Pulmonary masses in a patient with blue-gray cutaneous hyperpigmentation

Authors describe a case of pulmonary masses and estensive skin pigmentation: "blue-gray syndrome" occurred in a patient in amiodarone therapy who presented with progressive dyspnea, cough, and fever. The diagnosis was suspected by detection of a high attenuation of the pulmonary masses on the nonenhanced chest computed tomography (CT) and lots of foamy macrophages in the bronchoalveolar lavage fluid. Relief of respiratory symptoms and radiological improvement was achieved when amiodarone treatment was stopped.     

Hypotensive action of commercial intravenous amiodarone and polysorbate 80 in dogs

Commercial intravenous amiodarone has been reported to have antiarrhythmic actions and to cause only mild hypotension in humans. In the dog, however, amiodarone was observed to cause severe hypotension. Since commercial intravenous amiodarone is amiodarone compound (50 mg/ml) dissolved in water with polysorbate 80 (Tween 80) (100 mg/kg), the effects of amiodarone in ethanol (5 mg/kg) and polysorbate 80 (10 mg/kg) were studied individually, and in combination in anesthetized dogs. Commercial intravenous amiodarone and polysorbate 80 caused at least a 60% drop in mean blood pressure and left ventricular maximum dP/dt for at least 30 min, whereas amiodarone in ethanol did not. The drop in blood pressure was not principally due to peripheral vasodilation. Therefore, in dogs the diluent polysorbate 80 is the major cause of severe hypotension resulting from commercial intravenous amiodarone. These studies show that commercial intravenous amiodarone produces results different in dogs than has been previously reported in humans. Therefore: (a) canine models for studying the antiarrhythmic actions of commercial intravenous amiodarone would produce results complicated by severe hypotension; and (b) polysorbate 80 is not an inert substance, but is a potent cardiac depressant.     

皮秒755 nm激光与Q开关1064 nm激光治疗颧部褐青色痣的有效性及安全性比较

目的 比较755 nm皮秒激光与Q开关激光1 064 nm治疗颧部褐青色痣的有效性及安全性。方法 选择2020年1月至2021年1月在东莞台心医院就诊的180例颧部褐青色痣病人作为研究对象,按随机数字表法分为皮秒激光组(n=90)和Q开关激光组(n=90)。皮秒激光组采用755 nm皮秒激光治疗,Q开关激光组采用Q开关激光1 064 nm治疗,两组病人均每隔2.5个月治疗1次,连续治疗5次,比较两组病人每次治疗后的显效率、最终痊愈率,不良反应情况及病人满意率。结果 第1、2、3、4、5次治疗后,皮秒激光组病人的显效率为0、14.44%、43.33%、71.76%、93.33%,Q开关激光组病人的显效率为0、21.11%、47.73%、78.82%、94.37%,两组病人每次治疗后的显效率比较均差异无统计学意义(均P>0.05);Q开关激光组病人的最终痊愈率84.44%明显高于皮秒激光组的71.11%(P<0.05)。Q开关激光组患的色素沉着发生率25.56%明显低于皮秒激光组病人的40.00%(P<0.05);Q开关激光组患的病人满意率84.44%与皮秒激光组病人的8...     

Drug-induced cutaneous photosensitivity: some drugs warrant routine precautions

(1) Drug-induced cutaneous photosensitivity is defined as excessive or abnormal skin reactions to light, linked to systemic or topical administration of a drug. (2) The lesions appear after exposure to sunlight or an ultraviolet source, and are limited to or predominate in exposed areas. (3) Some drugs can induce occasionally severe skin burns after moderate exposure to sunlight. Other types of drug-related skin lesion include eczematous or urticarial eruptions, pseudoporphyria, abnormal pigmentation and pseudolichen. Photo-induced or photo-aggravated contact dermatitis can occur after application of a photosensitising drug. (4) Some drugs are particularly photosensitising, such as psoralens, tetracyclines, amiodarone and quinolones. (5) Patients treated with drugs known to cause cutaneous photosensitivity should be warned of the risk of cutaneous reactions on exposure to light and be encouraged to protect their skin from intense exposure to sunlight. (6) The possible responsibility of a drug should be borne in mind when a patient presents with skin lesions with a distribution typical of cutaneous photosensitivity. Drug withdrawal and subsequent avoidance can lead to recovery and avoid recurrences.     

Worsening of ventricular tachycardia by amiodarone

The details of worsening of ventricular tachycardia in 8 (4.1%) of 194 patients receiving treatment with amiodarone are reported. Two forms of amiodarone-induced tachycardia were recognized: first, the development of new tachycardias (three patients) and second, a change in the pattern of recurrence of clinical tachycardia (five patients). In retrospect, the time from the initiation of amiodarone to the initial documentation of worsening ranged from 1 to 23 days (mean +/- SD, 9.4 +/- 8.2 days) and the time from the initiation of therapy to the recognition of worsening ranged from 6 to 26 days (14.6 +/- 10.1 days). Seven patients survived the worsening of tachycardia and one died. The total dose of amiodarone received and the duration of administration did not correlate with time to manifestation or time to resolution of worsening. This report emphasizes that worsening of ventricular tachycardia as a result of amiodarone is often difficult to differentiate from inadequate drug loading or early recurrence of 2 patient's clinical tachycardia. Further, because of the pharmacokinetics of the drug, the manifestations of worsening may be prolonged. In the cases reported, it ranged from 2 to 26 days (7.9 +/- 8.3 days), which is longer than previously reported. Because of the potential for amiodarone to cause life-threatening worsening of ventricular tachycardia and in accordance with current results, a period of in-hospital monitoring of at least 10 days at the start of therapy with amiodarone is recommended.     

1例房颤合并真菌感染患者室性心动过速诱因分析

[摘 要]分析1例房颤合并真菌感染患者治疗过程中出现室性心动过速的诱因。可能导致本例室性心律失常的发生的因素有低钾血症、氟康唑与胺碘酮联用,但氟康唑加量至0.4g?d-1时联合使用胺碘酮风险更大。临床在不可避免将氟康唑与胺碘酮联用时,应注意氟康唑的给药剂量。     

A comparison of amiodarone and digoxin in the treatment of atrial fibrillation complicating suspected acute myocardial infarction

Thirty-four patients with atrial fibrillation complicating suspected acute myocardial infarction were randomised to treatment with intravenous amiodarone (n = 18) or intravenous digoxin (n = 16). After 24 h, similar proportions of patients in each group had reverted to sinus rhythm. However, there was a tendency towards earlier reversion with amiodarone. At 4 h, 72% of the amiodarone group had reverted to sinus rhythm, compared with 31% of the digoxin group (p less than 0.1). This tendency was more marked in patients with definite infarction (at 4 h, amiodarone 75% reversion, digoxin 10% reversion). Neither drug had a significant effect on blood pressure. Atrial fibrillation may cause serious haemodynamic deterioration in acute myocardial infarction. In comparison with digoxin, amiodarone offers more rapid control of the ventricular response rate and may, in addition, restore sinus rhythm more rapidly.     

Amiodarone use in patients with documented allergy to iodine-containing compounds

The popularity of amiodarone has grown due to its effectiveness in converting arrhythmia and its formulation availability. Formulations of the drug also contain iodine; the iodine content is 75 mg in a 200-mg tablet of amiodarone and 18.7 mg/ml in the intravenous solution. Approximately 10% of the iodine content of oral amiodarone is released into the circulatory system and may increase the risks of hypersensitivity reactions in iodine-sensitive patients. Documented allergies to contrast media or shellfish should not imply that a patient is allergic to iodine. Reactions to contrast media are likely due to the high osmolar or ionic content of the dye. The primary allergen in shellfish that stimulates allergic reactions is tropomyosin. Although amiodarone can cause thyroid disorders due to the high iodine load delivered to the body with each dose, no known association exists between amiodarone and reactions to contrast media or shellfish. Three patients whose medical charts listed an allergy to iodine were administered amiodarone for chemical cardioversion of arrhythmia to normal sinus rhythm. No anaphylactic or anaphylactoid reactions were observed in any of the patients during oral or intravenous amiodarone administration. In patients with true iodine hypersensitivity, however, the potential for such reactions exists.     

Cytotoxicity evaluation after coexposure to perchloroethylene and selected peroxidant drugs in rat hepatocytes.

There is evidence of hepatotoxic effects caused by Perchloroethylene (PCE), presumably due to reactive metabolic intermediates; lipid peroxidation is under study as a potential mechanism of toxicity. We aimed to verify if PCE levels comparable to those reached in the blood of exposed subjects can cause cell damage and lipid peroxidation. The association of PCE with lipid peroxidation inducing drugs (cyclosporine A, valproic acid and amiodarone) was also tested on rat isolated hepatocytes. AST and LDH release, MTT test and lipid peroxidation assay showed that PCE determines dose-dependent effects on rat isolated hepatocytes. The toxic potential resulting from our data would be valproic acid < cyclosporine A < amiodarone. While valproic acid and cyclosporine caused a mild toxicity, the effects of amiodarone were more severe; in particular, the association of PCE with amiodarone showed a clear additive effect. The role of lipid peroxidation in the liver toxicity exerted by the tested compounds was confirmed by our data, and resulted relevant after treatment of cells with amiodarone and PCE. Extrapolating these results to human, we can suggest that a subject professionally exposed to PCE, who chronically assumes a lipid peroxidation inducing drug like amiodarone, may be potentially exposed to a higher risk of liver toxicity.     

静脉应用胺碘酮治疗阵发性房颤的临床观察

目的观察静脉应用胺碘酮对阵发性心房颤动的疗效。方法 61例阵发性房颤的患者,首剂静脉注射150mg,10min内注入,继之以0.5mg/分维持静脉泵入,30min未转复为窦性心律且心室率仍快者,追加静脉注射150mg。结果 15例4小时内转复窦性心律,18例4～12小时后转复窦性心律,13例12～48小时后转复窦性心律。转复率为83.6%;用药期间,2例出现窦性心动过缓,无低血压、心衰加重、心绞痛加重及QT间期延长等不良反应。结论静脉应用胺碘酮治疗阵发性心房颤动安全有效。     

Economic analysis of intravenous plus oral amiodarone, atrial septal pacing, and both strategies to prevent atrial fibrillation after open heart surgery

STUDY OBJECTIVES: To compare the cost-effectiveness of intravenous plus oral amiodarone, atrial septal pacing, and both strategies combined to prevent atrial fibrillation after open heart surgery. Secondary objectives were to compare the cost-effectiveness of amiodarone versus no amiodarone and of pacing versus no pacing, and to compare hospitalization costs of the various strategies. DESIGN: Piggyback cost analysis of a randomized, 2 x 2 factorial trial. SETTING: Urban academic hospital. PATIENTS: One hundred and sixty patients with coronary artery and/or valvular disease. INTERVENTION: Patients were randomized to receive amiodarone or matching placebo and then further randomized to receive atrial septal pacing or no pacing. MEASUREMENTS AND MAIN RESULTS: The economic analysis was conducted from a hospital perspective. Charges were converted to costs using cost:charge ratios. For the cost-effectiveness analysis, a joint distribution of costs and effectiveness was performed using the nonparametric bootstrap method. Amiodarone plus pacing significantly decreased the frequency of atrial fibrillation after open heart surgery, compared with amiodarone alone, pacing alone, and placebo. Total costs (mean+/-SD) were $27,026+/-30,226 for the placebo group, $22,725+/-17,661 for the amiodarone group, $33,868+/-60,309 for the pacing group, and $18,697+/-8174 for the amiodarone plus pacing group (p=0.27). In the joint distribution cost-effectiveness analysis, when compared with placebo, the probability of lower cost but higher effect (superiority) was 67% for amiodarone, 15% for pacing, and 97% for amiodarone plus pacing. In the multivariate analysis, preoperative beta-blockers and amiodarone were negatively associated with hospital costs (p<0.05). CONCLUSIONS: Data suggest that both amiodarone alone and the combination of amiodarone plus pacing are cost-effective compared with placebo. Additional comparative studies of these strategies are warranted to confirm these findings.     

Liver and thyroid monitoring in ambulatory patients prescribed amiodarone in 10 HMOs

BACKGROUND: Amiodarone can cause liver and thyroid toxicity, but little is known about compliance with laboratory tests to evaluate liver and thyroid function among ambulatory patients who are dispensed amiodarone. OBJECTIVES: The primary objective of this study was to identify the proportion of ambulatory patients who had liver aminotransferase and thyroid function tests during amiodarone therapy. Secondary objectives were to (1) describe factors associated with receipt of laboratory tests and (2) determine the accuracy of administrative data for assessing aminotransferase and thyroid function monitoring. METHODS: This retrospective cohort study was conducted at 10 health maintenance organizations (HMOs) for the dates of service from January 1, 1999, through June 30, 2001. Participants included 1,055 patients dispensed amiodarone for at least 180 days within this date range; these patients were not necessarily new starts on amiodarone. Administrative claims data were analyzed to assess the percentage of patients with completed alanine/aspartate aminotransferase and thyroid function tests. Depending on the HMO site, electronic or paper medical records were reviewed to evaluate the validity of administrative claims data. Logistic regression models were used to explore factors associated with receipt of laboratory tests. RESULTS: Both aminotransferase and thyroid function tests were completed in 53.3% of patients within a 210-day follow-up period that included the 180-day period of amiodarone dispensings plus 30 days. Thyroid function, with or without liver function (aminotransferase tests), was assessed in 61.9% of patients, and aminotransferase tests, with or without thyroid function, were assessed in 68.2% of patients. After adjusting for patient characteristics and site, the factor most strongly associated with having both types of laboratory tests evaluated was concomitant therapy with a statin (adjusted odds ratio (OR) 1.55; 95% confidence interval (CI), 1.05-2.29). Other factors associated with having both types of laboratory tests evaluated included the number of outpatient visits in the 6 months before the period of amiodarone dispensings (adjusted OR 1.06; 95% CI, 1.00- 1.13 for each additional 5 visits) and living in a neighborhood where a higher median percentage of people had a high school or higher education (adjusted OR 1.09; 95% CI, 1.00-1.18 for every 10% increase in educational level at the block level). There was no association between monitoring and patient illness severity as measured by the number of comorbid conditions. On the basis of an evaluation of a randomly selected subset of 104 patient records, the sensitivity and specificity of automated data were 94.2% and 85.7% for aminotransferase tests and 83.3% and 81.1% for thyroid function tests, respectively. CONCLUSIONS: Approximately half of ambulatory patients dispensed amiodarone received both recommended laboratory tests for liver and thyroid function. Improved rates of testing for liver aminotransferase and thyroid function are needed for patients who receive amiodarone.     

Prevention of recurrences in patients with lone atrial fibrillation. The dose-dependent effect of angiotensin II receptor blockers.

BACKGROUND: Atrial fibrillation (AF) leads to the activation of the renin-angiotensin system (RAS), which seems to play an important role in atrial remodelling. It is not known yet whether RAS blockade may prevent recurrences in patients with lone AF. METHODS AND RESULTS: Patients with an episode of persistent AF for >7 days, in the absence of cardiac or extracardiac causes and with normal blood pressure values (lone AF), were recruited. Ninety patients were randomised and scheduled for electrical cardioversion. Three groups of patients were compared: Group I was treated with amiodarone 400 mg daily (30 patients), group II was treated with amiodarone 400 mg daily plus irbesartan 150 mg daily (30 patients) and group III with amiodarone 400 mg daily plus irbesartan 300 mg daily (30 patients). The primary endpoint was the time to a first recurrence of AF. The patients were cardioverted and followed. The Kaplan-Meier analysis of time to first recurrence during the follow-up period showed that patients treated with amiodarone 400 mg plus irbesartan 300 mg had a greater probability of remaining free of AF (77% vs. 52% for amiodarone and 65% for amiodarone+irbesartan 150 mg), hazard ratio for a recurrence in group III: 0.47 (95% CI 0.27-0.82; p=0.001). CONCLUSIONS: The combination of irbesartan plus amiodarone decreased the rate of AF recurrences, with a dose-dependent effect, in lone AF patients.     

Risk-benefit assessment of amiodarone in the treatment of cardiac arrhythmias

Cardiac arrhythmias are a cause of significant morbidity and mortality in patients with cardiac disease, and thus represent a major management problem. The recognition that antiarrhythmic drugs have the potential to aggravate as well as to attenuate arrhythmias has prompted clinicians to reconsider treatment strategies and weight the benefits of treatment against the risks. In this context, amiodarone has emerged as an effective antiarrhythmic agent and when used at the lowest effective dose has an acceptable side effect profile. This review focuses on the current clinical usage of amiodarone in a broad variety of cardiac arrhythmias, and addresses the risk-benefits arising from its use. It further discusses the current position of amiodarone in the management of sudden cardiac death.     

Creatinine elevation in patients receiving amiodarone correlates with serum amiodarone concentration.

Serum creatinine and drug concentrations were measured at 0, 1, 2, 3, 6, 9 and 12 months in 30 consecutive patients started on amiodarone. In 28 of these patients with no obvious cause for altered renal function, mean serum creatinine increased to 11% above baseline (P < 0.005). Rising creatinine concentrations correlated with amiodarone concentrations (y = 93.9 + 8.6x, r = 0.51, P < 0.0001). When assessing elevation of serum creatinine in a patient receiving amiodarone, physicians should be aware that it may be related to this drug.     

Dramatic inhibition of amiodarone metabolism induced by grapefruit juice

AIMS: Grapefruit juice increases blood concentrations of many drugs metabolized by CYP3A. Amiodarone is metabolized by CYP3A to N-desethylamiodarone (N-DEA). The aim of this study was to determine amiodarone kinetics when administrated with and without grapefruit juice. METHODS: Eleven healthy adult volunteers took part in a single sequence, repeated-measures design study. Each subject, who had been evaluated 6 months previously for amiodarone pharmacokinetics, was given a single oral dose of amiodarone (17 mg kg-1) with three glasses of 300 ml of grapefruit juice on the same day. RESULTS: Grapefruit juice completely inhibited the production of N-DEA, the major metabolite of amiodarone, in all subjects and increased the area-under-the-curve (AUC) and maximum concentration of amiodarone (Cmax) by 50% and 84%, respectively, as compared with the control period during which water had been administrated instead of grapefruit juice (AUC: 35.9 +/- 14.3 vs 23.9 +/- 11.2 microg ml-1 h, P < 0.005 and Cmax: 3.45 +/- 1.7 vs 1.87 +/- 0.6 microg ml-1, P < 0. 02, respectively) (means +/- s.d.). This inhibition of N-DEA production led to a decrease in the alterations caused by amiodarone on PR and QTc intervals. CONCLUSIONS: Grapefruit juice dramatically alters the metabolism of amiodarone with complete inhibition of N-DEA production. These results are in agreement with in vitro data pointing to the involvement of CYP3 A in the metabolism of amiodarone and suggests that this interaction should be taken into account when prescribing this antiarrhythmic drug.     

Myocardial amiodarone concentrations after short- and long-term treatment in patients with end-stage heart failure

Background: Pharmacokinetics and tissue concentrations of amiodarone may vary considerably in end-stage heart failure, but may be crucial for treatment efficiency and antiarrhythmic drug therapy. Objective: This study was undertaken to determine plasma amiodarone and desethylamiodarone concentrations and to determine whether they correlate with myocardial concentrations in explanted hearts from patients with end-stage heart failure. Patients and methods: Eight patients with idiopathic dilated cardiomyopathy and normal coronary arteries were included in the present study. Myocardial tissue samples (seven sites) and epicardial fat were taken from each explanted heart, and drug concentrations of amiodarone and desethylamiodarone were determined. In addition, plasma drug levels were measured and compared with the myocardial amiodarone/desethylamiodarone concentrations. Results: The mean cumulative amiodarone dose was 91 g and the mean plasma concentrations of amiodarone and desethylamiodarone were 0.68 and 0.84 μg · ml⁻¹, respectively. The tissue concentrations of amiodarone amounted to 13.2 and 28.3 μg · g⁻¹, respectively, in the atria and to 13.0 and 40.8 μg · g⁻¹, respectively, in the ventricles. The distribution of the drug and its metabolite were similar in the right and left ventricles. There was a good correlation between myocardial concentration of amiodarone and desethylamiodarone and the cumulative ingested dose of amiodarone. Tissue drug concentrations correlated only poorly with plasma amiodarone or desethylamiodarone levels. The highest drug levels were measured in the epicardial fat tissue, where the ratio of amiodarone 105 μg · g⁻¹ to desethylamiodarone 32 μg · g⁻¹ was reversed (3.3 compared with 0.29 in the ventricles). Thus, amiodarone concentrations in epicardial fat were approximately 10 times higher than myocardial and 150 times higher than plasma levels. Conclusions: Our data confirm the slow equilibrium of amiodarone and desethylamiodarone concentrations between plasma and myocardium. Myocardial tissue concentrations of desethylamiodarone and, to a lesser degree, amiodarone correlate with the cumulative ingested dose of amiodarone. Monitoring of the total cumulative dose may be more relevant clinically than monitoring plasma levels. These results support the clinical practice of reducing the maintenance dose of amiodarone in patients who are on long-term treatment. Received: 12 July 1997 / Accepted in revised form: 25 September 1997     

参松养心胶囊与胺碘酮联合治疗心律失常临床观察

目的:评价参松养心胶囊与胺碘酮联合治疗对器质性心脏病的心律失常的疗效。方法:将108例心律失常采取随机双盲法分为两组。按一定的治疗方案,分别服用参松养心胶囊加用乙胺胺碘酮和乙胺胺碘酮治疗。结果:治疗组总有效率为86.79%,对照组为60.00%,治疗组疗效明显优于对照组(P<0.05),且副作用发生率低于对照组。结论:参松养心胶囊与碘酮联合治疗与单用乙胺碘酮相比,更能有效地控制心律失常,并能改善心功能。     

胺碘酮与索他洛尔治疗心肌梗死合并心律失常的疗效比较

目的 :观察胺碘酮与索他洛尔对急性心肌梗死 (AMI)合并快速型心律失常的疗效。方法 :10 0例AMI合并快速型心律失常患者随机单盲分为 2组 ,胺碘酮组 :胺碘酮 0 2g ,tid ,有效后减至 0 2g ,po ,qd ,疗程 4wk ,随访 3a。索他洛尔组 :索他洛尔80mg ,po ,bid ,剂量随病情调整 ,疗程 4wk ,随访 3a。结果 :住院期间胺碘酮组梗死后心绞痛发生次数、应用硝酸甘油量、止痛药次数均较索他洛尔组少。经随访 3a ,胺碘酮组发生不稳定性心绞痛、再发心肌梗死、心力衰竭均较索他洛尔组少 (P <0 0 5 )。结论 :小剂量胺碘酮治疗AMI合并快速型心律失常作用可靠 ,值得应用。     

Pharmacokinetic characteristics of amiodarone in long-term oral therapy in Japanese population

To evaluate the pharmacokinetic properties and an optimum dose schedule of amiodarone in long-term oral therapy, serum concentrations of amiodarone and its metabolite, desethylamiodarone, were monitored from 345 Japanese inpatients who received amiodarone therapy for a variety of cardiac arrhythmias. Serum amiodarone and desethylamiodarone concentrations were determined by high performance liquid chromatography system. It was observed that the amiodarone and desethylamiodarone concentrations gradually increased with time. The frequency distribution in the amiodarone clearance of 245 subjects, who received fixed maintenance amiodarone therapy for at least 6 months, was nearly a unimodal one. The variation in the ratio of desetylamiodarone to amiodarone concentration in serum was very small. Although no differences in age, dose, dose duration, amiodarone or desethyamiodarone concentration or ratio were observed between men and women: however, the mean amiodarone clearance of women was significantly higer than that of men. The laboratory data were mostly within normal values and no significant relations were observed between serum amiodarone concentration and clinical laboratory data. These results suggest that the individual variation in pharmacokinetics of amiodarone is comparatively small, which might be sufficient to decide that the maintenance dose was the same one (200 mg/d) in long-term oral amiodarone therapy.