Analysis of the Efficacy of Low-Dose Betaloc Combined with Amiodarone in Treating Ventricular Arrhythmia

Objective:To explore and analyze the clinical effect of low-dose Betaloc combined with amiodarone in treating ventricular arrhythmia.Methods:70 patients with ventricular arrhythmia who were admitted to the Department of Cardiology of our hospital between August 2022 and August 2023 were selected as research subjects.They were divided into two groups using the coin-tossing method:the combination group(n=35)and the reference group(n=35).The combination group was treated with low-dose Betaloc and amiodarone,and the control group was treated with low-dose Betaloc alone.The treatment efficacy,cardiac function indicators,and related tested indicators of the two groups were compared.Results:The total efficacy of the treatment received by the combination group was much higher than that of the control group(P<0.05).Besides,after treatment,the cardiac function indicators such as left ventricular ejection fraction(LVEF),left ventricular end-systolic volume(LVESV),and cardiac index(CI)of the patients in the combination group were significantly better than those of the reference group(P<0.05).Furthermore,the high-sensitivity C-reactive protein(Hs-CRP),N-terminal prohormone of brain natriuretic peptide(NT-proBNP),adiponectin(APN),and other related test indicators of the patients in the combination group were significantly better than those of the reference group(P<0.05).Conclusion:Low-dose Betaloc combined with amiodarone has a noticeable effect in treating ventricular arrhythmia and deserves to be widely promoted.

Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids

Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.

Clinical Effect Analysis of Small and Medium Doses of Betaloc Combined with Amiodarone in the Treatment of Ventricular Arrhythmia

Objective:To explore and analyze the clinical effect of small and medium doses of Betaloc combined with amiodarone in the treatment of ventricular arrhythmia.Methods:60 patients with ventricular arrhythmia that were treated in the Department of Cardiology of our hospital from May 2018-May 2023 were selected for this study,and they were divided into a research group(n=30)and a reference group(n=30).The study group was treated with small doses of Betaloc and amiodarone,while the reference group was treated with conventional treatment.The total efficacy of medication,QRS interval,standard deviation of normal-to-normal(NN)intervals(SDNN),root mean square of successive differences between normal heartbeats(RMSSD),standard deviation of the average NN intervals(SDANN),and incidence of adverse reactions were compared between the groups.Results:The effectiveness of medication in the study group was significantly higher than that in the reference group(P<0.05).Besides,there was no statistically significant difference(P>0.05)in the QRS interval and SDNN between the two groups before treatment.After treatment,the QRS interval and SDNN of the study group were significantly lower than those of the reference group(P<0.05).Before treatment,there was no significant difference in RMSSD and SDANN between groups(P>0.05).After treatment,RMSSD and SDANN in the study group were significantly better than those in the reference group(P<0.05),and the difference was statistically significant.The incidence of adverse reactions in the study group was significantly lower than that in the reference group(P<0.05),and the difference was statistically significant.Conclusion:Small doses of Betoprolol and amiodarone is more effective in the treatment of ventricular arrhythmia,which has the value of popularization and application.

Adverse reactions of Amiodarone

Adverse drug reaction is defined by the World Health Organization as any response to a drug that is noxious and unintended and occurs at a dose normally used in man.Older people are at elevated risk of adverse drug reactions—because of changes in pharmacodynamics,concurrent use of multiple medications and the related drug interactions.However,adverse drug reactions are significantly underestimated in the elderly population that is also exposed to inappropriate drugs.Amiodarone is an antiarrhythmic drug used commonly for the treatment of atrial fibrillation and is increasingly prescribed in older people.While amiodarone is an efficient drug for rhythm control,it’s a carrier of different adverse reactions,and pro and cons must be carefully evaluated before its use especially in older people.

Effect of Lidocaine and Amiodarone on Transmural Heterogeneity of Ventricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

Summary： To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups： control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential （MAP） recording technique, MAPs of epicardium, midmyocardium and endocardium were simultaneously recorded across the left ventricular free wall in rabbit hearts perfused by low-flow ischemia （2. 5 mL/min） in Langendorff method to study the transmural dispcrsion of repolarization （TDR） and arrhythmic induced by ischemia.Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group （62. 5%）, but no case in lidocaine group （P〈0.01） and only 1 case in amiodarone group had ventrilar arrhythmia （P〈 0.01）. No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.

N-acetylcysteine treats intravenous amiodarone induced liver injury

We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver enzymes.While the specific mechanisms for the pathogenesis of IV amiodaroneDILI and the therapeutic action of IV NAC are both unknown, this case strongly implies at least some commonality.Because IV amiodarone is indicated for the treatment of serious cardiac arrhythmias in an intensive care unit setting, some degree of ischemic hepatitis is likely a cofactor in most cases.

Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone: A case report

The anti-arrhythmic agent amiodarone （AD） is associated with numerous adverse effects, but serious liver disease is rare. The improved safety of administration of daily low doses of AD has already been established and this regimen is used for long-term medication. Nevertheless, asymptomatic continuous liver injury by AD may increase the risk of step-wise progression of non-alcoholic fatty liver disease. We present an autopsy case of AD-induced liver cirrhosis in a patient who had been treated with a low dose of AD （200 rag/d） daily for 84 too. The patient was a 85-year-old male with a history of ischemic heart disease. Seven years after initiation of treatment with AD, he was admitted with cardiac congestion. The total dose of AD was 528 g. Mild elevation of serum aminotransferase and hepatomegaly were present. Liver biopsy specimens revealed cirrhosis, and under electron microscopy numerous lysosomes with electron-dense, whorled, lamellar inclusions characteristic of a secondary phospholipidosis were observed. Initially, withdrawal of AD led to a slight improvement of serum aminotransferase levels, but unfortunately his general condition deteriorated and he died from complications of pneumonia and renal failure. Long-term administration of daily low doses of AD carries the risk of progression to irreversible liver injury. Therefore, periodic examination of liver function and/or liver biopsy is required for the management of patients receiving long-term treatment with AD.

Acute hepatitis secondary to parenteral amiodarone does not preclude subsequent oral therapy

Amiodarone chlorhydrate is a diiodated benzofuran derivative used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone and symptomatic hepatic dysfunction occurs in less than 1% to 3% of patients taking amiodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity. A 29 year old woman with normal liver function was given amiodarone intravenously to treat her atrial fibrillation. She developed acute toxic hepatitis after 24 h. The intravenous form of amiodarone was immediately avoided and replaced by the oral form, using conventional loading doses as soon as the deranged liver function tests had normalized, without recurrence of the hepatitis. These observations show that the occurrence of acute hepatic impairment with intravenous amiodarone does not necessarily preclude the use of this drug by mouth and the necessity of monitoring the hepatic function of patients treated with amiodarone.

Ameliorative effect of grapefruit juice on amiodarone-induced cytogenetic and testicular damage in albino rats

Objective:To evaluate the ameliorative role of grapefruit juice on the cytogenetic and testicular damage induced by the antiarrythmic drug amiodarone in albino rats.Methods:Animals were divided into four groups.Group I was considered as control.Group II was given grapefruit juice at a dose level of 27 mL/kg body weight.Group III was orally administered amiodarone(18 mg/kg body weight)daily for 5 weeks.Animals were sacrificed after 5 weeks of treatment.Bone marrow was collected from the femurs for analysis of chromosomal aberrations and mitotic indices.Testes were removed and stained with H&E for histological examination.Sperms were collected from epidedymis for detection of sperm head abnormalities.Comet assay was used to detect DNA damage.Results:Amiodarone treatment caused a significant increase in the percentage of chromosomal aberrations,decreased the mitotic index and increased DNA damage.The testis showed many histopathological alterations,inhibition of spermatogenesis and morphometric changes.The number of sperm head abnormalities was increased.Treating animals with amiodarone and grapefruit juice caused a reduction in chromosomal aberrations,mitotic index,DNA damage and testicular alterations caused by amiodarone.Conclusions:The results of this study indicated that grapefruit juice ameliorates the cytotoxicty and testicular alterations induced by amiodarone in albino rats and this is may be due to the potent antioxidant effects of its components.

Acute pancreatitis and amiodarone:A case report

Amiodarone, a class Ⅲ antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia. Adverse effects of amiodarone including pulmonary toxicity, hepatotoxicity, aggravation of arrhythmia, and thyroid diseases are well understood. A 66-year old woman with acute pancreatitis was admitted to our hospital with the complaint of epigastralgia radiating to both flanks for two months. Her symptoms and elevation of pancreatic enzymes did not respond to conventional medical treatment of pancreatitis for 18 d. No known causal factors for pancreatitis such as biliary tract stone, hypertriglyceridemia and alcohol consumption could be identified. Under the suspicion of amiodarone-induced acute pancreatitis, amiodarone was substituted by propafenone. Her symptoms soon alleviated and serum lipase level declined. Three months after hospital discharge, the abdominal pain did not recur. Amiodarone was approved to treat recurrent ventricular fibrillation or sustained ventricular tachyarrhythmia that has been resistant to other medications since 1986. Pancreatitis is a very rare adverse effect associated with the use of amiodarone, and only four cases of amiodarone-induced pancreatitis have been reported in literature. We report a patient who developed acute pancreatitis during amiodarone therapy.

Amiodarone-induced hepatotoxicity-quantitative measurement of iodine density in the liver using dual-energy computed tomography:Three case reports

BACKGROUND Amiodarone is the drug most commonly used to manage arrhythmias.Long-term amiodarone administration causes hepatotoxicity due to iodine accumulation in the liver.Here,we present three cases of amiodarone-induced hepatotoxicity in patients on long-term oral amiodarone therapy who underwent dual-energy computed tomography(DECT).CASE SUMMARY We report the clinical and iodine density in the liver using DECT in three patients with amiodarone-induced hepatotoxicity.Liver enzymes were increased in these three patients,and abdominal DECT without contrast medium showed highly increased attenuation in the liver.Furthermore,the iodine concentration in the liver was increased.The first patient with amiodarone-induced reversible hepatotoxicity,showed a reversible course of liver function and a decrease in CT values after discontinuation of amiodarone.The second patient on long-term oral amiodarone had increased iodine concentration in the liver and liver damage,the patient eventually developed rapidly progressive pneumonia and died of multiple organ failure.The third patient,showed an increased iodine concentration in the liver and elevated liver enzymes.However,the patient refused radiofrequency ablation for atrial fibrillation and continued oral amiodarone to control atrial fibrillation,and routine liver function tests were required every 3-6 mo in this patient.CONCLUSION DECT is a potentially noninvasive diagnostic tool for quantifying iodine concentration in the liver and monitoring adverse reactions due to amiodarone.

Amiodarone hepatotoxicity complicating obstructive jaundice due to ampullary cancer

BACKGROUND:The presence of dual pathology can cause diagnostic dilemmas. We present a case of adenocarcinoma of the ampulla of Vater with concurrent amiodarone hepatotoxicity. METHODS:Painless jaundice associated with a palpable gallbladder was investigated clinically,radiologically endoscopically and via liver biopsy. RESULTS:Liver biopsy showed amiodarone hepatotoxicity Endoscopic biopsy identified an ampullary adenoma However,the endoscopic ultrasound and intra-operative findings suggested a malignancy,which was confirmed postoperatively. CONCLUSIONS:While the classic findings of Courvoisier’s Law are borne out in this case,the etiology of jaundice is twofold. Although dual pathology is uncommon it should always be considered.

Amiodarone-induced muscle tremor in an elderly patient:A case report

BACKGROUND Amiodarone is a Class III antiarrhythmic drug,which has been adopted for the treatment of atrial fibrillation and ventricular arrhythmia.However,the use of amiodarone can cause lower limb muscle tremors,which is recognized as a rare side effect of this medication.CASE SUMMARY An 84-year-old female was administrated with amiodarone for paroxysmal supraventricular tachycardia and frequent ventricular tachycardia.The patient developed a bilateral gastrocnemius tremor in the course of medication,and the strength of the patient’s bilateral knee flexor and extensor reached 4/5 and 3/5,respectively.After the use of amiodarone was stopped,and the patient was given a small dose of levetiracetam,the lower limb tremor symptoms were significantly mitigated,along with activity and function.CONCLUSION Attention should be paid to the significance of the side effects of drugs in the elderly,which may be atypical in the elderly.The relevant side effects of drugs may not be as rare as reported due to individual differences and different pharmacokinetics.If the side effects are generated,the medication should be adjusted in time,and the progress of the side effects should be intervened.

Amiodarone Modulation of Intracellular Transport of Calcium Ions in Cardiomyocites

The influence of amiodarone on intracellular transport of calcium ion in cardiomyocytes of rat was investigated. The experiments were performed on isolated papillary muscles of Wistar rats. Force-frequency dependence (0.7, 1, 2, 3, 4 Hz), extrasystolic and postextrasystolic contractions and post-rest (4-60 s) reactions of rat myocardium after amiodarone treatment (1 μM) were investigated. Decay potentiation coefficient of contraction force was estimated. Results. The analyses of force-frequency dependence has shown that amiodarone prevent the decreasing of the force contraction at increasing of the stimulation frequency. Amiodarone promotes increase of the time constant t1(T50), that indicate the drug promotes acceleration of Са2+ transport inside the SR resulting increase of Са2+ in the places of its release from the sarcoplasmic reticulum (SR). Treatment of papillary muscle with amiodarone decreased amplitude of extrasystolic contractions. As known, postextrasystolic and post-rest reactions of myocardium characterize the SR function. We have found amiodarone increased potentiation of postextrasystolic and post-rest contractions. Preliminary caffeine perfusion of muscles preparations cancelled the amiodarone-induced increasing postextrasystolic and post-rest potentiation. However, potentiation decay coefficient before and after treatment with amiodarone didn’t have difference. Conclusions, amiodarone influences on intracellular calcium ions homeostasis by modulation SR functions related with most likely are stipulated either by activation of Са2+ transport from uptake sites to release sites or by prevent of Са2+ leakage from the SR.

Amiodarone Therapy for Cardiac Arrhythmias: Is It Associated with the Development of Cancers?

Amiodarone is used worldwide to treat cardiac arrhythmias, as well as highly symptomatic cases of atrial fibrillation. With this expanded use, especially following its 1985 United States Food and Drug Administration approval, and its use as a long-term therapy in common practice, reports of cancers temporarily related to amiodarone have begun to increase. Animal studies, several clinical trials, numerous case reports, and a population-based cohort study have suggested that cancers may be associated with amiodarone use. This review focuses on the ever increasing evidence in the literature that suggests amiodarone therapy, especially with long-term use, may increase the potential risk of cancer development. It also expresses the need for more definitive studies to be conducted to provide clinicians with a clear answer to this important question.

A Chinese Compound Prescription Ding Xin Recipe Combined with Amiodarone for Treating Premature Ventricular Complexes: A Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial

Objective To evaluate the efficacy and safety of Ding Xin Recipe(DXR)combined with amiodarone in patients with PVCs.Methods A total of360patients with PVCs across7centers in China were randomly assigned in a1:1:1ratio to receive up to8weeks of amiodarone combined with DXR placebo(amiodarone group),DXR combined with amiodarone placebo(DXR group),or DXR combined with amiodarone(DCA group)from July2012to December2013.Randomization was conducted according to a centralized randomization schedule prepared by an independent steering committee.Staff and patients at all sites were masked to treatment allocation.All patients received best-evidence advice.The primary outcome was the efficacy for treating PVCs,with efficacy assessed by the reduction of premature ventricular contractions.Other outcome measures included PVCs-related symptom scores.All data were analyzed by intention to treat.Results The efficacy for treating PVCs in the DCA group(90.7%)significantly increased compared with that in the amiodarone group(72.3%)and the DXR group(73.9%).The frequency,the degree,and the duration per week of heart palpitations,chest tightness,shortness of breath and fatigue improved significantly in the DCA group in comparison with the amiodarone group and the DXR group(P<0.05),while no significant difference was observed in the improvement of insomnia among the three groups(P>0.05).With regard to laboratory parameters for safety,there were no clinically relevant changes in the three groups.Conclusion The present study demonstrates that DXR combined with amiodarone is significantly more effective than DXR or amiodarone alone for treating PVCs.

amiodarone 和 sodalol 治疗致死性心律失常疗效对比

对引起血液动力学异常改变的致死性心律失常患者２３例，分别投予抗心律失常药ａｍｉｏｄａｒｏｎｅ和ｓｏｄａｌｏｌ进行临床疗效等方面的对比观察。１临床资料１．１对象２３例患者均有基础心疾患并伴室性心动过速，其中男１８例，女５例。随机分为两组：ａｍｉｏｄａｒ...

Acute hepatitis after amiodarone infusion

Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.

In vitro study of lovastatin interactions with amiodarone and with carbon tetrachloride in isolated rat hepatocytes

AIM： To investigate the interactions at a metabolic level between Iovastatin, amiodarone and carbon tetrachloride in isolated rat hepatocytes.METHODS： For cell isolation two-step collagenase liver perfusion was performed. Lovastatin was administered alone in increasing concentrations （1μmol/L, 3μmol/L, 5μmol/L and 10μmol/L） and in combination with CCh （86μmol/L）. The cells were also pretreated with 14μmol/L amiodarone and then the other two compounds were added. RESULTS： Lovastatin promoted concentration-dependent significant toxicity estimated by decrease in cell viability and GSH level by 45% and 840, respectively, LDH- activity increased by 114% and TBARS content by 90%, CCl4 induced the expected severe damage on the examined parameters, CCh induced toxicity was attenuated after Iovastatin pretreatment, which was expressed in less increased values of LDH activity and TBARS levels, as well as in less decreased cell viability and GSH concentrations, However, the pretreatment of hepatocytes with amiodarone abolished the protective effect of Iovastatin. CONCLUSION： We suggest that the observed cytoprotective effect was due to interactions between Iovastatin, CCh and amiodarone at a metabolic level.

Inhibitory effects of amiodarone on simvastatin metabolism in human liver microsomes

Objective To investigate the effects ofamiodarone （AMD） on simvastatin （SV） in human liver microsomes and the possible underlying mechanisms. Methods Time-, NADPH- and concentration-dependent inhibitions were tested in HLM. The logarithm of relative inhibition values was plotted versus preincubation time （0, 5, 10, 15, 20min） for a series concentration of AMD used （0, 2, 5, 25, 50 umol/L）, and the slopes determined by linear regression. These slope values represente the observed inactivation rate constants （kobs ）. A double-reciprocal plot was then constructed using the reciprocal of the kobs （y-axis） and the reciprocal of the associated inhibitor concentration （x-axis） to estimate the values of kinact and K1, which were two principal kinetic constants that were specific for mechanism-based inhibition （MBI）.drug-drug interactions （DDI） potential was predicted based on in vitro data and by using the in vitro-in vivo extrapolation. Results The time-, concentration- and NADPH-dependent characteristics confirmed that when SV was the substrate of CYP3A4, the inhibition of AMD to CYP3A4 is MBI. KI and kinact value were calculated to be 5.1umol/L and 0.018minL The CLant of SV was reduced 2.96-5.63 fold when it was administrated with AMD. Conclusion Based on the results, AMD would inhibit SV metabolism via the mechanism-based manner, which would lead to DDI when they are taken together. Careful clinical observation is recommended when AMD and SV have to be simultaneously prescribed.