pectoris,arrhythmia and hypertension.Its has higher aqueous solubility and shorter elimination half-life.Methods:To overcome these drawbacks associated with diltiazem,an attempt has been made to develop a sustained release dosage form of diltiazem embedded alginate microbeads by ionotropic gelation technique employing various concentrations of polymer and keeping the drug concentration constant.Results:The beads were characterized for its particle size,drug content and in vitro release studies. The results revealed that the surface adhering drug was found to release immediately and a steady state of release was obtained up to 12 h from all the batches.The results indicated there was an inverse relationship between the concentration of alginate and drug release.The drug release was found to follow non-fickian diffusion obeying first order kinetics.Conclusion:The developed alginate microbeads offered a sustained release of diltiazem. Hence,the formulated microbeads were found to be potential,cost effective,possess satisfactory in vitro release studies.

Effect of calcium and diltiazem on phenylhydrazine-induced oxidative injury in goat erythrocytes

Lipid peroxidation, hemolysis and thiol contents were studied in intact goat erythrocytes exposed to phenylhydrazine. An increase in lipid peroxidation, hemolysis and thiol content was observed after phenylhydrazine treatment of erythrocyte. Extracellular Ca2+ potentiates the phenylhydrazine-induced lipid peroxidation and hemoly- sis of erythrocytes significantly. Ca2+ does not influence much the thiol content of phenylhydrazine treated erythrocytes. No effect of Ca2+ on control lipid peroxidation, hemolysis and thiol contents of erythrocytes was observed. Diltiazem and EDTA inhibited the increased responses of lipid peroxidation and hemolysis due to Ca2+. However the thiol content was not much influenced by either diltiazem or EDTA. The results suggest that oxidative damage of erythrocyte caused by phenyl hydrazine could be prevented by calcium channel antagonist, diltiazem, which may act as antioxidant also.

静脉应用地尔硫?治疗老年肺源性心脏病心衰伴心房颤动的临床疗效分析

目的 探究老年肺源性心脏病心衰伴心房颤动采用地尔硫?静脉应用治疗的效果。方法 选择2022年3月至2023年6月在临沂市中心医院住院治疗的84例老年肺源性心脏病心衰伴心房颤动患者。将所有患者采用信封抽签法分为治疗组以及对照组,每组42例。对照组应用去乙酰毛花苷注射液,治疗组应用地尔硫?治疗,观察两组治疗前后的血压、心率和血流动力学指标,对比两组的临床疗效。结果 治疗后,治疗组收缩压、心率低于对照组(P<0.05),两组舒张压对比差异无统计学意义(P>0.05)。治疗前两组患者的MPAP水平差异无统计学意义(P>0.05);治疗后治疗组MPAP水平低于对照组(P<0.05)。治疗组治疗总有效率高于对照组(90.48%vs.71.43%,χ^(2)=4.941,P=0.026)。结论 静脉应用地尔硫?治疗老年肺心病心衰伴心房颤动是安全有效的药物,可以帮助患者控制心室率,提高心功能,进而提升整体的临床效果。

盐酸地尔硫䓬异构体杂质合成研究

介绍重要心血管药物盐酸地尔硫䓬特性用途,叙述了盐酸地尔硫䓬合成过程中重要中间体(2S-cis)-(+)-2,3-二氢-3-羟基-2-(4-甲氧苯基)-1,5-苯并硫氮杂䓬-4(5H)-酮需要控制的3个异构体的制备方法,该方法收率高,成本低,操作简单,为制备盐酸地尔硫䓬中间体异构体杂质对照品提供了有效制备方法。

富马酸比索洛尔联合地尔硫卓对冠心病心绞痛患者心绞痛发作情况及血管内皮功能的影响

目的探讨富马酸比索洛尔联合地尔硫卓在冠心病心绞痛(CAP)患者中的应用效果。方法选择该院2022年9月—2023年9月收治的84例CAP患者为研究对象,按随机数字表法将患者分为对照组和观察组,各42例。对照组采用富马酸比索洛尔治疗,观察组采用富马酸比索洛尔联合地尔硫卓治疗,两组均持续治疗3个月。对比两组的心绞痛发作情况、血管内皮功能、临床疗效、不良反应发生情况。结果与对照组相比,观察组心绞痛发作次数较少,疼痛视觉模拟评分较低,持续时间较短,组间差异有统计学意义(P<0.05)。治疗后,观察组一氧化氮水平高于对照组,内皮素、血管内皮生长因子水平均低于对照组,组间差异有统计学意义(P<0.05)。观察组治疗总有效率为4.76%,高于对照组的19.05%,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论富马酸比索洛尔联合地尔硫卓在CAP患者中具有较好的应用效果,有利于改善心绞痛发作情况,改善血管内皮功能,提升临床疗效,且不会增加不良反应的发生,应用安全性较好。

Expression of receptor for advanced glycosylation end products(AGEP)and inhibition of AGEP-induced cytosolic calcium elevationbydiltiazeminculturedrataorticsmoothmusclecels

目的：探讨培养的主动脉平滑肌细胞（ＡＳＭＣ）上是否表达糖基化终产物（ＡＧＥＰ）高亲性受体和地尔硫对ＡＧＥＰ升高胞浆游离钙的抑制．方法：用放射配基结合方法研究ＡＳＭＣ与ＡＧＥＰ的相互作用；用钙离子荧光指示剂Ｆｕｒａ２ＡＭ测定ＡＳＭＣ胞浆游离钙．结果：ＡＳＭＣ上有ＡＧＥＰ高亲和性受体表达，其解离常数为６５３±１５ｎｍｏｌ·Ｌ－１，最大结合容量１５７±００４ｎｍｏｌ／ｇ细胞蛋白；通过该受体介导，平滑肌细胞可内化、代谢ＡＧＥＰ．ＡＧＥＰ使胞浆游离钙呈浓度依赖性升高；地尔硫呈时间、浓度依赖性抑制此效应．结论：大鼠ＡＳＭＣ上有ＡＧＥＰ高亲和性受体表达；地尔硫可抑制ＡＧＥＰ介导的胞浆游离钙升高．

地尔硫卓对冠心病心绞痛患者冠状动脉血流储备与血管内皮的影响

目的探讨地尔硫卓对冠状动脉粥样硬化性心脏病(冠心病)心绞痛患者冠状动脉(冠脉血流储备与血管内皮的影响。方法选自2018年1月至2021年12月于郑州市第七人民医院心脏外科收治的100例冠心病心绞痛患者随机分成对照组(富马酸比索洛尔治疗)与观察组(富马酸比索洛尔+地尔硫卓治疗),每组各50例,均治疗4周。观察两组的心绞痛发生情况(发作次数、疼痛程度、持续时间)、冠脉血流储备(D/R PDV、D/R PSV)、血管内皮指标(内皮素-1、血管内皮生长因子、一氧化氮)、临床疗效以及不良反应(恶心呕吐、头晕头痛、疲倦、失眠、皮疹)。结果观察组患者的心绞痛发作次数、疼痛程度评分、持续时间均低于对照组(P<0.05);两组治疗后的D/R PDV、D/R PSV均较治疗前增加(P<0.05),且观察组治疗后的D/R PDV、D/R PSV均高于对照组(P<0.05);两组治疗后的内皮素-1、血管内皮生长因子均降低(P<0.05),一氧化氮升高(P<0.05),且观察组治疗后的内皮素-1、血管内皮生长因子均低于对照组(P<0.05),一氧化氮高于对照组(P<0.05);观察组总有效率为86.00%,高于对照组的68.00%(P<0.05);两组不良反应发生率比较,无统计学差异(P>0.05)。结论地尔硫卓联合富马酸比索洛尔对冠心病心绞痛的疗效确切,可减少患者心绞痛的发作次数、持续时间,减轻疼痛程度,并能改善冠脉血流储备,减轻血管内皮损伤,有效性与安全性均较好,值得临床应用。

rhBNP联合地尔硫卓治疗对急性心肌梗死合并心力衰竭患者心率变异性及住院期间MACE发生率的影响

目的探究重组人B型钠尿肽(rhBNP)联合地尔硫卓对急性心肌梗死合并心力衰竭患者心率变异性(HRV)及住院期间不良心血管事件(MACE)发生率的影响。方法将182例急性心肌梗死合并心力衰竭患者随机分为对照组和观察组,对照组给予常规治疗,观察组在对照组基础上给予rhBNP联合地尔硫卓治疗;观察两组临床疗效,比较治疗前后心功能指标、HRV指标及相关实验室指标的变化,并统计患者住院期间MACE发生情况。结果观察组总治疗有效率为89.01%,高于对照组(P<0.05)。治疗后,两组LVEF均高于同组治疗前,LVEDV和LVESV均低于同组治疗前,且观察组LVEF高于对照组,LVEDV和LVESV低于对照组(P<0.05)。治疗后,对照组SDNN、SDANN、RMSSD及PNN50较治疗前均有所提高,仅SDNN和PNN50治疗前后比较有统计学意义(P<0.05);观察组治疗后上述指标均明显高于治疗前,且高于对照组(P<0.05)。治疗后,两组NT-proBNP、hs-CRP及Cr低于同组治疗前,且观察组上述指标低于对照组(P<0.05)。治疗期间,两组患者均未出现明显不良反应;住院期间,观察组MACE发生率为6.59%,低于对照组(P<0.05)。结论rhBNP联合地尔硫卓可明显改善急性心肌梗死合并心力衰竭患者心功能,提高HRV,降低MACE发生率,安全性高。

地尔硫䓬联合美托洛尔治疗冠心病不稳定型心绞痛的效果及对患者心功能的影响

目的 探讨地尔硫䓬联合美托洛尔治疗冠心病不稳定型心绞痛的效果。方法 选择2020年2月至2021年2月我院诊治的80例冠心病不稳定型心绞痛患者作为研究对象,将其随机分为对照组(40例,美托洛尔)与观察组(40例,地尔硫䓬联合美托洛尔)。比较两组的治疗效果。结果 观察组的治疗总有效率高于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的左室射血分数高于对照组,左室收缩末期内径、左室缩短分数小于对照组(P<0.05)。治疗后,观察组的组织型纤溶酶原激活物(t-PA)、高密度脂蛋白胆固醇(HDL-C)水平高于对照组,纤溶酶原激活剂抑制物-1(PAI-1)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平低于对照组(P<0.05)。结论 地尔硫䓬联合美托洛尔治疗冠心病不稳定型心绞痛的效果显著,值得临床推广与应用。

1例儿童系统性红斑狼疮的治疗与用药分析

临床药师参与1例系统性红斑狼疮患儿的治疗,并制定他克莫司个体化分剂量给药方案,从基因多态性角度分析他克莫司血药浓度偏低的原因,并对应用地尔硫提高他克莫司血药浓度这一超说明书用药的合理性进行评估。患儿经过个体化治疗后,他克莫司血药浓度达标,疗效稳定且未出现不良反应,同时给药便利性提高,经济负担减轻。

Intraoperative sudden arrhythmias in cervical spine surgery adjacent to the stellate ganglion:A case report

BACKGROUND Atrial arrhythmias such as paroxysmal supraventricular tachycardia(PSVT)and atrial flutter(AF)are common in the perioperative setting.They commonly resolve spontaneously.However,occasionally,they may continually progress to fatal arrhythmias or cause complications.Therefore,prompt and appropriate management is important.CASE SUMMARY A 46-year-old female patient diagnosed with cervical C6-7 radiculopathy characterized by decreased sensation in the right third,fourth and fifth fingers underwent C6-7 anterior cervical disc fusion surgery.Electrocardiography showed PSVT and ventricular tachycardia during C6-7 disc retraction.However,the patient remained stable.Initial treatment with esmolol and lidocaine for ventricular tachycardia was ineffective.Carotid massage and Valsalva maneuver were attempted but PSVT did not resolve.The surgery was paused,and the patient’s fraction of inspired oxygen was set to 100%.Adenosine was administered for pharmacological management of PSVT.The arrhythmia temporarily resolved.However,it then transformed into AF.Diltiazem was administered,which briefly decreased blood pressure,which immediately recovered.Surgery resumed while the patient was in normal sinus rhythm.She was discharged safely on postoperative day 6 without complications or abnormalities.Currently,she is living a healthy life without arrhythmia recurrence.CONCLUSION Ganglia associated with cardiac arrhythmias in the surgical site should be identified during cervical spine surgery.