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Sample records for amiodarone

  1. Hepatotoxicity of amiodarone

    DEFF Research Database (Denmark)

    Rumessen, J J

    1986-01-01

    of the hepatotoxicity of amiodarone is given. It is concluded that solid evidence exists of hepatic injury due to amiodarone treatment, including steatosis, alterations resembling alcoholic hepatitis, cholestatic hepatitis and micronodular cirrhosis of the liver. Patients receiving amiodarone should be regularly......Amiodarone has proved very effective in the treatment of otherwise resistant cardiac tachyarrhythmias. The use of amiodarone has, however, been limited due to its serious side-effects. A patient with cholestatic hepatitis due to amiodarone treatment is presented below and a review...... screened with respect to hepatic enzyme levels. Therapy should be discontinued on the suspicion of cholestatic injury or hepatomegaly....

  2. [Thyroid dysfunction and amiodarone].

    Science.gov (United States)

    Lima, Jandira; Carvalho, Patrícia; Molina, M Auxiliadora; Rebelo, Marta; Dias, Patrícia; Vieira, José Diniz; Costa, José M Nascimento

    2013-02-01

    Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

  3. Amiodarone-induced thyroid dysfunction

    African Journals Online (AJOL)

    multinodular disease or Graves' disease, who on exposure to an excessive .... where the cardiovascular status permitted this, radioactive ... antedating the initiation of amiodarone therapy in the current cohort. .... an evidence-based protocol.

  4. Amiodarone pulmonary toxicity: Case report

    Directory of Open Access Journals (Sweden)

    Vasić Nada

    2014-01-01

    Full Text Available Introduction. Amiodarone, an antiarrhythmic drug, which contains iodine compound, has a tendency to accumulate in some organs including the lungs. This is age, drug dosage and therapy duration dependent. Case Outline. We present a case of a 73-year-old man, a smoker, who was admitted as emergency case due to severe dyspnea, tachypnea with signs of cyanosis and respiratory insufficiency. Chest x-ray revealed bilateral diffuse pulmonary shadows in the middle and upper parts of the lungs, similar to those in tuberculosis. His illness history showed chronic obstructive pulmonary disease, arterial hypertension, and atrial fibrillation which has been treated with amiodarone for six years. Sputum smears were negative for mycobacteria, and by the diagnostic elimination method for specific, non-specific and malignant disease the diagnosis of amiodarone pulmonary toxicity was made. Fiberoptic bronchoscopy and pathohistological findings of bronchiolitis obliterans organizing pneumonia confirmed the diagnosis. As the first therapeutic approach, amiodarone therapy was stopped. Then, systemic therapy with methylprednisolone 21 (sodium succinate 40 mg i.v. daily during the first two weeks was initiated and continued with daily dose of methylprednisolone 30 mg orally during the next three months. The patient showed a marked subjective improvement during the first week, which was followed by the improvement of respiratory function and withdrawal of pulmonary changes with complete radiographic and CT resolution after eight months. Conclusion. Amiodarone pulmonary toxicity should be taken into consideration, especially in elderly patients with respiratory symptoms and pulmonary changes, even if only a low dose of amiodarone is administred over a longer time period.

  5. CT appearance of amiodarone-induced pneumonitis

    International Nuclear Information System (INIS)

    Nicholson, A.A.; Hayward, C.

    1989-01-01

    Basal peripheral pleuroparenchymal opacities are described on CT of early cryptogenic fibrosing alveolitis, asbestosis and bleomycin pneumonitis. These diseases may be caused by free radical effects on phospholipid metabolism causing cell wall damage. Amiodarone hydrochloride alters phospholipid synthesis metabolically. Amiodarone pneumonitis might be expected to show similar CT appearances. Sixteen patients who have developed new respiratory symptoms while taking amiodarone have been scanned prone and supine and at inspiration and expiration by means of a scanner with 2-mm sections at 1-cm intervals. All have been previously healthy nonsmokers with no relevant occupational history. Previous chest radiographs have been normal. Results are presented

  6. Ataxia caused by amiodarone in older people.

    Science.gov (United States)

    Hindle, J V; Ibrahim, Amin; Ramaraj, Radhakrishnan

    2008-05-01

    Amiodarone is recommended for the cardioversion of atrial fibrillation and prevention of paroxysmal atrial fibrillation in patients with structural heart disease, coronary artery disease or left ventricular dysfunction. It has well-recognised side-effects on the skin, lungs, liver, thyroid and eyes. Neurological side-effects, including ataxia and neuropathy, also occur, and may be more prevalent in older patients. These side-effects are reversible after cessation of amiodarone. Monitoring of amiodarone therapy should include assessment of the central and peripheral nervous system especially in older patients.

  7. Amiodarone induced pneumonitis and hyperthyroidism: case report.

    Science.gov (United States)

    Grabczak, Elzbieta Magdalena; Zielonka, Tadeusz M; Wiwała, Joanna; Bareła, Anna Dagmara; Opuchlik, Andrzej; Potulska, Anna; Ambroziak, Urszula; Chazan, Ryszarda

    2008-09-01

    Amiodarone is a highly effective antiarrhythmic agent used in life-threatening ventricular and supraventricular arrhythmias. Its long-term use may however lead to several adverse effects, including corneal deposits, liver and thyroid gland dysfunction, lung lesions, bone marrow injury, skin lesions, or neurological abnormalities. The article presents the case of a 56-year-old man with a history of a stroke, who after a few days of amiodarone therapy for an episode of atrial fibrillation was diagnosed with amiodarone-induced hyperthyroidism and interstitial pulmonary lesions. Clinical and laboratory symptoms of hyperthyroidism and radiographic signs of pulmonary involvement did not occur until several weeks after discontinuation of amiodarone therapy. Differential diagnosis of causes of hyperthyroidism and diseases causing nodular pulmonary lesions did not demonstrate any other pathologies. Empirical antibiotic therapy and administration of thiamazole and high doses of propranolol failed to improve the patient's clinical status. It was not until thiamazole was given in combination with glucocorticosteroids, when a slow relief of hyperthyroidism symptoms and resolution of radiographic pulmonary signs were observed. Based on the presented case, the risk of appearance of 2 serious concomitant adverse effects was demonstrated, even following a short-term amiodarone therapy. This paper also contains an overview of adverse effects which may be encountered during or after therapy with this effective antiarrhythmic agent. It was emphasized how important it is to select patients appropriately, and to monitor potential adverse effects during amiodarone therapy.

  8. Risk factors for amiodarone-induced thyroid dysfunction in Japan

    Directory of Open Access Journals (Sweden)

    Sayoko Kinoshita

    2016-12-01

    Conclusion: DCM and cardiac sarcoidosis were identified as risk factors for amiodarone-induced hyperthyroidism. Risk factors for amiodarone-induced hypothyroidism included higher baseline TSH level and lower baseline free T4 level, suggesting that subclinical hypothyroidism may be a potential risk factor for the development of amiodarone-induced hypothyroidism.

  9. Amiodarone-Induced Liver Injury and Cirrhosis.

    Science.gov (United States)

    Buggey, Jonathan; Kappus, Matthew; Lagoo, Anand S; Brady, Carla W

    2015-01-01

    We present a case report of an 80-year-old woman with volume overload thought initially to be secondary to heart failure, but determined to be amiodarone-induced acute and chronic liver injury leading to submassive necrosis and bridging fibrosis consistent with early cirrhosis. Her histopathology was uniquely absent of steatosis and phospholipidosis, which are commonly seen in AIC.

  10. Analysis of increased hepatic density during chronic amiodarone therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hirakawa, Koichi; Abe, Koichiro; Ayabe, Yoshiharu; Nishimura, Masao [Ageo Central General Hospital, Saitama (Japan)

    2003-05-01

    Amiodarone is an amphiphilic, iodinated, benzofuran derivative that is known to be effective for refractory ventricular tachyarrhythmia. Amiodarone also is known to cause a variety of side effects, related to its accumulation in multiple organs. The deposition of amiodarone and its metabolite, desethylamiodarone (DA), in liver elevates liver function tests and increases liver attenuation on computed tomography (CT). Although several groups have reported increased liver attenuation in patients receiving chronic amiodarone therapy, there is still no clear statistically significant relationship between liver CT attenuation and the cumulative dose of amiodarone, or between plasma levels of amiodarone and DA. CT scans were originally performed for the evaluation of pulmonary fibrosis in 13 patients (7 men and 6 women; mean age, 69.9 years, range 35 to 86 years) receiving chronic amiodarone therapy. Liver CT attenuation tended to increase in these patients. We found no significant correlation between liver CT attenuation and the cumulative dose of amiodarone. However, the CT attenuation of the liver was correlated significantly with the plasma level of amiodarone and DA. It was also suggested that liver CT scan is a useful means of evaluating the plasma levels of amiodarone and DA, and for estimating their deposition in liver. (author)

  11. Analysis of increased hepatic density during chronic amiodarone therapy

    International Nuclear Information System (INIS)

    Hirakawa, Koichi; Abe, Koichiro; Ayabe, Yoshiharu; Nishimura, Masao

    2003-01-01

    Amiodarone is an amphiphilic, iodinated, benzofuran derivative that is known to be effective for refractory ventricular tachyarrhythmia. Amiodarone also is known to cause a variety of side effects, related to its accumulation in multiple organs. The deposition of amiodarone and its metabolite, desethylamiodarone (DA), in liver elevates liver function tests and increases liver attenuation on computed tomography (CT). Although several groups have reported increased liver attenuation in patients receiving chronic amiodarone therapy, there is still no clear statistically significant relationship between liver CT attenuation and the cumulative dose of amiodarone, or between plasma levels of amiodarone and DA. CT scans were originally performed for the evaluation of pulmonary fibrosis in 13 patients (7 men and 6 women; mean age, 69.9 years, range 35 to 86 years) receiving chronic amiodarone therapy. Liver CT attenuation tended to increase in these patients. We found no significant correlation between liver CT attenuation and the cumulative dose of amiodarone. However, the CT attenuation of the liver was correlated significantly with the plasma level of amiodarone and DA. It was also suggested that liver CT scan is a useful means of evaluating the plasma levels of amiodarone and DA, and for estimating their deposition in liver. (author)

  12. [Thyroid and treatment with amiodarone diagnosis, therapy and clinical management].

    Science.gov (United States)

    Mikosch, Peter

    2008-01-01

    Amiodarone is a frequently used antiarrhythmic drug with a high antiarrhythmic potency. However, beside its antiarrhythmic effects Amiodarone also reveals a variety of adverse effects and drug-related complications. The affected organs include the eyes, skin, lungs, nervous system, liver, gastrointestinal tract and the thyroid. The thyroid is one of the most frequently affected organs by Amiodarone. An altered hormone equilibrium always occurs and has to be distinguished from Amiodarone induced hyperthyroidism and hypothyroidism. The differentiation of these states frequently causes problems and may even be a diagnostic and therapeutic challenge in certain cases. The article gives an overview on the interactions between Amiodarone and the thyroid, the diagnostic and therapeutic options and management strategies of patient on Amiodarone therapy in the view of thyroid function.

  13. [Acute onset pulmonary toxicity associated to amiodarone].

    Science.gov (United States)

    Ferreira, Pedro Gonçalo; Saraiva, Fátima; Carreira, Cláudia

    2012-01-01

    Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome.

  14. Amiodarone-induced thyroid dysfunction | Ross | South African ...

    African Journals Online (AJOL)

    Background. Little is known about the frequency of thyroid dysfunction (TD) associated with. amiodarone therapy in southern Africa. Objectives. To determine the incidence of TD in a cohort of patients initia ed on amiodarone therapy at a cardiac clinic in Cape Town, South Africa, believed to be an iodine-replete area.

  15. Amiodarone induced myxedema coma: Two case reports and literature review.

    Science.gov (United States)

    Hawatmeh, Amer; Thawabi, Mohammad; Abuarqoub, Ahmad; Shamoon, Fayez

    2018-05-21

    Amiodarone is a benzofuran derivative that contains 37% iodine by weight and is structurally similar to the thyroid hormones. Amiodarone has a complex effect on the thyroid gland, ranging from abnormalities of thyroid function tests to overt thyroid dysfunction, with either thyrotoxicosis or hypothyroidism. Myxedema coma secondary to amiodarone use has been rarely reported in the literature. Our two case reports are an add on to the literature, and illustrate that amiodarone is an important cause of thyroid dysfunction including hypothyroidism and myxedema coma. Hence, healthcare providers should have a high index of suspicion for these conditions while treating patients who are taking amiodarone therapy as early recognition and management are essential to optimize outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. [Prevention of recurrent amiodarone-induced hyperthyroidism by iodine-131].

    Science.gov (United States)

    Hermida, J S; Jarry, G; Tcheng, E; Moullart, V; Arlot, S; Rey, J L; Schvartz, C

    2004-03-01

    Amioradone-induced hyperthyroidism is a common complication of amiodarone therapy. Although definitive interruption of amiodarone is recommended because of the risks of aggravation of the arrhythmias, some patients may require the reintroduction of amiodarone several months after normalisation of thyroid function. The authors undertook a retrospective study of the effects of preventive treatment of recurrences of amiodarone-induced hyperthyroidism with I131. The indication of amiodarone therapy was recurrent, symptomatic, paroxysmal atrial fibrillation in 13 cases and ventricular tachycardia in 5 cases (M = 14, average age 64 +/- 13 years). The underlying cardiac disease was dilated cardiomyopathy (N = 5), ischaemic heart disease (N = 3), hypertensive heart disease (N = 2), arrhythmogenic right ventricular dysplasia (N = 2) or valvular heart disease (N = 2). Two patients had idiopathic atrial fibrillation. An average dose of 576 +/- 184 MBq of I131 was administered 34 +/- 37 months after an episode of amiodarone-induced hyperthyroidism. Amiodarone was reintroduced in 16 of the 18 patients after a treatment-free period of 98 +/- 262 days. Transient post-radioiodine hyperthyroidism was observed in 3 cases (17%). Sixteen patients (89%) developed hypothyroidism requiring replacement therapy with L-thyroxine. There were no recurrences of amiodarone-induced hyperthyroidism. After 24 +/- 17 months follow-up, the arrhythmias were controlled in 13 of the 16 patients (81%) who underwent the whole treatment sequence. The authors conclude that preventive treatment with I131 is an effective alternative to prevent recurrence of amiodarone-induced hyperthyroidism in patients requiring reintroduction of amiodarone to control their arrhythmias.

  17. Amiodaron in atrial fibrillation: post coronary artery bypass graft.

    Science.gov (United States)

    Habibollahi, Paria; Jam, Shahrzad Hashemi; Vahdati, Samad Shams; Baghi, Hamidreza Morteza; Amiri, Hassan

    2016-01-01

    Atrial fibrilation (AF) is the most common complication following heart surgeries; it often occurs in patients after coronary artery bypass graft (CABG). The purpose of this review is to categorize prophylaxes or treatment by administration of Amiodaron in patients with CABG. We searched google scholar, pubmed, and Cochrane Library databases (the period 1970-2010) for articles on Amiodaron in CABG and cardiac surgery. A total of 1 561 articles were identified, and 30 articles met the criteria and were enrolled in this review. Most studies supported Amiodarone for prophylaxi purpose in patients who were performed with CABG; few papers supported Amiodaron as a drug for treating CABG. The prophylaxis can decrease the incidence rate of AF in CABG, but if it uses as a treatment, the side effect of Amiodaron will decrease because all of the patients will not get Amiodarone. In the other hand use of Amiodarone as a treatment does not influence the length of hospital stay significantly but these kinds of study are so few. No appropriate therapeutic method has been defined for AF. At present, the common way of treating AF following cardiac surgery is mainly based on prophylaxis in medical books and references.

  18. Two cases of bilateral amiodarone-associated optic neuropathy.

    Science.gov (United States)

    Chassang, B; Bonnin, N; Moisset, X; Citron, B; Clavelou, P; Chiambaretta, F

    2014-03-01

    The widespread use of amiodarone is limited by its toxicity, notably to the optic nerve. We report two cases of bilateral optic nerve neuropathy due to amiodarone, and provide a detailed description of the disease. The first case was a 59-year-old man complaining from insidious monocular loss of vision within ten months of initiating amiodarone. Funduscopy and optical coherence tomography showed bilateral optic disc edema. The second case was a 72-year-old man presenting with a decrease in visual acuity in his left eye for a month. Funduscopy showed a left optic nerve edema, and fluorescein angiography showed bilateral papillitis. In both cases, the clinical presentation was not suggestive of ischemic neuropathy, because of the preservation of visual acuity and the insidious onset. In addition, both cardiovascular and inflammatory work-up were normal. An amiodarone-associated neuropathy was suspected, and amiodarone was discontinued with the approval of the cardiologist, with complete regression of the papilledema and a stabilization of visual symptoms. Differentiating between amiodarone-associated optic neuropathy and anterior ischemic optic neuropathy may be complicated by the cardiovascular background of such patients. The major criterion is the absence of a severe decrease in visual acuity; other criteria are the normality of cardiovascular and inflammatory work-up, and the improvement or the absence of worsening of symptoms after discontinuation of amiodarone. Amiodarone-associated neuropathy remains a diagnosis of exclusion, and requires amiodarone discontinuation, which can only be done with the approval of a cardiologist, and sometimes requires replacement therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. Bronchiolitis obliterans organising pneumonia in patients taking acebutolol or amiodarone.

    Science.gov (United States)

    Camus, P; Lombard, J N; Perrichon, M; Piard, F; Guérin, J C; Thivolet, F B; Jeannin, L

    1989-01-01

    Two patients, treated with acebutolol and amiodarone respectively, developed a disease clinically, radiologically, and pathologically indistinguishable from bronchiolitis obliterans organising pneumonia. In one case recovery followed discontinuation of acebutolol; in the other case cessation of amiodarone had no effect, and corticosteroids were required. In addition to these patients, several cases of bronchiolitis obliterans organising pneumonia have been reported during treatment with gold salts, amiodarone, and miscellaneous other drugs. Taken together, this information supports the view that bronchiolitis obliterans organising pneumonia may be a form of response by the lungs to insult by drugs. Images PMID:2588206

  20. Amiodarone-Induced Thyrotoxic Thyroiditis: A Diagnostic and Therapeutic Challenge

    Directory of Open Access Journals (Sweden)

    Umang Barvalia

    2014-01-01

    Full Text Available Amiodarone is an iodine-based, potent antiarrhythmic drug bearing a structural resemblance to thyroxine (T4. It is known to produce thyroid abnormalities ranging from abnormal thyroid function testing to overt hypothyroidism or hyperthyroidism. These adverse effects may occur in patients with or without preexisting thyroid disease. Amiodarone-induced thyrotoxicosis (AIT is a clinically recognized condition commonly due to iodine-induced excessive synthesis of thyroid, also known as type 1 AIT. In rare instances, AIT is caused by amiodarone-induced inflammation of thyroid tissue, resulting in release of preformed thyroid hormones and a hyperthyroid state, known as type 2 AIT. Distinguishing between the two states is important, as both conditions have different treatment implications; however, a mixed presentation is not uncommon, posing diagnostic and treatment challenges. We describe a case of a patient with amiodarone-induced type 2 hyperthyroidism and review the current literature on the best practices for diagnostic and treatment approaches.

  1. Systematic review of the use of intravenous amiodarone and nifekalant for cardiopulmonary resuscitation in Japan

    Directory of Open Access Journals (Sweden)

    Mari Amino, MD, PhD

    2014-06-01

    Conclusions: Amiodarone and nifekalant were equivalent in their prophylactic and defibrillation efficacy. Concerning the initial amiodarone dose, the 125 mg intravenous [i.v.] over 10 min seemed to be more appropriate for the Japanese population.

  2. Amiodarone Cost Effectiveness in Preventing Atrial Fibrillation After Coronary Artery Bypass Graft Surgery

    DEFF Research Database (Denmark)

    Zebis, Lars Riber; Christensen, Thomas Decker; Kristiansen, Ivar S.

    2008-01-01

    patients were included to receive either 300 mg amiodarone or placebo (5% aqueous dextrose solution) administered intravenously over 20 minutes followed by 600 mg amiodarone/placebo orally twice a day (8 am and 8 pm) for the first 5 postoperative days. RESULTS: In the amiodarone group, there were 14 cases...

  3. Incidence of drug-induced torsades de pointes with intravenous amiodarone

    Directory of Open Access Journals (Sweden)

    Jayaprakash Shenthar

    2017-11-01

    Conclusion: The incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors include female sex, left ventricular dysfunction, electrolyte abnormalities, baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future.

  4. SAFETY OF AMIODARONE USAGE IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME AND ATRIAL FIBRILLATION

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    D. A. Kuzhel

    2010-01-01

    Full Text Available Amiodarone is one of the basic antiarrhytmic drugs for atrial fibrillation treatment. However application of amiodarone in patients with atrial fibrillation and Wolff-Parkinson-White syndrome can induce ventricular fibrillation. Amiodarone usage in these patients should be accompanied by readiness for performance of resuscitation. This is confirmed by clinical case presentation.

  5. Phlebitis in amiodarone administration: incidence, contributing factors, and clinical implications.

    Science.gov (United States)

    Norton, Linda; Ottoboni, Linda K; Varady, Ann; Yang-Lu, Chia-Yu; Becker, Nancy; Cotter, Theresa; Pummer, Eileen; Haynes, Annette; Forsey, Lynn; Matsuda, Kelly; Wang, Paul

    2013-11-01

    Intravenous amiodarone is an important treatment for arrhythmias, but peripheral infusion is associated with direct irritation of vessel walls and phlebitis rates of 8% to 55%. Objectives To determine the incidence and factors contributing to the development of amiodarone-induced phlebitis in the coronary care unit in an academic medical center and to refine the current practice protocol. Medical records from all adult patients during an 18-month period who received intravenous amiodarone while in the critical care unit were reviewed retrospectively. Route of administration, location, concentration, and duration of amiodarone therapy and factors associated with occurrence of phlebitis were examined. Descriptive statistics and regression methods were used to identify incidence and phlebitis factors. In the final sample of 105 patients, incidence of phlebitis was 40%, with a 50% recurrence rate. All cases of phlebitis occurred in patients given a total dose of 3 g via a peripheral catheter, and one-quarter of these cases (n = 10) developed at dosages less than 1 g. Pain, redness, and warmth were the most common indications of phlebitis. Total dosage given via a peripheral catheter, duration of infusion, and number of catheters were significantly associated with phlebitis. Amiodarone-induced phlebitis occurred in 40% of this sample at higher drug dosages. A new practice protocol resulted from this study. An outcome study is in progress.

  6. Amiodarone-Associated Optic Neuropathy: A Critical Review

    Science.gov (United States)

    Passman, Rod S.; Bennett, Charles L.; Purpura, Joseph M.; Kapur, Rashmi; Johnson, Lenworth N.; Raisch, Dennis W.; West, Dennis P.; Edwards, Beatrice J.; Belknap, Steven M.; Liebling, Dustin B.; Fisher, Mathew J.; Samaras, Athena T.; Jones, Lisa-Gaye A.; Tulas, Katrina-Marie E.; McKoy, June M.

    2011-01-01

    Although amiodarone is the most commonly prescribed antiarrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System (FDA-AERS) and published case reports were reviewed. A total of 296 reports were identified: 214 from AERS, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone associated optic neuropathy (44%) was the most common presentation, and nearly one-third were asymptomatic. Optic disc edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (< 20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted. PMID:22385784

  7. Assistance algorithm of nursing for amiodarone intravenous infusion

    Directory of Open Access Journals (Sweden)

    Francimar Tinoco de Oliveira

    2014-12-01

    Full Text Available This study aimed at identifying scientific publication on phlebitis caused by amiodarone and proposes a nursing care algorithm for interventions in intravenous amiodarone administration grounded in the Infusion Nursing Society and the Center for Disease Control and Prevention. It is a descriptive study mediated by integrative review in MedLine, LILACS, IBECS, BDENF, Cochrane Library and Scielo bases, published from 2006 to 2013. The sample consisted of nine articles. The evidence pointed the incidence of phlebitis due to the infusion of amiodarone and the need to control this event. The algorithm proposed shows the materials to be used and the procedure of drug administration in order to minimize injury. Besides subsidizing the development of future studies, this algorithm also promotes the incorporation of the best recommendation for the interventionist clinical practice.

  8. Treatment of amiodarone-induced thyrotoxicosis resistant to conventional therapy

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    Nišić Tanja

    2017-01-01

    Full Text Available Introduction: Amiodarone as an antiarrhythmic medication is necessary in the prevention and treatment of malignant ventricular arrhythmias, however, it can induce thyroid dysfunction. Thyroid dysfunction may be either hypothyroidism or thyrotoxicosis, however, 50% of patients who have used amiodarone are euthyroid. Case report: A 27-year-old female patient, hospitalized at the Clinic for Endocrinology due to type 2 amiodarone-induced thyrotoxicosis. The patient had previously received amiodarone for two years. At age 25, the patient was diagnosed with dilated cardiomyopathy (EF 25%, EDD/ESD 56-57/47 mm with mild Ebstein’s anomaly, WPW Sy and recorded episodes of non-sustained VT. In order to reduce the risk of sudden death and prevent malignant ventricular arrhythmias, ICD-VR was implanted and amiodarone was prescribed. Treatment with propylthiouracil (PTU and dexamethasone was initiated after thyrotoxicosis was diagnosed. Three weeks after the introduction of PTU, hepatotoxicity was registered, thus the medication was discontinued. Thyrozol, which regulates the hepatotoxicity parameters, was introduced. Sodium perchlorate and glucocorticoid (per os, IV and intrathyroidal therapy was introduced. The treatment had lasted for fifty days and laboratory signs of thyrotoxicosis were still present, which is why a total of eight plasmapheresis sessions were performed. Each plasmapheresis resulted in a significant decrease in FT4 and a slight decrease in FT3. After seventy two days of treatment, an optimal hormonal status of the thyroid gland was established and total thyroidectomy was performed. Conclusion: Patient was treated for amiodarone-induced thyrotoxicosis (AIT type 2, which was resistant to conventional therapy for a long period of time. Successful treatment was achieved by applying plasmapheresis although the effect of perchlorate and glucocorticoids application cannot be disregarded.

  9. Amiodarone: Effects on thyroid function and the peripheral metabolism of the thyroid hormones

    International Nuclear Information System (INIS)

    Braverman, L.E.; Safran, M.; Bambini, G.; Pinchera, A.; Martino, E.

    1985-01-01

    In addition to the effects of Amiodarone on the peripheral metabolism of the thyroid hormones and on pituitary TSH secretion, a major complication of therapy is the relatively high frequency of iodide-induced thyroid dysfunction. The mean T 4 and T 3 concentration following Amiodarone application was measured in euthyroid, hypothyroid and hyperthyroid patients and in control patients with and without cardiac disorders. Furthermore, the serum TSH was determined in euthyroid Amiodarone-treated euthyroid patients. 131 I uptake was studied in patients with Amiodarone-associated thyrotoxicosis. The difficulties of the therapy of Amiodarone-induced hyper-thyroidism are outlined. Preliminary studied of the effect of Amiodarone and its analogues on the metabolism of thyroid hormones in the rat indicate that Amiodarone may act as a thyroid hormone agonist in the pituitary. (MG)

  10. Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats

    International Nuclear Information System (INIS)

    Agoston, Marta; Oersi, Ferenc; Feher, Erzsebet; Hagymasi, Krisztina; Orosz, Zsuzsa; Blazovics, Anna; Feher, Janos; Vereckei, Andras

    2003-01-01

    Several antioxidants have been shown to reduce lysosomal phospholipidosis, which is a potential mechanism of amiodarone toxicity, and prevent amiodarone toxicity by antioxidant and/or non-antioxidant mechanisms. The aim of this study was to test whether the co-administration of two structurally different antioxidants vitamin E and silymarin with amiodarone can reduce amiodarone-induced lysosomal phospholipidosis, and if yes, by reducing the tissue concentration of amiodarone and desethylamiodarone or by their antioxidant action. To this end, male Fischer 344 rats were treated by gavage once a day for 3 weeks and randomly assigned to the following four experimental groups: 1, control; 2, amiodarone (150 mg/(kg per day)); 3, amiodarone (150 mg/(kg per day)) plus vitamin E (100 mg/(kg per day)); 4, amiodarone (150 mg/(kg per day)) plus silymarin (60 mg/(kg per day)) treated groups. Total plasma phospholipid (PL), liver-conjugated diene, thiobarbituric acid reactive substances (TBARSs), amiodarone and desethylamiodarone concentrations were determined and the extent of lysosomal phospholipidosis in the liver was estimated by a semi-quantitative electron microscopic method. Amiodarone treatment increased significantly the liver-conjugated diene (P<0.001), TBARS (P=0.012), plasma total PL (P<0.001) concentrations compared with control. Antioxidants combined with amiodarone significantly decreased the liver-conjugated diene (P<0.001 for both), TBARS (P=0.016 for vitamin E, P=0.053 borderline for silymarin) and plasma total PL (P=0.058 borderline for vitamin E, P<0.01 for silymarin) concentrations compared with amiodarone treatment alone. Silymarin significantly (P=0.021) reduced liver amiodarone, but only tended to decrease desethylamiodarone concentration; however, vitamin E failed to do so. Amiodarone treatment increased lysosomal phospholipidosis (P<0.001) estimated by semi-quantitative electron microscopic method and both antioxidants combined with amiodarone reduced

  11. Treatment of amiodarone-induced hypothyroidism with potassium perchlorate

    NARCIS (Netherlands)

    van Dam, E. W.; Prummel, M. F.; Wiersinga, W. M.; Nikkels, R. E.

    1993-01-01

    The antiarrhythmic drug, amiodarone, induces thyroid dysfunction, which is potentially dangerous in cardiac patients. After discontinuation of the drug it takes several months before euthyroidism is restored. The potent antithyroid drug, potassium perchlorate (KClO4), is used successfully to treat

  12. Dronedarone and Amiodarone Induce Dyslipidemia and Thyroid Dysfunction in Rats

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    Li-Qin Jiang

    2016-05-01

    Full Text Available Background/Aims: Amiodarone, a thyroid hormone-like molecule, can induce dyslipidemia and thyroid dysfunction. However, the effects of dronedarone on lipid metabolism and of both dronedarone and amiodarone on thyroid function and lipid metabolism remain unknown. Methods: Fifty male Sprague-Dawley rats were randomly divided into 5 groups (10 in each group: normal control (NC, amiodarone-treated (AMT, dronedarone-treated (DRT, rats treated with amiodarone combined with polyene phosphatidylcholine (AC, and rats treated with dronedarone combined with polyene phosphatidylcholine (DC. Rats were given amiodarone (120 mg/kg/d, dronedarone (120 mg/kg/d, and polyene phosphatidylcholine (200 mg/kg/d for 13 weeks. At the end of weeks 4, 8, 12, and 13, plasma-free triiodothyronine (FT3, free thyroxine (FT4, triglycerides (TG, total cholesterol (TC, low-density lipoprotein cholesterol (LDL-c, and high-density lipoprotein cholesterol (HDL-c were determined. At the end of this protocol, rats were sacrificed and the thyroid glands were isolated, weighed, and examined histopathologically. The protein expression of Bcl-2 was measured by immunochemical staining. The mRNA expression of thyroglobulin (Tg, type-1 deiodinase (D1, and thyroid peroxidase (TPO were detected by polymerase chain reaction (PCR. Results: Compared with the NC group, FT3 and FT4 levels in the DRT and DC groups significantly increased at week 4 but declined thereafter. The AMT and AC groups had lower FT3 levels but comparable FT4 levels. The levels of TG, LDL-c, and HDL-c in the NC group were lower than those in the other groups whereas the LDL-c/HDL-c ratio was lowest in the AMT group. Bcl-2 expression significantly increased in the DRT group. The mRNA expression of Tg increased whereas the mRNA expression of D1 decreased. Dronedarone induced hyperthyroidism at the early stage and hypothyroidism at the late stage whereas amiodarone only caused hypothyroidism. Conclusion: Both dronedarone and

  13. Medical image of the week: acute amiodarone pulmonary toxicity

    Directory of Open Access Journals (Sweden)

    Mazursky K

    2015-10-01

    Full Text Available No abstract available. Article truncated after 150 words. A 71 year old man with a medical history significant for chronic obstructive pulmonary disease, coronary artery disease with post-operative status coronary artery bypass grafting, heart failure with reduced ejection fraction (25% and atrial fibrillation/flutter underwent an elective ablation of the tachyarrhythmia at another facility and was prescribed amiodarone post procedure. He started complaining of cough and dyspnea one day post procedure and was empirically treated with 2 weeks of broad spectrum antibiotics. He subsequently was transferred to our facility due to worsening symptoms. He also complained of nausea, anorexia with resultant weight loss since starting amiodarone, which was stopped 5 days prior to transfer. Infectious work up was negative. On arrival to our facility, he was diagnosed with small sub-segmental pulmonary emboli, pulmonary edema and possible acute amiodarone toxicity. His was profoundly hypoxic requiring high flow nasal cannula or 100% non-rebreather mask at all times. His symptoms persisted despite ...

  14. Medication Use Evaluation of Dronedarone in Comparison to Amiodarone

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    Adam Corey

    2016-12-01

    Full Text Available Amiodarone is the most effective rhythm-control for atrial fibrillation, but produces serious potential side effects. Dronedarone was designed to eliminate amiodarone toxicities, but increased the risk of mortality in clinical trials. This medication use evaluation compares one year of dronedarone use with a matched cohort of amiodarone patients at a single hospital in Greensboro, NC. Forty-eight patients were included with an average age of 71.8 years and 37.5% female population. No significant difference was found for the primary composite outcome of death, myocardial infarction, stroke, and systemic embolism (OR = 2.4, p = 0.148. Likewise, no statistical significance was demonstrated between the two groups for QTc prolongation, hypothyroidism, liver dysfunction or maintenance of normal sinus rhythm. In conclusion, the clinical decision process demonstrated no increased risk of death or other adverse events in the use of dronedarone. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties   Type: Student Project

  15. Amiodarone Hepatotoxicity with Absent Phospholipidosis and Steatosis: A Case Report and Review of Amiodarone Toxicity in Various Organs

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    Adela Cimic

    2013-01-01

    Full Text Available We present the first description of amiodarone toxicity in the liver without phospholipidosis or steatosis. In doing so, we will review the various effects of amiodarone toxicity in various organs. The patient is a young adult who had cardiac reconstruction as a child for transposition of the great vessels. A needle biopsy was taken due to elevated liver enzymes. Her ALT was 188 U/L (5–50 and AST 162 U/L (5–50. Alkaline phosphatase, total bilirubin, protein, and albumin were within normal limits. A serologic panel for viral hepatitis was negative. Antinuclear antibodies were positive at 260; however, anti-smooth muscle antibody and anti-mitochondrial antibody were negative. A protein electrophoresis showed a slightly elevated beta globulin 2 level of 0.5. Quantitative immunoglobulin levels were within normal limits except for a slightly elevated IgA 409 mg/dL (60–350. Liver ultrasound was unremarkable. The clinical differential was broad and included hepatic congestion along with autoimmune hepatitis. Sections showed only ballooned hepatocytes with Mallory-Denk bodies and perisinusoidal fibrosis. Arrival to the diagnosis was possible only after careful review of the patient’s medications. After discontinuation of amiodarone, the patient’s liver enzymes returned to normal levels.

  16. Analysis of computed tomography density of liver before and after amiodarone administration.

    Science.gov (United States)

    Matsuda, Masazumi; Otaka, Aoi; Tozawa, Tomoki; Asano, Tomoyuki; Ishiyama, Koichi; Hashimoto, Manabu

    2018-05-01

    To evaluate CT density of liver changes between before and after amiodarone administration. Twenty-five patients underwent non-enhanced CT including the liver before and after amiodarone administration. We set regions of interest (ROIs) at liver S8, spleen, paraspinal muscle, and calculated average CT density in these ROIs, then compared CT density between liver and other organs. Statistical differences between CT density of liver and various ratios before and after administration were determined, along with correlations between cumulative dose of amiodarone and liver density after administration, density change of liver, and various ratios after administration. Liver density, liver-to-spleen ratio, and liver-to-paraspinal muscle ratio differed significantly between before and after amiodarone administration. No significant correlations were found between cumulative doses of amiodarone and any of liver density after administration, density change of liver, or various ratios after administration. CT density of liver after amiodarone administration was significantly higher than that before administration. No correlations were identified between cumulative dose of amiodarone and either liver density after administration or density change of liver. Amiodarone usage should be checked when radiologists identify high density of the liver on CT.

  17. Amiodarone-induced hypothyroidism. A common complication of prolonged therapy: a report of eight cases

    International Nuclear Information System (INIS)

    Hawthorne, G.C.; Campbell, N.P.; Geddes, J.S.; Ferguson, W.R.; Postlethwaite, W.; Sheridan, B.; Atkinson, A.B.

    1985-01-01

    Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. The authors conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop in the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism

  18. Peripheral amiodarone-related phlebitis: an institutional nursing guideline to reduce patient harm.

    Science.gov (United States)

    Spiering, Mary

    2014-01-01

    Intravenous amiodarone is one of the most widely used antiarrythmics for the treatment of atrial fibrillation with rapid ventricular response. Peripheral amiodarone infusion, however, often causes pain during infusion and subsequent phlebitis.Data collection on a cardiac telemetry unit revealed a high rate of phlebitis. A multidisciplinary team developed and implemented amiodarone peripheral infusion guidelines. The pre-guideline phlebitis rate was 85% and post-guideline rate was 38%, representing a 47% change or improvement. An additional finding was that the severity of phlebitis was reduced, as well. The results of this study suggest that the implementation of a peripheral amiodarone infusion guideline reduced the incidence and severity of amiodarone-related phlebitis in the cardiac population.

  19. Effect of amiodarone therapy on mortality in patients with left ventricular dysfunction and asymptomatic complex ventricular arrhythmias: Argentine Pilot Study of Sudden Death and Amiodarone (EPAMSA).

    Science.gov (United States)

    Garguichevich, J J; Ramos, J L; Gambarte, A; Gentile, A; Hauad, S; Scapin, O; Sirena, J; Tibaldi, M; Toplikar, J

    1995-09-01

    The efficiency of prophylactic antiarrhythmic treatment with amiodarone in reducing 1-year mortality in patients with reduced left ventricular ejection fraction ( < 35%) and asymptomatic ventricular arrhythmias (Lown classes 2 and 4) was investigated in a prospective, multicenter, randomized, controlled study. Among 127 patients who entered the study, 61 were assigned to no antiarrhythmic therapy (control group [CG] and 66 to amiodarone treatment (amiodarone group [AG]). Amiodarone was administered at a dosage of 800 mg/day for 2 weeks followed by 400 mg/day thereafter. A 12-month follow-up was completed for 106 patients (57 in the AG and 49 in the CG). Amiodarone reduced the overall mortality rate, which was 10.5% in the AG versus 28.6% in the CG (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.10 to 0.84; log-rank test 0.02) and sudden death rate, which was 7.0% in the AG versus 20.4% in the CG (OR 0.29; 95% CI 0.08 to 1.00; log-rank test 0.04). Side effects were rare, and in only three patients did amiodarone treatment have to be discontinued.

  20. Severe congestive heart failure patient on amiodarone presenting with myxedemic coma: a case report.

    Science.gov (United States)

    Shaheen, Mazen

    2009-01-01

    This is a case report of myxedema coma secondary to amiodarone-induced hypothyroidism in a patient with severe congestive heart failure (CHF). To our knowledge and after reviewing the literature there is one case report of myxedema coma during long term amiodarone therapy. Myxedema coma is a life threatening condition that carries a mortality reaching as high as 20% with treatment. The condition is treated with intravenous thyroxine (T4) or intravenous tri-iodo-thyronine (T3). Patients with CHF on amiodarone may suffer serious morbidity and mortality from hypothyroidism, and thus may deserve closer follow up for thyroid stimulating hormone (TSH) levels. This case report carries an important clinical application given the frequent usage of amiodarone among CHF patients. The myriad clinical presentation of myxedema coma and its serious morbidity and mortality stresses the need to suspect this clinical syndrome among CHF patients presenting with hypotension, weakness or other unexplained symptoms.

  1. Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Hugo Van Herendael

    2010-06-01

    Full Text Available Hugo Van Herendael, Paul DorianDivision of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, CanadaAbstract: Amiodarone has emerged as the leading antiarrhythmic therapy for termination and prevention of ventricular arrhythmia in different clinical settings because of its proven efficacy and safety. In patients with shock refractory out-of-hospital cardiac arrest and hemodynamically destabilizing ventricular arrhythmia, amiodarone is the most effective drug available to assist in resuscitation. Although the superiority of the transvenous implantable cardioverter defibrillator (ICD over amiodarone has been well established in the preventive treatment of patients at high risk of life-threatening ventricular arrhythmias, amiodarone (if used with a beta-blocker is the most effective antiarrhythmic drug to prevent ICD shocks and treat electrical storm. Both the pharmacokinetics and the electrophysiologic profile of amiodarone are complex, and its optimal and safe use requires careful patient surveillance with respect to potential adverse effects.Keywords: amiodarone, ventricular fibrillation, unstable ventricular tachycardia

  2. Acute lung affection in an endurance-trained man under amiodarone medication

    Directory of Open Access Journals (Sweden)

    Saurbier, Bernward

    2005-06-01

    Full Text Available Patients undergoing treatment with amiodarone can develop severe pulmonary side effects. This effect, which is often highly underestimated, can lead to dyspnea, pneumonitis, and further fibrosis. A recent change in the labeling of amdiodarone by the American Food and Drug Administration (FDA supports this suspicion. Tracing the symptoms back to the causing agent can be difficult, as shown in our report. The subject of this case report is an endurance-trained 65 year old male marathon runner who appeared with atrial fibrillation during a routine check up in autumn 2003. After medical cardioversion with flecainide a complaint free interval of 8 months was followed by a relapse, which resulted in a change of medication to amiodarone. Due to misunderstandings the patient kept on taking the amiodarone loading dose for six weeks and returned with severe dyspnea on exertion. Losses in CO diffusing capacity, a lowered macrophages count and a positive lymphocyte transformation test were the only first hand clinical evidence of amiodarone intoxication, despite the sensation of dyspnea. This case shows that special care has to be taken in treatment with amiodarone. Side effects can be hard to trace and do not evidently show a clear connection to amiodarone.

  3. Sorption of amiodarone to polyvinyl chloride infusion bags and administration sets.

    Science.gov (United States)

    Weir, S J; Myers, V A; Bengtson, K D; Ueda, C T

    1985-12-01

    The loss of amiodarone from i.v. admixtures to flexible polyvinyl chloride (PVC) infusion bags and i.v. administration sets was studied. Admixtures containing amiodarone hydrochloride 600 micrograms/mL and either 5% dextrose injection or 0.9% sodium chloride injection were stored at room temperature in glass bottles (both with and without contact of the drug solution with the rubber bottle closure), in flexible PVC bags, or in rigid PVC bottles. After 120 hours, the contents of each flexible PVC bag were emptied and replaced by methanol, which was allowed to remain in the bag for an additional 120 hours and was then analyzed for amiodarone content. To determine availability of amiodarone after infusion through a 1.8-m PVC i.v. administration set, solutions stored in glass containers were run through the set at 0.5 mL/min for 90 minutes. Samples of drug solutions were collected at appropriate intervals and analyzed by a stability-indicating high-performance liquid chromatography (HPLC) assay. Admixtures containing 0.9% sodium chloride injection were not stable; visual incompatibility was evident after 24 hours of storage in glass bottles, and no further testing was performed. In admixtures containing 5% dextrose injection that were stored in 50-mL flexible PVC bags, 60% of the initial amiodarone concentration remained after 120 hours; approximately half of the lost drug was recovered with the methanol. In effluent collected from the PVC administration set, 82% of the initial amiodarone concentration remained. Amiodarone concentrations did not decrease appreciably, after storage in glass or rigid PVC bottles, indicating that drug loss was probably affected by the plasticizer, di-2-ethylhexyl phthalate.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. The Characteristics of Amiodarone-induced Thyrotoxicosis in a Moderate Iodine Deficit Area

    Directory of Open Access Journals (Sweden)

    Ancuța-Elena Cota

    2013-08-01

    Full Text Available Introduction: Amiodarone (AMI, a class III anti-arrhythmic drug, is associated with a number of side effects, including thyroid dysfunction (both hypo- and hyperthyroidism, which is due to amiodarone's high iodine content and its direct toxic effect on the thyroid. Objective: To evaluate the incidence of Amiodarone induced thyrotoxicosis (AIT (type, rate of occurrence and to identify the risk factors involved in its occurrence. Material and method: We examined patients treated with amiodarone, between January 2002 and December 2011, who presented to our Department of Endocrinology Târgu Mures for thyroid dysfunctions. Results: The retrospective study included 87 patients with thyroid dysfunctions; 58 (66.7% patients had AIT and 29 (33.3% had Amiodarone induced hypothyroidism (AIH. In the AIT group: 35 were women (60.3%, 23 were men (39.7%; the average age was 61.60 ± 12.39 years. Risk factors identified for the AIT group were male gender (RR = OR = 3.8; Chi-squer = 5.7, p = 0.004 and pre-existing thyroid abnormalities (RR = 2.5, Chi-square = 4.1, p = 0.005. The thyroid dysfunction occurrence was heterogeneous (0.2-183 months. The patients with previous thyroid abnormalities developed earlier thyroid dysfunction compared to those with an apparently normal thyroid gland (22.25 ± 4.14 months versus 32.09 ± 7.69 months, p = 0.02, T test. Conclusion: In the context of the specific iodine geoclimatic intake and the area of origin, amiodarone - induced thyroid dysfunction spectrum is dominated by thyrotoxicosis. Screening and monitoring of thyroid function for patiens under chronic amiodarone treatment is necessary

  5. Magnesium sulphate and amiodarone prophylaxis for prevention of postoperative arrhythmia in coronary by-pass operations

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    Huysal Kagan

    2009-02-01

    Full Text Available Abstract Background The aim of this study was to investigate the use of prophylactic magnesium sulphate and amiodarone in treating arrhythmias that may occur following coronary bypass grafting operations. Methods The study population consisted of 192 consecutive patients who were undergoing coronary artery bypass grafting (CABG. Sixty-four patients were given 3 g of magnesium sulphate (MgSO4 [20 ml = 24.32 mEq/L Mg+2] in 100 cc of isotonic 0.9% solution over 2 hours intravenously at the following times: 12 hours prior to the operation, immediately following the operation, and on postoperative days 1, 2, and 3 (Group 1. Another group of 64 patients was given a preoperative infusion of amiodarone (1200 mg on first post-operative day (Group 2. After the operation amiodarone was administered orally at a dose of 600 mg/day. Sixty-four patients in group 3 (control group had 100 cc. isotonic 0.9% as placebo, during the same time periods. Results In the postoperative period, the magnesium values were significantly higher in Group 1 than in Group 2 for all measurements. The use of amiodarone for total arrhythmia was significantly more effective than prophylactic treatment with magnesium sulphate (p = 0.015. There was no difference between the two drugs in preventing supraventricular arrhythmia, although amiodarone significantly delayed the revealing time of atrial fibrillation (p = 0.026. Ventricular arrhythmia, in the form of ventricular extra systole, was more common in the magnesium prophylaxis group. The two groups showed no significant differences in other operative or postoperative measurements. No side effects of the drugs were observed. Conclusion Prophylactic use of magnesium sulphate and amiodarone are both effective at preventing arrhythmia that may occur following coronary by-pass operations. Magnesium sulphate should be used in prophylactic treatment since it may decrease arrhythmia at low doses. If arrhythmia should occur despite this

  6. The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

    Science.gov (United States)

    White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

    2016-03-01

    Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

  7. Comparative efficacy of amiodarone with ivabradin combination or amiodarone with bisoprolol combination in the prevention of atrial fibrillation recurrence in pa- tients with left ventricular diastolic dysfunction

    Directory of Open Access Journals (Sweden)

    K. G. Adamyan

    2015-01-01

    Full Text Available Aim. To study the efficacy of use of amiodarone with ivabradine combination or amiodarone with bisoprolol combination in the prevention of atrial fibrillation (AF recurrence in patients (pts with left ventricular diastolic dysfunction (LVDD after conversion to sinus rhythm. Material and methods. 65 patients (40 males, 25 females aged 53±8 years with persistent AF and LVDD were included into the study and randomized into 3 groups to receive ivabradine and amiodarone (22 pts, bisoprolol and amiodarone (22 pts or amiodarone alone (21 pts. Left atrium (LA volume indices, LA longitudinal strain rate (LASR in systole, LV mass index, mean heart rate (HR, 24-hour HR variability and the incidence of AF by 96 h ECG monitoring were measured after the titration period, and after 3 and 6 months of follow-up. Results. After 6 months of follow-up group 1 revealed significantly lower maximum LA volume index (21.3±2.4 vs 25.2±3.0 and 28.7±3.6 ml/m2 in the 2nd and control groups, respectively, P-wave LA volume index (15.3±3.5 versus 18.1±3.8 and 20.4±4.0 ml/m2 in the 2nd and control groups, respectively, and LA systolic volume index (7.3±1.2 versus 9.4±1.6 and 9.6±1.7 ml/m2 in 2nd and control groups, respectively. The incidence of side effects in group 1 was significantly less than that in group 2 and was not different compared with control group. Conclusion. Ivabradine and amiodarone combination provides better prevention of AF recurrence and less side-effects in pts with LVDD and persistent AF after sinus rhythm restoration as compared with bisoprolol and amiodarone combination, it also reduces LA maximum, conduit and systolic volumes, and increases LASR.

  8. Incidence and severity of phlebitis in patients receiving peripherally infused amiodarone.

    Science.gov (United States)

    Boyce, Brenda A Brady; Yee, Barbara Homer

    2012-08-01

    Nurses noted that the rate of phlebitis was high when intravenous amiodarone was infused via a peripheral site. Hospital policy recommends a central vascular catheter, but this method is often not feasible because the drug is administered in emergent situations for short periods. To determine the rate and severity of phlebitis in patients given peripherally infused amiodarone. The literature, policy, and procedures for administration of amiodarone were reviewed; the pharmacy was consulted; and a data collection tool was developed. The tool was pilot tested and revised, and face validation was established. Data were collected during a 6-month period. A convenience sample was used. The study included a total of 12 patients. Each new infusion of intravenous amiodarone was considered a separate occurrence, for a total of 24 infusions. Various grades of phlebitis developed in 8 patients (67%). Phlebitis developed at 12 of the 24 infusion sites (50%). Patients receiving peripherally infused amiodarone are at high risk for phlebitis. This complication may lead to infection, additional medical intervention, delay in treatment, and prolonged hospitalization.

  9. Amiodarone-induced secondary thyroid dysfunctions in children

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    Larisa A. Balykova

    2017-09-01

    Full Text Available Introduction: The choice of effective and safe antiarrhytmic therapy for children and adolescents is relevant issue for public health. The difficulty in choising therpeutic tactics is caused by the variety of formation of arrhythmias and the side effects of drugs. Materials and Methods: The condition of thyroid system in 45 children (20 girls, 25 boys suffering from disturbances of a rhythm within a year after the end of treatment by Amiodaronum is analyzed. The average age of the surveyed patients was 8,26 ± 0,9 years. A comprehensive examination including an assessment of a hormonal profile (a thyroxin (T4, triodothyronine (T3, thyrotrophic hormone (TTG, antibodies to a thyroid peroxidase and a thyreoglobulin (AT to TPO and TG, ultrasound examination (US of a thyroid gland, a standard electrocardiography at rest (ECG and the Holter monitoring (HM before, in 3, 6 and 12 months of therapy was conducted. Results: It has been established that prescription of Amiodarone was followed by changes in the level the thyroid’s hormones, but in most cases within normal values. Thyroidopathya (subclinical are more often were diagnosed for three patients. In 4.4 % of cases the hypothyroid and in 2.2 % of cases the thyrotoxicosis were detected. Discussion and Conclusions: It was shown that reception of medicine resulted in changes the sizes of a thyroid gland, but rarely followed by violations of functions.

  10. [Successful treatment of fetal supraventricular tachycardia with a combination of digoxin and amiodarone].

    Science.gov (United States)

    Hajdú, J; Szabó, I; Német, J

    1996-10-06

    The supraventricular tachycardia is a life threatening state in the intrauterine life. It can cause non-immune hydrops fetalis, intrauterine death or complications during the delivery. The unexplained tachycardia can cause fetal distress and premature delivery. Usually the digoxin is the first drug of choice for transplacental cardioversion. If digitalisation does not achieve cardioversion, the second line antiarrhythmic drugs should be instituted. Amiodarone has been suggested as a therapeutic alternative after failure of digoxin-verapamil combination. We give a drug in standard therapeutic doses for four-five days and after it we determine whether it is effective or not. We should determine the newer therapy or termination of pregnancy. The transplacental administration of amiodarone may be dangerous because of fetal cretinism. Our case is the first in Hungary-in our best knowledge- and we suggest the amiodarone for transplacental therapy.

  11. Amiodarone is a cost-neutral way of preventing atrial fibrillation after surgery for lung cancer

    DEFF Research Database (Denmark)

    Riber, Lars P.; Christensen, Thomas D.; Pilegaard, Hans K.

    2014-01-01

    OBJECTIVES: Our aim was to estimate the costs and health benefits of routinely administered postoperative amiodarone as a prophylactic agent in reducing the risk of atrial fibrillation in patients undergoing surgery for lung cancer. METHODS: This was a cost-effectiveness study, based.......23). There were no signs of adverse developments referable to amiodarone in this prophylactic regime. CONCLUSIONS: For patients undergoing surgery for lung cancer, routine use of postoperative prophylactic intravenous bolus and five subsequent days of oral amiodarone therapy reduces the risk of atrial...... on the randomized, controlled, double-blinded PASCART study, using avoidance of atrial fibrillation as the measure of benefit. Two hundred and fifty-four eligible, consecutively enrolled patients, undergoing surgery for lung cancer at the department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital...

  12. The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations.

    Science.gov (United States)

    Slim, Ahmad M; Roth, Jason E; Duffy, Benjamin; Boyd, Sheri Y N; Rubal, Bernard J

    2007-12-01

    Postoperative atrial fibrillation following cardiothoracic surgery is common and frequently managed with intravenous (IV) amiodarone. Phlebitis is the most common complication with peripheral infusion of this agent. Current practice guidelines for peripheral IV administration of phlebitis. The present study examines the incidence of phlebitis in a postoperative patient population given current dose recommendations. A total of 273 patient charts were reviewed. The incidence of phlebitis in patients given IV amiodarone (n = 36) was 13.9% (95% confidence interval, 2.6-25.2%; p = 0.001). Logistic regression analysis with backward elimination of other therapeutic risk factors suggests that the odds ratio for phlebitis using current dose regimens without IV filters is 19-fold greater than baseline risk in this population. Phlebitis remains a significant complication associated with peripheral infusion of amiodarone within recommended dosing limits.

  13. Pulmonary hypertension and isolated right heart failure complicating amiodarone induced hyperthyroidism.

    Science.gov (United States)

    Wong, Sean-Man; Tse, Hung-Fat; Siu, Chung-Wah

    2012-03-01

    Hyperthyroidism is a common side effect encountered in patients prescribed long-term amiodarone therapy for cardiac arrhythmias. We previously studied 354 patients prescribed amiodarone in whom the occurrence of hyperthyroidism was associated with major adverse cardiovascular events including heart failure, myocardial infarction, ventricular arrhythmias, stroke and even death [1]. We now present a case of amiodarone-induced hyperthyroidism complicated by isolated right heart failure and pulmonary hypertension that resolved with treatment of hyperthyroidism. Detailed quantitative echocardiography enables improved understanding of the haemodynamic mechanisms underlying the condition. Copyright © 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  14. Acutely Onset Amiodarone-Induced Angioedema in a Patient with New Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Hossein Vakili

    2014-01-01

    Full Text Available A 50-year-old man was admitted to our emergency department due to new episode of palpitation. He had history of angioplasty of right coronary artery (RCA with drug eluting stent 2 years ago. His electrocardiogram revealed atrial fibrillation (AF. Intravenous amiodarone 150 mg during 10 minutes and then 1 mg/min infusion were started to achieve rate control and pharmacologic conversion to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed swelling of the skin around his mouth and eyes, and also mucosa of the mouth, eyes and tongue. To conclude, angioedema should be considered a rare side effect of amiodarone which is used broadly in cardiovascular field.

  15. Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass.

    Science.gov (United States)

    Bourron, Olivier; Ciangura, Cécile; Bouillot, Jean-Luc; Massias, Laurent; Poitou, Christine; Oppert, Jean-Michel

    2007-11-01

    Gastric bypass is increasingly used in morbidly obese patients to achieve significant reduction of body weight and fat mass and concurrent improvement in co-morbidities. We report the case of a 53-year-old male patient (141 kg, BMI 50 kg/m2), successfully treated by amiodarone for supraventricular arrythmia, who underwent Roux-en-Y gastric bypass (RYGBP). 6 months after surgery, he had lost 45% of his preoperative weight (44.8% of weight loss was lean mass) and developed amiodarone-induced subclinical hyperthyroidism. We hypothesize the following sequence of events: weight loss after RYGBP, therefore fat loss, decrease in distribution volume of amiodarone inducing iodine overload and hyperthyroidism, reinforcing weight loss and particularly loss of lean mass. This report emphasizes the importance of careful monitoring of weight and body composition changes after RYGBP. In this situation, checking thyroid status is recommended, especially when there is a history of thyroid disease or potentially toxic thyroid medication.

  16. The effects of sesame oil on the prevention of amiodarone-induced phlebitis.

    Science.gov (United States)

    Bagheri-Nesami, Masoumeh; Shorofi, Seyed Afshin; Hashemi-Karoie, Seyedeh Zahra; Khalilian, Alireza

    2015-01-01

    Phlebitis is the most common complication associated with peripheral intravenous infusion of amiodarone. The purpose of this study is to determine the effects of sesame oil on the prevention of amiodarone-induced phlebitis. This is a double-blind randomized controlled trial. Thirty-six patients hospitalized in a coronary care unit were randomly allocated into two groups using a convenience sampling method. Following peripheral intravenous cannulation, five drops of pure sesame oil were applied to the skin within a 10 cm radius of the infusion site prior to the administration of amiodarone in the intervention group. Sesame oil was rubbed on the skin at the infusion site every 6 h in the 24-h period of amiodarone infusion. In the control group, liquid paraffin, used as a placebo, was rubbed on the skin at the infusion site of amiodarone. Both groups were monitored for the development of phlebitis and its degree within the 24-h period of amiodarone infusion as well as 6 h after its administration. The incidence of phlebitis was confirmed and recorded by an assessor who was blind to the two groups. Data were analyzed using Statistical Package for Social Science (SPSS) version 18, and descriptive and inferential statistics such as Chi-square test, Kaplan-Meier, Hazard ratio, independent t-test, and Fisher's exact test. There was a statistically significant difference between the two groups in their catheter survival after 30 h and 10 min (P phlebitis, while 16.7% and 22.2% of the patients manifested signs of grade 2 and 3 phlebitis, respectively. In the control group, 22.2% of the patients showed no signs of phlebitis, while 5.6%, 27.8%, and 44.4% of the patients exhibited signs of grade 2, 3, and 4 phlebitis, respectively. The statistical analysis showed significant differences in the degree of phlebitis (P = 0.006) and the onset of phlebitis development (P phlebitis.

  17. Drug-induced lupus: simvastatin or amiodarone? A case report in elderly

    Directory of Open Access Journals (Sweden)

    Mauro Turrin

    2013-03-01

    Full Text Available Reports of systemic lupus erythematosus (SLE seen during treatment with amiodarone are rare in the literature. SLE or immunological abnormalities induced by treatment with statins are more frequent. In this issue we report a case of a 81-year-old male who, after a 2-year therapy with amiodarone, developed a clinical and serologic picture of drug-induced SLE (DILE. He was admitted for congestive heart failure in mechanical aortic valve prosthesis, permanent atrial fibrillation (anticoagulation with warfarin, hypercholesterolaemia, and hypothyroidism. Amiodarone was started two years earlier for polymorphic ventricular tachycardia, statin and L-thyroxine the following year. At admission he presented pleuro-pericardical effusion detected by CT-scan (also indicative of interstitial lung involvement and echocardiography. Serological main indicative findings were: elevation of inflammatory markers, ANA (Anti-Nuclear Antibodies titers = 1:320 (indirect immune-fluorescence – IIF – assay on HEp-2, homogeneous/fine speckled pattern, anti-dsDNA titers = 1:80 (IIF on Crithidia luciliae, negative ENA (Extractable Nuclear Antigens and antibodies anti-citrulline, rheumatoid factor = 253 KU/l, normal C3-C4, negative HbsAg and anti-HCV, negative anticardiolipin antibodies IgG and IgM, negative anti-beta2GPI IgG and IgM. Amiodarone was discontinued and methylprednisolone was started, since the patient was severely ill. At discharge, after a month, the patient was better and pleuro-pericardical effusion was reduced. Readmitted few weeks later for bradyarithmia and worsening of dyspnoea, pericardial effusion was further reduced but he died for refractory congestive heart failure and pneumonia. Clinical picture (sierositis, neither skin nor kidney involvement, other typical side effects of amiodarone (hypothyroidism and lung interstitial pathology and serological findings are suggestive of amiodarone-induced SLE.

  18. The effects of sesame oil on the prevention of amiodarone-induced phlebitis

    Directory of Open Access Journals (Sweden)

    Masoumeh Bagheri-Nesami

    2015-01-01

    Full Text Available Background: Phlebitis is the most common complication associated with peripheral intravenous infusion of amiodarone. The purpose of this study is to determine the effects of sesame oil on the prevention of amiodarone-induced phlebitis. Materials and Methods: This is a double-blind randomized controlled trial. Thirty-six patients hospitalized in a coronary care unit were randomly allocated into two groups using a convenience sampling method. Following peripheral intravenous cannulation, five drops of pure sesame oil were applied to the skin within a 10 cm radius of the infusion site prior to the administration of amiodarone in the intervention group. Sesame oil was rubbed on the skin at the infusion site every 6 h in the 24-h period of amiodarone infusion. In the control group, liquid paraffin, used as a placebo, was rubbed on the skin at the infusion site of amiodarone. Both groups were monitored for the development of phlebitis and its degree within the 24-h period of amiodarone infusion as well as 6 h after its administration. The incidence of phlebitis was confirmed and recorded by an assessor who was blind to the two groups. Data were analyzed using Statistical Package for Social Science (SPSS version 18, and descriptive and inferential statistics such as Chi-square test, Kaplan-Meier, Hazard ratio, independent t-test, and Fisher′s exact test. Results: There was a statistically significant difference between the two groups in their catheter survival after 30 h and 10 min ( P < 0.001. Over 60% of the patients (61.1% in the intervention group did not show any sign of phlebitis, while 16.7% and 22.2% of the patients manifested signs of grade 2 and 3 phlebitis, respectively. In the control group, 22.2% of the patients showed no signs of phlebitis, while 5.6%, 27.8%, and 44.4% of the patients exhibited signs of grade 2, 3, and 4 phlebitis, respectively. The statistical analysis showed significant differences in the degree of phlebitis ( P = 0

  19. Emerging role of Amiodarone and Dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis.

    Science.gov (United States)

    Oryan, A; Bemani, E; Bahrami, S

    2018-04-21

    Leishmaniasis is a group of human and animal diseases causing 20,000 to 40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca 2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Short-term amiodarone treatment for atrial fibrillation after catheter ablation induces a transient thyroid dysfunction

    DEFF Research Database (Denmark)

    Diederichsen, Søren Zöga; Darkner, Stine; Chen, Xu

    2016-01-01

    ablation in a randomised, double-blind clinical trial. METHODS: 212 patients referred for AF ablation at two centres were randomized to 8weeks of oral amiodarone or placebo. Thyroid function tests (TSH, thyroid stimulating hormone; T4, thyroxine; T3, triiodothyronine; fT4, free T4; fT3, free T3) were...

  1. Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene

    NARCIS (Netherlands)

    Bakker, O.; Hudig, F.; Meijssen, S.; Wiersinga, W. M.

    1998-01-01

    Treatment of patients with amiodarone, a potent anti arrhythmic drug, increases plasma LDL cholesterol levels, similar to that seen during hypothyroidism. This increase is the result of a decreased expression of the hepatic LDL receptor gene. We investigated the effects of thyroid hormone,

  2. Effect of Lactobacillus casei on the Pharmacokinetics of Amiodarone in Male Wistar Rats

    Czech Academy of Sciences Publication Activity Database

    Matušková, Z.; Anzenbacher, P.; Večeřa, R.; Siller, M.; Tlaskalová-Hogenová, Helena; Strojil, J.; Anzenbacherová, E.

    2017-01-01

    Roč. 42, č. 1 (2017), s. 29-36 ISSN 0378-7966 R&D Projects: GA ČR(CZ) GAP303/12/0535 Institutional support: RVO:61388971 Keywords : Lactobacillus casei * Amiodarone * Wistar Rats Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.400, year: 2016

  3. 2018 European Thyroid Association (ETA) Guidelines for the Management of Amiodarone-Associated Thyroid Dysfunction.

    Science.gov (United States)

    Bartalena, Luigi; Bogazzi, Fausto; Chiovato, Luca; Hubalewska-Dydejczyk, Alicja; Links, Thera P; Vanderpump, Mark

    2018-03-01

    Treatment with amiodarone is associated with changes in thyroid function tests, but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in apparently normal thyroid glands or in the presence of underlying thyroid abnormalities. AIH does not require amiodarone withdrawal, and is treated with levothyroxine replacement if overt, whereas subclinical forms may be followed without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a form of iodine-induced hyperthyroidism occurring in nodular goitres or latent Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic mechanisms. AIT 1 is best treated with thionamides that may be combined for a few weeks with sodium perchlorate to make the thyroid gland more sensitive to thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has been restored, AIT 2 patients are followed up without treatment, whereas AIT 1 patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite forms of AIT are treated with thionamides. Oral glucocorticoids can be added from the beginning if a precise diagnosis is uncertain, or after a few weeks if response to thionamides alone is poor. The decision to continue or to stop amiodarone in AIT should be individualized in relation to cardiovascular risk stratification and taken jointly by specialist cardiologists and endocrinologists. In the presence of rapidly deteriorating cardiac conditions, emergency thyroidectomy may be required for all forms of AIT.

  4. In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum

    Directory of Open Access Journals (Sweden)

    Mohammad Hosein Razi Jalali

    2014-09-01

    Full Text Available Background & objectives: The leishmaniases are considered among the major infectious diseases affecting public health in several regions. There are many chemical agents which are effective in treatment of visceral leishmaniasis. But, overall treatment of visceral leishmaniasis is often difficult. Thus, identification of new chemotherapeutic agents is important for treatment of disease. Since targeting of the ergosterol synthesis pathway of Leishmania may be useful therapeutically, the aim of this study was to investigate the effect of alone or in combination of amiodarone and ketoconazole on Leishmania infantum.   Methods : To obtain logarithmic promastigotes of L. infantum, the parasites were cultured in BHI medium with FCS 10% together with antibiotics of penicillin and streptomycin and incubated at 24° C. Amastigote forms were obtained in BHI medium supplemented with 20% FCS at pH of 5.5 which incubated in 37° C. L.infantum susceptibility to amiodarone and ketoconazole was evaluated by proliferation of parasites in the absence or presence of these drugs with MTT assay. For evaluation of antiproliferative synergism against promastigotes and axenic amastigotes, fractional inhibitory concentrations (FIC were calculated. An isobologram curve was constructed too.   Results: Amiodarone produced a marked reduction in the viability of L.infantum promastigotes and axenic amastigotes. On the other hand ketoconazole induced a dose dependent effect on the parasites proliferation for promastigotes and axenic amastigotes. When the drugs were used in combination, the results indicated clear synergistic as shown by a concave isobologram and FIC value.   Conclusion: The present study represents the evidence that the combination of amiodarone plus ketoconazole acts synergistically in controlling L. infantume in vitro. It is possible that amiodarone could be used in combination with ketoconazole to combat infection at low doses, thus reducing its side

  5. Effect of amiodarone-induced hyperthyroidism on left ventricular outflow obstruction after septal myectomy for hypertrophic cardiomyopathy.

    Science.gov (United States)

    Pokorney, Sean D; Stone, Neil J; Passman, Rod; Oyer, David; Rigolin, Vera H; Bonow, Robert O

    2010-12-01

    Patients with obstructive hypertrophic cardiomyopathy who undergo septal myectomy are at risk for developing postoperative atrial fibrillation. Amiodarone is effective in treating this arrhythmia but is associated with multiple adverse effects, often with delayed onset. A novel case is described of a patient who developed type 2 amiodarone-induced hyperthyroidism that presented as recurrence of outflow obstruction after septal myectomy. The patient's symptoms and echocardiographic findings of outflow obstruction resolved substantially with the treatment of the amiodarone-induced hyperthyroidism. Amiodarone-induced hyperthyroidism of delayed onset can be a subtle diagnosis, requiring a high index of suspicion. In conclusion, recognition of this diagnosis in patients with recurrence of outflow obstruction by symptoms and cardiac imaging after septal myectomy may avoid unnecessary repeat surgical intervention. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Sternal Route More Effective than Tibial Route for Intraosseous Amiodarone Administration in a Swine Model of Ventricular Fibrillation.

    Science.gov (United States)

    Burgert, James M; Martinez, Andre; O'Sullivan, Mara; Blouin, Dawn; Long, Audrey; Johnson, Arthur D

    2018-01-01

    The pharmacokinetics of IO administered lipid soluble amiodarone during ventricular fibrillation (VF) with ongoing CPR are unknown. This study measured mean plasma concentration over 5 minutes, maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) of amiodarone administered by the sternal IO (SIO), tibial IO (TIO), and IV routes in a swine model of VF with ongoing CPR. Twenty-one Yorkshire-cross swine were randomly assigned to three groups: SIO, TIO, and IV. Ventricular fibrillation was induced under general anesthesia. After 4 minutes in VF, 300 mg amiodarone was administered as indicated by group assignment. Serial blood specimens collected at 30, 60, 90, 120, 150, 180, 240, and 300 seconds were analyzed using high performance liquid chromatography with tandem mass spectrometry. The mean plasma concentration of IV amiodarone over 5 minutes was significantly higher than the TIO group at 60 seconds (P = 0.02) and 90 seconds (P = 0.017) post-injection. No significant differences in Cmax between the groups were found (P <0.05). The Tmax of amiodarone was significantly shorter in the SIO (99 secs) and IV (86 secs) groups compared to the TIO group (215 secs); P = 0.002 and P = 0.002, respectively. The SIO and IV routes of amiodarone administration were comparable. The TIO group took nearly three times longer to reach Tmax than the SIO and IV groups, likely indicating depot of lipid-soluble amiodarone in adipose-rich tibial yellow bone marrow. The SIO route was more effective than the TIO route for amiodarone delivery in a swine model of VF with ongoing CPR. Further investigations are necessary to determine if the kinetic differences found between the SIO and TIO routes in this study affect survival of VF in humans.

  7. Variable use of amiodarone is associated with a greater risk of recurrence of atrial fibrillation in the critically ill.

    Science.gov (United States)

    Mitrić, Goran; Udy, Andrew; Bandeshe, Hiran; Clement, Pierre; Boots, Rob

    2016-04-02

    Atrial fibrillation is a common rhythm disturbance in the general medical-surgical intensive care unit. Amiodarone is a popular drug in this setting but evidence to inform clinical practice remains scarce. We aimed to identify whether variation in the clinical use of amiodarone was associated with recurrent atrial fibrillation. This was a retrospective audit of 177 critically ill patients who developed new-onset atrial fibrillation after admission to a tertiary level medical-surgical trauma intensive care unit. Patterns of amiodarone prescription (including dosage schedule and duration) were assessed in relation to recurrence of atrial fibrillation during the intensive care unit stay. Known recurrence risk factors, such as inotrope administration, cardiac disease indices, Charlson Comorbidity Index, magnesium concentrations, fluid balance, and potassium concentrations, were also included in adjusted analysis using forward stepwise logistic regression modelling. The cohort had a median (interquartile range) age of 69 years (60-75), Acute Physiology and Chronic Health Evalution II score of 22 (17-28) and Charlson Comorbidity Index of 2 (1-4). A bolus dose of amiodarone followed by infusion (P = 0.02), in addition to continuing amiodarone infusion through to discharge from the intensive care unit (P < 0.001), were associated with less recurrent dysrhythmia. Recurrence after successful treatment was associated with ceasing amiodarone while an inotrope infusion continued (P < 0.001), and was more common in patients with a prior history of congestive cardiac failure (P = 0.04), and a diagnosis of systemic inflammatory response syndrome (P = 0.02). Amiodarone should be administered as a bolus dose followed immediately with an infusion when treating atrial fibrillation in the medical-surgical intensive care unit. Consideration should be given to continuing amiodarone infusions in patients on inotropes until they are ceased.

  8. Interaction of rivaroxaban with amiodarone, verapamil and diltiazem in patients with atrial fibrillation: terra incognita

    Directory of Open Access Journals (Sweden)

    S. N. Bel'diev

    2016-01-01

    Full Text Available Currently there are no generally accepted guidelines for the use of rivaroxaban together with amiodarone, verapamil or diltiazem in patients with creatinine clearance (CrCl<80 ml/min. Some researchers suggest that in renal failure amiodarone, verapamil and diltiazem contribute to a significant increase in plasma concentrations of rivaroxaban that is accompanied by increased risk of bleeding. According to preliminary calculations, it seems rational to reduce the dose of rivaroxaban when co-administered with these drugs: to 15 mg/day in patients with ClCr 50-79 ml/min and to 10 mg/day in patients with ClCr<50 ml/min.

  9. Inclusion complex of amiodarone hydrochloride with cyclodextrins: preparation, characterization and dissolution rate evaluation

    Directory of Open Access Journals (Sweden)

    Alexandre Machado Rubim

    2017-06-01

    Full Text Available ABSTRACT This study aimed to improve the water solubility of amiodarone hydrochloride (AMH via inclusion complexes with β-cyclodextrin, methyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Inclusion complexes were developed by physical mixture, coevaporation, spray-drying and freeze-drying. Solid state analysis was performed using X-ray powder diffraction, differential scanning calorimetry and scanning electronic microscopy. Thermodynamic studies demonstrate that the inclusion complexes of drug into different cyclodextrins were an exothermic process that occurred spontaneously. Water solubility and drug dissolution rates were significantly increased after the formation of inclusion complexes with the cyclodextrins evaluated in relation to the physical mixture and pure drug. The present study provides useful information for the potential application of complexation with amiodarone HCl. This may be a good strategy for the development of solid pharmaceutical dosage forms.

  10. Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration

    International Nuclear Information System (INIS)

    Trachsel, D.; Tschudi, P.; Portier, C.J.; Kuhn, M.; Thormann, W.; Scholtysik, G.; Mevissen, M.

    2004-01-01

    Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy minishetland ponies during the first 2 days after drug administration and to calculate pharmacokinetic parameters with a physiologically based pharmacokinetic model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that were determined by high-performance liquid chromatography (HPLC). As expected for a K + -channel-blocker, the main effect on the measured ECG could be seen on the ventricular complex, as the QT interval and the T wave showed statistically significant alterations. The doses investigated were well tolerated clinically. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans. It showed a rapid distribution in the tissue, beginning with the rapidly perfused tissue, like the heart, followed by slowly perfused tissues, and finally an accumulation in fat. The half-life for total elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The model predicts that approximately 96% of amiodarone is eliminated as desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2% as other metabolites

  11. Comparative in vitro and in vivo evaluation of three tablet formulations of amiodarone in healthy subjects

    Directory of Open Access Journals (Sweden)

    J Emami

    2010-09-01

    Full Text Available "nBackground and the purpose of the study:The relative in vivo bioavailability and in vitro dissolution studies of three chemically equivalent amiodarone generic products in healthy volunteers was evaluated in three separate occasions. The possibility of a correlation between in vitro and in vivo performances of these tablet formulations was also evaluated. "nMethods: The bioequivalence studies were conducted based on a single dose, two-sequence, cross over randomized design. The bioavailability was compared using AUC0-72, AUC0-∞, Cmax and Tmax. Similarity factor, dissolution efficiency (DE, and mean dissolution time (MDT was used to compare the dissolution profiles. Polynomial linear correlation models were tested using either MDT vs mean residence time (MRT or fraction of the drug dissolved (FRD vs fraction of the drug absorbed (FRA. "nResults: Significant differences were found in the dissolution performances of the tested formulations and therefore they were included in the development of the correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC0-∞, and Cmax of each two formulations in each bioequivalence studies were within the acceptable range of 80-125%. Differences were not observed between the untransformed Tmax values. Poor correlation was found between MRT and MDT of the products. A point-to-point correlation which is essential for a reliable correlation was not obtained between pooled FRD and FRA. The dissolution condition which was used for amiodarone tablets failed for formulations which were bioequivalent in vivo and significant difference between the dissolution characteristics of products (f2<50 did not reflect their in vivo properties. Major conclusions: Bioequivalence studies should be considered as the only acceptable way to ensure the interchangeability and in vivo equivalence of amiodarone generic drug products. The dissolution conditions used of the present study could be used for routine and in

  12. Study with radio aerosol of DTPA technetium-99 m in individuals with pulmonary disease by amiodarone

    International Nuclear Information System (INIS)

    Terra Filho, M.

    1989-01-01

    In order to evaluate the role of the clearance of 99 m Technetium chelated to diethylenetriamine-penta-acetate (99 m Tc-DTPA) in amiodarone induced pulmonary disease, 40 individuals were studied in four groups. After spirometry, where a volume-time curve was registered, all individuals inhaled 740 MBq of 99 m Tc-DTPA diluted in 4 ml of saline, for five minutes. Pulmonary images were obtained in a computerized scintillation camera and 9 regions of interest were selected. (author)

  13. Efficacy and safety of oral amiodarone in controlling heart rate in patients with persistent atrial fibrillation who have undergone digitalisation.

    Science.gov (United States)

    Kochiadakis, George E; Kanoupakis, Emmanuel M; Igoumenidis, Nikolaos E; Mavrakis, Hercules E; Kafarakis, Panagiotis K; Vardas, Panos E

    2005-01-01

    Oral amiodarone has been suggested by some authors for rate control in patients with persistent atrial fibrillation. In this study we evaluated the efficacy and safety of oral amiodarone versus placebo for rate control during exercise and daily activities in patients with chronic atrial fibrillation who had undergone digitalisation. The study group consisted of 53 patients (35 men, mean age 65 +/- 9 years) with persistent atrial fibrillation (mean duration 17 +/- 7 months). All patients had therapeutic levels of digitalis and were under anticoagulation treatment with acenocoumarol. Twenty-eight of them were treated with amiodarone (200 mg per day orally) and 25 received placebo. All patients were assessed with 24-hour ECG monitoring, a maximal symptom-limited cardiopulmonary exercise test and evaluation of adverse events. The mean exercise duration was similar in both groups. Amiodarone produced a lower heart rate than placebo at all exercise levels (p<0.0001 for all). VO2 was similar in both groups whereas O2 pulse was higher in the amiodarone group at all exercise levels. During daily life, heart rate showed a significant circadian pattern in both groups, with higher values during the day than at night (time effect for both p<0.001). The mean value of heart rate under amiodarone was lower than for placebo (75 +/- 10 vs. 86 +/- 12/min, p<0.001) but this difference was due to a significant difference during the day (p<0.001) that was not present during the night (p =0.48). Oral amiodarone is very effective when combined with digoxin for control of heart rate in patients with chronic atrial fibrillation and it should be considered as an alternative treatment when more traditional drugs, such as Ca(+2) inhibitors or b-blockers have proven ineffective or are contraindicated.

  14. Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients.

    Science.gov (United States)

    Iervasi, G; Clerico, A; Bonini, R; Nannipieri, M; Manfredi, C; Sabatino, L; Biagini, A; Donato, L

    1998-01-01

    Amiodarone, a potent class III antiarrhythmic agent with adrenergic antagonism properties, is administered increasingly to diabetic patients with cardiac arrhythmias refractory to all other available forms of therapy. Because a large percentage of diabetic patients show a perturbed autonomic regulation of the cardiovascular system, including a pertubed regulation of heart rate, we studied the antiarrhythmic response as well as the early effects (within 5 days) on heart rate of an intravenous amiodarone loading dose in diabetic patients. Seven type II (noninsulin-dependent) diabetic patients (age 64.7 +/- 9.7 years), affected by uncontrolled atrial fibrilation or atrial flutter, were enrolled for the study and a group of 12 well-matched (for age, sex and arrhythmia) nondiabetic patients served as a control group. It was found that before amiodarone administration, nondiabetic patients showed significantly wider variations in the circadian rhythm of heart rate values than diabetic patients (p = 0.0062, unpaired t-test). In all patients but one (who was nondiabetic), amiodarone treatment resulted in a cardioversion to sinus rhythm. After amiodarone administration, nondiabetic patients showed a significantly greater decrease (p = 0.0011) in heart rate values in comparison with the diabetic group (-35% vs. -20% on average, at the end of the study). Furthermore, in nondiabetic patients there was also an earlier significant fall (within the first 4 h after the start of treatment with amiodarone, p atrial fibrilation or atrial flutter may be delayed in comparison with nondiabetic patients. This altered response may be (at least in part) due to the diabetic autonomic neuropathy. Our study indicates that the presence of diabetes mellitus always must be taken into account when patients are enrolled for large, prospective, randomized trials, planned to evaluate the antiarrhythmic effects of amiodarone given intravenously.

  15. Comparison of amiodarone vs magnesium sulphate in the prevention of atrial fibrillation after coronary artery bypass grafting surgery

    International Nuclear Information System (INIS)

    Bashir, I.; Abbas, S.

    2013-01-01

    Background: Atrial fibrillation (AF) is common in patients after coronary artery bypass grafting (CABG) and can result in increased morbidity and mortality, increased length of hospital stay, and increased cost. In this study we compared the efficacy of amiodarone versus magnesium sulphate in the prophylaxis of post-CABG atrial fibrillation. Objective: This study was carried out to assess the efficacy of amiodarone in comparison to magnesium sulphate in the prevention of atrial fibrillation after coronary artery bypass grafting. Study Design: Randomized controlled trials. Place and duration of study: The study was carried out at Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi from July 2010 to December 2011 Patients and Methods: Total 240 patients were included in the study and randomly divided in two groups of 120 each using random number table. Patients in Group A (Amiodarone group) were given a loading dose of amiodarone 5 mg/Kg after induction of anesthesia which was then continued as infusion at 5 micro gm/Kg/minute on first postoperative day. This was followed by an oral dose of 600 mg/day postoperatively for 5 days. Those in Group B (Magnesium Sulphate group) received 2 g of magnesium sulphate in 100 ml of isotonic 0.9% solution intravenously over 1 hour at following times: preoperatively, immediately following the operation, and on postoperative days 1, 2, and 3. Results: Thirteen patients (10.8%) developed AF in Amiodarone group, compared to 31 patients (25.8%) in magnesium sulphate group. The results proved amiodarone to be more effective than magnesium sulphate in preventing post-CABG AF (p<0.001). Thirty one patients who developed AF postoperatively in the magnesium group were treated with amiodarone, and all patients recovered normal sinus rhythm. In the amiodarone prophylaxis group, 9 patients regained sinus rhythm in 6 - 8 hours, while for 4 remaining patients cardioversion was attempted out of which 2

  16. Amiodarone use after acute myocardial infarction complicated by heart failure and/or left ventricular dysfunction may be associated with excess mortality

    DEFF Research Database (Denmark)

    Thomas, Kevin L; Al-Khatib, Sana M; Lokhnygina, Yuliya

    2008-01-01

    , a randomized comparison of valsartan, captopril, or both in patients with acute myocardial infarction with HF and/or left ventricular systolic dysfunction. We compared baseline characteristics of 825 patients treated with amiodarone at randomization with 13,875 patients not treated with amiodarone. Using Cox...

  17. High-resolution sub-cellular imaging by correlative NanoSIMS and electron microscopy of amiodarone internalisation by lung macrophages as evidence for drug-induced phospholipidosis.

    Science.gov (United States)

    Jiang, Haibo; Passarelli, Melissa K; Munro, Peter M G; Kilburn, Matt R; West, Andrew; Dollery, Colin T; Gilmore, Ian S; Rakowska, Paulina D

    2017-01-26

    Correlative NanoSIMS and EM imaging of amiodarone-treated macrophages shows the internalisation of the drug at a sub-cellular level and reveals its accumulation within the lysosomes, providing direct evidence for amiodarone-induced phospholipidosis. Chemical fixation using tannic acid effectively seals cellular membranes aiding intracellular retention of diffusible drugs.

  18. Dysfunction of the thyroid gland during amiodarone therapy: a study of 297 cases

    Directory of Open Access Journals (Sweden)

    Czarnywojtek A

    2016-04-01

    Full Text Available Agata Czarnywojtek,1,2,* Maria Teresa Płazińska,3,* Małgorzata Zgorzalewicz-Stachowiak,4 Kosma Woliński,1 Adam Stangierski,1 Izabela Miechowicz,5 Joanna Waligórska-Stachura,1 Paweł Gut,1 Leszek Królicki,3 Maja Zioncheck,6 Marek Ruchała1 1Department of Endocrinology, Metabolism and Internal Medicine, 2Department of Pharmacology, Poznan University of Medical Sciences, Poznan, 3Nuclear Medicine Department, Medical University of Warsaw, Warsaw, 4Department of Health Prophylaxis, Laboratory of Medical Electrodiagnostics, 5Department of Computer Science and Statistics, 6Poznan University of Medical Sciences, Poznan, Poland *These authors contributed equally to this work Aim: This study aims to explore and compare the efficacy of radioiodine treatment (RIT in hyperthyroid and euthyroid patients who have been treated with amiodarone (AM in the past or are currently undergoing AM treatment. Clinical observation of a group of patients with amiodarone-induced hypothyroidism during a 12-month follow-up period was used for comparison.Design: This was a observational, two-centered study. Patients were assessed at baseline and at 2 months, 6 months, 8 months, and 12 months after RIT.Patients: Group A: At baseline (61 males [M] and 17 females [F], mean age 50±19 years, there were 78 euthyroid patients with cardiac arrhythmias, who were treated with AM and developed amiodarone-induced thyrotoxicosis, and currently require retreatment with AM. Group B: Hyperthyroid patients (92 M and 26 F, mean age 72±11.8 years after AM therapy in the past. Group C: Hyperthyroid patients (66 M and 13 F, mean age 63.9±13.2 years currently treated by AM. Group D: Hypothyroid patients (6 M and 16 F, mean age 61.4±10.4 years after AM therapy. The patients from Groups A, B, and C were retreated with AM after ~3–6 weeks of RIT.Results: In Group A, after 12 months of RIT therapy, recurrent thyrotoxicosis was observed in six (7.7% cases, and persistent

  19. Amiodarona y disfunción tiroidea Amiodarone and thyroid dysfunction

    Directory of Open Access Journals (Sweden)

    Leonardo F. L. Rizzo

    2012-02-01

    Full Text Available La amiodarona es un análogo estructural de la hormona tiroidea, y algunas de sus propiedades antiarrítmicas como así también su toxicidad son atribuibles a su interacción con los receptores nucleares de las hormonas tiroideas. Por ser muy lipofílica, la amiodarona se concentra en muchos tejidos y se elimina, por consecuencia, muy lentamente. Se emplea preferentemente para el tratamiento de arritmias graves tales como fibrilación y taquicardia ventriculares. Otras indicaciones incluyen la fibrilación auricular y el aleteo, la insuficiencia cardíaca congestiva grave, la prevención de la fibrilación auricular recurrente y situaciones de emergencia médica como la prevención de muerte súbita cardiaca¹. Nuestro objetivo es proporcionar un enfoque actualizado sobre la amiodarona y su influencia sobre la fisiología tiroidea y discutir y analizar en profundidad sus potenciales efectos adversos como el hipotiroidismo y la tirotoxicosis.Amiodarone is a structural analogue of thyroid hormone, and some of its anti-arrhythmic actions and toxicity are attributable to its interaction with nuclear receptors of thyroid hormones. Being highly lipophilic, amiodarone is concentrated in many tissues and is eliminated, consequently, very slowly. It is preferably employed to manage life-threatening arrhythmias, including ventricular fibrillation and unstable ventricular tachycardia. Other indications include atrial fibrillation and flutter, severe congestive heart failure, prevention of atrial fibrillation recurrence, and even in emergency medical situations to prevent sudden cardiac death. The aim of this review is to provide an updated approach on amiodarone and its influence on thyroid physiology and to discuss and analyze in depth its potential and not infrequent thyroidal adverse effects such as hypothyroidism and thyrotoxicosis.

  20. Effects of amiodarone therapy on thyroid iodine content as measured by x-ray fluorescence

    International Nuclear Information System (INIS)

    Fragu, P.; Schlumberger, M.; Davy, J.M.; Slama, M.; Berdeaux, A.

    1988-01-01

    Thyroid iodine content (TIC) was measured by x-ray fluorescence in 68 patients who had received amiodarone treatment for varying intervals (1 g/week for 1-120 months). Thirty-six patients were euthyroid; the mean TIC of the patients (n = 15), who had been treated for less than 12 months was 30 +/- 19 (+/- SD) mg, twice the normal mean value (14.6 +/- 5.0 mg), and it was 39 +/- 17 mg in those (n = 16) who had been treated for 12-60 months and 29 +/- 6 mg in those (n = 5) who had been treated longer (greater than 60 months). Nineteen patients were hyperthyroid and had elevated TIC values. Of them, 6 patients had a goiter; their TIC (50 +/- 19 mg) was not significantly different from that of the hyperthyroid patients with no goiter (55 +/- 29 mg), but they became hyperthyroid more rapidly. Thirteen patients were hypothyroid; none had TIC values above the normal range, and it was below 2.5 mg in 5 patients. A sequential study was undertaken in 11 euthyroid patients who had no detectable antithyroid antibodies. TIC did not increase during treatment in 2 patients; both developed hypothyroidism, which was transient in 1 despite continuation of amiodarone treatment. The TIC initially increased during amiodarone treatment in the other 9 patients, leveling off at the end of the first year. The TIC rose well above the upper limit of the normal range in 4 patients, of whom 2 became hyperthyroid during the second year of treatment. TIC remained within the normal range in the other 5 patients, of whom 3 became hypothyroid after 12-24 months of treatment (1 subclinical, 2 overt). Although the TIC was significantly higher in the patients with hyperthyroidism than in the patients who remained euthyroid, the TIC test cannot be used to predict the occurrence of hyperthyroidism

  1. Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats

    OpenAIRE

    Nasri, Hamid-Reza; Joukar, Siyavash; Kheradmand, Hamid; Poursalehi, Hamid-Reza; Dabiri, Shahriar

    2015-01-01

    Objective The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. Materials and Methods Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 we...

  2. Role of Pre-incision, Intravenous Prophylactic Amiodarone to Control Arrhythmias in Patients with Rheumatic Valvular Heart Disease undergoing Mitral Valve Replacement

    International Nuclear Information System (INIS)

    Ahmad, K.; Naqvi, S.

    2013-01-01

    Objective: To evaluate the effect of intra-operative single intra venous dose of amiodarone on post operative cardiac arrhythmias in patients undergoing valvular heart surgery. Study Design: Randomized controlled trials. Place and Duration of surgery: This study was performed at Armed forces Institute of Cardiology Rawalpindi from Jan 01, 2011 to Dec 31, 2011. Patients and Methods: In this study 80 patients with rheumatic valvular heart disease and undergoing elective mitral valve replacement were randomly divided into two groups. Group I, n = 40 (Amiodarone group) was given single intravenous dose of amiodarone (5 mg/kg in 100 ml of saline over 30 min) before sternotomy incision. Group II, n = 40(control / placebo group) was given 100 ml of saline over 30 min. Result: In the amiodarone group, after removal of aortic cross clamp 75% patients had sinus rhythm compared to 47.5% in control group. p=0.045. Similarly 15% had AF, 5% JR and 5% VT/VF in amiodarone group in contrast to 32.5% with AF, 12.5% JR and 7.5% Vt/VF in control group. (p=0.045). Response to cardioversion was positive in 75% of the patients requiring shocks in amiodarone group as against 43.75% in the control group. (p=0.044). Conclusion: A single intravenous bolus dose of amiodarone is effective in decreasing the incidence of cardiac arrhythmias after mitral valve replacement in patients with rheumatic MVD. (author)

  3. Efficacy of amiodarone and lidocaine for preventing ventricular fibrillation after aortic cross-clamp release in open heart surgery: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zheng, Yong; Gu, Qiang; Chen, Hong-Wu; Peng, Huai-Ming; Jia, Dong-Yu; Zhou, Yu; Xiang, Mei-Xiang

    The relative preventative efficacy of amiodarone and lidocaine for ventricular fibrillation (VF) after release of an aortic cross-clamp (ACC) during open heart surgery has not been determined. This meta-analysis was designed to systematically evaluate the influence of amiodarone, lidocaine, or placebo on the incidence of VF after ACC. Prospective randomized controlled trials (RCTs) that compared the VF-preventative effects of amiodarone with lidocaine, or amiodarone or lidocaine with placebo were included. PubMed, EMBASE, and the Cochrane Library were searched for relevant RCTs. Fixed or randomized effect models were applied according to the heterogeneity of the data from the selected studies. We included eight RCTs in the analysis. Pooled results suggested that the preventative effects of amiodarone and lidocaine were comparable (relative risk (RR)=1.12, 95% confidence interval (CI): 0.70 to 1.80, P=0.63), but both were superior to the placebo (amiodarone, RR=0.71, 95% CI: 0.51 to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI: 0.46 to 0.88, P=0.006). The percentage of patients requiring electric defibrillation counter shocks (DCSs) did not differ significantly among patients administered amiodarone (RR=0.21, 95% CI: 0.04 to 1.19, P=0.08), lidocaine (RR=2.44, 95% CI: 0.13 to 44.02, P=0.55), or the placebo (RR=0.56, 95% CI: 0.25 to 1.25, P=0.16). Amiodarone and lidocaine are comparably effective in preventing VF after ACC, but the percentage of patients who subsequently require DCSs does not differ among those administered amiodarone, lidocaine, or placebo.

  4. Effect of single intraoperative dose of amiodarone in patients with rheumatic valvular heart disease and atrial fibrillation undergoing valve replacement surgery

    Directory of Open Access Journals (Sweden)

    Selvaraj Thiruvenkadam

    2009-01-01

    Full Text Available Maintenance of sinus rhythm (SR is superior to rate control in atrial fibrillation (AF. In order to achieve SR, we administered single-dose intravenous amiodarone intraoperatively and evaluated its effect on conversion of rheumatic AF to SR in patients undergoing valvular heart surgery. Patients were randomly assigned to amiodarone ( n = 42 or control ( n = 40 group in a double blind manner. The amiodarone group received amiodarone (3 mg/kg intravenously prior to the institution of cardiopulmonary bypass and the control group received the same volume of normal saline. In the amiodarone group, the initial rhythm after the release of aortic cross clamp was noted to be AF in 14.3% ( n = 6 and remained so in 9.5% ( n = 4 of patients till the end of surgery. In the control group, the rhythm soon after the release of aortic cross clamp was AF in 37.5% ( n = 15 ( p = 0.035 and remained so in 32.5% ( n = 13 of patients till the end of surgery ( p = 0.01. At the end of first post-operative day 21.4% ( n = 9 of patients in amiodarone group and 55% ( n = 22 of patients in control group were in AF ( p = 0.002. The requirement of cardioversion/defibrillation was 1.5 (±0.54 in amiodarone group and 2.26 (±0.73 in the control group ( p = 0.014, and the energy needed was 22.5 (±8.86 joules in the amiodarone group and 40.53 (±16.5 in the control group ( p = 0.008. A single intraoperative dose of intravenous amiodarone increased the conversion rate of AF to normal sinus rhythm, reduced the need and energy required for cardioversion/defibrillation and reduced the recurrence of AF within one day.

  5. Amiodarone and Catheter Ablation as Cardiac Resynchronization Therapy for Children with Dilated Cardiomyopathy and Wolff-Parkinson-White Syndrome

    Science.gov (United States)

    Kim, Sung Hoon; Jeong, Soo In; Kang, I-Seok; Lee, Heung Jae

    2013-01-01

    Preexcitation by accessory pathways (APs) is known to cause dyssynchrony of the ventricle, related to ventricular dysfunction. Correction of ventricular dyssynchrony can improve heart failure in cases of dilated cardiomyopathy (DCMP) with preexcitation. Here, we report the first case of a child with DCMP and Wolff-Parkinson-White (WPW) syndrome treated with amiodarone and radiofrequency catheter ablation (RFCA) in Korea. A 7-year-old boy, who suffered from DCMP and WPW syndrome, showed improved left ventricular function and clinical functional class after treatment with amiodarone to eliminate preexcitation. QRS duration and left ventricular ejection fraction (LVEF) were inversely correlated with amiodarone dosage. After confirming the reduction of preexcitation effects in DCMP, successful RFCA of the right anterior AP resulted in LVEF improvement, along with the disappearance of preexcitation. Our findings suggest that ventricular dyssynchrony, caused by preexcitation in DCMP with WPW syndrome, can worsen ventricular function and amiodarone, as well as RFCA, which should be considered as a treatment option, even in young children. PMID:23407697

  6. Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

    Science.gov (United States)

    Pomponio, Giuliana; Zurich, Marie-Gabrielle; Schultz, Luise; Weiss, Dieter G; Romanelli, Luca; Gramowski-Voss, Alexandra; Di Consiglio, Emma; Testai, Emanuela

    2015-12-25

    The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24 h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14 days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Comparative Study of Nifekalant Versus Amiodarone for Shock-Resistant Ventricular Fibrillation in Out-of-Hospital Cardiopulmonary Arrest Patients

    NARCIS (Netherlands)

    Amino, Mari; Yoshioka, Koichiro; Opthof, Tobias; Morita, Seiji; Uemura, Shunryo; Tamura, Kozo; Fukushima, Tomokazu; Higami, Shigeo; Otsuka, Hiroyuki; Akieda, Kazuki; Shima, Makiyoshi; Fujibayashi, Daisuke; Hashida, Tadashi; Inokuchi, Sadaki; Kodama, Itsuo; Tanabe, Teruhisa

    2010-01-01

    Background: In Japan, intravenous nifekalant ( NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for

  8. Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components

    NARCIS (Netherlands)

    Stoykov, I.; van Beeren, H. C.; Moorman, A. F. M.; Christoffels, V. M.; Wiersinga, W. M.; Bakker, O.

    2007-01-01

    OBJECTIVE: In view of their different actions on thyroid hormone receptor (TR) isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron) have different and/or component-specific effects on cardiac gene expression. DESIGN: Rats were treated with AM or Dron and the expression

  9. Ready-to-use parenteral amiodarone : A feasibility study towards a long-term stable product formulation

    NARCIS (Netherlands)

    Jacobs, Maartje S.; Luinstra, Marianne; Moes, Jan Reindert; Chan, Tiffany C. Y.; Minovic, Isidor; Frijlink, Henderik W.; Woerdenbag, Herman J.

    Objectives To determine the feasibility of preparing a long-term stable ready-to-use parenteral amiodarone formulation using cyclodextrins as dissolution enhancer. Methods A preformulation study was performed with different molar ratios of hydroxypropyl-beta-cyclodextrin (HP-BCD) or

  10. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation

    DEFF Research Database (Denmark)

    Camm, A John; Capucci, Alessandro; Hohnloser, Stefan H

    2011-01-01

    with 32.8% of amiodarone patients; p = 0.0012). Serious adverse events or events leading to discontinuation of study drug were uncommon. There were no cases of torsades de pointes, ventricular fibrillation, or polymorphic or sustained ventricular tachycardia. Conclusions Vernakalant demonstrated efficacy...... amiodarone infusion, or a 60-min infusion of amiodarone (5 mg/kg) followed by a maintenance infusion (50 mg) over an additional 60 min, plus a sham vernakalant infusion. Results Conversion from AF to sinus rhythm within the first 90 min (primary end point) was achieved in 60 of 116 (51.7%) vernakalant...

  11. The effects of nifekalant hydrochloride on the spatial dispersion of repolarization after direct current defibrillation in patients with oral amiodarone and β-blocker therapy

    Directory of Open Access Journals (Sweden)

    Keiko Maeda

    2014-06-01

    Conclusions: NIF suppressed the deterioration of the SDR after ICD shock. This might be one of the mechanisms by which NIF suppresses recurrence of ventricular tachyarrhythmia just after ICD shock in patients with oral amiodarone and β-blocker therapy.

  12. Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA)

    Science.gov (United States)

    Doval, H C; Nul, D R; Grancelli, H O; Perrone, S V; Bortman, G R; Curiel, R

    1994-08-20

    In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias. The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure. Our prospective multicentre trial included 516 patients on optimal standard treatment for heart failure. Patients were randomised to 300 mg/day amiodarone (260) or to standard treatment (256). Intention-to-treat analysis showed 87 deaths in the amiodarone group (33.5%) compared with 106 in the control group (41.4%) (risk reduction 28%; 95% CI 4%-45%; log rank test p = 0.024). There were reductions in both sudden death (risk reduction 27%; p = 0.16) and death due to progressive heart failure (risk reduction 23%; p = 0.16). Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure (119 versus 149 in the control group; risk reduction 31%; 95% CI 13-46%; p = 0.0024). The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia. Side-effects were reported in 17 patients (6.1%); amiodarone was withdrawn in 12. Low-dose amiodarone proved to be an effective and reliable treatment, reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias.

  13. Thyroid iodine content measured by x-ray fluorescence in amiodarone-induced thyrotoxicosis: concise communication

    International Nuclear Information System (INIS)

    Leger, A.F.; Fragu, P.; Rougier, P.; Laurent, M.F.; Tubiana, M.; Savole, J.C.

    1983-01-01

    Iodine-induced thyrotoxicosis (IiT) is characterized by (a) a low radioiodine uptake, increased by exogenous TSH, and (b) a spontaneous evolution towards cure within a few months. An hypothetical pathogenesis of IiT is an initial inflation in the stores of thyroid hormones during iodine excess, followed by their sudden discharge into the circulation. Thyroid iodine content was measured by fluorescent scanning in 10 patients with amiodarone-induced thyrotoxicosis and in various control groups. Results were found to be high at the onset of the disease and to decrease during its course. The data agree with the hypothetical pathogenesis. Furthermore they may permit exclusion of a painless subacute thyroiditis, which is the main differential diagnosis of IiT

  14. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2016-02-01

    Full Text Available Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Patrick A Schweizer,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, Heidelberg University Hospital, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX.Aim: The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF and mortality after HTX.Methods: Five hundred and thirty patients (age ≥18 years receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year were compared to those without long-term use (none or <1 year of amiodarone. Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan–Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival.Results: Of the 530 patients, 74 (14.0% received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff–Parkinson–White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105. Further, Kaplan–Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this

  15. Simultaneous determination of amiodarone and its metabolite desethylamiodarone by high-performance liquid chromatography with chemiluminescent detection

    International Nuclear Information System (INIS)

    Perez-Ruiz, Tomas; Martinez-Lozano, Carmen; Garcia-Martinez, Maria Dolores

    2008-01-01

    A novel method was developed for the determination of amiodarone and desethylamiodarone by high-performance liquid chromatography (HPLC) coupled with chemiluminescent (CL) detection. The procedure is based on the post-column photolysis of the analytes into photoproducts which are active in the tris(2,2'-bipyridyl)ruthenium(III) [Ru(bpy) 3 3+ ] CL system. Ru(bpy) 3 3+ was on-line generated by photo-oxidation of the Ru(II) complex in the presence of peroxydisulfate. The separation was carried out on a Mediterranea C 18 column with isocratic elution using a mixture of methanol and 0.017 mol L -1 ammonium sulfate buffer of pH 6.8. Under the optimum conditions, analytical curves, based on standard solutions, were linear over the range 0.1-50 μg mL -1 for amiodarone and 0.5-25 μg mL -1 for desethylamiodarone. The detection limits of amiodarone and desethylamiodarone were 0.02 and 0.11 μg mL -1 , respectively. Intra- and inter-day precision values of 0.9% relative standard deviation (R.S.D.) (n = 10) and 1.6% R.S.D. (n = 15), respectively, were obtained. The method was applied successfully to the determination of these compounds in serum and pharmaceutical formulations

  16. Effects of injection-site splinting on the incidence of phlebitis in patients taking peripherally infused amiodarone: A randomized clinical trial.

    Science.gov (United States)

    Ayat-Isfahani, Farah; Pashang, Mina; Davoudi, Bita; Sadeghian, Saeed; Jalali, Arash

    2017-03-01

    Intravenous amiodarone is considered an effective treatment option for cardiac ventricular and atrial arrhythmias. Peripheral infusion of amiodarone may cause blood vessels irritation and phlebitis that is the most common complication of this drug by this route even when it is administered within recommended dosing limits. The effect of injection-site splinting on the occurrence of phlebitis among a group of cardiac arrhythmia patients receiving peripherally infused amiodarone. This research is a clinical trial on patients of Tehran Heart Center who were hospitalized due to cardiac arrhythmias. A sample of 60 patients with mean age 65 ± 14 years were randomly divided into control and test groups. In the experimental group with close splint and restrict the movement of the injection site until the end of the infusion and control groups without closing brace, at the same time received amiodarone. Injection protocol was similar for both groups. The results were analyzed with Spss18. The results of this research still significantly reduced the incidence of amiodarone injection-site phlebitis in the injection time (P = .005). Copyright © 2016 Society for Vascular Nursing, Inc. Published by Elsevier Inc. All rights reserved.

  17. Amiodarone increases the accumulation of DEA in a human alveolar epithelium-derived cell line.

    Science.gov (United States)

    Seki, Satoru; Itagaki, Shirou; Kobayashi, Masaki; Hirano, Takeshi; Iseki, Ken

    2008-07-01

    Amiodarone (AMD)-induced pulmonary toxicity (AIPT) is the most life-threatening side-effect of AMD treatment. N-Monodesethylamiodarone (DEA), an active metabolite of AMD, also exhibits cytotoxicity and tends to accumulate in the lung more intensively than AMD. In this study, we characterized the mechanism of DEA accumulation using A549 cells as a model of the alveolar epithelium. Typical ATP-depletion compounds caused an approximately 30% increase in the accumulation of DEA in A549 cells, although these effects were less than those in Caco-2 cells. Triiodothyronine (T(3)), which exhibited an inhibitory effect on DEA efflux in Caco-2 cells, did not affect the accumulation of DEA in A549 cells. On the other hand, 100 microM AMD caused an approximately 200% increase in DEA content in A549 cells, although AMD accumulation was not affected by 100 microM DEA. Since the reducing effect of AMD on cellular ATP levels and that of FCCP were similar, the mechanism by which DEA accumulation is increased by AMD might be different from the ATP-dependent DEA efflux mechanism. The decrease in cell viability by DEA in the presence of AMD (IC(50) value of DEA for A549 cell viability: 25.4+/-2.4 microM) was more pronounced than that by DEA alone (IC(50) value: 11.5+/-3.0 microM). This further DEA accumulation by AMD might be a factor responsible for the greater accumulation of DEA than that of AMD in the lung in long-term AMD-treated patients.

  18. Improvement of the myocardial performance index in atrial fibrilation patients treated with amiodarone after cardioversion.

    Science.gov (United States)

    Besli, Feyzullah; Basar, Cengiz; Kecebas, Mesut; Turker, Yasin

    2015-03-01

    This study evaluated the response to electrical cardioversion (EC) and the effect on the myocardial performance index (MPI) in patients with persistent and long-standing persistent atrial fibrillation (AF). We enrolled 103 patients (mean age 69.6 ± 8.9 years, 40.7% males) with a diagnosis of persistent and long-standing persistent AF. EC was applied to all patients after one g of amiodarone administration. Echocardiographic findings before EC were compared in patients with successful versus unsuccessful cardioversions and in patients with maintained sinus rhythm (SR) versus those with AF recurrence at the end of the first month. We also compared echocardiographic data before EC versus at the end of the first month in the same patients with maintained SR. SR was achieved in 72.8% of patients and was continued at the end of the first month in 69.3% of the patients. The MPI value of all patients was found to be 0.73 ± 0.21. The size of the left atrium was determined to be an independent predictor of the maintenance of SR at 1 month. In subgroup analyses, when we compared echocardiographic findings before EC and at the end of the first month in patients with maintained SR, the MPI (0.66 ± 0.14 vs 0.56 ± 0.09, p < 0.001) values were significantly decreased. Our study is the first to show impairment of the MPI, which is an indicator of systolic and diastolic function, in patients with persistent and long-standing persistent AF and improvement of the MPI after successful EC.

  19. Effects of Amiodarone and N-Desethylamiodarone on Cardiac Voltage-gated Sodium Channels

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza eGhovanloo

    2016-03-01

    Full Text Available Amiodarone (AMD is a potent antiarrhythmic drug with high efficacy for treating atrial fibrillation and tachycardia. The pharmacologic profile of AMD is complex. AMD possesses biophysical characteristics of all of class I, II, III, and IV agents. Despite its adverse side effects, AMD remains the most commonly prescribed antiarrhythmic drug. AMD was described to prolong the QT interval and can lead to torsades de pointes. Our goal was to study the effects of AMD on peak and late sodium currents (INa,P and INa,L and determine whether these effects change as AMD is metabolized into N-Desethylamiodarone (DES. We hypothesized that AMD and DES block both INa,P and INa,L with similar profiles due to structural similarities. Given the inherent small amounts of INa,L in NaV1.5, we screened AMD and DES against the Long QT-3-causing mutation, ∆KPQ, to better detect any drug-mediated effect on INa,L. Our results show that AMD and DES do not affect WT or ∆KPQ activation; however, both drugs altered the apparent valence of steady-state fast-inactivation. In addition, AMD and DES preferentially block ∆KPQ peak conductance compared to WT. Both compounds significantly increase INa,L and window currents. We conclude that both compounds have pro-arrhythmic effects on NaV1.5, especially ∆KPQ; however, DES seems to have a greater pro-arrhythmic effect than AMD.

  20. Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis.

    Science.gov (United States)

    Lombardi, Angela; Inabnet, William Barlow; Owen, Randall; Farenholtz, Kaitlyn Ellen; Tomer, Yaron

    2015-01-01

    Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2α (eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.

  1. Heart rate is a marker of amiodarone mortality reduction in severe heart failure. The GESICA-GEMA Investigators. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina-Grupo de Estudios Multicéntricos en Argentina.

    Science.gov (United States)

    Nul, D R; Doval, H C; Grancelli, H O; Varini, S D; Soifer, S; Perrone, S V; Prieto, N; Scapin, O

    1997-05-01

    The impact of amiodarone on mortality in patients with severe congestive heart failure (CHF) (New York Heart Association functional classes II [advanced], III and IV; left ventricular ejection fraction Insuficiencia Cardiaca en Argentina (GESICA) trial was analyzed in relation to initial mean baseline heart rate (BHR) and its change after 6 months of follow-up. Trials of amiodarone therapy in CHF have produced discordant results, suggesting that the effect is not uniform in all patient subgroups with regard to survival. The present analysis was carried out in 516 patients randomized to receive amiodarone, 300 mg/day (n = 260), or nonantiarrhythmic therapy (n = 256, control group) and followed up for 2 years. Survival was evaluated for patients with a BHR > or = 90 beats/min (control: n = 132; amiodarone: n = 122) and or = 90 beats/min, amiodarone therapy reduced mortality to 38.4% compared with 62.4% in control patients (relative risk [RR] 0.55, 95% confidence interval [CI] 0.35 to 0.95, p or = 90 beats/min, which was reduced at 6 months. Elevated rest heart rates in severe CHF identify a subgroup of patients who benefit from treatment with amiodarone. Amiodarone-induced heart rate slowing may be an important benefit for patients.

  2. Effect of amiodarone on the conversion of thyroxine to triiodotironine in rat myocardium in vivo and in vitro

    International Nuclear Information System (INIS)

    Ceppi, J.A.; Gonzalez, M.R.; Zaninovich, A.A.

    1988-01-01

    It was studied the effect of the antiarrhythmic drug amiodarone, on the conversion of T 4 to T 3 by rat myocardium and liver. Wistar rats were injected with amiodarone (AM) or iopanoic acid (IOP), afterwards the liver and the heart were homogenized in krebs-ringer phosphate. Aliquots of 400μl of the homogenized were separated and DTT 8mM and 10 -2 μCi 125 I-T 4 or 125 I-T 3 were added (either the conversion of T 4 to T 3 or degradation of T 3 are measured). In vitro: were added AM 0,1 mM or IOP 10mM. Incubation proceeded for 2 hours at 37 deg C and aliquots were chromatographied. The conversion of T 4 to T 3 in the myocardium and liver in vivo decreased, but in vitro did not have any deiodination of T 4 and the IOP reduced the production of T 3 by heart. Neither drug altered the deiodination of T 3 by heart or liver homogenates. Serum TSH and T 3 were decreased by AM and serum T 4 increased. IOP caused similar variations in T 4 and T 3 , but serum TSH was increased. It is concluded that blocking the T 3 miocardial production by AM may not be the cause of the antiarrhythmic effect of the drug. (M.E.L.) [es

  3. AMIODARONE INDUCES THE SYNTHESIS OF HSPS IN SACCHAROMYCES CEREVISIAE AND ARABIDOPSIS THALIANA CELLS

    Directory of Open Access Journals (Sweden)

    Pyatrikas D.V.

    2012-08-01

    Full Text Available Many biotic and abiotic stresses cause an increase of cytosolic Ca2+ level in cells. Calcium is one of the most important second messengers, regulating many various activities in the cell and was known to affect expression of stress activated genes. Mild heat shock induces the expression of heat shock proteins (Hsps which protect cell from drastic heat shock exposure. There are some literature data permitting to suggest that transient elevation of cytosolic Ca2+ level in plant cells is important for activation of Hsps expression. On the other hand mitochondria are known to regulate the intracellular calcium and reactive oxygen species signaling. It has been shown recently that mild heat shock induces hyperpolarization of inner mitochondrial membrane in plant and yeast cells and this event is critically important for activation of Hsps expression. To reveal the relationship between mitochondrial activity, intracellular calcium homeostasis and Hsps expression an antiarrhythmic drug amiodarone (AMD have been used. AMD is known to cause transient increase of cytosolic Ca2+ level in Saccharomyces cerevisiae. Obtained results have showed that AMD treatment induced the synthesis of Hsp104p in S. cerevisiae cells and Hsp101p in A. thaliana cell culture. Induction of Hsp104p synthesis leads to enhanced yeast capability to survive lethal heat shock exposure. Development of S. cerevisiae thermotolerance depended significantly on the presence of Hsp104p. Elevation of Hsp104p level in the result of AMD treatment was shown to be governed by activity of Msn2p and Msn4p transcription factors. Deletion of the MSN2 and MSN4 genes abrogated the AMD ability to induce Hsp104p synthesis. Mild heat shock and AMD treatment induced the hyperpolarization of the inner mitochondrial membrane in yeast and Arabidopsis cells which accompanied by HSP synthesis and development of thermotolerance. It was suggested that increase of cytosolic Ca2+ level after AMD treatment

  4. Amiodarone therapy in chronic heart failure and myocardial infarction: a review of the mortality trials with special attention to STAT-CHF and the GESICA trials. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina.

    Science.gov (United States)

    Pinto, J V; Ramani, K; Neelagaru, S; Kown, M; Gheorghiade, M

    1997-01-01

    Amiodarone appears to reduce sudden death in patients with left ventricular dysfunction resulting from an acute MI or a primary dilated cardiomyopathy, particularly if complex ventricular arrhythmias are present. Amiodarone's beneficial effect on mortality in these patients could be unrelated to its antiarrhythmic effects. Multiple factors could account for the improvement in mortality such as the drug's antiischemic effects, neuromodulating effects, its effect on left ventricular function and on heart rate. Moreover, patients with LV dysfunction who have survived an episode of sudden death would potentially benefit from amiodarone therapy. Future trials are needed to determine the precise subsets(s) of patients who would benefit from the drug and the most efficacious dosing regimen for the drug. Based on available data, amiodarone is the only antiarrhythmic agent which has not been shown to increase mortality in patients with chronic heart failure.

  5. Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo).

    Science.gov (United States)

    Kudenchuk, Peter J; Leroux, Brian G; Daya, Mohamud; Rea, Thomas; Vaillancourt, Christian; Morrison, Laurie J; Callaway, Clifton W; Christenson, James; Ornato, Joseph P; Dunford, James V; Wittwer, Lynn; Weisfeldt, Myron L; Aufderheide, Tom P; Vilke, Gary M; Idris, Ahamed H; Stiell, Ian G; Colella, M Riccardo; Kayea, Tami; Egan, Debra; Desvigne-Nickens, Patrice; Gray, Pamela; Gray, Randal; Straight, Ron; Dorian, Paul

    2017-11-28

    Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo ( P discharge ( P =0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias

  6. Combined etiology of anaphylactic cardiogenic shock: Amiodarone, epinephrine, cardioverter defibrillator, left ventricular assist devices and the Kounis syndrome

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    Nicholas G Kounis

    2015-01-01

    Full Text Available Anaphylactic shock is a life-threatening condition which needs detailed and mediculous clinical assessment and thoughtful treatment. Several causes can join forces in order to degranulate mast cells. Amiodarone which is an iodine-containing highly lipophilic benzofuran can induce allergic reactions and anaphylactic shock in sensitized patients. Epinephrine is a life saving drug, but in sulfite allergic patients it should be given with caution due its metabisulfite preservative. Metals covering cardiac defibrillators and pacemakers can act as antigens attached to serum proteins and induce allergic reactions. In anaphylactic shock, myocardial involvement due to vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome should be always considered. Clinically, combined treatment targeting the primary cause of anaphylaxis together with protection of cardiac tissue seems to be of paramount importance.

  7. Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage.

    Science.gov (United States)

    Carrasco, H A; Vicuña, A V; Molina, C; Landaeta, A; Reynosa, J; Vicuña, N; Fuenmayor, A; López, F

    1985-12-01

    Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

  8. Efficacy of topical chamomile on the incidence of phlebitis due to an amiodarone infusion in coronary care patients: a double-blind, randomized controlled trial.

    Science.gov (United States)

    Sharifi-Ardani, Maryam; Yekefallah, Leili; Asefzadeh, Saeed; Nassiri-Asl, Marjan

    2017-09-01

    Amiodarone is a useful antiarrhythmic drug. Phlebitis, caused by intravenous amiodarone, is common in patients in coronary care units (CCUs). The aim of this study was to evaluate the effect of topical chamomile on the incidence of phlebitis due to the administration of an amiodarone infusion into the peripheral vein. This was a randomized, double-blind clinical trial, conducted on 40 patients (n = 20 per group) in two groups-an intervention group (chamomile ointment) and a control group (lanoline, as a placebo), hospitalized in the CCUs and undergoing an amiodarone infusion into the peripheral vein over 24 h. Following the cannulation and commencement of the infusion, placebo or chamomile ointment was rubbed in, up to 10 cm superior to the catheter and repeated every eight hours for three days. The cannula site was then assessed based on the phlebitis checklist. The incidence and time of occurrence of phlebitis, relative risk, severity of phlebitis were the main outcome measures. Nineteen patients (19/20) in the control group had phlebitis on the first day of the study and one patient (20/20) on the second day. In the intervention group, phlebitis occurred in 13 cases (13/20) on the first day and another two (2/7) was found on the second day. The incidence of phlebitis was significantly different between two groups (P = 0.023). The cumulative incidence of phlebitis in the intervention group (15/20) is significantly later and lower than that in the control group (20/20) during two days (P = 0.008). Two patients in the intervention group did not develop phlebitis at all during the 3-day study. Also, the relative risk of phlebitis in the two groups was 0.68 (P = 0.008 5). A significant difference was not observed with regard to phlebitis severity in both groups. It seems that phlebitis occurred to a lesser extent and at a later time frame in the intervention group compared to control group. Topical chamomile may be effective in decreasing the incidence of phlebitis

  9. Preparation of liposomal amiodarone and investigation of its cardiomyocyte-targeting ability in cardiac radiofrequency ablation rat model

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    Zhuge Y

    2016-05-01

    Full Text Available Ying Zhuge,1,* Zhi-Feng Zheng,1,* Mu-Qing Xie,2 Lin Li,2 Fang Wang,1 Feng Gao2,3 1Department of Cardiology, Shanghai First People’s Hospital of Nanjing Medical University, 2Department of Pharmaceutics, School of Pharmacy, 3Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: The objective of this study was to develop an amiodarone hydrochloride (ADHC-loaded liposome (ADHC-L formulation and investigate its potential for cardiomyocyte targeting after cardiac radiofrequency ablation (CA in vivo. The ADHC-L was prepared by thin-film method combined with ultrasonication and extrusion. The preparation process was optimized by Box–Behnken design with encapsulation efficiency as the main evaluation index. The optimum formulation was quantitatively obtained with a diameter of 99.9±0.4 nm, a zeta potential of 35.1±10.9 mV, and an encapsulation efficiency of 99.5%±13.3%. Transmission electron microscopy showed that the liposomes were spherical particles with integrated bilayers and well dispersed with high colloidal stability. Pharmacokinetic studies were investigated in rats after intravenous administration, which revealed that compared with free ADHC treatment, ADHC-L treatment showed a 5.1-fold increase in the area under the plasma drug concentration–time curve over a period of 24 hours (AUC0–24 h and an 8.5-fold increase in mean residence time, suggesting that ADHC-L could facilitate drug release in a more stable and sustained manner while increasing the circulation time of ADHC, especially in the blood. Biodistribution studies of ADHC-L demonstrated that ADHC concentration in the heart was 4.1 times higher after ADHC-L treatment in CA rat model compared with ADHC-L sham-operated treatment at 20 minutes postinjection. Fluorescence imaging studies further proved that the heart

  10. Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis.

    Science.gov (United States)

    Hoffman, Ewelina; Patel, Aateka; Ball, Doug; Klapwijk, Jan; Millar, Val; Kumar, Abhinav; Martin, Abigail; Mahendran, Rhamiya; Dailey, Lea Ann; Forbes, Ben; Hutter, Victoria

    2017-12-01

    Progress to the clinic may be delayed or prevented when vacuolated or "foamy" alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Cell health, morphology and lipid content were comparable (p content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.

  11. Rational design and synthesis of water-compatible molecularly imprinted polymers for selective solid phase extraction of amiodarone.

    Science.gov (United States)

    Muhammad, Turghun; Cui, Liu; Jide, Wang; Piletska, Elena V; Guerreiro, Antonio R; Piletsky, Sergey A

    2012-01-04

    Novel water-compatible molecularly imprinted polymers (MIPs) selective for amiodarone (AD) were designed via a new methodology which relies on screening library of non-imprinted polymers (NIPs). The NIP library consisted of eighteen cross-linked co-polymers synthesized from monomers commonly used in molecular imprinting. The binding capacity of each polymer in the library was analyzed in two different solvents. Binding in water was used to assess non-specific (hydrophobic) interactions and binding in an appropriate organic solvent was used to assess specific interactions. A good correlation was found between the screening tests and modeling of monomer-template interactions performed using computational approach. Additionally, analysis of template-monomer interactions was performed using UV-vis spectroscopy. As the result, 4-vinylpyridine (4-VP) was selected as the best monomer for developing MIP for AD. The 4-VP-based polymers demonstrated imprinting factor equal 3.9. The polymers performance in SPE was evaluated using AD and its structural analogues. The recovery of AD was as high as 96% when extracted from spiked phosphate buffer (pH 4.5) solution and 82.1% from spiked serum samples. The developed MIP shown as a material with specific binding to AD, comparing to its structural analogues, 1-(2-diethylaminoethoxy)-2,6-diiodo-4-nitrobenzene and lidocaine, which shown 9.9% and 25.4% of recovery from the buffer solution, correspondingly. We believe that the screening of NIP library could be proposed as an alternative to commonly used computational and combinatorial approaches. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Amiodarona causa vasodilatação dependente do endotélio em artérias coronárias caninas Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries

    Directory of Open Access Journals (Sweden)

    Alfredo José Rodrigues

    2005-03-01

    Full Text Available OBJETIVO: Avaliar os efeitos vasodilatadores da amiodarona em artérias coronárias caninas empregando soluções de amiodarona dissolvida em polisorbato 80 ou em água. MÉTODOS: Anéis de artéria coronária, com e sem o endotélio íntegro, foram imersos em solução de krebs e conectadas a um transdutor para aferição de força isométrica promovida por contração vascular. As artérias foram expostas a concentrações crescentes de polisorbato 80, amiodarona dissolvida em água, amiodarona dissolvida em polisorbato 80 e uma apresentação comercial da amiodarona (Cordarone®. Os experimentos foram conduzidos na presença e na ausência dos seguintes bloqueadores enzimáticos: apenas indometacina, Nômega-nitro-L-arginina associada à indometacina e apenas Nômega-nitro-L-arginina. RESULTADOS: O polisorbato 80 causou pequeno relaxamento não dependente do endotélio. O Cordarone®, a amiodarona dissolvida em água e em polisorbato 80 promoveram relaxamento dependente do endotélio, que foi de maior magnitude para a amiodarona dissolvida em polisorbato e para o Cordarone®. Apenas a associação de indometacina com a Nômega-nitro-L-arginina foi capaz de abolir o relaxamento dependente do endotélio provocado pela amiodarona dissolvida em polisorbato 80. CONCLUSÃO: Os resultados obtidos indicam que a vasodilatação promovida pela amiodarona em artérias coronárias caninas é causada principalmente pela estimulação da liberação de óxido nítrico e fatores endoteliais relaxantes dependentes das ciclo-oxigenases.OBJECTIVE: To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water. METHODS: Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of

  13. Disfunção tireoidiana e conduta dos cardiologistas em pacientes usando amiodarona Thyroid dysfunction and cardiological management in patients receiving amiodarone

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    Anna Gabriela Fuks

    2004-06-01

    Full Text Available OBJETIVO: Determinar a prevalência de disfunção tireoidiana em pacientes usando amiodarona e os possíveis fatores associados. Verificar através de questionário aplicado a cardiologistas, a importância do fármaco causar alterações na função tireoidiana. MÉTODO: Avaliados 56 pacientes em uso crônico (> 3 meses de amiodarona com dosagens séricas de TSH, T4 livre, T3 total e Anti-TPO e definidos como portadores de disfunção tireoidiana (DT pacientes com TSH alterado. RESULTADOS: A prevalência de disfunção tireoidiana foi de 33,9%. Não houve diferença entre este grupo e os pacientes sem disfunção, exceto em relação à prevalência de anti-TPO positivo maior nos pacientes com DT (p=0,02. Hipotireoidismo subclínico foi diagnosticado em 10 (17,9% pacientes e hipotireoidismo clínico em 6 (10,7%. A prevalência de hipertireoidismo subclínico foi de 3,6% e de hipertireoidismo clínico de 1,8%. Anticorpos anti-TPO foram positivos em 5 (8% pacientes (dos quais 4 apresentavam disfunção. Quando comparados aos doentes sem anti-TPO positivo este grupo teve maior prevalência de disfunção (80% vs 29,4%; p=0,04. Verificado que apenas 49,2% dos cardiologistas faziam acompanhamento da função tireoidiana rotineiramente e a prevalência de disfunção referida na experiência da maioria era de 1 a 10%. CONCLUSÃO: A prevalência de disfunção tireoidiana na nossa população foi elevada, mostrando a necessidade de implementação de uma rotina laboratorial. Houve grande divergência entre os cardiologistas em relação ao tipo de acompanhamento utilizado nos pacientes em uso de amiodarona.OBJECTIVE: To determine the prevalence of thyroid dysfunction in patients receiving amiodarone, and the possible associated factors. The study also aimed at assessing the effect of amiodarone on thyroid function through the application of a questionnaire to cardiologists. METHOD: Fifty-six patients chronically (> 3 months receiving amiodarone were

  14. Results of preventive radioiodine therapy in euthyroid patients with history of hyperthyroidism prior to administration of amiodarone with permanent atrial fibrillation--a preliminary study.

    Science.gov (United States)

    Czarnywojtek, Agata; Zgorzalewicz-Stachowiak, Małgorzata; Woliński, Kosma; Płazińska, Maria Teresa; Miechowicz, Izabela; Kwiecińska, Barbara; Czepczyński, Rafał; Królicki, Leszek; Ruchała, Marek

    2014-01-01

    Radioiodine (RAI) therapy is a standard procedure in the treatment of hyperthyroidism. However, the use of RAI in euthyroid patients requiring chronic administration of amiodarone (AM) where other antiarrhythmic drugs may lack efficacy is still controversial. The aim of this study was to assess the safety and efficacy of an AM therapy prior to treatment with radioiodine therapy in euthyroid patients with permanent atrial fibrillation (PAF), who had been treated for hyperthyroidism in the past. This was a retrospective observational study. Patients were assessed at baseline and two, six, eight, and 12 months after RAI therapy. 17 euthyroid patients with PAF were qualified to the RAI (female/male 3/14; age range 65 to 87, median 71). The patients required chronic administration of AM as a prophylaxis against sudden death. Each patient received an ablative dose of 800 MBq (22 mCi) of 131I. At baseline and during follow-up, no side effects of the therapy and no signs of drug intolerance were observed. Subclinical hyperthyroidism occurred in two (11.8%) cases after two months of RAI and five weeks of AM administration. In this situation, RAI therapy was repeated. Three patients (17.6%) after six months, and another two (11.8%) after eight months, required an additional dose of 131I due to amiodarone-induced thyrotoxicosis (AIT). Twelve patients (70.6%) returned to spontaneous sinus rhythm within two months. Fourteen patients (82.4%) had sinus rhythm during follow-up after six and 12 months of treatment. Preventive RAI in euthyroid (but previously hyperthyroid) patients with PAF before administration of AM may be the method of choice. This is particularly important for patients who will require permanent AM administration as a life-saving drug.

  15. Methanolic extract of Moringa oleifera leaf and low doses of gamma radiation alleviated amiodarone-induced lung toxicity in albino rats

    Directory of Open Access Journals (Sweden)

    Hasan Hesham F.

    2016-01-01

    Full Text Available This study aimed to evaluate the effects of methanolic extract of Moringa oleifera (MO and/or low doses of gamma radiation (LDR on amiodarone (AMD-induced lung toxicity in rats. AMD administered to female albino rats (100 mg/kg body weight for 10 consecutive days. Rats received methanolic extract of MO (250 mg/kg bwt for 15 successive days and/or were exposed to whole body LDR (0.25Gy on the 1st and 10th days, up to a total dose of 0.5Gy. MO administration induced a significant decrease in serum tumor necrosis factor-alpha (TNF-α and transforming growth factor-beta (TGF-β levels as well as lactate dehydrogenase (LDH activity. Also, the content of malondialdehyde (MDA and hydroxyproline (HYP was significantly decreased in lung tissue. Furthermore, MO significantly increased reduced glutathione (GSH content in lung tissue as compared with AMD. The histopathological investigation of lung tissue revealed the appearance of interstitial pneumonia in rats treated with AMD. The oral administration of MO and/or exposure to LDR reversed the biochemical and histopathological alterations induced by AMD. It can be posited that MO and LDR might have a considerable role in the prevention of lung toxicity induced by AMD.

  16. Tumor necrosis factor-alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress.

    Science.gov (United States)

    Lu, Jingtao; Miyakawa, Kazuhisa; Roth, Robert A; Ganey, Patricia E

    2013-01-01

    Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity. Activation of caspases 9 and 3/7 was observed in AMD/TNF-cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity. Intracellular reactive oxygen species (ROS) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment. Adding water-soluble antioxidants (trolox, N-acetylcysteine, glutathione, or ascorbate) produced only minor attenuation of AMD/TNF-induced cytotoxicity and did not influence the effect of AMD alone. On the other hand, α-tocopherol (TOCO), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD/TNF cotreatment. α-TOCO plus a pancaspase inhibitor completely abolished AMD/TNF-induced cytotoxicity. In summary, activation of caspases and oxidative stress were observed after AMD/TNF cotreatment, and caspase inhibitors and a lipid-soluble free-radical scavenger attenuated AMD/TNF-induced cytotoxicity.

  17. Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation

    Science.gov (United States)

    Robinson, Erik; Kaushal, Sunjay; Alaboson, Justice; Sharma, Sudhish; Belagodu, Amogh; Watkins, Claire; Walker, Brandon; Webster, Gregory; McCarthy, Patrick; Ho, Dean

    2016-02-01

    Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 +/- 6.8 s vs. 187.6 +/- 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 +/- 1.2 s vs. 103.2 +/- 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to

  18. Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats.

    Science.gov (United States)

    Morvay, Nikolett; Baczkó, István; Sztojkov-Ivanov, Anita; Falkay, György; Papp, Julius Gy; Varró, András; Leprán, István

    2015-09-01

    The aim of this investigation was to compare the effectiveness of long-term pretreatment with amiodarone (AMIO) and its active metabolite desethylamiodarone (DEA) on arrhythmias induced by acute myocardial infarction in rats. Acute myocardial infarction was induced in conscious, male, Sprague-Dawley rats by pulling a previously inserted loose silk loop around the left main coronary artery. Long-term oral pretreatment with AMIO (30 or 100 mg·(kg body mass)(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days) or DEA (15 or 50 mg·kg(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days), was applied for 1 month before the coronary artery occlusion. Chronic oral treatment with DEA (50 mg·kg(-1)·day(-1)) resulted in a similar myocardial DEA concentration as chronic AMIO treatment (100 mg·kg(-1)·day(-1)) in rats (7.4 ± 0.7 μg·g(-1) and 8.9 ± 2.2 μg·g(-1)). Both pretreatments in the larger doses significantly improved the survival rate during the acute phase of experimental myocardial infarction (82% and 64% by AMIO and DEA, respectively, vs. 31% in controls). Our results demonstrate that chronic oral treatment with DEA resulted in similar cardiac tissue levels to that of chronic AMIO treatment, and offered an equivalent degree of antiarrhythmic effect against acute coronary artery ligation induced ventricular arrhythmias in conscious rats.

  19. A tomografia computadorizada de alta resolução na avaliação da toxicidade pulmonar por amiodarona High-resolution computed tomography of amiodarone pulmonary toxicity

    Directory of Open Access Journals (Sweden)

    Daniela Peixoto Consídera

    2006-04-01

    Full Text Available OBJETIVO: Avaliar as principais alterações identificadas na tomografia computadorizada de alta resolução do tórax em pacientes com toxicidade pulmonar pela amiodarona. MATERIAIS E MÉTODOS: Foram avaliadas dez tomografias computadorizadas de alta resolução de tórax de pacientes com pneumonite pela amiodarona, seis desses pacientes do sexo masculino e quatro do sexo feminino, com idade média de 73,5 anos. RESULTADOS: Os achados tomográficos mais relevantes foram opacidades lineares ou reticulares em seis casos (60%, pequenos nódulos com densidade elevada em seis casos (60%, consolidações densas em três casos (30% e aumento da densidade do parênquima hepático em cinco de oito casos em que havia estudo tomográfico do abdome superior (62,5%. CONCLUSÃO: A tomografia computadorizada de alta resolução é um exame importante na avaliação de pacientes com toxicidade pulmonar pela amiodarona, devendo ser realizada sempre que houver suspeita deste diagnóstico. O achado de espessamento de septos interlobulares associado a lesões com aumento de densidade é altamente sugestivo deste diagnóstico.OBJECTIVE: To evaluate the main findings of chest high-resolution computed tomography in patients with amiodarone pulmonary toxicity. MATERIALS AND METHODS: Ten patients - six male and four female, average age of 73.5 years - with amiodarone-induced pneumonitis have undergone chest high-resolution computed tomography. RESULTS: The most relevant tomographic findings were linear or reticular opacities in six cases (60%, small high density nodules in six cases (60%, dense consolidations in three cases (30% and increased density in the hepatic parenchyma in five of eight cases in which there was a superior abdomen CT scan (62.5%. CONCLUSION: The high-resolution computed tomography is a valuable non-invasive test for evaluating patients with amiodarone pulmonary toxicity and should always be performed when one suspects of the presence of this

  20. Estudo prospectivo dos efeitos da amiodarona na função tiroidiana de pacientes chagásicos em área de deficiência de iodo Prospective study of amiodarone effects on thyroid function of chagasic patients in an iodine deficient area

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Enes de Barros

    1994-09-01

    Full Text Available Com o objetivo de avaliar a junção tiroidiana após uso crônico da amiodarona, em área de deficiência de iodo e endemia chagásica, 24 pacientes foram analisados antes e após três e nove meses de uso da droga. A avaliação constou de exame clínico, dosagem sérica de T4, T3, rT3, TSH, anticorpo antitiroglobulina e TSH 30 minutos após infusão venosa de uma ampola de 200µg de TRH. A captação do iodo radioativo 131 e a cintilografia datiróide foram realizadas antes e aos 9 meses após tratamento. Disfunção tiroidiana ocorreu em 20,8% dos pacientes sendo 12,5% de hipertiroidismo e 8,3% de hipotiroidismo, com anticorpos antitiroglobulina negativos. Captação do iodo radioativo 131 foi positiva em um paciente hipertiroideo com bócio. O diagnóstico de hipertiroidismo foi melhor evidenciado pela resposta reduzida ou bloqueada do TSH ao TRH e não pela concentração do T3 no soro e o de hipotiroidismo pela concentração elevada do TSH. O TSH elevado desde o início do tratamento pode predispor ao aparecimento de bócio. Concluímos que o uso da amiodarona em nossa região deve serjudiciosamente analisado, sendo a função tiroidiana cuidadosamente monitorizada antes e durante o tratamento.In order to evaluate the development of thyroid dysfunction during chronic amiodarone treatment in an area deficient in iodine and endemic for Chagas 'disease, a group of 24patients wasprospectively studied. Clinical examination and measurement of serum T4, T3, rT3, TSH and antithyroglobulin antibodies were performed before and at 3 and 9 months of use of amiodarone. A TSH response 30 minutes after IV injection of 200µg of TRH was also compared to TSH basal levels before and during amiodarone treatment. Thyroid radioative uptake and scan were obtained before and nine months after amiodarone was started. Elevated rT3 concentrations were unexpectedly found in two thirds of the patients before treatment. Thyroid dysfunction developed during

  1. Emprego de altas doses de amiodarona via oral na reversão da fibrilação atrial no pós-operatório de cirurgia cardíaca High dose amiodarone for the reversion of atrial fibrillation during the postoperative period of cardiac surgery

    Directory of Open Access Journals (Sweden)

    João Carlos Vieira da Costa Guaragna

    1997-12-01

    Full Text Available OBJETIVO: Relatar a experiência no emprego de altas doses de amiodarona via oral (1800mg/d na reversão da fibrilação atrial (FA em pacientes submetidos à cirurgia cardíaca. MÉTODOS: Analisados, retrospectivamente, 80 pacientes que apresentaram FA no pós operatório de cirurgia cardíaca, constituindo 2 grupos: grupo A com 28 pacientes em uso de amiodarona e grupo B recebendo digital, sendo que este grupo foi subdividido no grupo C com 21 pacientes onde foi associada amiodarona, quando não houvesse reversão da arritmia em 48h. As diferenças foram consideradas significativas para um valor de PPURPOSE: To report our experience using high dose oral amiodarone (1,800mg/day for the reversion of atrial fibrillation to sinus rhythm in patients submitted to cardiac surgery. METHODS: We retrospectively analyzed the records of 80 patients who had atrial fibrillation during the postoperative period after cardiac surgery, initially divided in two groups: group A, 28 patients that used amiodarone, and group B composed of patients receiving digoxin. The latter group was divided further in a third group (C, with 21 patients in which amiodarone was associated with digoxin if there was no reversion of the arrhythmia after 48 hours of treatment. The observed differences were considered significant at P<0.05. RESULTS: Atrial fibrillation occurred in 19.4% of the patients submitted to surgery, predominating in males, 60 to 69 years-old. In group A there was reversion to sinus rhythm in 78.6% of the cases. In group B digoxin succeeded in 60%, and in group C 90% of the patients reverted to sinus rhythm. CONCLUSION: High dose oral amiodarone, alone or combined to digoxin, can be safe and effective for the treatment of atrial fibrillation after cardiac surgery.

  2. Interaction between amiodarone and hepatitis-C virus nucleotide inhibitors in human induced pluripotent stem cell-derived cardiomyocytes and HEK-293 Cav{sub 1.2} over-expressing cells

    Energy Technology Data Exchange (ETDEWEB)

    Lagrutta, Armando, E-mail: armando_lagrutta@merck.com; Zeng, Haoyu; Imredy, John; Balasubramanian, Bharathi; Dech, Spencer; Lis, Edward; Wang, Jixin; Zhai, Jin; DeGeorge, Joseph; Sannajust, Frederick

    2016-10-01

    Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases. AMIO co-applied with SOF or MNI-1 increased beating rate or field potential (FP) rate and decreased impedance (IMP) and Ca{sup 2+} transient amplitudes in hiPSC-CM syncytia. This action resembled that of Ca{sup 2+} channel blockers (CCBs) in the model, but CCBs did not substitute for AMIO in the DDI. AMIO analog dronedarone (DRON) did not substitute for, but competed with AMIO in the DDI. Ryanodine and thapsigargin, decreasing intracellular Ca{sup 2+} stores, and SEA-0400, a Na{sup +}/Ca{sup 2+} exchanger-1 (NCX1) inhibitor, partially antagonized or suppressed DDI effects. Other agents affecting FP rate only exerted additive or subtractive effects, commensurate with their individual effects. We also describe an interaction between AMIO and MNI-1 on Cav{sub 1.2} ion channels in an over-expressing HEK-293 cell line. MNI-1 enhanced Cav{sub 1.2} channel inhibition by AMIO, but did not affect inhibition of Cav{sub 1.2} by DRON, verapamil, nifedipine, or diltiazem. Our data in hiPSC-CMs indicate that HCV-NI agents such as SOF and MNI-1 interact with key intracellular Ca{sup 2+}-handling mechanisms. Additional study in a Cav{sub 1.2} HEK-293 cell-line suggests that HCV-NIs potentiate the inhibitory action of AMIO on L-type Ca{sup 2+} channels. - Highlights: • Adverse clinical interaction between amiodarone and HCV-NI drugs is captured by in vitro models. • Human iPSC-derived cardiomyocyte

  3. Interaction between amiodarone and hepatitis-C virus nucleotide inhibitors in human induced pluripotent stem cell-derived cardiomyocytes and HEK-293 Cav1.2 over-expressing cells.

    Science.gov (United States)

    Lagrutta, Armando; Zeng, Haoyu; Imredy, John; Balasubramanian, Bharathi; Dech, Spencer; Lis, Edward; Wang, Jixin; Zhai, Jin; DeGeorge, Joseph; Sannajust, Frederick

    2016-10-01

    Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases. AMIO co-applied with SOF or MNI-1 increased beating rate or field potential (FP) rate and decreased impedance (IMP) and Ca(2+) transient amplitudes in hiPSC-CM syncytia. This action resembled that of Ca(2+) channel blockers (CCBs) in the model, but CCBs did not substitute for AMIO in the DDI. AMIO analog dronedarone (DRON) did not substitute for, but competed with AMIO in the DDI. Ryanodine and thapsigargin, decreasing intracellular Ca(2+) stores, and SEA-0400, a Na(+)/Ca(2+) exchanger-1 (NCX1) inhibitor, partially antagonized or suppressed DDI effects. Other agents affecting FP rate only exerted additive or subtractive effects, commensurate with their individual effects. We also describe an interaction between AMIO and MNI-1 on Cav1.2 ion channels in an over-expressing HEK-293 cell line. MNI-1 enhanced Cav1.2 channel inhibition by AMIO, but did not affect inhibition of Cav1.2 by DRON, verapamil, nifedipine, or diltiazem. Our data in hiPSC-CMs indicate that HCV-NI agents such as SOF and MNI-1 interact with key intracellular Ca(2+)-handling mechanisms. Additional study in a Cav1.2 HEK-293 cell-line suggests that HCV-NIs potentiate the inhibitory action of AMIO on L-type Ca(2+) channels. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Comportamiento de la TSH y la T4 en una cohorte de pacientes con arritmia cardiaca tratados con amiodarona u otros antiarrítmicos Behavior of TSH and T4 in a cohort of patients with cardiac arrhythmia treated with amiodarone or other antiarrhythmics

    Directory of Open Access Journals (Sweden)

    Erwing A Vargas

    2008-08-01

    77 patients that received different type of antiarrhythmics, that had no risk factors associated to thyroid dysfunction and that were recruited in the hospital ward. TSH samples were taken at the beginning of the study and at three months of follow-up. 26% (43 patients had normal TSH plasma levels with a tendency to higher value levels after 3 months in the group receiving amiodarone. Additionally, a higher proportion of thyroid gland disorders were described in the male population.

  5. Therapeutic effects of Laser and L-carnitine against amiodarone ...

    African Journals Online (AJOL)

    Pulmonary toxicity is considered a life- threatening complication of ... Research Center, Faculty of Medicine, Ain .... Laser therapy restores the balance between oxidants and ... No conflict of interest associated with this work. Contribution of .... Fitness. 2014; 149-159. 21. Lee BJ, Lin JS, Lin YC, Lin PT. Effects of L-carnitine.

  6. Glycosaminoglycan synthesis in amiodarone-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    Farinas, E.M.

    1986-01-01

    Glycosaminoglycans (GAG) have previously been demonstrated to be synthesized in greater than normal amounts following a single intratracheal insufflation of bleomycin in hamsters. This suggests that GAG may play a role in the propagation of pulmonary fibrotic reactions. To further test this hypothesis, GAG synthesis was studied in a new hamster model of interstitial lung injury, induced by the cardiac drug, aminodarone. Animals received a single intratracheal instillation of 1.25 mg aminodarone. At 4, 9, and 21 days post-insufflation, the animals were sacrificed, their lungs removed, and 1 mm fragments placed in explant culture for 6 hours at 37 0 C in the presence of 35 S-sulfate. The labeled GAG were isolated and measured for 35 S incorporation. The author then isolated the hexosamine portions of the respective GAGs, Heparan Sulfate (HEP S), Chondroitin-6-Sulfate (Ch-6-S) and Chondroitin-4-Sulfate and Dermatan Sulfate (CH-4-S and DS) using the enzyme ABC and paper chromatography. They also studied the GAG content and distribution in hamster lung fibroblasts incorporated with 35 S for 48 hours and subjected to either 0, 0.01 mg, 0.1 mg, or 1 mg of aminodarone. GAG synthesis is increased at an early stage following the induction of lung injury by aminodarone and remains elevated for a 3 week period. The change in GAG distribution boards elevated CH-4-S and DS may be characteristic of interstitial diseases in general. The GAGs that are synthesized by fibroblasts may be responsible for the increased CH-4-S and DS synthesis

  7. Terapia de resgate com amiodarona em crianças com grave disfunção ventricular esquerda causada por veneno de escorpião Terapia de rescate con amiodarona en niños con severa disfunción ventricular izquierda ocasionada por veneno de escorpión Antiadrenergic rescue therapy with amiodarone in children with severe left ventricular dysfunction secondary to scorpion envenomation

    Directory of Open Access Journals (Sweden)

    Justo J. Santiago

    2010-01-01

    ón endotraqueal y soporte respiratorio, electrocardiograma, radiografía de tórax, ecocardiograma y determinación sérica de la norepinefrina y troponina I. Los análisis se repitieron tras 12, 24 y 48 horas. Las siguientes medicaciones intravenosas se administraron: dobutamina 4-6 mcg/kg/min; amiodarona 3 mg/kg durante dos horas, con dosis de mantenimiento de 5 mg/kg/día; y furosemida 0.5 mg/kg. Amiodarona, dobutamina y furosemida se administraron durante las primeras 48 horas. Bloqueante betaadrenergicos e inhibidores de la enzima convertidora de la angiotensina se administraron hasta 48 tras la internación, una vez que el estado clínico había mejorado y la fracción de eyección ventricular izquierda se hallaba superior a un 0,35%. RESULTADOS: Al ingreso, la dosificación de la norepinefrina fue 1727,50± 794,96 pg/ml, la de troponina I 24,53 ± 14,09 ng/ml y la fracción de eyección del ventrículo izquierdo fue 0,20 ± 0,056. Tras 12 horas, los niveles séricos de norepinefrina y de troponina I disminuyeron para la mitad de los valores iniciales y la fracción de eyección aumentó para 0,32 ± 0,059. Durante las 24 y 48 horas subsiguientes, la fracción de eyección se elevó para 0,46 ± 0,045 (pBACKGROUND: Children with scorpion envenomation have massive sympathetic activation and variable degrees of left ventricular systolic dysfunction. OBJECTIVE: To evaluate a rescue protocol for children with severe left ventricular dysfunction secondary to scorpion envenomation. METHODS: Four children, after scorpion envenomation, were subjected to a rescue protocol for acute left ventricular dysfunction: Endotracheal intubation and respiratory assistance, electrocardiograms, chest x-Ray, echocardiograms and blood samples for norepinephrine and troponin I serum levels. Samples and echocardiograms were repeated at 12, 24 and 48 hours. Intravenous medications: Dobutamine: 4-6 μg/kg/min. Amiodarone: 3 mg/kg during a 2 hour period. Maintenance: 5 mg/kg/day. Furosemide: 0.5 mg

  8. ORIGINAL ARTICLES

    African Journals Online (AJOL)

    Hypothyroidism is easily controlled by amiodarone withdrawal and a short course of potassium perchlorate if the condition is transient, or by L-thyroxine replacement in permanent forms. In contrast, amiodarone-induced hyperthyroidism is a more complex therapeutic challenge. Proposed treatment regimens have not been ...

  9. The protective effect of grape seed and Ginkgo biloba against hepatotoxicity induced by the antidysrhythmic drug “amiodarone” in male albino rats

    Directory of Open Access Journals (Sweden)

    Manal Abdul-Hamid

    2018-06-01

    Full Text Available Amiodarone was an orally effective antiarrhythmic drug widely used throughout the world, had long-term administration side effects such as hepatotoxicity. The actions of two antioxidants; grape seed and Ginkgo biloba on the extent of tissue damage in amiodarone-induced hepatotoxicity were elucidated in this study. We equally divided thirty-six albino rats into six groups given doses by gastric tube daily for 8 weeks as follow; the 1st group (G1 served as an untreated control group under the same laboratory conditions and was given distilled water, the 2nd group (G2 grape seed-treated group that received (100 mg/kg/day, the 3rd group (G3 Ginkgo biloba-treated group that received (100 mg/kg/day, the 4th group (G4 amiodarone-treated group that received (40 mg/kg/day, the 5th group (G5 received amiodarone parallel with grape seed at the same time and the 6th group (G6 received amiodarone parallel with Ginkgo biloba at the same time. The current histological study revealed that amiodarone caused marked change in the liver including degeneration, proliferation of bile duct, inflammatory cells infiltration and fatty changes of hepatocytes in addition to deposition of collagen fibers in the hepatic tissue moreover, ultra-structural observations in the liver including vacuolation, fibrosis and pyknotic nuclei. In addition, histochemical study revealed depletion of glycogen and comet assay revealed marked of DNA damage.Treatment with the two used antioxidants reduced the extent of liver damage induced by amiodarone as indicated by decreased Aspartate aminotransferase (AST and Alanine aminotransferase (ALT activities. These antioxidants ameliorated the histopathological, histochemical and ultrastructure alternations of the liver tissue. In conclusion, grape seed was markedly effective than Ginkgo biloba in protecting rats against amiodarone. Keywords: Amiodarone, Grape seed, Ginkgo biloba, Comet assay, Hepatotoxicity, Histopathology, Ultrastructure

  10. ORIGINAL ARTICLES Potential for medical error: Incorrectly ...

    African Journals Online (AJOL)

    Drugs that affect thyroid hormone transport. Oestrogen. Tamoxifen. Heroin. Methadone. Androgens. Glucocorticoids. Salicylates. Anabolic steroids. Drugs that increase hepatic metabolism of T4 and T3. Phenobarbitol. Rifampicin. Phenytoin. Carbamazepine. Decreased T4 5'-deiodinase activity. Amiodarone. Glucocorticoids.

  11. Disease: H01719 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available sease include demyelinating, inflammatory, toxic, nutritional, compressive, infiltrative, hereditary, trauma...09] Linezolid [DR:D00947] Amiodarone [DR:D00636] ... Corticosteroids Mecobalamin [DR:D03246] (for nutrition

  12. Potent synergistic in vitro interaction between nonantimicrobial membrane-active compounds and itraconazole against clinical isolates of Aspergillus fumigatus resistant to itraconazole.

    NARCIS (Netherlands)

    Afeltra, J.; Vitale, R.G.; Mouton, J.W.; Verweij, P.E.

    2004-01-01

    To develop new approaches for the treatment of invasive infections caused by Aspergillus fumigatus, the in vitro interactions between itraconazole (ITZ) and seven different nonantimicrobial membrane-active compounds--amiodarone (AMD), amiloride, lidocaine, lansoprazole (LAN), nifedipine (NIF),

  13. Clinical studies on thyroid diseases

    NARCIS (Netherlands)

    Eskes, S.A.

    2014-01-01

    This thesis focuses on some aspects of thyroid disease: prevention of autoimmune thyroid disease (AITD), diagnosis of related conditions as autoimmune hypophysitis in autoimmune hypothyroidism (Hashimoto’s disease), and treatment of amiodarone-induced thyrotoxicosis (AIT).

  14. Epididymitis

    Science.gov (United States)

    ... to treat the infection. Sexually transmitted infections need antibiotics. Your sexual partners should also be treated. You may need pain medicines and anti-inflammatory medicines. If you are taking amiodarone, you may ...

  15. [Thyroid hormones and cardiovascular system].

    Science.gov (United States)

    Límanová, Zdeňka; Jiskra, Jan

    Cardiovascular system is essentially affected by thyroid hormones by way of their genomic and non-genomic effects. Untreated overt thyroid dysfunction is associated with higher cardiovascular risk. Although it has been studied more than 3 decades, in subclinical thyroid dysfunction the negative effect on cardiovascular system is much more controversial. Large meta-analyses within last 10 years have shown that subclinical hyperthyroidism is associated with higher cardiovascular risk than subclinical hypothyroidism. Conversely, in patients of age > 85 years subclinical hypothyroidism was linked with lower mortality. Therefore, subclinical hyperthyroidism should be rather treated in the elderly while subclinical hypothyroidism in the younger patients and the older may be just followed. An important problem on the border of endocrinology and cardiology is amiodarone thyroid dysfunction. Effective and safe treatment is preconditioned by distinguishing of type 1 and type 2 amiodarone induced hyperthyroidism. The type 1 should be treated with methimazol, therapeutic response is prolonged, according to recent knowledge immediate discontinuation of amiodarone is not routinely recommended and patient should be usually prepared to total thyroidectomy, or rather rarely 131I radioiodine ablation may be used if there is appropriate accumulation. In the type 2 there is a promt therapeutic response on glucocorticoids (within 1-2 weeks) with permanent remission or development of hypothyroidism. If it is not used for life-threatening arrhytmias, amiodarone may be discontinuated earlier (after several weeks). Amiodarone induced hypothyroidism is treated with levothyroxine without amiodarone interruption.Key words: amiodarone induced thyroid dysfunction - atrial fibrillation - cardiovascular risk - heart failure - hyperthyroidism - hypothyroidism - thyroid stimulating hormone.

  16. Medication Review and Transitions of Care: A Case Report of a Decade-Old Medication Error.

    Science.gov (United States)

    Comer, Rachel; Lizer, Mitsi

    2017-10-01

    A 69-year-old Caucasian male with a 25-year history of paranoid schizophrenia was brought to the emergency department because of violence toward the staff in his nursing facility. He was diagnosed with a urinary tract infection and was admitted to the behavioral health unit for medication stabilization. History included a five-year state psychiatric hospital admission and nursing facility placement. Because of poor cognitive function, the patient was unable to corroborate medication history, so the pharmacy student on rotation performed an in-depth chart review. The review revealed a transcription error in 2003 deleting amantadine 100 mg twice daily and adding amiodarone 100 mg twice daily. Subsequent hospitalization resulted in another transcription error increasing the amiodarone to 200 mg twice daily. All electrocardiograms conducted were negative for atrial fibrillation. Once detected, the consulted cardiologist discontinued the amiodarone, and the primary care provider was notified via letter and discharge papers. An admission four months later revealed that the nursing facility restarted the amiodarone. Amiodarone was discontinued and the facility was again notified. This case reviews how a 10-year-old medication error went undetected in the electronic medical records through numerous medication reconciliations, but was uncovered when a single comprehensive medication review was conducted.

  17. Preparation and determination of desethylamiodarone in dog lung by HPLC-MS.

    Science.gov (United States)

    Hong, Liu Xue; Ying, Yang Chuan; Lei, Zheng; Chen, Guo Rui

    2011-11-01

    A novel method was developed for the preparation and determination of desethylamiodarone in dog lung by high-performance liquid chromatography (HPLC) with amiodarone as a standard. The selected dog was orally given amiodarone, then executed and the active metabolite desethylamiodirone in lung tissue was isolated, concentrated and purified by Waters C18 column (25 mm x 250 mm, 10 microm) with mobile phase of acetonitrile-100 mmol/L acetic acid containing 15 mmol/L diethylamine (55:45 v/v) at a flow rate of 10.0 mL/min. Hypersil ODS2 column (4.6 mm x 250 mm 5 microm) was used to analyze amiodarone and desethylamiodarone, with the same mobile phase at a flow rate of 1.0 mL/min, the detection wavelength was 237.5 nm. Atmosperic pressure electronic spray ionization (AP-ESI) and ion mass spectral (m/z) of 618.1(M + H) were selected to validate desethylamiodarone. The f(i) of desethylamiodarone and amiodarone were 1.04 +/- 0.02 and 1.020 +/- 0.01, respectively. It indicated that desethylamiodarone can be separated and purified by preparational HPLC after Mass Spectrometry (MS) validation and quantified according to f(i) of amiodarone indirectly. The proposed method enables the preparation and determination of desethylamiodarone in dog lung successfully.

  18. Proarrhythmic potential of dronedarone: emerging evidence from spontaneous adverse event reporting.

    Science.gov (United States)

    Kao, David P; Hiatt, William R; Krantz, Mori J

    2012-08-01

    To characterize the frequency and type of cardiac events, including torsade de pointes, associated with dronedarone and its structural analog, amiodarone, outside of the clinical trial setting. Retrospective analysis. Spontaneous reports in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database generated between July 1, 2009, and June 30, 2011. All reports of adverse events during the study period were reviewed to identify cardiac events associated with any approved drug in the United States. The type and number of cardiac events associated with dronedarone and amiodarone were determined. Active ingredients were identified using the Drugs@FDA database, and the Medical Dictionary for Regulatory Activities (MedDRA) was used to aggregate related adverse events. To avoid redundant reporting, all statistics were generated in reference to unique case identifiers. Dronedarone was associated with more adverse cardiovascular event reports than amiodarone (810 vs 493 reports) during the study period. Dronedarone was also associated with the most reports of torsade de pointes of any approved drug in the United States (37 reports), followed by amiodarone (29 reports). Reports of ventricular arrhythmias and cardiac arrest (138 vs 113 reports) as well as heart failure (179 vs 126 reports) were more common with dronedarone than amiodarone. Dronedarone was associated with reports of ventricular arrhythmia, cardiac arrest, and torsade de pointes in clinical practice. Whether this observation accounts for the increased risk of fatal arrhythmia observed in a recent prospective trial requires further investigation. © 2012 Pharmacotherapy Publications, Inc. All rights reserved.

  19. SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

    Directory of Open Access Journals (Sweden)

    E. L. Artanova

    2011-01-01

    Full Text Available Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, amiodarone therapy were considered among clinical characteristics. Results. Adjusted warfarin dose was significantly higher in obesity , and it was lower in case of experienced myocardial infarction. The INR highest levels and maximal amplitudes of its fluctuations were observed in patients with thyroid gland nodes and smokers. Period of warfarin dose titration was longer in patients treated with amiodarone. Conclusion. Warfarin dose titration in patients with atrial fibrillation depends on the presence of myocardial infarction, obesity , thyroid nodular changes, smoking and amiodarone treatment.

  20. Biomarkers to monitor drug-induced phospholipidosis

    International Nuclear Information System (INIS)

    Baronas, Elizabeth Tengstrand; Lee, Ju-Whei; Alden, Carl; Hsieh, Frank Y.

    2007-01-01

    Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) was identified as a promising phospholipidosis (PL) biomarker in rats treated with either amiodarone, gentamicin, or azithromycin. Sprague-Dawley rats received either amiodarone (150 mg/kg), gentamicin (100 mg/kg) or azithromycin (30 mg/kg) once daily for ten consecutive days. Histopathological examination of tissues by transmission electron microscopy (TEM) indicated different degrees of accumulation of phospholipidosis in liver, lung, mesenteric lymph node, and kidney of drug-treated rats but not controls. Liquid chromatography coupled to mass spectrometry (LC/MS) was used to identify levels of endogenous biochemical profiles in rat urine. Urinary levels of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) correlated with induction of phospholipidosis for amiodarone, gentamicin and azithromycin. Rats treated with gentamicin also had increased urinary levels of several phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) species

  1. Antiarrhythmic therapy and risk of death in patients with atrial fibrillation: a nationwide study

    DEFF Research Database (Denmark)

    Andersen, Søren Skøtt; Hansen, Morten Lock; Gislason, Gunnar H

    2009-01-01

    AIMS: To examine the risk of death associated with antiarrhythmic drug (AAD) therapy in a nationwide unselected cohort of patients with atrial fibrillation (AF). METHODS AND RESULTS: All patients admitted with AF in Denmark from 1995 to 2004 and their subsequent use of AADs were identified...... with flecainide, 3745 (2.6%) propafenone, 23,346 (16.5%) sotalol, and 10,376 (7.3%) amiodarone. Annualized mortality rates were 2.54, 4.25, 5.29, and 7.42 per year per 100 person years for flecainide, propafenone, sotalol, and amiodarone, respectively. Multivariable Cox proportional-hazard models did not show...

  2. Successful resuscitation of a patient with electrical storm.

    Science.gov (United States)

    Moulik, P K; Attar, M N; Rose, E L; Khaleeli, A A

    2003-05-01

    A 41 year old woman with type 2 diabetes, hypertension, and hyperlipidaemia but no known heart disease received 130 DC shocks for repeated cardiac arrests due to ventricular tachyarrhythmias over 48 hours. She was stabilised by intravenous amiodarone and had a defibrillator implanted. Serial ECGs did not change, but raised troponin I confirmed myocardial infarction as the underlying cause. Electrical storm is an uncommon and dramatic but usually treatable syndrome of recurrent ventricular arrhythmias. Frequent precipitants of electrical storm include recent worsening heart failure, hypokalaemia, hypomagnesaemia and myocardial ischaemia. Amiodarone is the antiarrhythmic agent of choice and implantable cardioverter defibrillator improves long term outcome.

  3. A review on dronedarone: Pharmacological, pharmacodynamic and pharmacokinetic profile

    Directory of Open Access Journals (Sweden)

    Farah Iram

    2016-03-01

    Full Text Available Dronedarone, a benzofuran containing chemical compound, is a derivative of amiodarone which is classified as a Class III antiarrhythmic agent. It is prescribed to the cardiovascular patients who have paroxysmal or persistent atrial fibrillation to lower the chances of hospitalization. Amiodarone, sotalol, procainamide dofetilide, quinidine, ibutilide, flecainide, and propafenone are the other useful medicinal products used to treat atrial fibrillation or cardiac arrhythmia. Dronedarone was approved for clinical use in atrial fibrillation by the Food and Drug Administration in 2009. The generic name for dronedarone is Multaq (Sanofi Aventis. This article briefly highlights the important pharmacological, pharmacodynamic and pharmacokinetic properties of dronedarone.

  4. TREATMENT AND PREVENTION OF ATRIAL TACHYARRHYTHMIAS IN CRITICALLY ILL PATIENT: THE ROLEOF MAGNESIUM SULFATE

    Directory of Open Access Journals (Sweden)

    M. MOJTAHEDZADEH

    1999-09-01

    Full Text Available In this prospective, randomized study, in the general intensive care unit at Shanatee teaching hospital, we evaluated twenty patients, mean age 52+18 years and mean acute physiology and chronic health evaluation II score of 20±8, who were experiencing atrial tachyarrhythmias for more than 1 hour. After correction of their plasma potassium concentration to more than 4.0 mmof/1, patients were randomized to receive either 40 mg/kg magnesium sulfate bolus followed by 30 mg/kg/hr or 5mg/kg amiodarone bolus and 10 mg/kg/24hr infusion. Therapeutic end point was conversion to sinus rhythm over 24 hours. By logistic regression, the probability of conversion to sinus rhythm was significantly better for magnesium than for amiodarone at time 0-4 (0.6 vs.0.4, 12 (0.72 vs 0.45, and 24 (0.72vs.0.45 hours. In patients not converting to sinus rhythm, a significant decrease in ventricular response rate occurred at time zero to 0.5 hour (mean decrease 22 beats/min, P=0.0001, but there was no specific treatment effect between the magnesium and the amiodarone groups. Magnesium sulfate is superior to amiodarone in the conversion of acute atrial tachyarrhythmias, while initial slowing of ventricular response rate in non-converters appears equally efficacious with both agents.

  5. Desethylamiodarone is a competitive inhibitor of the binding of thyroid hormone to the thyroid hormone alpha 1-receptor protein

    NARCIS (Netherlands)

    van Beeren, H. C.; Bakker, O.; Wiersinga, W. M.

    1995-01-01

    Desethylamiodarone (DEA), the major metabolite of the potent antiarrythmic drug amiodarone, is a non-competitive inhibitor of the binding of thyroid hormone (T3) to the beta 1-thyroid hormone receptor (T3R). In the present study, we investigated whether DEA acts in a similar way with respect to the

  6. Application of X-ray microanalysis to the study of drug uptake in cell culture

    International Nuclear Information System (INIS)

    Reasor, M.J.; Lee, P.; Kirk, R.G.

    1990-01-01

    X-ray microanalysis has been used previously to study the accumulation of iodine in alveolar macrophages of rats treated with the iodinated drug, amiodarone. Due to metabolism of the drug in vivo, primarily to desethylamiodarone, it was not possible to identify the source of the iodine signal. In the present study we have utilized primary cell cultures of alveolar macrophages to study the intracellular accumulation of each of these drug species in vitro. Neither drug is metabolized by these cells in culture, permitting characterization of the accumulation of each independent of the other. Cells were incubated with equimolar concentrations of either amiodarone or desethylamiodarone for 42 hr, and X-ray microanalysis of freeze-dried cryosections of cells was used to quantify accumulation by monitoring the iodine signal associated with each drug. For both drug exposures, the highest iodine content was present in amorphous bodies and dense granules, consistent with the pattern following in vivo exposure. Higher levels of desethylamiodarone, compared to amiodarone, were measured in all compartments of the cells. The results of the in vitro investigation further demonstrate the utility of X-ray microanalysis in the study of the cellular response to amiodarone and desethylamiodarone

  7. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Vol. 47/No. RR-4.

    Science.gov (United States)

    1998-04-17

    suppression. • The following drugs may increase ZDV concentration (and therefore potential toxicity): probenecid, atovaquone, methadone , valproic acid...antihistamines (e.g., astemizole orterfenadine); certain cardiac drugs (e.g., amiodarone, bepridil hydrochloride , encainide hydrochlo- ride, flecainide...flurazepam hydrochloride , midazolam, triazolam, or zolpidem tartrate); certain psychotropic drugs (e.g., bupropion hydrochloride , clozapine, or pimoz

  8. Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence

    NARCIS (Netherlands)

    van Beeren, H. C.; Jong, W. M. C.; Kaptein, E.; Visser, T. J.; Bakker, O.; Wiersinga, W. M.

    2003-01-01

    Dronedarone (Dron), without iodine, was developed as an alternative to the iodine-containing antiarrhythmic drug amiodarone (AM). AM acts, via its major metabolite desethylamiodarone, in vitro and in vivo as a thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(1) antagonist. Here we

  9. Action of Specific Thyroid Hormone Receptor alpha(1) and beta(1) Antagonists in the Central and Peripheral Regulation of Thyroid Hormone Metabolism in the Rat

    NARCIS (Netherlands)

    van Beeren, Hermina C.; Kwakkel, Joan; Ackermans, Mariëtte T.; Wiersinga, Wilmar M.; Fliers, Eric; Boelen, Anita

    2012-01-01

    Background: The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) alpha(1)

  10. Pharmacotherapy Evaluation and Utilization in Coronary Artery Bypass Grafting Patients in Kosovo during the Period 2016-2017

    Directory of Open Access Journals (Sweden)

    Armond Daci

    2018-03-01

    CONCLUSION: The study showed that beta blockers, statins, aspirin, nitrates (before the operation, furosemide and spironolactone are the most utilized drugs. However, we found low utilization rate for ACEi, ARBs, clopidogrel, nadroparin, warfarin, xanthines, amiodarone, calcium blockers. Daily dosages were different compared to before CABG only in metoprolol, losartan, and furosemide.

  11. Administration of a Probiotic Can Change Drug Pharmacokinetics: Effect of E. coli Nissle 1917 on Amidarone Absorption in Rats

    Czech Academy of Sciences Publication Activity Database

    Matusková, Z.; Anzenbacherová, E.; Večeřa, R.; Tlaskalová-Hogenová, Helena; Kolář, M.; Anzenbacher, P.

    2014-01-01

    Roč. 9, č. 2 (2014) E-ISSN 1932-6203 R&D Projects: GA ČR GAP303/12/0535; GA ČR(CZ) GAP304/11/1252; GA MZd(CZ) NT13483 Institutional support: RVO:61388971 Keywords : STRAIN NISSLE-1917 * GUT MICROBIOTA * AMIODARONE Subject RIV: EC - Immunology Impact factor: 3.234, year: 2014

  12. A benefit-risk assessment of class III antiarrhythmic agents

    DEFF Research Database (Denmark)

    Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian

    2002-01-01

    , which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary...... prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide......-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone...

  13. Treatment by iodine 131 and thyroid pathologies 14 Nfs iatrogenic 'Around France of that particular medical treatment'

    International Nuclear Information System (INIS)

    Baldet, L.

    2000-01-01

    In the case of hyperthyroidism bound to amiodarone, the iodine 131 prescription appears able to cure this disease in 84% of cases; the use of iodine 131 before amiodarone to prevent a hyperthyroidism, in case of goiter or thyroid nodules is little used (17% of practitioners) when it is more used in case of past history of induced hyperthyroidism (34% of physicians). This prescription is nevertheless efficient in the both cases. The use of iodine 131 is little used in the case of hyperthyroidism appeared during the use of cytokines (22% of physicians). The induction of hypothyroidism by iodine 131 in the case of severe cardiopathies is becoming little frequent (9% of physicians). (N.C.)

  14. Antiarrhythmia drugs for cardiac arrest: a systemic review and meta-analysis

    OpenAIRE

    Huang, Yu; He, Qing; Yang, Min; Zhan, Lei

    2013-01-01

    Introduction Antiarrhythmia agents have been used in the treatment of cardiac arrest, and we aimed to review the relevant clinical controlled trials to assess the effects of antiarrhythmics during cardiopulmonary resuscitation. Methods We searched databases including Cochrane Central Register of Controlled Trials; MEDLINE, and EMBASE. Clinical controlled trials that addressed the effects of antiarrhythmics (including amiodarone, lidocaine, magnesium, and other new potassium-channel blockers) ...

  15. Class III antiarrhythmic agents in cardiac failure: lessons from clinical trials with a focus on the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA).

    Science.gov (United States)

    Doval, H C

    1999-11-04

    The results of previous clinical trials, in a variety of clinical settings, showed that class I agents may consistently increase mortality in sharp contrast to the effects of beta blockers. Attention has therefore shifted to class III compounds for potential beneficial effects on long-term mortality among patients with underlying cardiac disease. Clinical trials with d-sotalol, the dextro isomer (devoid of beta blockade) of sotalol, showed increased mortality in patients with low ejection fraction after myocardial infarction and in those with heart failure; whereas in the case of dofetilide, the impact on mortality was neutral. Because of the complex effects of its actions as an alpha-adrenergic blocker and a class III agent, the impact on mortality of amiodarone in patients with heart failure is of particular interest. A meta-analysis of 13 clinical trials revealed significant reductions in all-cause and cardiac mortality among patients with heart failure or previous myocardial infarction. Among these were 5 controlled clinical trials that investigated the effects of amiodarone on mortality among patients with heart failure. None of these trials was large relative to the beta-blocker trials in the postinfarction patients. However, the larger 2 of the 5 amiodarone trials produced discordant effects on mortality, neutral in one and significantly positive in the other. Some of the differences may be accounted for by the differences in eligibility criteria and baseline characteristics. Future trials that may be undertaken to resolve the discrepancies may need to allow for the newer findings on the effects of concomitant beta blockers, implantable devices, and possibly, spironolactone. All these modalities of treatment have been shown in controlled clinical trials to augment survival in patients with impaired ventricular function or manifest heart failure. Additional trials, some of which are currently in progress, compare amiodarone with implantable devices and other

  16. Determination of Drug Toxicity Using 3D Spheroids Constructed From an Immortal Human Hepatocyte Cell Line

    DEFF Research Database (Denmark)

    Fey, S. J.; Wrzesinski, Krzysztof

    2012-01-01

    that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC50 data (mM) for six common drugs (acetaminophen, amiodarone...... different from 2D cultures and are more representative of the liver in vivo....

  17. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Henrique Horta Veloso

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  18. Buerger's Disease and Anaesthesia: The Neglected Cardiac Angle

    Directory of Open Access Journals (Sweden)

    Shagun Bhatia Shah

    2015-08-01

    Full Text Available Distal limb amputations and respiratory complications are common in patients with Buerger’s disease. Nicotine in cigarette is arrhythmogenic as it blocks cardiac potassium channels. Preoperative Holter ECG monitoring may be useful if preoperative electrocardiogram is normal. If the patient is undergoing major surgery, preservative free lignocaine & amiodarone infusions and a cardioverter defibrillator should be available for the intraoperative cardiac rhythm disturbances.

  19. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Veloso Henrique Horta

    2003-01-01

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  20. Intracellular Drug Uptake-A Comparison of Single Cell Measurements Using ToF-SIMS Imaging and Quantification from Cell Populations with LC/MS/MS.

    Science.gov (United States)

    Newman, Carla F; Havelund, Rasmus; Passarelli, Melissa K; Marshall, Peter S; Francis, Ian; West, Andy; Alexander, Morgan R; Gilmore, Ian S; Dollery, Colin T

    2017-11-21

    ToF-SIMS is a label-free imaging method that has been shown to enable imaging of amiodarone in single rat macrophage (NR8383) cells. In this study, we show that the method extends to three other cell lines relevant to drug discovery: human embryonic kidney (HEK293), cervical cancer (HeLa), and liver cancer (HepG2). There is significant interest in the variation of drug uptake at the single cell level, and we use ToF-SIMS to show that there is great diversity between individual cells and when comparing each of the cell types. These single cell measurements are compared to quantitative measurements of cell-associated amiodarone for the population using LC/MS/MS and cell counting with flow cytometry. NR8383 and HepG2 cells uptake the greatest amount of amiodarone with an average of 2.38 and 2.60 pg per cell, respectively, and HeLa and Hek 293 have a significantly lower amount of amiodarone at 0.43 and 0.36 pg per cell, respectively. The amount of cell-associated drug for the ensemble population measurement (LC/MS/MS) is compared with the ToF-SIMS single cell data: a similar amount of drug was detected per cell for the NR8383, and HepG2 cells at a greater level than that for the HEK293 cells. However, the two techniques did not agree for the HeLa cells, and we postulate potential reasons for this.

  1. Contrast induced hyperthyroidism due to iodine excess

    OpenAIRE

    Mushtaq, Usman; Price, Timothy; Laddipeerla, Narsing; Townsend, Amanda; Broadbridge, Vy

    2009-01-01

    Iodine induced hyperthyroidism is a thyrotoxic condition caused by exposure to excessive iodine. Historically this type of hyperthyroidism has been described in areas of iodine deficiency. With advances in medicine, iodine induced hyperthyroidism has been observed following the use of drugs containing iodine—for example, amiodarone, and contrast agents used in radiological imaging. In elderly patients it is frequently difficult to diagnose and control contrast related hyperthyroidism, as most...

  2. [Thyroid and cardiovascular disorders].

    Science.gov (United States)

    Zyśko, Dorota; Gajek, Jacek

    2004-05-01

    In this study three problems concerning interactions between thyroid and cardiovascular system are discussed. Cardiac arrhythmias, congestive heart failure, pleural effusion, hyperlipidaemia, arterial hypertension may be consequences of thyroid disorders leading to inappropriate hormone secretion. During such illnesses as heart failure, myocardial infarction and in patients undergoing coronary artery bypass surgery profound changes may occur in thyroid hormone metabolism known as sick euthyroid syndrome. Treatment with amiodarone may lead to changes in thyroid tests results and to development of hypothyroidism or thyrotoxicosis.

  3. Ventricular tachycardia induced by weight loss pills

    DEFF Research Database (Denmark)

    Pareek, Manan; Hansson, Nils Henrik; Grove, Erik Lerkevang

    2013-01-01

    A previously healthy 29-year-old man was admitted with palpitations, dizziness, and near-syncope after he had recently started taking weight loss pills purchased on the internet. The pills contained caffeine and ephedrine. An electrocardiogram and telemetry revealed multiple episodes of non......-sustained monomorphic ventricular tachycardia, which was successfully treated with amiodarone. In conclusion, unauthorized weight loss pills can be harmful. In particular, ephedrine-containing drugs carry a risk of ventricular tachycardia and should be discouraged....

  4. Kombinationsbehandling med fluconazol og andre QTc-forlængende lægemidler forlænger QTc- intervallet

    DEFF Research Database (Denmark)

    Buch, Tina; Andersen, Stig Ejdrup

    2015-01-01

    Several drugs have a QTc-prolonging effect and are metabolized by CYP3A4. The combination of QTc-prolonging drugs may act additive of the QTc interval. The risk increases additionally by co-administration of a CYP3A4-inhibiting substrate. This case report describes an incident with QTc prolongati...... which was probably caused by an interaction induced by a combination of amiodarone, clarithromycin and the CYP3A4-inhibitor fluconazole....

  5. July 2012 pulmonary case of the month: pulmonary infiltrates - getting to the heart of the problem

    Directory of Open Access Journals (Sweden)

    Ronan B

    2012-07-01

    Full Text Available No abstract available. Article truncated at 150 words. History of Present IllnessA 63 year old man was transferred from outside facility with ventricular tachycardia. He has a past history of ventricular tachycardia and had an intracardiac defibrillator (ICD placed due to a low ejection fraction. The ICD had administered several shocks to the patient prior to admission. His present medications included: •Lisinopril 10 mg bid •Diazepam 10 mg bid •Amiodarone 400 mg daily •Dutasteride 0.5 mg daily •Tamsulosin 0.4 mg daily •Dexlansoprazole 60 mg daily •Levothyroxine 100 mcg daily The patient underwent and electrophysiology (EP procedure. He was intubated prior to the procedure. He developed sustained ventricular tachycardia when the ICD was turned off. Eleven cardioversions were required with an accumulated 108 seconds of ventricular tachycardia. He became hypotensive and received 6.2 L boluses of fluids and 5, 400 mg boluses of amiodarone and was placed on an amiodarone drip...

  6. Managing atrial fibrillation in the elderly: critical appraisal of dronedarone

    Directory of Open Access Journals (Sweden)

    Trigo P

    2011-12-01

    Full Text Available Paula Trigo, Gregory W FischerDepartment of Anesthesiology, Mount Sinai School of Medicine, New York, NY, USAAbstract: Atrial fibrillation is the most commonly seen arrhythmia in the geriatric population and is associated with increased cardiovascular morbidity and mortality. Treatment of the elderly with atrial fibrillation remains challenging for physicians, because this unique subpopulation is characterized by multiple comorbidities requiring chronic use of numerous medications, which can potentially lead to severe drug interactions. Furthermore, age-related changes in the cardiovascular system as well as other physiological changes result in altered drug pharmacokinetics. Dronedarone is a new drug recently approved for the treatment of arrhythmias, such as atrial fibrillation and/or atrial flutter. Dronedarone is a benzofuran amiodarone analog which lacks the iodine moiety and contains a methane sulfonyl group that decreases its lipophilicity. These differences in chemical structure are responsible for making dronedarone less toxic than amiodarone which, in turn, results in fewer side effects. Adverse events for dronedarone include gastrointestinal side effects and rash. No dosage adjustments are required for patients with renal impairment. However, the use of dronedarone is contraindicated in the presence of severe hepatic dysfunction.Keywords: atrial fibrillation, elderly, antiarrhythmic agents, amiodarone, dronedarone

  7. Antiarrhythmic drugs for the maintenance of sinus rhythm: risks and benefits.

    Science.gov (United States)

    Camm, John

    2012-03-22

    Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice, and its complications impose a significant economic burden. The development of more effective agents to manage patients with AF is essential. While clinical trials show no major differences in outcomes between rate and rhythm control strategies, some patients with AF require treatment with antiarrhythmic drugs (AADs) to maintain sinus rhythm, reduce symptoms, improve exercise tolerance, and improve quality of life. Currently available AADs, while effective, have limitations including limited efficacy, adverse events, toxicity, and proarrhythmic potential. The 6 most commonly used AADs (amiodarone, disopyramide, dofetilide [USA but not Europe], flecainide, propafenone, sotalol) have proarrhythmic effects (fewer with amiodarone). Amiodarone is the most effective AAD, but its safety profile limits its usefulness. Recent advances in AAD therapy include dronedarone and vernakalant. Dronedarone, approved by the United States Food and Drug Administration and the European Medicines Authority and others, has been proven efficacious in maintaining sinus rhythm and reducing the incidence of hospitalization due to cardiovascular events or death in patients with AF. The intravenous formulation of vernakalant is approved in the European Union, Iceland, and Norway. Oral vernakalant is currently undergoing evaluation for preventing AF recurrence and appears to be effective with an acceptable safety profile. Treatment should be individualized to the patient with consideration of pharmacologic risks and benefits according to AF management guidelines. Accumulating efficacy and safety data for new and emerging AADs holds promise for improved AF management and outcomes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Iodine-induced hyperthyroidism as combination of different etiologies: an overlooked entity in the elderly.

    Science.gov (United States)

    Foppiani, Luca; Cascio, Christian; Lo Pinto, Giuliano

    2016-10-01

    Iodine-induced thyrotoxicosis, which raises several diagnostic and therapeutical challenges, is often overlooked. Hyperthyroidism can induce atrial fibrillation, a harmful arrhythmia which can precipitate heart failure and cause stroke. We report the case of an elderly man who was diagnosed with tachyfibrillation secondary to hyperthyroidism. Thyroid hyperfunction was subsequently related both to previous amiodarone therapy (probably mixed form) and the recent use of iodinated contrast medium for computed tomography scan. Thyroid ultrasonography showed a plongeant multinodular goitre. After initial worsening, thyroid function improved slowly but progressively on high-dose thyreostatic therapy combined with steroid therapy; tachyfibrillation caused heart failure and a thrombus in the left atrium, and proved initially resistant to combined antiarrhythmic treatments. Progressive reduction in thyroid hormone levels, together with combined cardiologic therapies, controlled the heart rate, though atrial fibrillation persisted; anticoagulant therapy resolved the atrial thrombus. Alterations in thyroid function are common in amiodarone-treated patients, who therefore require regular hormonal checks. The different forms of amiodarone-induced thyrotoxicosis must be investigated, since they require different therapies, though mixed forms often occur. The superimposition of further iodine excess due to other causes may be catastrophic and cause severe cardiac problems in these patients.

  9. Fibrose pulmonar secundária à amiodarona – A propósito de um caso clínico

    Directory of Open Access Journals (Sweden)

    Marta N. Silva

    2006-11-01

    Full Text Available Resumo: A amiodarona é um eficaz fármaco anti-arrítmico usado para tratar arritmias ventriculares e supra-ventriculares, mas não isento de reacções adversas. A toxicidade pulmonar é uma delas, relativamente rara (5 a 10% dos casos, e pode ser fatal. Há vários factores que aumentam a susceptibilidadade para esta toxicidade, tais como a idade avançada e a doença pulmonar preexistente.Apresentamos um caso clínico de toxicidade pulmonar induzida pela amiodarona (fibrose pulmonar num doente do sexo masculino, de 81 anos. Estava medicado com este fármaco, desde há 5 anos, com uma dose diária de 200 mg.Após a suspensão do fármaco e tratamento com corticosteróides sistémicos, houve melhoria clínica, funcional e radiológica.Este caso clínico realça a necessidade de uma monitorização e diagnóstico precoce dos efeitos adversos do tratamento com a amiodarona e a dificuldade no seu diagnóstico, devido à inespecificidade dos sintomas, das manifestações clínicas e dos resultados dos exames complementares de diagnóstico.Rev Port Pneumol 2006; XII (6: 725-730 Abstract: Amiodarone is an antiarrhytmic drug and it is used to treat supraventricular or ventricular rhythm disturbances. Nevertheless it is not free of side effects. Amiodarone-induced pulmonary toxicity is one of them and is relatively rare (5 to 10% of cases and can be fatal. There are several cumulative factors that may enhance susceptibility to pulmonary toxicity, such as advanced age and pre-existing pulmonary dysfunction.We present a case study of amiodarone-induced toxicity (pulmonary fibrosis in an 81-year-old man. The patient had been treated with amiodarone for five years in daily dose 200 mg/day.After withdrawing the drug and systemic corticoste-roid therapy, clinical, functional and radiological improvement was observed.This case confirms the needs of a vigilant monitoring and early diagnosis of

  10. Effect of voltage-gated sodium channels blockers on motility and viability of human sperm in vitro

    Directory of Open Access Journals (Sweden)

    Hammad Ahmad Gakhar

    2018-01-01

    Full Text Available Objective: To test the effect of voltage-gated sodium channels (VGSCs blockers on the motility and viability of human sperm in-vitro and to evaluate the tested compounds as potential contact spermicidal.Methods: Sperm samples were obtained from healthy nonsmoking volunteers of age 25-30 years who had not taken any drug 3 months before and during the course of the study. The effect of VGSCs blockers evaluated from two pharmacological classes including antiarrhythmic (amiodarone, procainamide and disopyramide and antiepileptic (carbamazepine, oxcarbazepine, phenytoin, and lamotrigine drugs. They were tested on the in-vitro motility and viability of human sperm using Computer Assisted Semen Analyzer.Results: All tested drugs except oxcarbazepine showed dose dependent inhibition of total motility with significant reduction (P<0.05 at the maximum concentration of 200 μΜ when compared with the control. The concentrations of drugs that reduced total sperm motility to 50% of control (half maximal inhibitory concentration were 2.76, 14.16 and 20.29 μΜ for phenytoin, lamotrigine and carbamazepine, respectively; and 2.53, 5.32 and 0.37 μΜ for amiodarone, procainamide and disopyramide, respectively. The anti-motility effects were reversible to various degrees. There was statistically insignificant difference in the inhibition of sperm viability among amiodarone, procainamide and disopyramide. Phenytoin demonstrated the most potent spermicidal action.Conclusions: VGSCs blockers have significant adverse effects on in-vitro motility of human spermatozoa. So in-vivo studies are required to determine their potential toxicological effects on human semen quality, which is an important factor regarding fertility. Moreover, these drugs have the potential to be developed into contact spermicidal.

  11. Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent.

    Science.gov (United States)

    Yang, Zhi-fang; Li, Ci-zhen; Wang, Wei; Chen, Ying-min; Zhang, Ying; Liu, Yuan-mou; Wang, Hong-wei

    2011-03-01

    To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone. Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells. Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (V(max)) of the fAP by 24.4%, and Na(+) current (I(Na)) by 18.0%, while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and V(max) of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca(2+) current (I(CaL)) and the K(+) tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and V(max) of the fAP and sAP, and both slowed the automatic heart rate. Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit I(Na), I(CaL), and I(Kr) currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.

  12. Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Patrick A Schweizer

    2011-01-01

    Full Text Available Patrick A Schweizer, Rüdiger Becker, Hugo A Katus, Dierk ThomasDepartment of Cardiology, Medical University Hospital, Heidelberg, GermanyAbstract: Atrial fibrillation (AF is the most common sustained arrhythmia. Management of AF includes rate control, rhythm control if necessary, prevention of thromboembolic events, and treatment of the underlying disease. Rate control is usually achieved by pharmacological suppression of calcium currents or by applying β-blockers or digitalis compounds. In contrast, the number of compounds available for rhythm control is still limited. Class Ic agents increase mortality in patients with structural heart disease, and amiodarone harbors an extensive side effect profile despite its efficacy in maintaining sinus rhythm. Furthermore, rhythm control by these compounds has not been shown to reduce patient mortality. Dronedarone is a new antiarrhythmic drug that has been developed to provide rhythm and rate control in AF patients with fewer side effects compared with amiodarone. This review primarily focuses on clinical trials evaluating efficacy and safety of the novel drug. Conclusions from these studies are critically reviewed, and recommendations for clinical practice are discussed. Dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation (ATHENA trial. However, dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm (DIONYSOS trial and is contraindicated in severe or deteriorating heart failure (ANDROMEDA trial. In summary, dronedarone represents a valuable addition to the limited spectrum of antiarrhythmic drugs and is currently recommended in patients with paroxysmal and persistent AF to achieve rate and rhythm control, excluding cases of severe or unstable congestive heart failure.Keywords: dronedarone, atrial fibrillation, antiarrhythmic therapy

  13. Comparison of the effects of sternal and tibial intraosseous administered resuscitative drugs on return of spontaneous circulation in a swine model of cardiac arrest.

    Science.gov (United States)

    O'Sullivan, Mara; Martinez, Andre; Long, Audrey; Johnson, Michelle; Blouin, Dawn; Johnson, Arthur D; Burgert, James M

    2016-01-01

    Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest. Prospective, randomized, between subjects, experimental design. Laboratory. Male Yorkshire-cross swine (N = 35), seven per group. Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed. Rate of ROSC, time to ROSC, and odds of ROSC. There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group. There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

  14. Assessing the Risk for Peripheral Neuropathy in Patients Treated With Dronedarone Compared With That in Other Antiarrhythmics.

    Science.gov (United States)

    Wu, Chuntao; Tcherny-Lessenot, Stephanie; Dai, Wanju; Wang, Yunxun; Kechemir, Hayet; Gandhi, Sampada; Lin, Stephen; Juhaeri, Juhaeri

    2018-03-01

    There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities. The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person-years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21-1.34) compared with propafenone, to 0.94 (95% CI, 0.38-2.30) compared with sotalol. A new-user analysis showed similar results. The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  15. La n?phrotoxicite secondaire ? l'hyperbilribinemie: ? propos d'un cas

    OpenAIRE

    Jomni, Med Taieb; Largueche, Mouna; Kaab, Badreddine Ben; Abdelaal, Imen; Bellakhal, Syrine; Douggui, Med H?di

    2015-01-01

    L'hyperbilirubin?mie ? des taux ?lev?s est nephrotoxique par divers m?canismes allant de la tubulopathie proximale aux d?p?ts massifs de bilirubine. Cette entit? bien que d?crite depuis le d?but du vingti?me si?cle est souvent m?connue dans la litt?rature moderne. Nous rapportons le cas d'un patient pr?sentant une cirrhose probablement d'origine m?dicamenteuse (Amiodarone*), dont la fonction r?nale s'est alt?r?e parall?lement ? la majoration de l'hyperbilirubin?mie. Aucune autre cause de l'in...

  16. Microgravity spheroids as a reliable, long-term tool for predictive toxicology

    DEFF Research Database (Denmark)

    Fey, S. J.; Wrzesinski, Krzysztof

    2013-01-01

    those seen in vivo. Studies with 5 common drugs (acetaminophen, amiodarone, metformin, phenformin, and valproic acid) have shown that they are more predictive of lethally-toxic plasma levels in vivo than published studies using primary human hepatocytes. Shotgun proteomics has revealed that the gain...... this time they are metabolically stable for at least 24 days more; grow slowly (a doubling time of >20 days); produce physiological levels of urea, cholesterol and ATP; exhibit stable gene expression (for selected liver relevant genes); and can post translationally modify proteins in a manner which mirrors...

  17. Successful Treatment of Refractory Electrical Storm With Landiolol After More Than 100 Electrical Defibrillations.

    Science.gov (United States)

    Kanamori, Kenta; Aoyagi, Takashi; Mikamo, Takashi; Tsutsui, Kenta; Kunishima, Tomoyuki; Inaba, Hideko; Hayami, Noriyuki; Murakawa, Yuji

    2015-01-01

    Electrical storm (ES) was observed in an 82-year-old man with recent myocardial infarction. Conventional therapy, including amiodarone, could not suppress the ES. After more than 100 electrical defibrillations, we were finally able to control the ES with the administration of landiolol. It is known that landiolol can inhibit ES. However, we hesitate to use landiolol in patients with low cardiac output. We would like to emphasize that careful use of landiolol should be considered in patients with refractory ES after myocardial infarction, although cardiac output is severely reduced.

  18. Epidemiology of subtypes of hypothyroidism in Denmark

    DEFF Research Database (Denmark)

    Carlé, Allan; Laurberg, Peter; Pedersen, Inge B.

    2006-01-01

    in the cohort; the incidence rate was 32.8 per 100 000 person-years (standardised to the Danish population). Nosological types of hypothyroidism were: spontaneous (presumably autoimmune) 84.4%, post-partum 4.71%, amiodarone-associated 4.0%. subacute thyroiditis 1.8%. previous radiation or surgery 1.......8%. congenital 1.6% and lithium-associated 1.6%. Crude incidence rates were 29.0 around Aalborg and 40.6 in an area of Copenhagen. The higher incidence rate of hypothyroidism in the area with higher iodine intake was caused solely by more cases of spontaneous (presumably autoimmune) hypothyroidism, whereas...

  19. Cure of chronic hepatitis C virus infection in an HIV-coinfected patient with multiple comorbidities and drug interaction challenges.

    Science.gov (United States)

    Álvarez, Hortensia; Mariño, Ana; Valcarce, Nieves; Khoo, Saye; Bhagani, Sanjay; Schapiro, Jonathan; Llibre, Josep M

    2018-01-01

    Curing hepatitis C virus (HCV) infection in patients harbouring multiple severe comorbidities is a medical challenge. Evidence-based data are lacking regarding HCV treatment with direct-acting antiviral regimens in particular populations of HCV/HIV-coinfected patients with cirrhosis and chronic kidney disease on haemodialysis. Here, we present the HCV treatment challenges facing a patient with HIV coinfection, prior failure of both HIV-1 and HCV therapy, cirrhosis, end-stage renal failure on haemodialysis, as well as management of drug-drug interactions, especially given the need to receive long-term amiodarone therapy.

  20. Pharmacological conversion of recent-onset atrial fibrillation: a systematic review.

    Science.gov (United States)

    Heldal, Magnus; Atar, Dan

    2013-02-01

    Recent-onset (duration ≤ 1 week) atrial fibrillation (AF) has a high rate of spontaneous conversion to sinus rhythm (SR); still anti-arrhythmic drugs (AAD) are given for conversion purposes. We assessed the effect of AADs by reviewing the literature regarding conversion rates of available drugs in a systematic manner. PubMed searches were performed using the terms "drug name", "atrial fibrillation", and "clinical study/RCT", and a list of 1302 titles was generated. These titles, including abstracts or complete papers when needed, were reviewed for recent-onset of AF, the use of a control group, and the endpoint of SR within 24 hours. Postoperative and intensive care settings were excluded. Five AADs were demonstrated to have an effect, and these were Amiodarone, Ibutilide (only one study and risk of torsade de pointes), Flecainide and Propafenone (only to be used in patients without structural heart disease) and Vernakalant. The time taken for conversion differed markedly; Vernakalant converted after 10 minutes, while Amiodarone converted only after 24 hours; Propafenone and Flecainide had conversion times in-between. For a rapid response in a broad group of patients, Vernakalant appears to be a reasonable first choice, while Flecainide and Propafenone can be used in patients without structural heart disease.

  1. A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

    Science.gov (United States)

    Nakamura, Makiko; Sunagawa, Osahiko; Hokama, Ryo; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi

    2016-09-28

    The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

  2. Atrial fibrillation after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Nair Suresh

    2010-01-01

    Full Text Available Once considered as nothing more than a nuisance after cardiac surgery, the importance of postoperative atrial fibrillation (POAF has been realized in the last decade, primarily because of the morbidity associated with the condition. Numerous causative factors have been described without any single factor being singled out as the cause of this complication. POAF has been associated with stroke, renal failure and congestive heart failure, although it is difficult to state whether POAF is directly responsible for these complications. Guidelines have been formulated for prevention of POAF. However, very few cardiothoracic centers follow any form of protocol to prevent POAF. Routine use of prophylaxis would subject all patients to the side effects of anti-arrhythmic drugs, while only a minority of the patients do actually develop this problem postoperatively. Withdrawal of beta blockers in the postoperative period has been implicated as one of the major causes of POAF. Amiodarone, calcium channel blockers and a variety of other pharmacological agents have been used for the prevention of POAF. Atrial pacing is a non-pharmacological measure which has gained popularity in the prevention of POAF. There is considerable controversy regarding whether rate control is superior to rhythm control in the treatment of established atrial fibrillation (AF. Amiodarone plays a central role in both rate control and rhythm control in postoperative AF. Newer drugs like dronedarone and ranazoline are likely to come into the market in the coming years.

  3. Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

    Science.gov (United States)

    Bondon-Guitton, Emmanuelle; Mourgues, Thibaut; Rousseau, Vanessa; Cousty, Sarah; Cottin, Judith; Drablier, Guillaume; Micallef, Joëlle; Montastruc, Jean-Louis

    2017-09-01

    Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Dronedarone.

    Science.gov (United States)

    Hoy, Sheridan M; Keam, Susan J

    2009-08-20

    Oral dronedarone is a non-iodinated benzofurane derivative structurally related to amiodarone. Although it is considered a class III antiarrhythmic agent like amiodarone, it demonstrates multi-class electrophysiological activity. Data from the ATHENA study demonstrated that patients receiving oral dronedarone 400 mg twice daily for 12-30 months had a significantly lower risk of experiencing first hospitalization due to a cardiovascular event or death from any cause than those receiving placebo. Dronedarone exhibited rate- and rhythm-controlling properties in patients with atrial fibrilation (AF) or atrial flutter, significantly reducing the risk of a first recurrence of AF versus placebo following 12 months' therapy in the ADONIS and EURIDIS studies. In the ERATO study, dronedarone was also significantly more effective than placebo in terms of ventricular rate control. Furthermore, the beneficial effects of oral dronedarone on ventricular rate control were maintained during exercise and sustained with continued therapy. Oral dronedarone was generally well tolerated in the treatment of adult patients with AF and/or atrial flutter in clinical studies. The incidence of diarrhoea, nausea, bradycardia, rash and QT-interval prolongation was significantly higher with oral dronedarone than placebo in the large ATHENA study; however, serious cardiac-related adverse events were observed in <1% of oral dronedarone recipients.

  5. Delayed Onset of Atrial Fibrillation and Ventricular Tachycardia after an Automobile Lightning Strike.

    Science.gov (United States)

    Drigalla, Dorian; Essler, Shannon E; Stone, C Keith

    2017-11-01

    Lightning strike is a rare medical emergency. The primary cause of death in lightning strike victims is immediate cardiac arrest. The mortality rate from lightning exposure can be as high as 30%, with up to 70% of patients left with significant morbidity. An 86-year-old male was struck by lightning while driving his vehicle and crashed. On initial emergency medical services evaluation, he was asymptomatic with normal vital signs. During his transport, he lost consciousness several times and was found to be in atrial fibrillation with intermittent runs of ventricular tachycardia during the unconscious periods. In the emergency department, atrial fibrillation persisted and he experienced additional episodes of ventricular tachycardia. He was treated with i.v. amiodarone and admitted to cardiovascular intensive care unit, where he converted to a normal sinus rhythm on the amiodarone drip. He was discharged home without rhythm-control medications and did not have further episodes of dysrhythmias on follow-up visits. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Lightning strikes are one of the most common injuries suffered from natural phenomenon, and short-term mortality ordinarily depends on the cardiac effects. This case demonstrates that the cardiac effects can be multiple, delayed, and recurrent, which compels the emergency physician to be vigilant in the initial evaluation and ongoing observation of patients with lightning injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Using statistical anomaly detection models to find clinical decision support malfunctions.

    Science.gov (United States)

    Ray, Soumi; McEvoy, Dustin S; Aaron, Skye; Hickman, Thu-Trang; Wright, Adam

    2018-05-11

    Malfunctions in Clinical Decision Support (CDS) systems occur due to a multitude of reasons, and often go unnoticed, leading to potentially poor outcomes. Our goal was to identify malfunctions within CDS systems. We evaluated 6 anomaly detection models: (1) Poisson Changepoint Model, (2) Autoregressive Integrated Moving Average (ARIMA) Model, (3) Hierarchical Divisive Changepoint (HDC) Model, (4) Bayesian Changepoint Model, (5) Seasonal Hybrid Extreme Studentized Deviate (SHESD) Model, and (6) E-Divisive with Median (EDM) Model and characterized their ability to find known anomalies. We analyzed 4 CDS alerts with known malfunctions from the Longitudinal Medical Record (LMR) and Epic® (Epic Systems Corporation, Madison, WI, USA) at Brigham and Women's Hospital, Boston, MA. The 4 rules recommend lead testing in children, aspirin therapy in patients with coronary artery disease, pneumococcal vaccination in immunocompromised adults and thyroid testing in patients taking amiodarone. Poisson changepoint, ARIMA, HDC, Bayesian changepoint and the SHESD model were able to detect anomalies in an alert for lead screening in children and in an alert for pneumococcal conjugate vaccine in immunocompromised adults. EDM was able to detect anomalies in an alert for monitoring thyroid function in patients on amiodarone. Malfunctions/anomalies occur frequently in CDS alert systems. It is important to be able to detect such anomalies promptly. Anomaly detection models are useful tools to aid such detections.

  7. Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence.

    Science.gov (United States)

    Van Beeren, H C; Jong, W M C; Kaptein, E; Visser, T J; Bakker, O; Wiersinga, W M

    2003-02-01

    Dronedarone (Dron), without iodine, was developed as an alternative to the iodine-containing antiarrhythmic drug amiodarone (AM). AM acts, via its major metabolite desethylamiodarone, in vitro and in vivo as a thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(1) antagonist. Here we investigate whether Dron and/or its metabolite debutyldronedarone inhibit T(3) binding to TRalpha(1) and TRbeta(1) in vitro and whether dronedarone behaves similarly to amiodarone in vivo. In vitro, Dron had a inhibitory effect of 14% on the binding of T(3) to TRalpha(1), but not on TRbeta(1). Desethylamiodarone inhibited T(3) binding to TRalpha(1) and TRbeta(1) equally. Debutyldronedarone inhibited T(3) binding to TRalpha(1) by 77%, but to TRbeta(1) by only 25%. In vivo, AM increased plasma TSH and rT(3), and decreased T(3). Dron decreased T(4) and T(3), rT(3) did not change, and TSH fell slightly. Plasma total cholesterol was increased by AM, but remained unchanged in Dron-treated animals. TRbeta(1)-dependent liver low density lipoprotein receptor protein and type 1 deiodinase activities decreased in AM-treated, but not in Dron-treated, animals. TRalpha(1)-mediated lengthening of the QTc interval was present in both AM- and Dron-treated animals. The in vitro and in vivo findings suggest that dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor.

  8. Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all.

    Science.gov (United States)

    Sorrentino, Annalise

    2005-04-01

    Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.

  9. Prevalence of thyroid dysfunction in patients with acute atrial fibrillation attended at a cardiology emergency room

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    Juarez Neuhaus Barbisan

    Full Text Available CONTEXT: Atrial fibrillation occurs frequently in patients with thyrotoxicosis, while it has low prevalence in adults of the general population. The prevalence of thyroid dysfunction in subjects with atrial fibrillation is 0 to 24%, a wide variation that is attributed to the different methodologies applied. However, continuous use of amiodarone in patients with previous atrial fibrillation may interfere with these prevalence rates. OBJECTIVE: In this study, we present the prevalence of thyroid dysfunction in adult patients who presented at a cardiac emergency room with acute atrial fibrillation, using a sensitive thyroid-stimulating hormone (TSH assay and triiodothyronine (T3 and thyroxine (T4 determination. TYPE OF STUDY: Cross-sectional study SETTING: Emergency room of a tertiary care facility. PARTICIPANTS: A total of 72 patients with atrial fibrillation who presented at the emergency room not more than 48 hours after its onset. PROCEDURES: A standardized questionnaire and 12-lead electrocardiogram were applied, and T3, T4 and TSH were determined. MAIN MEASUREMENTS: TSH, T3 and T4 determination. RESULTS: Among these patients, 16.6% had altered thyroid function tests: 6.9% had hyperthyroidism, 5.6% hypothyroidism and 4.2% had increased T4 levels, by means of amiodarone use. CONCLUSION: The high prevalence of thyroid dysfunction in our study, especially hyperthyroidism, suggests that routine thyroid testing with sensitivethyroid-stimulating hormone assay is required in patients with acute atrial fibrillation.

  10. Managing atrial fibrillation in the elderly: critical appraisal of dronedarone.

    Science.gov (United States)

    Trigo, Paula; Fischer, Gregory W

    2012-01-01

    Atrial fibrillation is the most commonly seen arrhythmia in the geriatric population and is associated with increased cardiovascular morbidity and mortality. Treatment of the elderly with atrial fibrillation remains challenging for physicians, because this unique subpopulation is characterized by multiple comorbidities requiring chronic use of numerous medications, which can potentially lead to severe drug interactions. Furthermore, age-related changes in the cardiovascular system as well as other physiological changes result in altered drug pharmacokinetics. Dronedarone is a new drug recently approved for the treatment of arrhythmias, such as atrial fibrillation and/or atrial flutter. Dronedarone is a benzofuran amiodarone analog which lacks the iodine moiety and contains a methane sulfonyl group that decreases its lipophilicity. These differences in chemical structure are responsible for making dronedarone less toxic than amiodarone which, in turn, results in fewer side effects. Adverse events for dronedarone include gastrointestinal side effects and rash. No dosage adjustments are required for patients with renal impairment. However, the use of dronedarone is contraindicated in the presence of severe hepatic dysfunction.

  11. Direct evaluation of thyroid 127I and iodine overload: in vivo study by X-ray fluorescence and in vitro by SIMS microscopy

    International Nuclear Information System (INIS)

    Briancon, C.; Jeusset, J.; Halpern, S.; Fragu, P.

    1992-01-01

    This review describes the two methods which allow direct estimation of stable iodine ( 127 I) within thyroid gland either in vivo by X-ray fluorescence or in vitro by secondary ion mass spectrometry (SIMS) microscopy on tissue section. Although the measurement of thyroid iodine content (TIC) by X-ray fluorescence has little relevance for routine explorations of thyroid function, this is a valuable method for understanding complex pathophysiological conditions such as the thyroid adaptation to iodine overload. On the other hand, SIMS microscopy which is able to characterize the functional activity of thyroid tissue by measuring 127 I concentration within the thyroid follicles, can be used to determine the extent to which exogeneous iodine affects the regulation of iodine within the thyroid follicles. Both methods were used to evaluate the quantitative changes in thyroid 127 I induced by amiodarone iodine overload. TIC measurements shows that hyperthyroidism occured only in patients who increased their iodine stores, while the patients who developed hypothyroidism has low iodine stores. The SIMS microscopy data obtained in mice demonstrated that the thyroid response to amiodarone is related to dietary iodine intake leading to an increase in local iodine concentration in iodine deficient mice and to a decrease in iodine supplemented mice. This response is specific and different from that induced by an iodine overload. These results could explain that hyperthyroidism with high thyroid iodine content occured in areas with low thyroid iodine content in areas with a supplemented iodine diet

  12. Drug-induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Daba, Mohammad H.; Al-Arifi, Mohammad N; Gubar, Othman A.; El-Tahir, Kamal E.

    2004-01-01

    Pulmonary fibrosis is characterized by the accumulation of excessive connective tissue in the lungs. Its causes include chronic administration of some drugs for example bleomycin, cyclophosphamide, amiodarone, procainamide, penicillamine, gold and nitrofurantoin; exposure to certain environmental factors such as gases, asbestos and silica and bacterial or fungal infections. Some systemic diseases also predispose to the disease for example rheumatoid arthritis and systemic lupus erythematosus. The disease is associated with release of oxygen radicals and some mediators such as tumor necrosis factor-alpha TNF-alpha, transforming growth factor-beta Tbgf-beta, PDGF, If-I, Et-I and interleukins 1, 4, 8 and 13. The symptoms of the disease include dyspne a, non-productive cough, fever and damage to the lung cells. It is diagnosed with the aid of chest radiography, high resolution computed tomographic scanning and the result of pulmonary function tests. Drug-induced pulmonary fibrosis may involve release of free oxygen radicals and various cytokines for example Il-I beta and TNF-alpha via activation of nuclear transcription factor Nf-beta as in the case of bleomycin and mitomycin or via release of TGF-beta as in case of tamoxifen or via inhibition of macrophages and lymphocytes phospholipases as in the case of amiodarone with the resultant accumulation of phospholipids and reduction of the immune system. (author)

  13. Amiodarona numa Unidade de Cuidados Intensivos Pneumológicos. Revisão de utilizaçao

    Directory of Open Access Journals (Sweden)

    Jorge Dionísio

    1998-03-01

    Full Text Available RESUMO: Sendo a amiodarona o fármaco mais utilizado para controle das taquidisritmias supraventriculares na unidade em que trabalhamos, efectuámos um estudo retrospectivo para avaliar a sua eficáciá em função da estratégia terapêutica empregue e perfil tóxico.Foram analisados os processos de 28 doentes tratados com amiodarona parentérica, sendo 23 homens e 5 mulheres, com uma média etária de 68.3 anos, todos com patologia pulmonar e necessidade de ventilação mecânica.As arritmias identificadas foram fibrilhação auricular em 16 doentes, taquicardia paroxistica supraventricular em 7, nutter auricular em 3 e extrassistolia em 2. A amiodarona foi administrada por via endovenosa na dose de indução de 300 mg em 30 minutos seguida de uma dose média de manutenção de 11 μg/Kg/min durante urn tempo medio de administração de 33 horas.Este fármaco foi considerado inicialmente eficaz em 23 doentes (82,1%, havendo a referir, contudo, a existencia de 8 recidivas (28,6%.Foram detectados 8 casos de toxicidade (28,6%. 4 de bradicardia (14,3% e 4 de hepatite aguda (14,3%.Concluimos que apesar de uma eficácia inicial de acordo com a literatura. encontramos um elevado numero de recidivas o que nos leva a propor uma modificação na nossa estratégia. O elevado número de doentes com alteração da função hepática levanos a sugerir uma maior vigilância destes parâmetros durante a utilização da amiodarona, principalmente em doentes em cuidados intensivos.REV PORT PNEUMOL 1998; IV (2: 207-216 SUMMARY: Amiodarone is the drug most used to control supraventricular tachyarrhytbmias in our intensive care uit. A retrospective study was performed to evaluate its efficacy and toxicity.Clinical records of 28 patients treated with amiodarone were analyzed: 23 were man, 5 were women, with a mean age of 68.3 yean, all suffering from lung disease and submitted to

  14. Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling.

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    Aruna D Balgi

    Full Text Available BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC1 is a protein kinase that relays nutrient availability signals to control numerous cellular functions including autophagy, a process of cellular self-eating activated by nutrient depletion. Addressing the therapeutic potential of modulating mTORC1 signaling and autophagy in human disease requires active chemicals with pharmacologically desirable properties. METHODOLOGY/PRINCIPAL FINDINGS: Using an automated cell-based assay, we screened a collection of >3,500 chemicals and identified three approved drugs (perhexiline, niclosamide, amiodarone and one pharmacological reagent (rottlerin capable of rapidly increasing autophagosome content. Biochemical assays showed that the four compounds stimulate autophagy and inhibit mTORC1 signaling in cells maintained in nutrient-rich conditions. The compounds did not inhibit mTORC2, which also contains mTOR as a catalytic subunit, suggesting that they do not inhibit mTOR catalytic activity but rather inhibit signaling to mTORC1. mTORC1 inhibition and autophagosome accumulation induced by perhexiline, niclosamide or rottlerin were rapidly reversed upon drug withdrawal whereas amiodarone inhibited mTORC1 essentially irreversibly. TSC2, a negative regulator of mTORC1, was required for inhibition of mTORC1 signaling by rottlerin but not for mTORC1 inhibition by perhexiline, niclosamide and amiodarone. Transient exposure of immortalized mouse embryo fibroblasts to these drugs was not toxic in nutrient-rich conditions but led to rapid cell death by apoptosis in starvation conditions, by a mechanism determined in large part by the tuberous sclerosis complex protein TSC2, an upstream regulator of mTORC1. By contrast, transient exposure to the mTORC1 inhibitor rapamycin caused essentially irreversible mTORC1 inhibition, sustained inhibition of cell growth and no selective cell killing in starvation. CONCLUSION/SIGNIFICANCE: The observation that drugs already

  15. Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.

    Science.gov (United States)

    Slavik, R S; Tisdale, J E; Borzak, S

    2001-01-01

    This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method

  16. Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

    Science.gov (United States)

    Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

    2015-01-01

    Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

  17. Fatty liver and drugs: the two sides of the same coin.

    Science.gov (United States)

    Miele, L; Liguori, A; Marrone, G; Biolato, M; Araneo, C; Vaccaro, F G; Gasbarrini, A; Grieco, A

    2017-03-01

    Drug-induced liver injury (DILI) is a common and underestimated cause of liver disease. Several drugs and other xenobiotics can be the cause of different clinicopathologic patterns of liver disease. Steatosis and steatohepatitis are rare but well-documented types of DILI. Over the past decades commonly used drugs like amiodarone, tamoxifen, irinotecan, methotrexate, valproic acid and glucocorticoids have been recognized to be associated with steatosis. Even though the pathophysiological pathways are still only partially understood, inhibition of mitochondrial beta-oxidation, reduced very low-density lipoprotein secretion, insulin resistance induction and increased de novo synthesis or increased liver uptake of fatty acids are considered the main pathogenic mechanisms through which drugs can lead to hepatic steatosis. On the other hand, fatty liver itself is a very common clinical condition, and there is a growing awareness of the potential risk factors for DILI due to the underlying metabolic condition itself.

  18. Serious arrhythmias in patients with apical hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Okishige, Kaoru; Sasano, Tetsuo; Yano, Kei; Azegami, Kouji; Suzuki, Kou; Itoh, Kuniyasu [Yokohama Red Cross Hospital (Japan)

    2001-05-01

    We report cases of serious arrhythmias associated with apical hypertrophic cardiomyopathy (AHCM). Thirty-one patients were referred to our institute to undergo further assessment of their AHCM from 1988 to 1999. Three patients with nonsustained ventricular tachycardia demonstrated an {sup 123}I-MIBG regional reduction in the tracer uptake. In two patients with ventricular fibrillation (VF), the findings from {sup 123}I-MIBG imaging revealed regional sympathetic denervation in the inferior and lateral regions. Electrophysiologic study demonstrated reproducible induction of VF in aborted sudden death and presyncopal patients, resulting in the need for an implantable defibrillator device and amiodarone in each patient. Patients with refractory atrial fibrillation with a rapid ventricular response suffered from serious congestive heart failure. A prudent assessment and strategy in patients with this disease would be indispensable in avoiding a disastrous outcome. (author)

  19. A case report of cardiotoxicity due to homeopathic drug overdose

    Directory of Open Access Journals (Sweden)

    MilindChandurkar,Girish Patrike, NitinChauhan, SanketMulay, Manoj Vethekar, JaweedAkhtar, Mallikarjun Reddy

    2014-11-01

    Full Text Available Aconite is one of the most toxic plants. Aconitine and related alkaloids found in the Aconitum species are highly toxic cardiotoxins and neurotoxins. Severe aconite poisoning can occur after accidental ingestion of the wild plant or consumption of an herbal decoction made from aconite roots. The toxic components of Aconitum as aconitine and related alkaloids cause cardiotoxicity, neurotoxicity and gastrointestinal toxicity through their actions on sodium channels. Cardiac manifestations include hypotension and ventricular tachyarrhythmias. Ventricular tachyarrhythmias and refractory cardiovascular collapse, such as in the case of this patient account for life-threatening toxicities in severe aconite poisoning. In general, vagal slowing is seen in 10 to 20% of fatal intoxications. If higher concentrations are present, supraventricular tachycardia, ventricular tachycardia, torsades de pointes, and other conduction disturbances may be seen. Ventricular fibrillation may be seen, and is often the cause of death. Available clinical evidence suggests that drugs like amiodarone and flecainide are reasonable first-line treatment.

  20. Atrial fibrillation with wide QRS tachycardia and undiagnosed Wolff-Parkinson-White syndrome: diagnostic and therapeutic dilemmas in a pediatric patient.

    Science.gov (United States)

    Panduranga, Prashanth; Al-Farqani, Abdullah; Al-Rawahi, Najib

    2012-11-01

    A 10-year-old girl presented to the emergency department of a regional hospital with 1 episode of generalized tonic-clonic seizures. Postictal monitoring followed by a 12-lead electrocardiogram showed fast atrial fibrillation with intermittent wide QRS regular tachycardia. Immediately following this, her rhythm changed to wide QRS irregular tachycardia without hemodynamic compromise. She was suspected to have ventricular tachycardia and was treated with intravenous amiodarone with cardioversion to sinus rhythm. Subsequent electrocardiogram in sinus rhythm showed typical features of manifest Wolff-Parkinson-White (WPW) accessory pathway. This case illustrates the diagnostic and therapeutic dilemmas in patients with atrial fibrillation, wide QRS tachycardia, and undiagnosed WPW syndrome with antidromic conduction of atrial arrhythmias through the accessory pathway. Furthermore, this case demonstrates that undiagnosed wide QRS tachycardias need to be treated with drugs acting on the accessory pathway, thus keeping in mind underlying WPW syndrome as a possibility to avoid potentially catastrophic events.

  1. Electroversion in treatment of arrhythmia in a patient with Wolff-Parkinson-White syndrome and cervical spinal cord injury

    Directory of Open Access Journals (Sweden)

    SHEN Peng

    2013-06-01

    Full Text Available 【Abstract】We report electroversion in treatment of atrial fibrillation (AF and atrioventricular nodal reentry ta-chycardia (AVNRT in a patient with Wolff-Parkinson-White syndrome and cervical spinal cord injury. At first, the pa-tient sustained respiratory failure and weak cough reflex, thereafter repeated bronchoscopy was used to aspirate the sputum as well as control the pneumonia, which resulted in arrhythmia (AF and AVNRT. Two doses of intravenous amiodarone failed to correct the arrhythmia. After restora-tion of sinus rhythm by electroversion, he was successfully weaned from mechanical ventilation and discharged from the intensive care unit without recurrent arrhythmia. Key words: Arrhythmia, cardiac; Atrial fibrillation; Electric countershock; Wolff-Parkinson-White syndrome; Spinal cord injuries

  2. Electrical storm: case series and review of management.

    Science.gov (United States)

    Srivatsa, Uma N; Ebrahimi, Ramin; El-Bialy, Adel; Wachsner, Robin Y

    2003-09-01

    Electrical storm is defined as a recurrent episode of hemodynamically destabilizing ventricular tachyarrhythmia that usually requires electrical cardioversion or defibrillation. We describe three cases presenting with electrical storm under differing circumstances: (1) a 57-year-old man with ST-elevation myocardial infarction within 1 week of a posterior circulation stroke who developed refractory sustained ventricular tachycardia 10 days after an acute myocardial infarction; (2) a 65-year-old man who developed polymorphic ventricular tachycardia and ventricular fibrillation following dobutamine echocardiography; and (3) a 20-year-old woman who developed intractable ventricular fibrillation following an overdose of a weight-reduction pill. The management of electrical storm is discussed, and evolving literature supporting the routine use of intravenous amiodarone and beta-blockers in place of intravenous lidocaine is critically examined.

  3. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

    Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

  4. Practical aspects of apixaban use in clinical practice: continuing the theme

    Directory of Open Access Journals (Sweden)

    S. N. Bel'diev

    2015-01-01

    Full Text Available Currently there are no generally accepted guidelines for the use of apixaban together with CYP3A4 and/or P-glycoprotein (P-gp inhibitors. Analysis of clinical and pharmacological studies suggests that apixaban dose should be reduced to 2.5 mg twice daily when co-administered with a strong CYP3A4 and P-gp inhibitors, such as azole antimycotics, HIV protease inhibitors and clarithromycin. However, it is preferred to avoid apixaban combination with strong CYP3A4 and P-gp inhibitors in patients with a creatinine clearance (CrCl <30 mL/min. According to preliminary calculations, apixaban dose should also be adjusted in patients with CrCl <70-80 ml/min, receiving less potent inhibitors of CYP3A4 and/or P-gp, such as diltiazem, naproxen, verapamil, amiodarone and quinidine. 

  5. Increased mortality after dronedarone therapy for severe heart failure

    DEFF Research Database (Denmark)

    Køber, Lars; Torp-Pedersen, Christian; McMurray, John J V

    2008-01-01

    BACKGROUND: Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure....... METHODS: In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite...... of death from any cause or hospitalization for heart failure. RESULTS: After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance...

  6. Ventricular Tachycardia or not? An Unexpected Reason of Wide QRS Complex Tachycardia in a Young Healthy Man: Sodium Bicarbonate.

    Science.gov (United States)

    Eyuboglu, Mehmet

    2016-10-01

    Ventricular tachycardia (VT) is life-threatening subgroup of wide QRS complex tachycardia (WCT). VT is usually associated with structural heart diseases, but it can occur in the absence of any cardiovascular diseases. Adverse cardiac effect of sodium bicarbonate in healthy subjects is not well described. A 30-year-old healthy man with excessive intake of sodium bicarbonate-related VT is presented. He was using sodium bicarbonate during last 2 months to lose weight. He has no risk factors and any cardiovascular or systemic diseases. After intravenous administration of amiodarone, tachycardia ended and his rhythm converted to sinus rhythm with normal electrocardiogram. Patient is asymptomatic, and no VT was observed without any medications at 1 year of follow-up.

  7. Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Satoshi Yamasaki

    2013-09-01

    Full Text Available A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.

  8. Surface atrial frequency analysis in patients with atrial fibrillation: a tool for evaluating the effects of intervention.

    Science.gov (United States)

    Raine, Dan; Langley, Philip; Murray, Alan; Dunuwille, Asunga; Bourke, John P

    2004-09-01

    The aims of this study were to evaluate (1) principal component analysis as a technique for extracting the atrial signal waveform from the standard 12-lead ECG and (2) its ability to distinguish changes in atrial fibrillation (AF) frequency parameters over time and in response to pharmacologic manipulation using drugs with different effects on atrial electrophysiology. Twenty patients with persistent AF were studied. Continuous 12-lead Holter ECGs were recorded for 60 minutes, first, in the drug-free state. Mean and variability of atrial waveform frequency were measured using an automated computer technique. This extracted the atrial signal by principal component analysis and identified the main frequency component using Fourier analysis. Patients were then allotted sequentially to receive 1 of 4 drugs intravenously (amiodarone, flecainide, sotalol, or metoprolol), and changes induced in mean and variability of atrial waveform frequency measured. Mean and variability of atrial waveform frequency did not differ within patients between the two 30-minute sections of the drug-free state. As hypothesized, significant changes in mean and variability of atrial waveform frequency were detected after manipulation with amiodarone (mean: 5.77 vs 4.86 Hz; variability: 0.55 vs 0.31 Hz), flecainide (mean: 5.33 vs 4.72 Hz; variability: 0.71 vs 0.31 Hz), and sotalol (mean: 5.94 vs 4.90 Hz; variability: 0.73 vs 0.40 Hz) but not with metoprolol (mean: 5.41 vs 5.17 Hz; variability: 0.81 vs 0.82 Hz). A technique for continuously analyzing atrial frequency characteristics of AF from the surface ECG has been developed and validated.

  9. Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach.

    Science.gov (United States)

    Martín-Pérez, Mar; Gaist, David; de Abajo, Francisco J; Rodríguez, Luis A García

    2018-03-01

     To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels.  Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between 2005 and 2013 ( N  = 121,962) was followed until the first qualifying prescription for the potential interacting drugs was evaluated. Sixteen sub-cohorts, one for each study drug, and a control sub-cohort of warfarin were ascertained. Short-term changes in INR levels were assessed by comparing INR values measured before and after initiation of the interacting drug with paired Student's t -test. We also evaluated the proportion of patients with INR values outside the therapeutic range (INR: 2-3).  Miconazole use was associated with the highest mean increase in INR (+3.35), followed by amiodarone (+1.28), fluconazole (+0.79), metronidazole (+0.75) and nystatin (+0.65). After subtracting the natural INR variation observed in the control sub-cohort, supra-therapeutic levels (INR > 3) were found in 53.2% (miconazole), 45.5% (amiodarone), 23.3% (metronidazole), 23.2% (fluconazole) and 17.6% (nystatin) of patients initiating treatment with these drugs. Carbamazepine use was associated with a mean INR decrease of -0.63 and infra-therapeutic levels (INR < 2) were observed in 46.2% of patients initiating carbamazepine. For all other drugs, the change was small to moderate, in absolute INR units (+0.23 to +0.55) and in the proportion of patients with INR levels out of therapeutic range (<16%).  Clinically potentially important interactions were observed in several study drugs. The majority of them, although confirmed, had little impact after adjusting for standard INR variability in the general population of warfarin users. Schattauer GmbH Stuttgart.

  10. Labelled antibody assays for measuring free triiodothyronine: evaluation and comparison with a labelled analog method

    International Nuclear Information System (INIS)

    Sapin, R.; Gasser, F.; Schlienger, J.L.; Chambron, J.

    1993-01-01

    We evaluated analytically and clinically two new one-step labelled antibody assays for measuring free triiodothyronine (FT3): the first, radiolabelled with 125 I, Amerlex-MAB (MAB) from Kodak diagnostic, and the second, labelled with peroxidase, Enzymum-test FT3 (BM) from Boehringer Mannheim adapted for the Boehringer ES 600 analyzer. The clinical results were compared with those obtained with a radiolabelled analog tracer kit, Amerlex-M (M) from Kodak diagnostic. The latter kit is known to give low FT3 results in sera with low albumin concentrations. Analytical performances of the automated method (BM) were better than those obtained with the manual method (MAB): intra-assay reproducibility (CV<3% vs CV about 5%), inter-assay reproducibility (CV<4% vs CV between 4 and 8%) and mean drift (+1.25% vs -4.3%). The detection limit was low for both kits (<1 pmol/l). In the euthyroid reference group (n = 98) we observed a significant difference between outpatient and hospitalized patient FT3 concentrations as measured with the M kit only. Clinical sensitivity for hyperthyroidism (n = 38) was better for the MAB (92%) than for the BM kit (76%). Specificity in euthyroid L-thyroxine (T4) treated patients (n = 26) was good for both kits (MAB: 92%; BM: 88%) . Hypoalbuminemia (n = 8) decreased FT3 results as follows: M, very significantly; BM, significantly; MAB, only slightly. In patients treated with amiodarone (n = 5), a drug known to lower the metabolic conversion of T4 to T3, the increase of the MAB FT3 results contrasted with the decrease of the BM and M results. In conclusion, results of the two new kits were not strongly influenced by hypoalbuminemia. The MAB results showing lack of decrease in patients with non-thyroidal illness without hypoalbuminemia and in amiodarone-treated patients were unexpected

  11. Surgical management of hyperthyroidism.

    Science.gov (United States)

    Quérat, C; Germain, N; Dumollard, J-M; Estour, B; Peoc'h, M; Prades, J-M

    2015-04-01

    Hyperthyroidism includes several clinical and histopathological situations. Surgery is commonly indicated after failure of medical treatment. The aim of this study was to analyze the indications and complications of surgery as well as endocrine results. Patients operated on for hyperthyroidism between 2004 and 2012 were included in a retrospective study. Total thyroidectomy was performed for Graves' disease, toxic multinodular goiter and amiodarone-associated thyrotoxicosis; patients with toxic nodule underwent hemithyroidectomy. Pathologic analysis assessed surgical specimens; postoperative complications and resolution of hyperthyroidism were noted. Two hundred patients from 15 to 83 years old were included. One hundred and eighty-eight underwent primary surgery and 12 were re-operated for recurrent goiter (6 with subtotal thyroidectomy for multinodular goiter 25 years previously; 6 with hemithyroidectomy for solitary nodule 15 years previously). Eighty-two patients suffered from toxic multinodular goiter, 78 from Graves' disease, 35 from solitary toxic nodules and 5 from amiodarone-associated thyrotoxicosis. Fourteen papillary carcinomas (including 11 papillary microcarcinomas) and 34 healthy parathyroid glands (17%) were identified in the pathological specimens. Postoperative complications comprised 4% permanent recurrent laryngeal nerve palsy (1 year follow-up), 9% hematoma requiring surgical revision, and 3% definitive hypocalcemia. Normalization of thyroid hormone levels was observed in 198 patients. Two recurrences occurred due to incomplete resection (1 case of Graves' disease and 1 intrathoracic toxic goiter that occurred respectively 18 and 5 months after resection). Postoperative complications were more frequent in multinodular goiter (23%) than in Graves' disease (13%) (ns: P>0.05). Surgical management of hyperthyroidism enables good endocrinal control if surgery is complete. Patients need to be fully informed of all possible postoperative complications

  12. Effect of Toxicants on Fatty Acid Metabolism in HepG2 Cells

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    David Grünig

    2018-04-01

    Full Text Available Impairment of hepatic fatty acid metabolism can lead to liver steatosis and injury. Testing drugs for interference with hepatic fatty acid metabolism is therefore important. To find out whether HepG2 cells are suitable for this purpose, we investigated the effect of three established fatty acid metabolism inhibitors and of three test compounds on triglyceride accumulation, palmitate metabolism, the acylcarnitine pool and dicarboxylic acid accumulation in the cell supernatant and on ApoB-100 excretion in HepG2 cells. The three established inhibitors [etomoxir, methylenecyclopropylacetic acid (MCPA, and 4-bromocrotonic acid (4-BCA] depleted mitochondrial ATP at lower concentrations than cytotoxicity occurred, suggesting mitochondrial toxicity. They inhibited palmitate metabolism at similar or lower concentrations than ATP depletion, and 4-BCA was associated with cellular fat accumulation. They caused specific changes in the acylcarnitine pattern and etomoxir an increase of thapsic (C18 dicarboxylic acid in the cell supernatant, and did not interfere with ApoB-100 excretion (marker of VLDL export. The three test compounds (amiodarone, tamoxifen, and the cannabinoid WIN 55,212-2 depleted the cellular ATP content at lower concentrations than cytotoxicity occurred. They all caused cellular fat accumulation and inhibited palmitate metabolism at similar or higher concentrations than ATP depletion. They suppressed medium-chain acylcarnitines in the cell supernatant and amiodarone and tamoxifen impaired thapsic acid production. Tamoxifen and WIN 55,212-2 decreased cellular ApoB-100 excretion. In conclusion, the established inhibitors of fatty acid metabolism caused the expected effects in HepG2 cells. HepG cells proved to be useful for the detection of drug-associated toxicities on hepatocellular fatty acid metabolism.

  13. Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients

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    David C Evans

    2014-01-01

    Full Text Available Purpose: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Materials and Methods: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB, beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Results: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%. Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Conclusions: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.

  14. Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

    Science.gov (United States)

    Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

    2016-01-01

    Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

  15. Pharmacological cardioversion of atrial fibrillation with vernakalant: evidence in support of the ESC Guidelines.

    Science.gov (United States)

    Savelieva, Irene; Graydon, Richard; Camm, A John

    2014-02-01

    Pharmacological rhythm control (often including electrical or pharmacological cardioversion) is an integral part of therapy for atrial fibrillation (AF) worldwide. Antiarrhythmic drug strategies would be preferred in many patients provided effective and safe antiarrhythmic agents are available. Also, pharmacological cardioversion could be the preferred option if the limitations of currently available drugs, such as restriction to patients without structural heart disease (flecainide and propafenone), risk of torsade de pointes (ibutilide), and slow onset of action (amiodarone), were overcome. The intravenous formulation of vernakalant (Brinavess, Cardiome) has been approved for pharmacological cardioversion of recent-onset AF (≤7 days) and early (≤3 days) post-operative AF in the European Union, Iceland, and Norway. Vernakalant has a high affinity to ion channels specifically involved in repolarization of atrial tissue and has minimal effects in the ventricles and thus, is thought to have a low proarrhythmic potential. Vernakalant is administered as a 10 min infusion of 3 mg/kg, and if AF persists after 15 min, an additional dose of 2 mg/kg can be given. The efficacy and safety of the drug has been extensively investigated in randomized controlled trials against placebo and an active comparator (amiodarone). The placebo-extracted efficacy of vernakalant is ∼47%. A significant advantage is a rapid effect, with the median to conversion ranging between 8 and 14 min, with the majority of patients (75-82%) converting after the first dose. Vernakalant retained its efficacy in subgroups of patients with associated cardiovascular disease such as hypertension and ischaemic heart disease, but its benefit may be lower and risk of adverse effects is higher in patients with heart failure. In the post-market reports, cardioversion rates with vernakalant are 65-70%. This review focuses on the role of vernakalant in pharmacological cardioversion for AF.

  16. Predictors of the risk of falls among elderly with chronic atrial fibrillation

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    Angela Cristina Silva dos Santos

    2012-01-01

    Full Text Available OBJECTIVES: Though elderly persons with chronic atrial fibrillation have more comorbidities that could limit indications for the chronic use of anticoagulants, few studies have focused on the risk of falls within this particular group. To evaluate the predictors of the risk of falls among elderly with chronic atrial fibrillation, a cross-sectional, observational study was performed. METHODS: From 295 consecutive patients aged 60 years or older with a history of atrial fibrillation who were enrolled within the last 2 years in the cardiogeriatrics outpatient clinic of the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 107 took part in this study. Their age was 77.9±6.4 years, and 62 were female. They were divided into two groups: a no history of falls in the previous year and b a history of one or more falls in the previous year. Data regarding the history of falls and social, demographic, anthropometric, and clinical information were collected. Multidimensional assessment instruments and questionnaires were applied. RESULTS: At least one fall was reported in 55 patients (51.4%. Among them, 27 (49.1% presented recurrent falls, with body lesions in 90.4% and fractures in 9.1% of the cases. Multivariate logistic regression showed that selfreported difficulty maintaining balance, use of amiodarone, and diabetes were independent variables associated with the risk of falls, with a sensitivity of 92.9% and a specificity of 44.9%. CONCLUSION: In a group of elderly patients with chronic atrial fibrillation who were relatively independent and able to attend an outpatient clinic, the occurrence of falls with recurrence and clinical consequences was high. Difficulty maintaining balance, the use of amiodarone and a diagnosis of diabetes mellitus were independent predictors of the risk for falls. Thus, simple clinical data predicted falls better than objective functional tests.

  17. Torsades de Pointes

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    Richard J Chen, MD

    2018-04-01

    Full Text Available History of present illness: 70-year-old male with a history ventricular arrhythmia, AICD (automated implantable cardioverter defibrillator, coronary artery disease and cardiac stents presented to the Emergency Department after three AICD discharges with dyspnea but no chest pain. During triage, he was found to have an irregular radial pulse and was placed on a cardiac monitor. Significant findings: The patient was found to be in a polymorphic ventricular tachycardia; he was alert, awake and asymptomatic. A rhythm strip showed a wide complex tachycardia with the QRS complex varying in amplitude around the isoelectric line consistent with Torsades de Pointes. Discussion: Torsades de Pointes (TdP is a specific type of polymorphic ventricular tachycardia. The arrhythmia’s characteristic morphology consists of the QRS complex “twisting” around the isoelectric line with gradual variation of the amplitude, reflecting its literal translation of “twisting of the points.”1 This arrhythmia occurs in the context of prolonged QT. The most common form of acquired QT prolongation is medication induced. Common causes include antiarrhythmics, antipsychotics, antiemetics, and antibiotics.2 Patient specific risk factors include female sex, bradycardia, hypokalemia, hypomagnesemia, hypocalcemia, hypothermia and heart disease.3 In the setting of prolonged QT, the repolarization phase is extended. TdP is initiated when a PVC (premature ventricular contraction occurs during this repolarization, known as an ‘R on T’ phenomenon. TdP is often asymptomatic and self-limited. The danger in TdP is its potential to deteriorate into ventricular fibrillation. A mainstay of management of TdP is prevention of risk factors when possible.4 Unstable patients should be treated with synchronized cardioversion. Magnesium sulfate should be administered in all cases of TdP.1 If a patient is not responsive to magnesium, consider isoproterenol, amiodarone, and overdrive

  18. Outcomes of ventricular tachycardia ablation in patients with structural heart disease: The impact of electrical storm.

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    Bashar Aldhoon

    Full Text Available To investigate predictors of long-term outcomes after catheter ablation (CA for ventricular tachycardia (VT and the impact of electrical storm (ES prior to index ablation procedures.We studied consecutive patients with structural heart disease and VT (n = 328; age: 63±12 years; 88% males; 72% ischaemic cardiomyopathy; LVEF: 32±12% who had undergone CA. According to presenting arrhythmia at baseline, they were divided into ES (n = 93, 28% and non-ES groups. Clinical predictors of all-cause mortality were investigated and a clinically useful risk score (SCORE was constructed.During a median follow-up of 927 days (IQR: 564-1626, 67% vs. 60% of patients (p = 0.05 experienced VT recurrence in the ES vs. the non-ES group, respectively; and 41% vs. 32% patients died (p = 0.02, respectively. Five factors were independently associated with mortality: age >70 years (hazard ratio (HR: 1.6, 95% confidence interval (CI: 1.1-2.4, p = 0.01, NYHA class ≥3 (HR: 1.9, 95% CI: 1.2-2.9, p = 0.005, a serum creatinine level >1.3 mg/dL (HR: 1.6, 95% CI: 1.1-2.3, p = 0.02, LVEF ≤25% (HR: 2.4, 95% CI: 1.6-3.5, p = 0.00004, and amiodarone therapy (HR: 1.5, 95% CI: 1.0-2.2, p = 0.03. A risk SCORE ranging from 0-4 (1 point for either high-risk age, NYHA, creatinine, or LVEF correlated with mortality. ES during index ablation independently predicted mortality only in patients with a SCORE ≤1.Advanced LV dysfunction, older age, higher NYHA class, renal dysfunction, and amiodarone therapy, but not ES, were predictors of poor outcomes after CA for VT in the total population. However, ES did predict mortality in a low-risk sub-group of patients.

  19. Drug-induced interstitial lung diseases. Often forgotten; Medikamenteninduzierte interstitielle Lungenerkrankungen. Haeufig vergessen

    Energy Technology Data Exchange (ETDEWEB)

    Poschenrieder, F.; Stroszczynski, C. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Hamer, O.W. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Lungenfachklinik Donaustauf, Donaustauf (Germany)

    2014-12-15

    Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.) [German] Medikamenteninduzierte interstitielle Lungenerkrankungen (engl. ''drug-induced interstitial lung diseases'', DILD) sind wahrscheinlich haeufiger, als sie diagnostiziert werden. Aufgrund ihrer potenziellen Reversibilitaet ist eine erhoehte Vigilanz gegenueber DILD auch seitens der Radiologie angebracht, da diese regelmaessig ein radiomorphologisches Korrelat in der hochaufloesenden Computertomographie (''high-resolution CT'', HRCT) der Lunge aufweisen. Typische, nach eigener Erfahrung relativ haeufige Manifestationsformen von DILD sind der diffuse Alveolarschaden (engl. ''diffuse alveolar damage'', DAD), die eosinophile Pneumonie (EP), die Hypersensitivitaetspneumonitis (HP), die organisierende

  20. Effect of an interactive cardiopulmonary resuscitation assist device with an automated external defibrillator synchronised with a ventilator on the CPR performance of emergency medical service staff: a randomised simulation study.

    Science.gov (United States)

    Nitzschke, Rainer; Doehn, Christoph; Kersten, Jan F; Blanz, Julian; Kalwa, Tobias J; Scotti, Norman A; Kubitz, Jens C

    2017-04-04

    The present study evaluates whether the quality of advanced cardiac life support (ALS) is improved with an interactive prototype assist device. This device consists of an automated external defibrillator linked to a ventilator and provides synchronised visual and acoustic instructions for guidance through the ALS algorithm and assistance for face-mask ventilations. We compared the cardiopulmonary resuscitation (CPR) quality of emergency medical system (EMS) staff members using the study device or standard equipment in a mannequin simulation study with a prospective, controlled, randomised cross-over study design. Main outcome was the effect of the study device compared to the standard equipment and the effect of the number of prior ALS trainings of the EMS staff on the CPR quality. Data were analysed using analyses of covariance (ANCOVA) and binary logistic regression, accounting for the study design. In 106 simulations of 56 two-person rescuer teams, the mean hands-off time was 24.5% with study equipment and 23.5% with standard equipment (Difference 1.0% (95% CI: -0.4 to 2.5%); p = 0.156). With both types of equipment, the hands-off time decreased with an increasing cumulative number of previous CPR trainings (p = 0.042). The study equipment reduced the mean time until administration of adrenaline (epinephrine) by 23 s (p = 0.003) and that of amiodarone by 17 s (p = 0.016). It also increased the mean number of changes in the person doing chest compressions (0.6 per simulation; p < 0.001) and decreased the mean number of chest compressions (2.8 per minute; p = 0.022) and the mean number of ventilations (1.8 per minute; p < 0.001). The chance of administering amiodarone at the appropriate time was higher, with an odds ratio of 4.15, with the use of the study equipment CPR.com compared to the standard equipment (p = 0.004). With an increasing number of prior CPR trainings, the time intervals in the ALS algorithm until the

  1. Potential drug-drug interactions with direct oral anticoagulants in elderly hospitalized patients.

    Science.gov (United States)

    Forbes, Heather L; Polasek, Thomas M

    2017-10-01

    To determine the prevalence and nature of potential drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly hospitalized patients. This was a retrospective observational study. Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or dabigatran; and admitted to the Repatriation General Hospital between April 2014 and July 2015. A list of clinically relevant 'perpetrator' drugs was compiled from product information, the Australian Medicines Handbook, the Australian National Prescribing Service resources, and local health network guidelines. The prevalence and nature of potential DDIs with DOACs was determined by comparing inpatient drug charts with the list of perpetrator drugs. There were 122 patients in the study with a mean age of 82 years. Most patients had nonvalvular atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%). Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti-inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking drugs that increase DOAC plasma concentrations (amiodarone, erythromycin, diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC plasma concentrations (carbamazepine, primidone or phenytoin). There were no cases of patients taking contraindicated interacting drugs. Potential DDIs with DOACs in elderly hospital inpatients are relatively common, particularly interactions that may increase the risk of bleeding. The risk-benefit ratio of DOACs in elderly patients on polypharmacy should always be carefully considered.

  2. [Effect of Environmental Factors on the Ecotoxicity of Pharmaceuticals and Personal Care Products].

    Science.gov (United States)

    Sugihara, Kazumi

    2018-01-01

     In recent years, pharmaceuticals and personal care products (PPCPs) have emerged as significant pollutants of aquatic environments and have been detected at levels in the range of ng/L to μg/L. The source of PPCPs is humans and livestock that have been administered pharmaceuticals and subsequently excreted them via urine and feces. Unlike agricultural chemicals, the environmental dynamics of PPCPs is not examined and they would undergo structural transformation by environmental factors, e.g., sunlight, microorganisms and treatments in sewage treatment plants (STPs). Processing at STPs can remove various PPCPs; however, they are not removed completely and some persist in the effluents. In this study, we examined the degradation of 9 pharmaceuticals (acetaminophen, amiodarone, dapsone, dexamethasone, indomethacin, raloxifene, phenytoin, naproxen, and sulindac) by sunlight or UV, and investigated the ecotoxicological variation of degradation products. Sunlight (UVA and UVB) degraded most pharmaceuticals, except acetaminophen and phenytoin. Similar results were obtained with UVB and UVA. All the pharmaceuticals were photodegraded by UVC, which is used for sterilization in STPs. Ecotoxicity assay using the luminescent bacteria test (ISO11348) indicated that UVC irradiation increased the toxicity of acetaminophen and phenytoin significantly. The photodegraded product of acetaminophen was identified as 1-(2-amino-5-hydroxyphenyl)ethanone and that of phenytoin as benzophenone, and the authentic compounds showed high toxicity. Photodegraded products of PPCPs are a concern in ecotoxicology.

  3. Thyroid Hormone Receptor Antagonists: From Environmental Pollution to Novel Small Molecules.

    Science.gov (United States)

    Mackenzie, Louise S

    2018-01-01

    Thyroid hormone receptors (TRs) are nuclear receptors which control transcription, and thereby have effects in all cells within the body. TRs are an important regulator in many basic physiological processes including development, growth, metabolism, and cardiac function. The hyperthyroid condition results from an over production of thyroid hormones resulting in a continual stimulation of thyroid receptors which is detrimental for the patient. Therapies for hyperthyroidism are available, but there is a need for new small molecules that act as TR antagonists to treat hyperthyroidism. Many compounds exhibit TR antagonism and are considered detrimental to health. Some drugs in the clinic (most importantly, amiodarone) and environmental pollution exhibit TR antagonist properties and thus have the potential to induce hypothyroidism in some people. This chapter provides an overview of novel small molecules that have been specifically designed or screened for their TR antagonist activity as novel treatments for hyperthyroidism. While novel compounds have been identified, to date none have been developed sufficiently to enter clinical trials. Furthermore, a discussion on other sources of TR antagonists is discussed in terms of side effects of current drugs in the clinic as well as environmental pollution. © 2018 Elsevier Inc. All rights reserved.

  4. An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells

    International Nuclear Information System (INIS)

    Noor, Fozia; Niklas, Jens; Mueller-Vieira, Ursula; Heinzle, Elmar

    2009-01-01

    Efficient and accurate safety assessment of compounds is extremely important in the preclinical development of drugs especially when hepatotoxicty is in question. Multiparameter and time resolved assays are expected to greatly improve the prediction of toxicity by assessing complex mechanisms of toxicity. An integrated approach is presented in which Hep G2 cells and primary rat hepatocytes are compared in frequently used cytotoxicity assays for parent compound toxicity. The interassay variability was determined. The cytotoxicity assays were also compared with a reliable alternative time resolved respirometric assay. The set of training compounds consisted of well known hepatotoxins; amiodarone, carbamazepine, clozapine, diclofenac, tacrine, troglitazone and verapamil. The sensitivity of both cell systems in each tested assay was determined. Results show that careful selection of assay parameters and inclusion of a kinetic time resolved assay improves prediction for non-metabolism mediated toxicity using Hep G2 cells as indicated by a sensitivity ratio of 1. The drugs with EC 50 values 100 μM or lower were considered toxic. The difference in the sensitivity of the two cell systems to carbamazepine which causes toxicity via reactive metabolites emphasizes the importance of human cell based in-vitro assays. Using the described system, primary rat hepatocytes do not offer advantage over the Hep G2 cells in parent compound toxicity evaluation. Moreover, respiration method is non invasive, highly sensitive and allows following the time course of toxicity. Respiration assay could serve as early indicator of changes that subsequently lead to toxicity.

  5. Pharmacologic Therapy in the Elderly with Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Shih-Huang Lee

    2008-03-01

    Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia, and its prevalence significantly increases with age. Morphologic changes in the atrial myocardium associated with AF may result from underlying cardiovascular disease and/or physiologic aging processes. Congestive heart failure, tachycardia-induced cardiomyopathy and thromboembolic events resulting from AF are more common in elderly patients. It is important to assess any comorbidity and potential triggers of AF before considering pharmacologic therapy for AF. Proper rate control should include control in response to exercise, together with an avoidance of bradycardias and symptomatic pauses in patients with AF. Digoxin, β-blockers and calcium channel blockers can all be effective in controlling ventricular rate in elderly patients with AF. In the elderly, amiodarone is probably the safest drug for short-term administration to exert chemical cardioversion, facilitate electrical cardioversion, and prevent recurrence of AF. Warfarin has been shown to be highly effective in preventing stroke in the elderly with AF; however, many studies also have documented underuse of warfarin, may be because of the increased risk of warfarin-induced hemorrhage in such patients. These findings have raised concerns regarding quality of care, physician adherence to guidelines, and translation of clinical trial results into real-world practice in anticoagulation therapy in the elderly with AF. [International Journal of Gerontology 2008; 2(1: 1–6

  6. Three Vessel Coronary Cameral Fistulae Associated with New Onset Atrial Fibrillation and Angina Pectoris

    Directory of Open Access Journals (Sweden)

    Murat Yuksel

    2014-01-01

    Full Text Available Coronary cameral fistulas are abnormal communications between a coronary artery and a heart chamber or a great vessel which are reported in less than 0.1% of patients undergoing diagnostic coronary angiography. All three major coronary arteries are even less frequently involved in fistula formation as it is the case in our patient. A 68-year-old woman was admitted to cardiology clinic with complaints of exertional dyspnea and angina for two years and a new onset palpitation. Standard 12-lead electrocardiogram revealed atrial fibrillation (AF with a ventricular rate of 114 beat/minute and accompanying T wave abnormalities and minimal ST-depression on lateral derivations. Transthoracic echocardiographic examination was normal except for diastolic dysfunction, minimally mitral regurgitation, and mild to moderate enlargement of the left atrium. Sinus rhythm was achieved by medical cardioversion with amiodarone infusion. Coronary angiography revealed diffuse and multiple coronary-left ventricle fistulas originating from the distal segments of both left and right coronary arterial systems without any stenosis in epicardial coronary arteries. The patient’s symptoms resolved almost completely with medical therapy. High volume shunts via coronary artery to left ventricular microfistulas may lead to increased volume overload and subsequent increase in end-diastolic pressure of the left ventricle and may cause left atrial enlargement.

  7. Atrial Fibrillation in Eight New World Camelids.

    Science.gov (United States)

    Bozorgmanesh, R; Magdesian, K G; Estell, K E; Stern, J A; Swain, E A; Griffiths, L G

    2016-01-01

    There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). Describe clinical signs and outcome of AF in NWC. Eight New World Camelids admitted with AF. A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  8. Polarized light microscopy reveals physiological and drug-induced changes in surfactant membrane assembly in alveolar type II pneumocytes.

    Science.gov (United States)

    Haller, Thomas; Cerrada, Alejandro; Pfaller, Kristian; Braubach, Peter; Felder, Edward

    2018-05-01

    In alveolar type II (AT II) cells, pulmonary surfactant (PS) is synthetized, stored and exocytosed from lamellar bodies (LBs), specialized large secretory organelles. By applying polarization microscopy (PM), we confirm a specific optical anisotropy of LBs, which indicates a liquid-crystalline mesophase of the stored surfactant phospholipids (PL) and an unusual case of a radiation-symmetric, spherocrystalline organelle. Evidence is shown that the degree of anisotropy is dependent on the amount of lipid layers and their degree of hydration, but unaffected by acutely modulating vital cell parameters like intravesicular pH or cellular energy supply. In contrast, physiological factors that perturb this structure include osmotic cell volume changes and LB exocytosis. In addition, we found two pharmaceuticals, Amiodarone and Ambroxol, both of which severely affect the liquid-crystalline order. Our study shows that PM is an easy, very sensitive, but foremost non-invasive and label-free method able to collect important structural information of PS assembly in live AT II cells which otherwise would be accessible by destructive or labor intense techniques only. This may open new approaches to dynamically investigate LB biosynthesis - the incorporation, folding and packing of lipid membranes - or the initiation of pathological states that manifest in altered LB structures. Due to the observed drug effects, we further suggest that PM provides an appropriate way to study unspecific drug interactions with alveolar cells and even drug-membrane interactions in general. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Patterns of direct oral anticoagulant drug prescription in France in 2010-2013: a study in the Midi-Pyrénées area.

    Science.gov (United States)

    Diaz, Hugo; Bagheri, Haleh; Palmaro, Aurore; Rousseau, Vanessa; Bourrel, Robert; Montastruc, Jean-Louis; Birebent, Jordan

    2018-03-27

    The aim of our study was to study the pattern of prescription of direct-acting oral anticoagulants (DOACs) according to the French recommendations. We performed a cross-sectional study using anonymous data of patients covered by the French National Health Insurance information system (SNIIRAM) from 1 January 2010 to 31 December 2013 in the area of Midi-Pyrénées (southwest of France). Of the 355,608 patients identified, 325,216 (91.5%) were included, of whom 22,142 received at least one DOAC. About 39.1% (8,652 patients) had DOAC in an orthopedic indication, 46.5% (10,303 patients) in a cardiac indication, and 16.1% (3568 patients) in an indeterminate indication. Overall, guidelines were largely followed as for renal function monitoring, prescribing in orthopedic indications, in cardiac indications in patients aged 80 years and older, and in the case of concomitant use of verapamil. However, inappropriate prescriptions were observed for cardiac indications, and for dosage adjustments in orthopedic indications, with respect to both the age of patients (75 years and older) and those taking verapamil or amiodarone concomitantly. Guidelines were more followed in women and patients aged 80 or more. Among patients receiving DOACs, 58% were exposed to a prescription falling outside the guidelines. This study on DOAC prescription patterns revealed insufficiencies in the compliance with the French guidelines in certain indications.

  10. Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

    Directory of Open Access Journals (Sweden)

    Liane Rabinowich

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI. The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

  11. Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

    Science.gov (United States)

    Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

    2010-01-01

    To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

  12. Peripheral venous malformations and pulmonary hypertension: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Nambakam Tanuja Subramanyam

    2015-01-01

    Full Text Available Extensive pure peripheral venous malformations are rare. We report occurrence of peripheral venous malformations associated with pulmonary hypertension in a middle-aged male, who had nodular, irregular, soft, compressible, painless, non-pulsatile swellings over dependant positions such as forearms, hands, axilla, and genitalia, with overgrowth of hands and fingers enlarging slowly since early childhood. He had right ventricular failure signs. Plain films showed soft-tissue mass with diffuse calcifications (phleboliths. Doppler study showed low flow vascular channels, compressible hypoechoic lesions along with occasional hyperechoeic lesion corresponding with phleboliths. Magnetic resonance imaging (MRI, T1-weighted showed polypoidal mass with heterogenous hypo to intermediate signal with no flow voids. T2-weighted MRI showed high-signal intensity mass. Computed tomography (CT pulmonary angiogram showed pulmonary hypertension, no thrombi or vascular malformation. He was treated with angiotensin-converting enzyme inhibitors, diuretics, amiodarone, antiplatelets, and venous stockings. Specific therapy such as sclerosis and surgical resection could not be done as he was discharged against medical advice.

  13. Rare acute kidney injury secondary to hypothyroidism-induced rhabdomyolysis.

    Science.gov (United States)

    Cai, Ying; Tang, Lin

    2013-01-01

    Acute kidney injury (AKI) caused by hypothyroidism-induced rhabdomyolysis is a rare and potentially life-threatening syndrome. The aim of this study was to investigate the clinical characteristics of such patients. We retrospectively analyzed five patients treated at the Second Affiliated Hospital of Chongqing Medical University with AKI secondary to hypothyroidism- induced rhabdomyolysis from January 2006 to December 2010. Of the five cases reviewed (4 males, age range of 37 to 62 years), adult primary hypothyroidism was caused by amiodarone (1 case), chronic autoimmune thyroiditis (1 case), and by uncertain etiologies (3 cases). All patients presented with facial and lower extremity edema. Three patients presented with weakness, while two presented with blunted facies and oliguria. Only one patient reported experiencing myalgia and proximal muscle weakness, in addition to fatigue and chills. Creatine kinase, lactate dehydrogenase, and renal function normalized after thyroid hormone replacement, except in two patients who improved through blood purification. Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Moreover, further investigation into the etiology of the hypothyroidism is warranted.

  14. Assessment of pathophysiology based on the left ventricular shape in five patients with midventricular obstructive hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Aoki, Mayumi; Uekita, Kazumi; Obata, Hiromi; Makiguchi, Noriko; Mitsuoka, Takao; Kikuchi, Kenjiro

    2007-01-01

    The pathophysiology of midventricular obstructive hypertrophic cardiomyopathy (MVO) is unknown. Patients with MVO and MVO-like cardiomyopathy were classified into three groups based on the cardioimaging morphological characteristics of the left ventricle to investigate their complications and treatment. Four patients with MVO and one patient with disease-like MVO were admitted in our hospital from 1999 to 2005. Group A consisted of one patient with indications of pressure gradient at mid-ventricle without apical aneurysm, Group B consisted of three patients with indications of pressure gradient and apical aneurysm, and Group C consisted of one patient with hour-glass appearance with apical aneurysm and decreased left ventricular systolic function without pressure gradient. The diagnosis was established during examination for sustained ventricular tachycardia (SVT, three patients), paroxysmal atrial fibrillation (one patient), and coronary artery disease (one patient). Cardiogenic embolization was observed in all cases which originated from atrial fibrillation (one case) and apical aneurysm (two cases). No embolic event occurred in any patient after warfarin therapy. SVT occurred in patients in Groups B and C. SVT refractory to beta-blocker and mexiletine was treated by amiodarone. Apical aneurysmectomy and cryoablation could prevent recurrent SVT with drug resistance. Four of the five patients with MVO had arrhythmia (atrial fibrillation, SVT) and three had cardiogenic embolization. MVO could be classified into three groups depending on the morphological characteristics and complications. Treatment of MVO should be based on these characteristics. (author)

  15. [Atrial fibrillation].

    Science.gov (United States)

    Spinar, J; Vítovec, J

    2003-09-01

    Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

  16. [Classification and etiology of hyperthyroidism].

    Science.gov (United States)

    Łacka, Katarzyna; Fraczek, Magdalena Maria

    2014-03-01

    The prevalence of hyperthyroidism in women is between 0.5-2% and it is 10 times less common in men. The most common causes are Graves' disease, toxic multinodular goiter, and autonomously functioning thyroid adenoma. Rare causes of hyperthyroidisms are as follow: pituitary adenoma, autoimmune thyroiditis (Hashitoxicosis), levothyroxine overdose, inadequate iodine supplementation (including amiodaron induced hyperthyroidism, iodine-based contrast media), hCG excess (pregnancy, gestational trophoblastic disease, germ-cell tumors), drug induced hyperthyroidism, differentiated thyroid carcinomas and/or their metastases, struma ovarii, and familial nonautoimmune hyperthyroidism. This article focuses on the current data of etiopathogenesis of hyperthyroidisms. Genetic factors (like HLA-DR3,CD40, CTLA-4, PTPN22, FOXP3 CD25) and thyroid specific genes (thyroglobulin, TSHR, G(s)alpha) and environmental and endogenous factors (such as age, iodine, selenium, emotional stress, smoking, gender, pregnancy, sex hormones, fetal microchimerism, fetal growth, bacterial infections, viral infections, allergies, drugs (alemtuzumab, interferon alpha, iplimumab/tremelimumab, tyrosine kinase inhibitors, denileukindiftitox, thalidomide/lenalidomide, exposition to fallout and radiotherapy) have been described.

  17. Is Graves' disease a primary immunodeficiency? New immunological perspectives on an endocrine disease.

    Science.gov (United States)

    Struja, Tristan; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Mueller, Beat; Recher, Mike; Schuetz, Philipp

    2017-09-25

    Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

  18. Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

    Science.gov (United States)

    Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

    2016-01-01

    The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

  19. Medical image of the week: Wolff-Parkinson-White syndrome

    Directory of Open Access Journals (Sweden)

    Van Hook C

    2017-04-01

    Full Text Available No abstract available. Article truncated at 150 words. A 38-year-old man developed sustained rapid heart rate while rock climbing. The patient reported that he had experienced rare bouts of self-limited palpitations in the past. Blood pressure on arrival to the emergency department was 112/ 65 mm Hg. The patient’s initial EKG demonstrated a regular, narrow complex supraventricular tachycardia, with a rate of 232 (Figure 1. Intravenous adenosine was administered with no change in his rate or rhythm. The patient then received amiodarone by intravenous bolus, with subsequent conversion to sinus rhythm (Figure 2. Wolff-Parkinson-White (WPW syndrome is a congenital cardiac condition present in approximately 0.15% of the general population. WPW is characterized by the abnormal presence of conduction tissue that creates an accessory atrioventricular pathway and thus potentiates reentrant tachycardia (1. The classic resting EKG findings in WPW are: a shortened PR interval (less than 0.12 seconds, an indistinct initial upslope of the QRS complex (known as the …

  20. Thyroid storm in a patient with Wolff-Parkinson-White syndrome.

    Science.gov (United States)

    Naqvi, Syed Yaseen; Luebbert, Jeffrey J; Rosen, Stephen G

    2015-12-15

    A 44-year-old woman with no medical history presented to the emergency department with a 2 h history of sudden onset chest pressure, palpitations, diaphoresis and shortness of breath. She reported a 90-pound unintentional weight loss, increased appetite, irritability, night sweats and palpitations for 2 months. Physical examination revealed a heart rate (HR) of 269 bpm and a blood pressure of 116/94 mm Hg. Her ECG revealed a wide-complex tachycardia with right bundle branch morphology and an HR of 265 bpm. Intravenous adenosine was administered with resolution of the arrhythmia and symptoms. Her subsequent ECG revealed sinus tachycardia with δ waves, which was consistent with Wolff-Parkinson-White (WPW) syndrome. Laboratory findings confirmed thyroid storm and treatment began with intravenous hydrocortisone, methimazole, metoprolol, amiodarone and iodine drops. Graves' disease was confirmed based on the presence of serum thyroid-stimulating hormone receptor antibody. The patient underwent successful WPW accessory tract ablation 6 weeks after initial presentation. 2015 BMJ Publishing Group Ltd.

  1. A patient with severely reduced LV function and electrical storm saved by wearable cardioverter-defibrillator: a case report.

    Science.gov (United States)

    Strauss, Margit; Kouraki, Kleopatra; Skarlos, Alexandros; Zahn, Ralf; Kleemann, Thomas

    2013-06-01

    The wearable cardioverter-defibrillator (WCD) is indicated in patients who are considered to be at temporarily high risk for sudden cardiac death (SCD), when an implantable defibrillator is not yet clearly indicated. We report the case of a 41-year-old patient with a newly diagnosed severely reduced left ventricular (LV) function for suspected myocarditis and repeated nonsustained ventricular tachycardia (VT). This patient was supplied with a WCD who came back to the hospital 4 weeks after discharge with an electrical storm and adequate discharge of the WCD. After application of amiodarone, no further arrhythmias were detected during intrahospital course. For further risk stratification, we performed a magnetic field imaging (MFI), that was reported to be useful in risk assessment of SCD in patients with ischemic cardiomyopathy. This measurement showed a normal result, but we decided to give an implantable cardioverter-defibrillator (ICD) to the patient. During a follow-up of 1 year, no further arrhythmias occurred. With this case, we report the efficacy of a WCD, which is a novel tool in patients at temporarily high risk of SCD and we report a novel method of risk stratification in patients with a high risk of SCD.

  2. "Rescue" ablation of electrical storm in arrhythmogenic right ventricular cardiomyopathy in pregnancy.

    Science.gov (United States)

    Stec, Sebastian; Krynski, Tomasz; Baran, Jakub; Kulakowski, Piotr

    2013-08-13

    Radiofrequency ablation (RFCA) became a treatment of choice in patients with recurrent ventricular tachycardia, ventricular fibrillation, and appropriate interventions of implanted cardioverter-defibrillator (ICD), however, electrical storm (ES) ablation in a pregnant woman has not yet been reported. We describe a case of a successful rescue ablation of recurrent ES in a 26-year-old Caucasian woman during her first pregnancy (23rd week). The arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) was diagnosed 3 years earlier and several drugs as well as 2 ablations failed to control recurrences of ventricular tachycardia. RFCA was performed on the day of the third electric storm. The use of electroanatomic mapping allowed very low X-ray exposure, and after applications in the right ventricular outflow tract, arrhythmia disappeared. Three months after ablation, a healthy girl was delivered without any complications. During twelve-month follow-up there was no recurrence of ventricular tachycardia or ICD interventions. This case documents the first successful RFCA during ES due to recurrent unstable ventricular arrhythmias in a patient with ARVD/C in pregnancy. Current guidelines recommend metoprolol, sotalol and intravenous amiodarone for prevention of recurrent ventricular tachycardia in pregnancy, however, RFCA should be considered as a therapeutic option in selected cases. The use of 3D navigating system and near zero X-ray approach is associated with minimal radiation exposure for mother and fetus as well as low risk of procedural complication.

  3. [Electrical storm].

    Science.gov (United States)

    Barnay, C; Taieb, J; Morice, R

    2007-11-01

    Electrical storm is defined as repeated occurrence of severe ventricular arrhythmias requiring multiple cardioversions, two or more or three or more following different studies. The clinical aspect can sometimes be made of multiple, self aggravating, life threatening accesses. There are three main clinical circumstances of occurrence: in patients equipped with intracardiac defibrillators, during the acute phase of myocardial infarction and in Brugada syndrome. 10 to 15% of patients with cardiac defibrillators are subject to electrical storms in a period of two years. The causative arrhythmia is most often ventricular tachycardia than ventricular fibrillation, especially in secondary prevention and if the initial arrhythmias justifying the device was a ventricular tachycardia. Precipitaing factors are present in one third of cases, mainly acute heart failure, ionic disorders and arrhythmogenic drugs. Predictive factors are age, left ventricular ejection fractionelectrical shock in 50% of cases, antitachycardi stimulation in 30% and in 20% by association of the two. Treatment, after elimination of inappropriate shocks, is mainly based on beta-blockers and amiodarone, class I antiarrhythmics, lidocaïne or bretylium in some cases, and sedation pushed to general anesthesia in some cases. Radio-frequency ablation and even heart transplantation have been proposed in extreme cases. Quinidine has been proved efficient in cases of Brugada syndrome.

  4. The evaluation and management of electrical storm.

    Science.gov (United States)

    Eifling, Michael; Razavi, Mehdi; Massumi, Ali

    2011-01-01

    Electrical storm is an increasingly common and life-threatening syndrome that is defined by 3 or more sustained episodes of ventricular tachycardia, ventricular fibrillation, or appropriate shocks from an implantable cardioverter-defibrillator within 24 hours. The clinical presentation can be dramatic. Electrical storm can manifest itself during acute myocardial infarction and in patients who have structural heart disease, an implantable cardioverter-defibrillator, or an inherited arrhythmic syndrome. The presence or absence of structural heart disease and the electrocardiographic morphology of the presenting arrhythmia can provide important diagnostic clues into the mechanism of electrical storm. Electrical storm typically has a poor outcome.The effective management of electrical storm requires an understanding of arrhythmia mechanisms, therapeutic options, device programming, and indications for radiofrequency catheter ablation. Initial management involves determining and correcting the underlying ischemia, electrolyte imbalances, or other causative factors. Amiodarone and β-blockers, especially propranolol, effectively resolve arrhythmias in most patients. Nonpharmacologic treatment, including radiofrequency ablation, can control electrical storm in drug-refractory patients. Patients who have implantable cardioverter-defibrillators can present with multiple shocks and may require drug therapy and device reprogramming. After the acute phase of electrical storm, the treatment focus should shift toward maximizing heart-failure therapy, performing revascularization, and preventing subsequent ventricular arrhythmias. Herein, we present an organized approach for effectively evaluating and managing electrical storm.

  5. Atypical size and location of a right atrial myxoma: a case report

    Directory of Open Access Journals (Sweden)

    Nina Vinícius JS

    2012-01-01

    Full Text Available Abstract Introduction Primary intracardiac tumors are rare and approximately 50% are myxomas. The majority of myxomas are located in the left atrium and have variable clinical presentation. We report a case of a large myxoma in the right atrium, which is an uncommon location for this type of tumor. Case presentation A 45-year-old Caucasian woman with a history of palpitation had dyspnea on great exertion and discrete weight loss. A cardiac evaluation showed splitting of S1. An echocardiogram showed a large mass in the right atrium, suggesting myxoma; chest computed tomography confirmed the diagnostic hypothesis. Our patient underwent surgical treatment with excision of a 10 cm multilobulated mass. She presented with supraventricular tachycardia during the operation. She was placed in the intensive care unit and her condition improved after the use of amiodarone. The diagnosis of myxoma was confirmed by histopathological study. Conclusions In this case report, we emphasize the rarity of large myxomas in the right atrium and the difficulty of differential diagnosis given their dimension and location.

  6. Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

    Science.gov (United States)

    Tylutki, Zofia; Polak, Sebastian

    2015-03-12

    Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  7. An Unexpected Cause of Bradycardia in a Patient with Bacterial Meningitis

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    Petros Ioannou

    2017-01-01

    Full Text Available Sinus bradycardia which is a sinus rhythm with a resting heart rate of less than 60 bpm is caused by intrinsic cardiac disorders like sick sinus syndrome or inferior myocardial infarction, metabolic and environmental causes (such as hypothyroidism and electrolyte disorders, medications (such as beta-blockers and amiodarone, infection (such as myocarditis, increased intracranial pressure, and toxic exposure, while it can sometimes be a normal phenomenon, especially during sleep, in athletes, and during pregnancy. Symptomatic sinus bradycardia should warrant a thorough work-up in order to identify any reversible causes; otherwise, placement of a permanent pacemaker could be needed. We present the case of a patient who was admitted due to confusion and fever and was found to have pneumococcal meningitis and bacteremia, and during his hospital stay he developed symptomatic sinus bradycardia that was of intractable cause and persistent. Placement of a permanent pacemaker was chosen until the night staff of the hospital discovered by chance the neglected cause of his bradycardia.

  8. Wolf-Parkinson-White syndrome in young men presenting with palpitation: the pattern of delta waves in predicting location of accessory pathway

    Directory of Open Access Journals (Sweden)

    Miryanti Cahyaningtias

    2011-11-01

    Full Text Available Palpitation is a common presenting symptom in the emergency department. Wolf-Parkinson White (WPW syndrome is a cardiac conduction disorder that may present with palpitation and lead to sudden cardiac death. WPW could be detected by  electrocardiogram (ECG. In this case report, we present two young male patients with WPW syndrome admitted to our hospital with history of repeated and progressive palpitation. ECG of the first patient revealed supraventricular tachycardia which converted to sinus rhythm after propanolol treatment. ECG showed sinus rhythm with delta wave in lead II,III,aVF, V1 suggesting the presence of accessory pathway (AP in left lateral wall. Electrophysiology study confirmed the presence of AP and radio frequency catheter ablation was successfully done resulted in disappearance of delta on outpatient clinic ECG. Patient has no symptom and he do not have to take medication. ECG of the second patient revealed supraventricular tachycardia with abberancy. After amiodarone infusion, ECG showed sinus rhythm with delta wave in lead I,II,aVL suggesting the presence of accessory pathway in anteroseptal wall. Electrophysiology study and catheter ablation did not perform for this patient because of financial problem, however amidarone has to be taken regularly to prevent the recurrence of supraventricular tachycardia. (Med J Indones 2011; 20:298-301Keywords: ECG, palpitation, supraventricular tachycardia, Wolf- Parkinson White syndrome

  9. March 2016 critical care case of the month

    Directory of Open Access Journals (Sweden)

    Loftsgard T

    2016-03-01

    Full Text Available No abstract available. Article truncated at 150 words. History of Present Illness: A 58-year-old man was admitted to the ICU in stable condition after an aortic valve replacement with a mechanical valve. Past Medical History: He had with past medical history significant for endocarditis, severe aortic regurgitation related to aortic valve perforation, mild to moderate mitral valve regurgitation, atrial fibrillation, depression, hypertension, hyperlipidemia, obesity, and previous cervical spine surgery. As part of his preop workup, he had a cardiac catheterization performed which showed no significant coronary artery disease. Pulmonary function tests showed an FEV1 of 55% predicted and a FEV1/FVC ratio of 65% consistent with moderate obstruction. Medications: Amiodarone 400 mg bid, digoxin 250 mcg, furosemide 20 mg IV bid, metoprolol 12.5 mg bid. Heparin nomogram since arrival in the ICU. Physical Examination: He was extubated shortly after arrival in the ICU. Vitals signs were stable. His weight had increased 3 Kg compared to admission. He was awake ...

  10. Appropriate evaluation and treatment of heart failure patients after implantable cardioverter-defibrillator discharge: time to go beyond the initial shock.

    Science.gov (United States)

    Mishkin, Joseph D; Saxonhouse, Sherry J; Woo, Gregory W; Burkart, Thomas A; Miles, William M; Conti, Jamie B; Schofield, Richard S; Sears, Samuel F; Aranda, Juan M

    2009-11-24

    Multiple clinical trials support the use of implantable cardioverter-defibrillators (ICDs) for prevention of sudden cardiac death in patients with heart failure (HF). Unfortunately, several complicating issues have arisen from the universal use of ICDs in HF patients. An estimated 20% to 35% of HF patients who receive an ICD for primary prevention will experience an appropriate shock within 1 to 3 years of implant, and one-third of patients will experience an inappropriate shock. An ICD shock is associated with a 2- to 5-fold increase in mortality, with the most common cause being progressive HF. The median time from initial ICD shock to death ranges from 168 to 294 days depending on HF etiology and the appropriateness of the ICD therapy. Despite this prognosis, current guidelines do not provide a clear stepwise approach to managing these high-risk patients. An ICD shock increases HF event risk and should trigger a thorough evaluation to determine the etiology of the shock and guide subsequent therapeutic interventions. Several combinations of pharmacologic and device-based interventions such as adding amiodarone to baseline beta-blocker therapy, adjusting ICD sensitivity, and employing antitachycardia pacing may reduce future appropriate and inappropriate shocks. Aggressive HF surveillance and management is required after an ICD shock, as the risk of sudden cardiac death is transformed to an increased HF event risk.

  11. Photodegradation of pharmaceuticals in the aquatic environment by sunlight and UV-A, -B and -C irradiation.

    Science.gov (United States)

    Kawabata, Kohei; Sugihara, Kazumi; Sanoh, Seigo; Kitamura, Shigeyuki; Ohta, Shigeru

    2013-01-01

    In order to investigate the effect of sunlight on the persistence and ecotoxicity of pharmaceuticals contaminating the aquatic environment, we exposed nine pharmaceuticals (acetaminophen (AA), amiodarone (AM), dapsone (DP), dexamethasone (DX), indomethacin (IM), naproxen (NP), phenytoin (PH), raloxifene (RL), and sulindac (SL)) in aqueous media to sunlight and to ultraviolet (UV) irradiation at 254, 302 or 365 nm (UV-C, UV-B or UV-A, respectively). Degradation of the pharmaceuticals was monitored by means of high-performance liquid chromatography (HPLC). Sunlight completely degraded AM, DP and DX within 6 hr, and partly degraded the other pharmaceuticals, except AA and PH, which were not degraded. Similar results were obtained with UV-B, while UV-A was less effective (both UV-A and -B are components of sunlight). All the pharmaceuticals were photodegraded by UV-C, which is used for sterilization in sewage treatment plants. Thus, the photodegradation rates of pharmaceuticals are dependent on both chemical structure and the wavelength of UV exposure. Toxicity assay using the luminescent bacteria test (ISO11348) indicated that UV irradiation reduced the toxicity of some pharmaceuticals to aquatic organisms by decreasing their amount (photodegradation) and increased the toxicity of others by generating toxic photoproduct(s). These results indicate the importance of investigating not only parent compounds, but also photoproducts in the risk assessment of pharmaceuticals in aquatic environments.

  12. Effects of drugs in subtoxic concentrations on the metabolic fluxes in human hepatoma cell line Hep G2

    International Nuclear Information System (INIS)

    Niklas, Jens; Noor, Fozia; Heinzle, Elmar

    2009-01-01

    Commonly used cytotoxicity assays assess the toxicity of a compound by measuring certain parameters which directly or indirectly correlate to the viability of the cells. However, the effects of a given compound at concentrations considerably below EC 50 values are usually not evaluated. These subtoxic effects are difficult to identify but may eventually cause severe and costly long term problems such as idiosyncratic hepatotoxicity. We determined the toxicity of three hepatotoxic compounds, namely amiodarone, diclofenac and tacrine on the human hepatoma cell line Hep G2 using an online kinetic respiration assay and analysed the effects of subtoxic concentrations of these drugs on the cellular metabolism by using metabolic flux analysis. Several changes in the metabolism could be detected upon exposure to subtoxic concentrations of the test compounds. Upon exposure to diclofenac and tacrine an increase in the TCA-cycle activity was observed which could be a signature of an uncoupling of the oxidative phosphorylation. The results indicate that metabolic flux analysis could serve as an invaluable novel tool for the investigation of the effects of drugs. The described methodology enables tracking the toxicity of compounds dynamically using the respiration assay in a range of concentrations and the metabolic flux analysis permits interesting insights into the changes in the central metabolism of the cell upon exposure to drugs.

  13. [Incidence of phlebitis due to peripherally inserted venous catheters: impact of a catheter management protocol].

    Science.gov (United States)

    Ferrete-Morales, C; Vázquez-Pérez, M A; Sánchez-Berna, M; Gilabert-Cerro, I; Corzo-Delgado, J E; Pineda-Vergara, J A; Vergara-López, S; Gómez-Mateos, J

    2010-01-01

    To assess the impact on the incidence of PPIVC by implementing a catheter management protocol and to determine risk factors for PPIVC development in hospitalized patients. A total of 3978 episodes of venous catheterization were prospectively included from September 2002 to December 2007. A catheter management protocol was implemented during this period of time. The incidence and variables associated to the occurrence of PPIVC were determined. The incidence of PPIVC from 2002 to 2007 was 4.8%, 4.3%, 3.6%, 2.5%, 1.3% and 1.8% (phistory of phlebitis was the only factor independently associated to phlebitis due to peripherally inserted central venous catheters (AOR 3.24; CI at 95% CI= 1.05-9.98, p=0.04). A catheter management protocol decreases the incidence of PPIVC in hospitalized patients. The risk of PPIVC increases for peripherally inserted central venous catheters when the patients have a history of phlebitis and for peripheral venous catheters when amiodarone or cefotaxime are infused. Catheterization of peripheral veins performed during morning shifts is associated with a lower incidence of PPIVC when compared with night shift catheterizations.

  14. Drug-induced interstitial lung diseases. Often forgotten

    International Nuclear Information System (INIS)

    Poschenrieder, F.; Stroszczynski, C.; Hamer, O.W.

    2014-01-01

    Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.) [de

  15. Cardiovascular drugs inducing QT prolongation: facts and evidence.

    Science.gov (United States)

    Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

    2010-01-01

    Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

  16. [Unexpected atrial fibrillation when monitoring in operating room. Case of the trimester].

    Science.gov (United States)

    2014-05-01

    A real case reported to the SENSAR database of incidents is presented. In a patient scheduled for nose fracture repair surgery an unexpected atrial fibrillation was found when monitored in the operating room. The operation was not delayed. After induction of general anaesthesia heart rate suddenly increased and hemodinamic situation was impaired. Cardioversion was required. Two electric countershocks were given but sinus rhythm was not restored. Heart rate was controlled with amiodarone infusion. Optimal defibrillation characteristics are described in these cases. Increased risk of thromboembolism (1-2%) following cardioversion is present even if atrial thrombi are ruled out. The mainstay therapies of are rhythm and rate control and prevention of thromboembolic complications. We describe recommendations on the management of these critical situations with emphasis in learning through the creation of protocols and training practice in simulation. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  17. TR{alpha}- and TSH-mRNA levels after temporal exposition with methimazole in zebrafish, Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Schulz, A.E.I.; Stocker, A.; Hollosi, L.; Schramm, K.W. [Inst. of Ecological Chemistry, GSF - National Research Center for Environment and Health (Germany)

    2004-09-15

    The group of dioxin and dioxin-like substances are highly persistent in the environment. There are evidences from present investigations that a variety of substances are capable of disrupting the endocrine system in the aquatic environment. These substances are called endocrine disruptors. Dioxin and related compounds can act as endocrine disruptors. Aquatic animals like amphibian and fish are especially affected of the impact of these compounds. Investigations concerned so far in particular the domain of reproduction biology and the thyroid axis especially. Recent investigations showed that the TR{alpha}-mRNA level change after a short temporal expression with T3, methimazole and amiodarone. The objective of the project is to identify effects of thyroid endocrine disruptors on the regulation of gene expression of the thyroid receptors TR{alpha}a, TR{beta} and thyroid stimulating hormone TSH and associated effects on other system. In preliminary studies the effects of the drug methimazole as model substance on gene expression of TR{alpha} and TSH were investigated. Methimazole is an inhibitor of the thyroid peroxidase so that the formation of thyroid hormones is disrupted.

  18. TRAb negative entities of hyperthyroid syndrome: Our experience of the past 5 years

    Directory of Open Access Journals (Sweden)

    Paunković Nebojša

    2013-01-01

    Full Text Available Over the past five years, since we moved to private practice, we continued with testing of TSH receptor antibodies. So far we have carried out 775 tests and examined 260 patients. We used TRAb human, BRAHMs. We carried out our research on 192 patients with untreated immune hyperthyroidism and 37 with the disease in remission. As the subject of this study was TRAb negative hyperthyroidism, the examination of this group of patients was comprehensive. The largest was a group of patients with Plummer disease (13 in total - 4 with toxic adenoma, 7 with multinodular toxic goiter and 2 with disseminated thyroid autonomy.Nine experienced thyroid destruction (eight with painful thyroiditis, one with post-partal thyroiditis and one with thyroid infarction. Five patients had amiodaron induced hyperthyroidism. Diagnosis was based on the following criteria: clinical features and symptoms, 'free' thyroxin concentration, concentration of ultrasensitive TSH, ultrasonography of thyroid gland and scinigraphy with Tc 99m pertehnetat. The analysis of each method was used for diagnosis and differential diagnosis of each type of occurrences of TRAb negative hyperthyroidism.

  19. Hyperthyroidism: diagnosis and treatment.

    Science.gov (United States)

    Reid, Jeri R; Wheeler, Stephen F

    2005-08-15

    The proper treatment of hyperthyroidism depends on recognition of the signs and symptoms of the disease and determination of the etiology. The most common cause of hyperthyroidism is Graves' disease. Other common causes include thyroiditis, toxic multinodular goiter, toxic adenomas, and side effects of certain medications. The diagnostic workup begins with a thyroid-stimulating hormone level test. When test results are uncertain, measuring radionuclide uptake helps distinguish among possible causes. When thyroiditis is the cause, symptomatic treatment usually is sufficient because the associated hyperthyroidism is transient. Graves' disease, toxic multinodular goiter, and toxic adenoma can be treated with radioactive iodine, antithyroid drugs, or surgery, but in the United States, radioactive iodine is the treatment of choice in patients without contraindications. Thyroidectomy is an option when other treatments fail or are contraindicated, or when a goiter is causing compressive symptoms. Some new therapies are under investigation. Special treatment consideration must be given to patients who are pregnant or breastfeeding, as well as those with Graves' ophthalmopathy or amiodarone-induced hyperthyroidism. Patients' desires must be considered when deciding on appropriate therapy, and dose monitoring is essential.

  20. Permanent and temporary pacemaker implantation after orthotopic heart transplantation

    Directory of Open Access Journals (Sweden)

    Bacal Fernando

    2000-01-01

    Full Text Available PURPOSE:To determine the indication for and incidence and evolution of temporary and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A retrospective review of 114 patients who underwent orthotopic heart transplantation InCor (Heart Institute USP BR between March 1985 and May 1993. We studied the incidence of and indication for temporary pacing, the relationship between pacing and rejection, the need for pemanent pacing and the clinical follow-up. RESULTS: Fourteen of 114 (12%heart transplant recipients required temporary pacing and 4 of 114 (3.5% patients required permanent pacing. The indication for temporary pacing was sinus node dysfunction in 11 patients (78.5% and atrioventricular (AV block in 3 patients (21.4%. The indication for permanent pacemaker implantation was sinus node dysfunction in 3 patients (75% and atrioventricular (AV block in 1 patient (25%. We observed rejection in 3 patients (21.4% who required temporary pacing and in 2 patients (50% who required permanent pacing. The previous use of amiodarone was observed in 10 patients (71.4% with temporary pacing. Seven of the 14 patients (50% died during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication for temporary and permanent pacemaker implantation in cardiac transplant recipients. The need for pacing was related to worse prognosis after cardiac transplantation.

  1. Electrical storm in patients with an implanted defibrillator: a matter of definition.

    Science.gov (United States)

    Israel, Carsten W; Barold, S Serge

    2007-10-01

    The term "electrical storm" (ES) indicates a state of cardiac electrical instability manifested by several episodes of ventricular tachyarrhythmias (VTs) within a short time. In patients with an implantable cardioverter defibrillator (ICD), ES is best defined as 3 appropriate VT detections in 24 h, treated by antitachycardia pacing, shock or eventually untreated but sustained in a VT monitoring zone. The number of shocks and inappropriate detections are irrelevant for the definition. ES occurs in approximately 25% of ICD patients within 3 years, with typically 5-55 individual VTs within one storm. Potential triggers can be found in approximately 66% of patients and include new/worsened heart failure, changes in antiarrhythmic medication, context with other illness, psychological stress, diarrhea, and hypokalemia. In most patients, ES consists of monomorphic VT indicating the presence of reentry while ventricular fibrillation indicating acute ischemia is rare. ES seems to have a low immediate mortality (1%) but frequently (50-80%) leads to hospitalization. Long-term prognostic implications of ES are unclear. The key intervention in ES is reduction of the elevated sympathetic tone by beta blockers and frequently benzodiazepines. Amiodarone i.v. has also been successful and azimilide seems promising while class I antiarrhythmic drugs are usually unsuccessful. Substrate mapping and VT ablation may be useful in treatment and prevention of ES. Prevention of ES requires ICD programming systematically avoiding unnecessary shocks (long VT detection, antitachycardia pacing where ever possible) which otherwise can fuel the sympathetic tone and prolong ES.

  2. Targeted toxicological screening for acidic, neutral and basic substances in postmortem and antemortem whole blood using simple protein precipitation and UPLC-HR-TOF-MS

    DEFF Research Database (Denmark)

    Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal

    2016-01-01

    -HR-TOF-MS was achieved in one injection. This method covered basic substances, substances traditionally analyzed in negative ESI (e.g., salicylic acid), small highly polar substances such as beta- and gamma-hydroxybutyric acid (BHB and GHB, respectively) and highly non-polar substances such as amiodarone. The new method......A broad targeted screening method based on broadband collision-induced dissociation (bbCID) ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry (UPLC-HR-TOF-MS) was developed and evaluated for toxicological screening of whole blood samples. The acidic, neutral...... was performed on spiked whole blood samples and authentic postmortem and antemortem whole blood samples. For most of the basic drugs, the established cut-off limits were very low, ranging from 0.25ng/g to 50ng/g. The established cut-off limits for most neutral and acidic drugs, were in the range from 50ng...

  3. Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.

    Science.gov (United States)

    Kuroda, Yukihiro; Saito, Madoka

    2010-03-01

    An in vitro method to predict phospholipidosis-inducing potential of cationic amphiphilic drugs (CADs) was developed using biochemical and physicochemical assays. The following parameters were applied to principal component analysis, as well as physicochemical parameters: pK(a) and clogP; dissociation constant of CADs from phospholipid, inhibition of enzymatic phospholipid degradation, and metabolic stability of CADs. In the score plot, phospholipidosis-inducing drugs (amiodarone, propranolol, imipramine, chloroquine) were plotted locally forming the subspace for positive CADs; while non-inducing drugs (chlorpromazine, chloramphenicol, disopyramide, lidocaine) were placed scattering out of the subspace, allowing a clear discrimination between both classes of CADs. CADs that often produce false results by conventional physicochemical or cell-based assay methods were accurately determined by our method. Basic and lipophilic disopyramide could be accurately predicted as a nonphospholipidogenic drug. Moreover, chlorpromazine, which is often falsely predicted as a phospholipidosis-inducing drug by in vitro methods, could be accurately determined. Because this method uses the pharmacokinetic parameters pK(a), clogP, and metabolic stability, which are usually obtained in the early stages of drug development, the method newly requires only the two parameters, binding to phospholipid, and inhibition of lipid degradation enzyme. Therefore, this method provides a cost-effective approach to predict phospholipidosis-inducing potential of a drug. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  4. Gene expression profiling in rat liver treated with compounds inducing phospholipidosis

    International Nuclear Information System (INIS)

    Hirode, Mitsuhiro; Ono, Atsushi; Miyagishima, Toshikazu; Nagao, Taku; Ohno, Yasuo; Urushidani, Tetsuro

    2008-01-01

    We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA using these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity

  5. Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement

    Directory of Open Access Journals (Sweden)

    R D’Arcy

    2017-09-01

    Full Text Available A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH and free thyroxine (T4. Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T3 was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1–6.8 pmol/L. No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging (123I demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement.

  6. Heart Surgery Experience in Hitit University Faculty of Medicine Corum Research and Training Hospital: First Year Results

    Directory of Open Access Journals (Sweden)

    Adem Diken

    2014-03-01

    Full Text Available Aim: We aimed to assess the clinical outcomes of our department of cardiac surgery which was newly introduced in Hitit University Corum Education and Research Hospital. Material and Method: Between November 2012 and November 2013, a total of 110 open-heart surgeries were performed. Ten out of these (9.1% were emergency operations for acute ST elevation myocardial infarction Off-pump technique was used in 31 (29.2% patients and cardiopulmonary bypass was used in 75 (70.8%. A total of 106 patients received coronary artery bypass grafting, 1 received mitral reconstruction, 1 received Bentall procedure, 1 received tricuspid valve repair, 1 received mitral valve replacement, 1 received aortic valve replacement with aortic root enlargement and 1 received aortic supracoronary graft replacement. Results: Hospital mortality occurred in 1 (0.9% patient. Four patients (3.6% who were on dual antiaggregants underwent a revision for bleeding on the day of the operation. Morbidities occurred in 3 (2.7% patients. Atrial fibrillation occurred in 11 (10% patients and the normal sinus rhythm was achieved by amiodarone. Intraaortic balloon counterpulsation was used in 5 (4.5% patients. Discussion: The newly introduced cardiac surgery department of the Hitit University Corum Education and Research Hospital, which provides tertiary care to a wide rural community, serves with low morbidity and mortality.

  7. [Non alcoholic steatohepatitis].

    Science.gov (United States)

    Manero, E; Findor, J A; Avagnina, A; de Elizalde, S; Elsner, B

    1994-01-01

    A prospective study of 21 patients with the diagnosis of non-alcoholic steatohepatitis (NASH) was carried out. All patients had hepatomegaly and in 10 (48%) image studies were consistent with steatosis and/or fibrosis. Biochemically, there was increase of AST, ALT and cholesterol in 48%, of GGT in 52% and of alkaline phosphatase in 38%. 18 patients were obese, 2 of them diabetic, 2 others had a history of exposure to drugs (amiodarone and isopropilic alcohol) and the last one presented hypothyroidism. Liver biopsies were studied using a semiquantitative scale to evaluate the degree of steatosis, inflammation and fibrosis in a scale from 1 to 3. Results showed a medium score of 2.6 for steatosis, 1.5 for inflammation and 1.8 for fibrosis. Four patients had cirrhosis and Mallory bodies were found in 11 cases (52%). NASH is an oligosymptomatic disease that can be found in different clinical conditions, mainly obesity, and is more frequent in women. It is histologically indistinguishable from alcoholic steatohepatitis. It is frequently underdiagnosed clinically and must be taken into account as a possible cause of cryptogenetic cirrhosis.

  8. Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Stephen K Roberts

    Full Text Available Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

  9. Serum cytokine levels in autoimmune and non-autoimmune hyperthyroid states

    Directory of Open Access Journals (Sweden)

    L.S. Ward

    2000-01-01

    Full Text Available Although the role of interleukin-2 (IL-2 and interferon gamma (gIFN is still poorly understood in hyperthyroid diseases, it is reasonable to assume that these cytokines may be present at higher levels in Graves' disease (GD than in other primarily non-autoimmune thyroid diseases. In order to look for an easy method to distinguish GD from primarily non-autoimmune causes of hyperthyroidism, we compared 13 healthy individuals with 21 treated and untreated hyperthyroid GD patients and with 19 patients with hyperthyroidism due to other etiologies: 7 cases of multinodular goiter, 5 cases of excessive hormone replacement and 7 cases of amiodarone-associated hyperthyroidism. All patients presented low TSH levels and a dubious clinical thyroid state. We found a good correlation between TSH and serum IL-2 levels (r = 0.56; PgIFN (P<0.01 levels were lower in the hyperthyroid group of patients than in control subjects, suggesting a depressed TH1 pattern in the T-cell subset of hyperthyroid patients. GD had normal IL-2 levels, while patients with other forms of thyrotoxicosis presented decreased IL-2 levels (P<0.05. There was no difference between treated and untreated GD patients. We suggest that the direct measurement of serum IL-2 level may help to confirm hyperthyroidism caused by GD.

  10. Safety and efficacy of vernakalant for acute cardioversion of atrial fibrillation: an update

    Science.gov (United States)

    Tsuji, Yukiomi; Dobrev, Dobromir

    2013-01-01

    Intravenous vernakalant has recently been approved in Europe as an atrial-selective antiarrhythmic drug for the conversion of recent-onset atrial fibrillation (AF). It inhibits atrial-selective K+ currents (IK,ACh and IKur) and causes rate-dependent atrial-predominant Na+ channel block, with only a small inhibitory effect on the rapid delayed rectifier K+ current (IKr) in the ventricle. Due to its atrial-selective properties, vernakalant prolongs the effective refractory period of the atria with minimal effects on the ventricles, being associated with a low proarrhythmic risk for torsades de pointes arrhythmias. Five pivotal clinical trials consistently demonstrated that vernakalant rapidly terminates AF with stable maintenance of sinus rhythm for up to 24 hours. A head-to-head comparative trial showed that the 90-minute conversion rate of vernakalant was substantially higher than that of amiodarone. Initially, a longer-acting oral formulation of vernakalant was shown to be effective and safe in preventing AF recurrence after cardioversion in a Phase IIb study. However, the clinical studies testing oral vernakalant for maintenance of sinus rhythm after AF cardioversion were prematurely halted for undisclosed reasons. This review article provides an update on the safety and efficacy of intravenous vernakalant for the rapid cardioversion of AF. PMID:23637539

  11. Acute thyrotoxicosis secondary to destructive thyroiditis associated with cardiac catheterization contrast dye.

    Science.gov (United States)

    Calvi, Laura; Daniels, Gilbert H

    2011-04-01

    Thyrotoxicosis caused by destructive thyroiditis is self-limited and results from the subacute release of preformed thyroid hormone. Common etiologies include painful subacute thyroiditis and silent (painless) subacute thyroiditis (including postpartum thyroiditis, amiodarone-associated destructive thyroiditis, and lithium-associated thyroiditis). Thyrotoxicosis commonly evolves slowly over a matter of weeks. We report a unique case of severe thyrotoxicosis caused by acute- onset painful destructive thyroiditis in a patient who received large amounts of nonionic contrast dye Hexabrix® for cardiac catheterization. The results of thyroid function and physical examination were normal before the catheterization. The acute onset of severe thyroid pain, rapid increase in serum Free Thyroxine Index, and thyroglobulin concentrations with a triiodothyronine to free thyroxine index ratio of thyroiditis, likely related to direct toxicity from the iodinated contrast material. In light of the large number of patients who receive these contrast agents during cardiac catheterization, clinicians should be advised of this potentially serious complication, particularly in the setting of unstable cardiac disease.

  12. A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients.

    Directory of Open Access Journals (Sweden)

    Jinxing Chen

    Full Text Available Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551, warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%, CYP2C9*3(7.0%, body surface area(4.2%, age(2.7%, target INR(1.4%, CYP4F2 rs2108622 (0.7%, amiodarone use(0.6%, diabetes mellitus(0.6%, and digoxin use(0.5%, which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236, the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, P<0.001. Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients.

  13. A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients

    Science.gov (United States)

    Luo, Fang; Wang, Jin'e; Shi, Yi; Tan, Yu; Chen, Qianlong; Zhang, Yu; Hui, Rutai; Wang, Yibo

    2014-01-01

    Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236), the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, Pwarfarin use in Northern Chinese patients. PMID:25126975

  14. [Arrhythmogenic right ventricular cardiomyopathy. Case report and a brief literature review].

    Science.gov (United States)

    Izurieta, Carlos; Curotto-Grasiosi, Jorge; Rocchinotti, Mónica; Torres, María J; Moranchel, Manuel; Cañas, Sebastián; Cardús, Marta E; Alasia, Diego; Cordero, Diego J; Angel, Adriana

    2013-01-01

    A 51-year-old man was admitted to this hospital because of palpitations and a feeling of dizziness for a period of 2h. The electrocardiogram revealed a regular wide-QRS complex tachycardia at a rate of 250 beats per minute, with superior axis and left bundle branch block morphology without hemodynamically decompensation, the patient was cardioverted to sinus rhythm after the administration of a loading and maintenance dose of amiodarone. The elechtrophysiological study showed the ventricular origin of the arrhythmia. In order to diagnose the etiology of the ventricular tachycardia we performed a coronary arteriography that showed normal epicardial vessels, thus ruling out coronary disease. Doppler echocardiography revealed systolic and diastolic functions of both left and right ventricles within normal parameters, and normal diameters as well. A cardiac magnetic resonance with late enhancement was done, showing structural abnormalities of the right ventricle wall with moderate impairment of the ejection fraction, and a mild dysfunction of the left ventricle. The diagnosis of arrhythmogenic right ventricular cardiomyopathy was performed as 2 major Task Force criteria were met. We implanted an automatic cardioverter defibrillator as a prophylactic measure. The patient was discharged without complications. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  15. Stable Overexpression of the Constitutive Androstane Receptor Reduces the Requirement for Culture with Dimethyl Sulfoxide for High Drug Metabolism in HepaRG Cells.

    Science.gov (United States)

    van der Mark, Vincent A; Rudi de Waart, D; Shevchenko, Valery; Elferink, Ronald P J Oude; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

    2017-01-01

    Dimethylsulfoxide (DMSO) induces cellular differentiation and expression of drug metabolic enzymes in the human liver cell line HepaRG; however, DMSO also induces cell death and interferes with cellular activities. The aim of this study was to examine whether overexpression of the constitutive androstane receptor (CAR, NR1I3), the nuclear receptor controlling various drug metabolism genes, would sufficiently promote differentiation and drug metabolism in HepaRG cells, optionally without using DMSO. By stable lentiviral overexpression of CAR, HepaRG cultures were less affected by DMSO in total protein content and obtained increased resistance to acetaminophen- and amiodarone-induced cell death. Transcript levels of CAR target genes were significantly increased in HepaRG-CAR cultures without DMSO, resulting in increased activities of cytochrome P450 (P450) enzymes and bilirubin conjugation to levels equal or surpassing those of HepaRG cells cultured with DMSO. Unexpectedly, CAR overexpression also increased the activities of non-CAR target P450s, as well as albumin production. In combination with DMSO treatment, CAR overexpression further increased transcript levels and activities of CAR targets. Induction of CYP1A2 and CYP2B6 remained unchanged, whereas CYP3A4 was reduced. Moreover, the metabolism of low-clearance compounds warfarin and prednisolone was increased. In conclusion, CAR overexpression creates a more physiologically relevant environment for studies on hepatic (drug) metabolism and differentiation in HepaRG cells without the utilization of DMSO. DMSO still may be applied to accomplish higher drug metabolism, required for sensitive assays, such as low-clearance studies and identification of (rare) metabolites, whereas reduced total protein content after DMSO culture is diminished by CAR overexpression. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European Registry in Atrial Fibrillation (PREFER in AF).

    Science.gov (United States)

    Kirchhof, Paulus; Ammentorp, Bettina; Darius, Harald; De Caterina, Raffaele; Le Heuzey, Jean-Yves; Schilling, Richard John; Schmitt, Josef; Zamorano, Jose Luis

    2014-01-01

    We sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology. The PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard deviation). Thirty per cent patients had paroxysmal, 24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent AF. Oral anticoagulation was used in the majority of patients: 4799 patients (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate 60-100 bpm). Half of the patients (50.7%) received rhythm control therapy by electrical cardioversion (18.1%), pharmacological cardioversion (19.5%), antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol 5.5%, dronedarone 4.0%), and catheter ablation (5.0%). The management of AF patients in 2012 has adapted to recent evidence and guideline recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given to over 80% of eligible patients, including those at risk for bleeding. Rate is often adequately controlled, and rhythm control therapy is widely used.

  17. Sex differences in the prehospital management of out-of-hospital cardiac arrest.

    Science.gov (United States)

    Mumma, Bryn E; Umarov, Temur

    2016-08-01

    Sex differences exist in the diagnosis and treatment of several cardiovascular diseases. Our objective was to determine whether sex differences exist in the use of guideline-recommended treatments in out-of-hospital cardiac arrest (OHCA). We included adult patients with non-traumatic OHCA treated by emergency medical services (EMS) in the Resuscitation Outcomes Consortium Prehospital Resuscitation using an IMpedance valve and Early versus Delayed (ROC PRIMED) database during 2007-2009. Outcomes included prehospital treatment intervals, procedures, and medications. Data were analysed using multivariable linear and logistic regression models that adjusted for sex, age, witnessed arrest, public location, bystander cardiopulmonary resuscitation (CPR), and first known rhythm of ventricular tachycardia/fibrillation. We studied 15,584 patients; 64% were male and median age was 68 years (interquartile range 55-80). In multivariable analyses, intervals from EMS dispatch to first rhythm capture (p=0.001) and first EMS CPR (p=0.001) were longer in women than in men. Women were less likely to receive successful intravenous or intraosseous access (OR 0.78, 95% CI 0.71-0.86) but equally likely to receive a successful advanced airway (OR 0.94, 95% CI 0.86-1.02). Women were less likely to receive adrenaline (OR 0.81, 95% CI 0.74-0.88), atropine (OR 0.86, 95% CI 0.80-0.92), and lidocaine or amiodarone (OR 0.68, 95% CI 0.61-0.75). Women were less likely than men to receive guideline-recommended treatments for OHCA. The reasons for these differences require further exploration, and EMS provider education and training should specifically address these sex differences in the treatment of OHCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Atrial Fibrillation Ablation in Systolic Dysfunction: Clinical and Echocardiographic Outcomes

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    Tasso Julio Lobo

    2015-01-01

    Full Text Available Background: Heart failure and atrial fibrillation (AF often coexist in a deleterious cycle. Objective: To evaluate the clinical and echocardiographic outcomes of patients with ventricular systolic dysfunction and AF treated with radiofrequency (RF ablation. Methods: Patients with ventricular systolic dysfunction [ejection fraction (EF <50%] and AF refractory to drug therapy underwent stepwise RF ablation in the same session with pulmonary vein isolation, ablation of AF nests and of residual atrial tachycardia, named "background tachycardia". Clinical (NYHA functional class and echocardiographic (EF, left atrial diameter data were compared (McNemar test and t test before and after ablation. Results: 31 patients (6 women, 25 men, aged 37 to 77 years (mean, 59.8±10.6, underwent RF ablation. The etiology was mainly idiopathic (19 p, 61%. During a mean follow-up of 20.3±17 months, 24 patients (77% were in sinus rhythm, 11 (35% being on amiodarone. Eight patients (26% underwent more than one procedure (6 underwent 2 procedures, and 2 underwent 3 procedures. Significant NYHA functional class improvement was observed (pre-ablation: 2.23±0.56; postablation: 1.13±0.35; p<0.0001. The echocardiographic outcome also showed significant ventricular function improvement (EF pre: 44.68%±6.02%, post: 59%±13.2%, p=0.0005 and a significant left atrial diameter reduction (pre: 46.61±7.3 mm; post: 43.59±6.6 mm; p=0.026. No major complications occurred. Conclusion: Our findings suggest that AF ablation in patients with ventricular systolic dysfunction is a safe and highly effective procedure. Arrhythmia control has a great impact on ventricular function recovery and functional class improvement.

  19. Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients.

    Science.gov (United States)

    Fischer, Michael A; Solomon, Daniel H; Teich, Jonathan M; Avorn, Jerry

    2003-11-24

    Many hospitalized patients continue to receive intravenous medications longer than necessary. Earlier conversion from the intravenous to the oral route could increase patient safety and comfort, reduce costs, and facilitate earlier discharge from the hospital without compromising clinical care. We examined the effect of a computer-based intervention to prompt physicians to switch appropriate patients from intravenous to oral medications. This study was performed at Brigham and Women's Hospital, an academic tertiary care hospital at which all medications are ordered online. We targeted 5 medications with equal oral and intravenous bioavailability: fluconazole, levofloxacin, metronidazole, ranitidine, and amiodarone. We used the hospital's computerized order entry system to prompt physicians to convert appropriate intravenous medications to the oral route. We measured the total use of the targeted medications via each route in the 4 months before and after the implementation of the intervention. We also measured the rate at which physicians responded to the intervention when prompted. The average intravenous defined daily dose declined by 11.1% (P =.002) from the preintervention to the postintervention period, while the average oral defined daily dose increased by 3.7% (P =.002). Length of stay, case-mix index, and total drug use at the hospital increased during the study period. The average total monthly use of the intravenous preparation of all of the targeted medications declined in the 4 months after the intervention began, compared with the 4 months before. In 35.6% of 1045 orders for which a prompt was generated, the physician either made a conversion from the intravenous to the oral version or canceled the order altogether. Computer-generated reminders can produce a substantial reduction in excessive use of targeted intravenous medications. As online prescribing becomes more common, this approach can be used to reduce excess use of intravenous medications

  20. Identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-COOH-glu) in hair by ultra-performance liquid chromatography tandem mass spectrometry as a potential hair biomarker of cannabis use.

    Science.gov (United States)

    Pichini, Simona; Marchei, Emilia; Martello, Simona; Gottardi, Massimo; Pellegrini, Manuela; Svaizer, Fiorenza; Lotti, Andrea; Chiarotti, Marcello; Pacifici, Roberta

    2015-04-01

    We developed and validated an ultra-high-pressure liquid chromatography-tandem mass spectrometry method to identify and quantify 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in hair of cannabis consumers. After hair washing with methyl alcohol and diethyl ether and subsequent addition of amiodarone as internal standard hair samples were treated with 500 μl VMA-T M3 buffer reagent for 1 h at 100 °C. After cooling, 10 μl VMA-T M3 extract were injected into chromatographic system. Chromatographic separation was carried out on a reversed phase column using a linear gradient elution with two solvents: 5 mM ammonium formate pH 3.0 (solvent A) and 0.1% formic acid in acetonitrile (solvent B). The flow rate was kept constant at 0.4 ml/min during the analysis. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode via positive electrospray ionization. Linear calibration curves were obtained for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide with correlation coefficients (r(2)) of 0.99 and a limit of quantification of 0.25 pg/mg hair. Analytical recovery was between 79.6% and 100.7% and intra- and inter-assay imprecision and inaccuracy were always lower than 15%. Ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of 20 different hair samples of cannabis consumers disclosed the presence of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in the range of 0.5-8.6 pg/mg hair. These data provided a good start to consider 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide as alternative hair biomarker of cannabis consumption. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Recent developments in pharmacologic prophylaxis of atrial fibrillation in patients undergoing surgical revascularization.

    Science.gov (United States)

    Rostagno, Carlo

    2009-04-01

    Atrial fibrillation is a frequent complication after CABG. It occurs in 20-50% of patients, most often between the 2nd and 3rd postoperative day. About 40 % of patients experience more than 1 episode. Postoperative AF (POAF) is associated with an increase in adverse events and hospital stay and, therefore, costs of care. The incidence of POAF is not influenced by the technique of CABG with or without cardiopulmonary by-pass Neurohormonal activation, electrolyte imbalance, fluid overload, surgical practices and finally an exaggerated inflammatory response has been proposed to be etiological factor. Advanced age, history of AF or heart failure, COPD, postoperative withdrawal of beta-blockers are independent risk factors of postoperative AF. Conversely, postoperative administration of beta-blockers, ACE inhibitors, potassium supplementation and NSAID were associated with a reduced risk of POAF. Pharmacological strategies for prevention of POAF may be divided in two main groups : the first one encompasses the use of antiarrhythmic drugs (amiodarone, metoprolol, sotalol) before and /or after surgery and has been extensively investigated in the last two decades. Recently an Italian study has shown that PUFA administration during hospitalization in patients undergoing CABG significantly decreased the incidence of POAF and was associated with a shorter hospital stay. Since an exaggerated inflammatory reaction may play a significant role in POAF, treatments directed to antagonize inflammation are presently under investigation. Despite different action mechanisms both hydrocortisone and statins have been shown to decrease post-operative AF risk. These two prophylactic regimens are not mutually exclusive and some data suggest that their association may be useful to further decrease the risk of POAF.

  2. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    International Nuclear Information System (INIS)

    Chatterjee, Sagnik; Richert, Lysiane; Augustijns, Patrick; Annaert, Pieter

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  3. Clinical application of low energy intracardiac cardioversion of atrial fibrillation

    International Nuclear Information System (INIS)

    Wu Liqun; Gu Gang; Su Kan; Su Renying; Shen Yongchu; Shen Weifeng

    2002-01-01

    Objective: To evaluate the efficacy and safety of low energy intracardiac cardioversion in persistent atria fibrillation. Methods: Low energy intracardiac cardioversion was performed by delivering R wave-synchronized biphasic shocks in 7 patients (4 men, 3 women) with persistent atrial fibrillation. Prior to the procedure, all patients underwent transesophageal echocardiographic examinations to rule out the presence of intracardiac thrombus and received subcutaneous injection of low molecular weight heparin for 3-5 days. Two custom-made 6 Fr catheters (Rhythm Technologies of Getz, USA) were used for de-fibrillation shock delivery. One catheter was positioned in the lower right atrium so that the majority of the catheter electrodes had firm contact with the right atrial free wall. The second catheter was placed randomly either in coronary sinus through right internal jugular vein or in the left pulmonary artery through femoral vein. In addition, a standard diagnostic 6-F quadrupolar catheter was placed at the right ventricular apex for ventricular synchronization and postshock ventricular pacing. Shocks were delivered by Implant Support Device (Model 4510, Teleceronics). After conversion, all patients were treated with intravenous amiodarone in the first 24 hours followed by oral administration. Results: In all 7 patients cardioversion of atrial fibrillation to sinus rhythm was successfully obtained. A mean of 2 ± 1 shocks per patient has been delivered with a total amount of 13 shocks. The average delivered energy was 7.8 ± 2.2 Joules. No complication occurred. At a mean follow-up of 18 ± 9 months, 4 of the 7 patients treated successfully showed sinus rhythm there after. Atrial fibrillation recurred in 3 patients at the second, fifth day and eighth month after cardioversion. Conclusions: Low energy intracardiac cardioversion is effective and safe, and can be easily performed in patients without general anesthesia. It offers a new option for restoring sinus

  4. Dobutamine stress echocardiography related sustained ventricular tachycardia in a patient with ischaemic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Amrit S Lota

    2014-01-01

    Full Text Available A 66 year-old Asian man; with a complex history of ischaemic heart disease presented with cardiac and troponin negative chest pain. His ECG showed sinus bradycardia with old left bundle branch block. The transthoracic echocardiography showed severely impaired left ventricular systolic function (EF 30-35%. The patient had had coronary artery bypass grafting at age of 42 years and remained asymptomatic until age of 56 years when he presented with incessant ventricular tachycardia requiring amiodarone, lidocaine and electrical cardioversion. Coronary angiography at that time showed occluded vein grafts to the circumflex and diagonal arteries. The right coronary artery (RCA was small and received collaterals from the left system. A myocardial perfusion scan showed extensive inferolateral infarction but no evidence for reversible ischaemia. An implantable cardiac defibrillator (ICD was thus inserted. Over the following years, the patient underwent multiple PCI procedures with rotational atherectomy to the native LAD and associated vein graft, but subsequently developed in-stent restenosis. He also had PCI to the native RCA. He declined a minimally invasive grafting of the left internal mammary artery (LIMA to the LAD and re-implantation of a new ICD after ex-plantation of the original one due to sepsis. His coronary artery disease remained stable following a recent admission with Troponin positive event which was confirmed by a repeat angiogram, therefore, had up-titrated anti-anginal medications. A low dose beta-blockade was discontinued due to documented sinus pauses up to 3 seconds. Following the recent admission, a joint cardiology-cardiothoracic meeting discussion recommended a stress echocardiogram with highdose dobutamine to guide towards considering re-do bypass grafting.

  5. Identification of high risk patients with hypertrophic cardiomyopathy in a northern Greek population

    Directory of Open Access Journals (Sweden)

    Karvounis Charalambos

    2009-07-01

    Full Text Available Abstract Background The percentage of hypertrophic cardiomyopathy (HCM patients who are in high risk for Sudden Death (SD constitutes only a minority of all HCM population but the incidence of SD in this subset is high (at least 5% annually. The identification of this small but important proportion of high risk HCM patients has been the clue in the clinical evaluation of these patients. Methods Our study cohort consisted from 123 patients with HCM who are currently followed up in our Institution. Five clinical risk factors were assessed: a family history of premature SD, unexplained syncope, Non Sustained Ventricular Tachycardia (NSVT on 24-h ECG monitoring, Abnormal Blood Pressure Response (ABPR during upright exercise testing and Maximum left ventricular Wall Thickness (MWT ≥30 mm. The purpose of our study was the identification of high risk HCM patients coming from Northern Greece. Results Fifteen patients (12.2% of the whole cohort had MWT ≥ 30 mm, 30 patients (24.4% had an ABPR to exercise, 17 patients (13.8% had episodes of NSVT in 24-h Holter monitoring, 17 patients (13.8% suffered from syncope, and 8 patients (6.5% had a positive family history of premature SD. Data analysis revealed that 74 patients (60.1% had none risk factor. Twenty four patients (19.5% had 1 risk factor, 17 patients (13.8% had 2 risk factors, 4 patients (3.25% had 3 risk factors, and 4 patients (3.25% had 4 risk factors, while none patient had 5 risk factors. Twenty five patients (20.3% had 2 or more risk factors. Conclusion This study for the first time confirms that, although a 60% of patients with HCM coming from a regional Greek population are in low risk for SD, a substantial proportion (almost 20% carries a high risk for SD justifying prophylactic therapy with amiodaron or ICD implantation.

  6. Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

    International Nuclear Information System (INIS)

    Nozaki, Yumiko; Honda, Yayoi; Tsujimoto, Shinji; Watanabe, Hitoshi; Kunimatsu, Takeshi; Funabashi, Hitoshi

    2014-01-01

    Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K + channel and Ca 2+ channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I Kr and I Ks blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca 2+ channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I Kr blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans

  7. Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

    Energy Technology Data Exchange (ETDEWEB)

    Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp [Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma. Co., Ltd., Chuo-ku, Tokyo 104-0031 (Japan); Watanabe, Hitoshi, E-mail: hitoshi-1-watanabe@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Kunimatsu, Takeshi, E-mail: takeshi-kunimatsu@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Funabashi, Hitoshi, E-mail: hitoshi-funabashi@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan)

    2014-07-01

    Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.

  8. High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays

    Energy Technology Data Exchange (ETDEWEB)

    Gilchrist, Kristin H., E-mail: kgilchrist@rti.org; Lewis, Gregory F.; Gay, Elaine A.; Sellgren, Katelyn L.; Grego, Sonia

    2015-10-15

    Microelectrode arrays (MEAs) recording extracellular field potentials of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) provide a rich data set for functional assessment of drug response. The aim of this work is the development of a method for a systematic analysis of arrhythmia using MEAs, with emphasis on the development of six parameters accounting for different types of cardiomyocyte signal irregularities. We describe a software approach to carry out such analysis automatically including generation of a heat map that enables quick visualization of arrhythmic liability of compounds. We also implemented signal processing techniques for reliable extraction of the repolarization peak for field potential duration (FPD) measurement even from recordings with low signal to noise ratios. We measured hiPS-CM's on a 48 well MEA system with 5 minute recordings at multiple time points (0.5, 1, 2 and 4 h) after drug exposure. We evaluated concentration responses for seven compounds with a combination of hERG, QT and clinical proarrhythmia properties: Verapamil, Ranolazine, Flecainide, Amiodarone, Ouabain, Cisapride, and Terfenadine. The predictive utility of MEA parameters as surrogates of these clinical effects were examined. The beat rate and FPD results exhibited good correlations with previous MEA studies in stem cell derived cardiomyocytes and clinical data. The six-parameter arrhythmia assessment exhibited excellent predictive agreement with the known arrhythmogenic potential of the tested compounds, and holds promise as a new method to predict arrhythmic liability. - Highlights: • Six parameters describing arrhythmia were defined and measured for known compounds. • Software for efficient parameter extraction from large MEA data sets was developed. • The proposed cellular parameter set is predictive of clinical drug proarrhythmia.

  9. Quality of the cardiovascular drugs prescribing in Zagreb during the period 2001- 2004

    Directory of Open Access Journals (Sweden)

    Dražen Stojanović

    2009-02-01

    Full Text Available Aim To investigate the outpatient utilisation of cardiovasculardrugs in Zagreb, during the 2001-2004 period, and to identify thepossible association between the increase in the utilisation of particulardrug groups and decrease in the number of hospital admissions.Methods The number of DDD per thousand inhabitants per day(DDDs/TID was calculated from data on the number and size ofdispensed drug packages, obtained from the Zagreb Pharmacies.Drug Utilisation 90% (DU90% method was used on assessmentof drug prescribing quality.Results Total utilisation of the cardiovascular drugs was high inZagreb during the 2001-2004 period (between 402.9 DDDs/TIDand 406.9 DDDs/TID. Agents acting on the renin-angiotensinsystem (C09 (121.3 DDDs/TID and calcium channel blockers(C08 (87.5 DDDs/TID accounted for more than 50% of drugsused for the treatment of hypertension in 2004. The greatest utilisationincrease was observed for statins (78.3%. Comparison ofDU90% segment between 2001 and 2004 revealed pentoxifyllineand amiodarone to be absent, whereas cilazapril and ramipril intheir combination with HCTZ, bisoprolol, valsartan and losartanalone or in their combination with HCTZ were added in 2004,DU90% segment still contain doxazosin and propafenone, whichhad no grounds in therapeutic guidelines.Conclusion The outpatient utilisation of cardiovascular drugs washigh during the 2001-2004 period. The utilization pattern was improved.The result was a decrease in the number of hospital admissionsfor main cardiovascular events.

  10. Paroxysmal supraventricular tachycardia: physiopathology and management

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    Paola Neroni

    2014-06-01

    Full Text Available Paroxysmal supraventricular tachycardia (PSVT is the most frequent arrhythmia in newborns and infants. Most supraventricular tachycardias affect structurally healthy hearts. Apart from occasional detection by parents, most tachycardias in this age group are revealed by heart failure signs, such as poor feeding, sweating and shortness of breath. The main symptom reported by school-age children is palpitations. The chronic tachycardia causes a secondary form of dilative cardiomyopathy. Treatment of acute episode usually has an excellent outcome. Vagal manoeuvres are effective in patients with atrioventricular reentrant tachycardia. Adenosine is the drug of choice at all ages for tachycardias involving the atrioventricular node. Its key advantage is its short half life and minimum or no negative inotropic effects. Verapamil is not indicated in newborns and children as it poses a high risk of electromechanical dissociation. Antiarrhythmic prophylaxis of PSVT recurrence is usually recommended in the first year of life, because the diagnosis of tachycardia may be delayed up to the appearance of symptoms. Digoxin can be administered in all forms of PSVT involving the atrioventricular node, except for patients with Wolff-Parkinson-White syndrome below one year of age. Patients with atrioventricular reentrant PSVT can be treated effectively by class Ic drugs, such as propaphenone and flecainide. Amiodarone has the greatest antiarrhythmic effect, but should be used with caution owing to the high incidence of side effects. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  11. Electrical storm in patients with implantable cardioverter-defibrillators: can it be forecast?

    Science.gov (United States)

    Emkanjoo, Zahra; Alihasani, Narges; Alizadeh, Abolfath; Tayyebi, Mohammad; Bonakdar, Hamid; Barakpour, Hamid; Sadr-Ameli, Mohammad Ali

    2009-01-01

    The aim of this retrospective study was to determine the prevalence and predictors of electrical storm in 227 patients who had received implantable cardioverter-defibrillators (ICDs) and had been monitored for 31.7 +/- 15.6 months. Of these, 174 (77%) were men. The mean age was 55.8 +/- 15.5 years (range, 20-85 yr), and the mean left ventricular ejection fraction (LVEF) was 0.30 +/- 0.14. One hundred forty-six of the patients (64%) had underlying coronary artery disease. Cardioverter-defibrillators were implanted for secondary (80%) and primary (20%) prevention. Of the 227 patients, 117 (52%) experienced events that required ICD therapy. Thirty patients (mean age, 57.26 +/- 14.3 yr) had > or = 3 episodes requiring ICD therapy in a 24-hour period and were considered to have electrical storm. The mean number of events was 12.75 +/- 15 per patient. Arrhythmia-clustering occurred an average of 6.1 +/- 6.7 months after ICD implantation. Clinical variables with the most significant association with electrical storm were low LVEF (P = 0.04; hazard ratio of 0.261, and 95% confidence interval of 0.08-0.86) and higher use of class IA antiarrhythmic drugs (P = 0.018, hazard ratio of 3.84, and 95% confidence interval of 1.47-10.05). Amiodarone treatment and use of beta-blockers were not significant predictors when subjected to multivariate analysis. We conclude that electrical storm is most likely to occur in patients with lower LVEF and that the use of Class IA antiarrhythmic drugs is a risk factor.

  12. New-onset atrial fibrillation is a predictor of subsequent hyperthyroidism: a nationwide cohort study.

    Directory of Open Access Journals (Sweden)

    Christian Selmer

    Full Text Available AIMS: To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF, but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism. METHODS AND RESULTS: All patients admitted with new-onset AF in Denmark from 1997-2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males of whom 3% (4,620 events; 62.2% women developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women in the general population (n = 3,866,889. In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done. CONCLUSION: New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.

  13. New-onset atrial fibrillation is a predictor of subsequent hyperthyroidism: a nationwide cohort study.

    Science.gov (United States)

    Selmer, Christian; Hansen, Morten Lock; Olesen, Jonas Bjerring; Mérie, Charlotte; Lindhardsen, Jesper; Olsen, Anne-Marie Schjerning; Madsen, Jesper Clausager; Schmidt, Ulla; Faber, Jens; Hansen, Peter Riis; Pedersen, Ole Dyg; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar

    2013-01-01

    To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism. All patients admitted with new-onset AF in Denmark from 1997-2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done. New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.

  14. Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    Wu Xiaosan

    2013-01-01

    Full Text Available Abstract Background Atrial arrhythmia (AA is the most common complication after coronary artery bypass grafting (CABG. Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG. Methods We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible. Results Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR 1.12, 95% confidence interval (CI 0.86-1.47, P = 0.40. Magnesium in addition to beta-blocker did not significantly affect LOS (weighted mean difference −0.14 days of stay, 95% CI −0.58 to 0.29, P = 0.24 or the overall mortality (OR 0.59, 95% CI 0.08-4.56, P = 0.62. However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone (OR 2.80, 95% CI 1.66-4.71, P = 0.0001. Conclusions This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium.

  15. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  16. Provider and pharmacist responses to warfarin drug–drug interaction alerts: a study of healthcare downstream of CPOE alerts

    Science.gov (United States)

    Boro, Maureen S; Korman, Nancy E; Davoren, J Ben

    2011-01-01

    Objective To categorize the appropriateness of provider and pharmacist responses to warfarin critical drug–drug interaction (cDDI) alerts, assess responses and actions to the cDDI, and determine the occurrence of warfarin adverse drug events (ADE) after alerts. Design An 18-month, retrospective study of acute care admissions at a single Veterans Affairs medical center using computerized provider order entry (CPOE). Measurements Patients included had at least one warfarin cDDI alert. Chart reviews included baseline laboratory values and demographics, provider actions, patient outcomes, and associated factors, including other interacting medications and number of simultaneously processed alerts. Results 137 admissions were included (133 unique patients). Amiodarone, vitamin E in a multivitamin, sulfamethoxazole, and levothyroxine accounted for 75% of warfarin cDDI. Provider responses were clinically appropriate in 19.7% of admissions and pharmacist responses were appropriate in 9.5% of admissions. There were 50 ADE (36.6% of admissions) with warfarin; 80% were rated as having no or mild clinical effect. An increased number of non-critical alerts at the time of the reference cDDI alert was the only variable associated with an inappropriate provider response (p=0.01). Limitations This study was limited by being a retrospective review and the possibility of confounding variables, such as other interacting medications. Conclusion The large number of CPOE alerts may lead to inappropriate responses by providers and pharmacists. The high rate of ADE suggests a need for improved medication management systems for patients on warfarin. This study highlights the possibility of alert fatigue contributing to the high prevalence of inappropriate alert over-ride text responses. PMID:22037888

  17. Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Iwasaki, Tsutomu; Suzuki, Tadashi [Gunma Univ., Maebashi (Japan). School of Medicine; Hoshizaki, Hiroshi; Oshima, Shigeru; Taniguchi, Koichi; Nagai, Ryozo

    2000-07-01

    This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59{+-}13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 {mu}g/kg/min before treatment. Patients were divided into good responders (LVEF increase {>=}15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with {beta}-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28{+-}6 to 17{+-}12 (p<0.05), H/M ratio increased from 1.79{+-}0.26 to 2.07{+-}0.32 (p<0.05), LVEF increased from 29{+-}8% to 48{+-}10% (p<0.01), and LVDd decreased from 65{+-}4 mm to 58{+-}5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

  18. Anesthesia Approach in Endovascular Aortic Reconstruction

    Directory of Open Access Journals (Sweden)

    Ayşin Alagöl

    2013-03-01

    Full Text Available Introduction: We have analyzed our initial results of our anesthesia techniques in our new-onset endovascular aortic reconstruction cases.Patients and Methods: The perioperative data of 15 elective and emergent endovascular aortic reconstruction cases that were operated in 2010-2011 were collected in a database. The choice of anesthesia was made by the risk factors, surgical team’s preferences, type and location of the aortic pathology and by the predicted operation duration. The data of local and general anesthesia cases were compared.Results: Thirteen (86.7% cases were male and 2 (13.3% female. Eleven patients were in ASA Class III. The demographic parameters, ASA classifications, concurrent diseases were similar in both groups. Thirteen (86.7% cases had infrarenal abdominal aortic aneurysm and 2 (13.3% had Type III aortic dissection. The diastolic arterial pressures were lower in general anesthesia group in 20th and 40th minutes’ measurements just like the mean arterial pressure measurements at the 40th, 100th minutes and during the deployment of the graft. Postoperative mortality occurred in 3 (20.0% patients and they all had general anesthesia and they were operated on emergency basis. Postoperative morbidity occurred in four patients that had general anesthesia (acute renal failure, multi-organ failure and pneumonia. The other patient had atrial fibrillation on the 1st postoperative day and was converted to sinus rhythm with amiodarone infusion.Conclusion: Edovascular aortic reconstruction procedures can safely be performed with both general and local anesthesia less invasively compared to open surgery. General anesthesia may be preferred for the better hemodynamic control.

  19. Determination of Drug Toxicity Using 3D Spheroids Constructed From an Immortal Human Hepatocyte Cell Line

    Science.gov (United States)

    Fey, Stephen J.; Wrzesinski, Krzysztof

    2012-01-01

    Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal of this study was to investigate whether this observation could be extended to the determination of LD50 values and whether 3D data could be correlated to in vivo observations. We developed a noninvasive means to estimate the amount of protein present in a 3D spheroid from it is planar area (± 21%) so that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC50 data (mM) for six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid) to LD50 data (mg compound/mg cellular protein) showed that the variation in LD50 values was generally less than that suggested by the original LC50 data. Toxicological analysis of these six compounds in 3D spheroid culture (either published or presented here) demonstrated similar LD50 values. Although in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo. PMID:22454432

  20. Diagnosis and therapy of atrial tachyarrhythmias in the dual chamber implantable cardioverter defibrillator.

    Science.gov (United States)

    Dijkman, B; Wellens, H J

    2000-11-01

    Devices capable of monitoring and treating atrial tachyarrhythmias provide information about the natural history of the arrhythmias and potentially can influence their natural course by electrical therapy early after onset. Types of atrial arrhythmias and efficacy of device therapies were evaluated in 30 patients implanted with the Medtronic model 7250 Jewel AF implantable cardioverter defibrillator (ICD). All patients had structural heart disease and documented sustained ventricular and atrial arrhythmias (27 with atrial fibrillation [AF]) before implant. Twenty patients were taking amiodarone, and three were taking sotalol. During 20+/-10 months of follow-up, 600 atrial arrhythmia recurrences were documented in 50% of patients. AF was diagnosed in 19%, fast polymorphic atrial tachycardia (AT) in 20%, fast monomorphic AT in 57%, and slow AT in 4% of episodes. The two adaptive pacing therapies, burst and ramp, together with the 50-Hz burst, were successful in 57% of detected atrial arrhythmias. Burst and ramp were responsible for 49% and 50-Hz burst for 51% of successfully treated arrhythmias; 33% of the episodes terminated spontaneously. No ventricular proarrhythmia was observed due to atrial pacing therapies. In 30% of episodes, dual chamber pacing was required due to post termination bradycardia. Atrial arrhythmia recurrences in patients with dilated cardiomyopathy were not amenable to pacing therapies. Several aspects of atrial arrhythmia diagnosis, therapy, and documentation that are specific for functioning of the Jewel AF are discussed. Atrial arrhythmias in ICD patients with diseased hearts who are taking Class III antiarrhythmics frequently had longer cycle lengths than AF. Half of these arrhythmias could be terminated with pacing therapies; one third terminated spontaneously.

  1. New-Onset Atrial Fibrillation Is a Predictor of Subsequent Hyperthyroidism: A Nationwide Cohort Study

    Science.gov (United States)

    Selmer, Christian; Hansen, Morten Lock; Olesen, Jonas Bjerring; Mérie, Charlotte; Lindhardsen, Jesper; Olsen, Anne-Marie Schjerning; Madsen, Jesper Clausager; Schmidt, Ulla; Faber, Jens; Hansen, Peter Riis; Pedersen, Ole Dyg; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar

    2013-01-01

    Aims To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism. Methods and Results All patients admitted with new-onset AF in Denmark from 1997–2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done. Conclusion New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted. PMID:23469097

  2. An analytical method for cyclosporine using liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Kanduru, Srividya V; Somayaji, Vishwa; Lavasanifar, Afsaneh; Brocks, Dion R

    2010-02-01

    A liquid chromatographic mass spectrometric (LC-MS) assay has been developed for cyclosporine A (CyA) in rat plasma using amiodarone as internal standard (IS). Rat plasma (100 microL) containing drug and IS were extracted using liquid-liquid extraction with 4 mL of 95:5 ether:methanol. After evaporation of the organic layer the residue was reconstituted with 500 microL of water. Then the aqueous layer was transferred to LC-MS sample vials. A 10 microL volume was injected. The analysis was performed on a C(8) column 3.5 microm (2.1 x 50 mm) heated to 60 degrees C with a mobile phase consisting of acetonitrile:methanol:0.2% NH(4)OH (60:20:20) at an isocratic flow-rate of 0.2 mL/min. The ions used for quantitation of CyA and IS were m/z 1202.8 and 645.9, with retention times of 3.35 and 4.72 min, respectively. Linear relationships (r(2) > 0.99) were achieved between plasma or blood concentration and peak height ratios (drug:IS) over the concentration range 50-5000 ng/mL. The CV% and mean error were <19%. Based on validation data, the lower limit of quantification for the assay was 50 ng/mL. The reported assay method displayed high measures of linearity, sensitivity, reliability and precision, allowing its applicability in pharmacokinetic studies in rat. (c) 2009 John Wiley & Sons, Ltd.

  3. Action of specific thyroid hormone receptor α(1) and β(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat.

    Science.gov (United States)

    van Beeren, Hermina C; Kwakkel, Joan; Ackermans, Mariëtte T; Wiersinga, Wilmar M; Fliers, Eric; Boelen, Anita

    2012-12-01

    The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) α(1) and β(1) antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a selective TRα(1) antagonist. In the present study, Amio and Dron were used as tools to discriminate between TRα(1) or TRβ(1) regulated genes in central and peripheral thyroid hormone metabolism. Three groups of male rats received either Amio, Dron, or vehicle by daily intragastric administration for 2 weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3 mRNA expressions and activities, and thyroid hormone transporters monocarboxylate transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion transporter 1C1 (OATP1C1). Amio treatment decreased serum T(3), while serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression, while increasing pituitary TSHβ and MCT10 mRNA expression. Amio decreased the pituitary D2 activity. By contrast, Dron treatment resulted in decreased hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3) concentration decreased substantially compared to Dron and control rats (50%, p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1, mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. Our results suggest an important role for TRα1 in the regulation of hypothalamic TRH mRNA expression, whereas TRβ plays a dominant role in pituitary and liver thyroid

  4. Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

    Science.gov (United States)

    Bucsa, Camelia; Farcas, Andreea; Leucuta, D; Mogosan, Cristina; Bojita, M; Dumitrascu, D L

    2015-01-01

    The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

  5. Basic and advanced paediatric cardiopulmonary resuscitation - guidelines of the Australian and New Zealand Resuscitation Councils 2010.

    Science.gov (United States)

    Tibballs, James; Aickin, Richard; Nuthall, Gabrielle

    2012-07-01

    Guidelines for basic and advanced paediatric cardiopulmonary resuscitation (CPR) have been revised by Australian and New Zealand Resuscitation Councils. Changes encourage CPR out-of-hospital and aim to improve the quality of CPR in-hospital. Features of basic CPR include: omission of abdominal thrusts for foreign body airway obstruction; commencement with chest compression followed by ventilation in a ratio of 30:2 or compression-only CPR if the rescuer is unwilling/unable to give expired-air breathing when the victim is 'unresponsive and not breathing normally'. Use of automated external defibrillators is encouraged. Features of advanced CPR include: prevention of cardiac arrest by rapid response systems; restriction of pulse palpation to 10 s to diagnosis cardiac arrest; affirmation of 15:2 compression-ventilation ratio for children and for infants other than newly born; initial bag-mask ventilation before tracheal intubation; a single direct current shock of 4 J/kg for ventricular fibrillation (VF) and pulseless ventricular tachycardia followed by immediate resumption of CPR for 2 min without analysis of cardiac rhythm and avoidance of unnecessary interruption of continuous external cardiac compressions. Monitoring of exhaled carbon dioxide is recommended to detect non-tracheal intubation, assess quality of CPR, and to help match ventilation to reduced cardiac output. The intraosseous route is recommended if immediate intravenous access is impossible. Amiodarone is strongly favoured over lignocaine for refractory VF and adrenaline over atropine for severe bradycardia, asystole and pulseless electrical activity. Family presence at resuscitation is encouraged. Therapeutic hypothermia is acceptable after resuscitation to improve neurological outcome. Extracorporeal circulatory support for in-hospital cardiac arrest may be used in equipped centres. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal

  6. Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

    Science.gov (United States)

    Naito, M; Michelson, E L; Kmetzo, J J; Kaplinsky, E; Dreifus, L S

    1981-01-01

    Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

  7. Review of pharmacological interactions of oral anticancer drugs provided at pharmacy department

    Directory of Open Access Journals (Sweden)

    E. Sánchez Gómez

    2014-07-01

    Full Text Available Abstract: Objective: To identify the pharmacologic interactions of oral anti-cancer drugs provided at an outpatient clinic. Material and methods: Anti-cancer drugs included in the Phamacotherapeutic Guideline of the Hospital were identified. A literature search was carried out on the pharmacologic interactions in MEDLINE® and EMBASE® (with the filer language English or Spanish, and the descriptors: “name of the anti-cancer drug” AND (“drug interactions” OR “pharmacokinetic”, Up-to-date®, MICROMEDEX® and the drug information sheet for the EMA and the FDA. Information was also gathered from the abstract presented to European and Spanish scientific meetings for the last 4 years. When an interaction was analyzed and had clinical relevance, the best pharmacotherapeutic interaction-free alternative was sought. Results: Twenty-three drugs were identified, of which Chlorambucil, Fludarabine, Lenalidomide, Melphalan, and Thalidomide were the active compounds with the lowest likelihood of producing a pharmacologic interaction. Tyrosine kinase inhibitors (particularly Erlotinib, Imatinib, Lapatinib, and Pazopanib are the drugs with highest number of pharmacologic interactions described, many of them with severe clinical consequences, with increases and decreases of the plasma levels of anti-cancer drugs. The active compounds identified that may have pharmacologic interactions with anticancer drugs were mainly: Allopurinol, Amiodarone, Carbamazepine, Dabigatran, Digoxin, Spironolactone, Phenytoin, Itraconazol, Repaglinide, Silodosin, Tamoxifen, Verapamil, and Warfarin. Pharmacologic interactions through the cytochrome P450 1A2, 2D6, 2C8, 2C9, 3A4 were the most important for tyrosine kinase inhibitors. Other non-pharmacologic compounds, with an important potential of producing relevant pharmacologic interaction were immunomodulators (Echinacea extracts and Hypericum perforatum. Conclusions: Oral anticancer drugs have numerous pharmacologic

  8. Effects of thyroid hormones on the heart.

    Science.gov (United States)

    Vargas-Uricoechea, Hernando; Bonelo-Perdomo, Anilsa; Sierra-Torres, Carlos Hernán

    2014-01-01

    Thyroid hormones have a significant impact on heart function, mediated by genomic and non-genomic effects. Consequently, thyroid hormone deficiencies, as well as excesses, are expected to result in profound changes in cardiac function regulation and cardiovascular hemodynamics. Thyroid hormones upregulate the expression of the sarcoplasmic reticulum calcium-activated ATPase and downregulate the expression of phospholamban. Overall, hyperthyroidism is characterized by an increase in resting heart rate, blood volume, stroke volume, myocardial contractility, and ejection fraction. The development of "high-output heart failure" in hyperthyroidism may be due to "tachycardia-mediated cardiomyopathy". On the other hand, in a hypothyroid state, thyroid hormone deficiency results in lower heart rate and weakening of myocardial contraction and relaxation, with prolonged systolic and early diastolic times. Cardiac preload is decreased due to impaired diastolic function. Cardiac afterload is increased, and chronotropic and inotropic functions are reduced. Subclinical thyroid dysfunction is relatively common in patients over 65 years of age. In general, subclinical hypothyroidism increases the risk of coronary heart disease (CHD) mortality and CHD events, but not of total mortality. The risk of CHD mortality and atrial fibrillation (but not other outcomes) in subclinical hyperthyroidism is higher among patients with very low levels of thyrotropin. Finally, medications such as amiodarone may induce hypothyroidism (mediated by the Wolff-Chaikoff), as well as hyperthyroidism (mediated by the Jod-Basedow effect). In both instances, the underlying cause is the high concentration of iodine in this medication. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  9. Hepatocellular toxicity of benzbromarone: Effects on mitochondrial function and structure

    International Nuclear Information System (INIS)

    Felser, Andrea; Lindinger, Peter W.; Schnell, Dominik; Kratschmar, Denise V.; Odermatt, Alex; Mies, Suzette; Jenö, Paul; Krähenbühl, Stephan

    2014-01-01

    Highlights: • Benzbromarone impairs the electron transport chain and uncouples mitochondria. • Benzbromarone impairs mitochondrial β-oxidation by inhibiting fatty acid activation. • Benzbromarone disrupts the mitochondrial network and induces apoptosis. - Abstract: Benzbromarone is an uricosuric structurally related to amiodarone and a known mitochondrial toxicant. The aim of the current study was to improve our understanding in the molecular mechanisms of benzbromarone-associated hepatic mitochondrial toxicity. In HepG2 cells and primary human hepatocytes, ATP levels started to decrease in the presence of 25–50 μM benzbromarone for 24–48 h, whereas cytotoxicity was observed only at 100 μM. In HepG2 cells, benzbromarone decreased the mitochondrial membrane potential starting at 50 μM following incubation for 24 h. Additionally, in HepG2 cells, 50 μM benzbromarone for 24 h induced mitochondrial uncoupling,and decreased mitochondrial ATP turnover and maximal respiration. This was accompanied by an increased lactate concentration in the cell culture supernatant, reflecting increased glycolysis as a compensatory mechanism to maintain cellular ATP. Investigation of the electron transport chain revealed a decreased activity of all relevant enzyme complexes. Furthermore, treatment with benzbromarone was associated with increased cellular ROS production, which could be located specifically to mitochondria. In HepG2 cells and in isolated mouse liver mitochondria, benzbromarone also reduced palmitic acid metabolism due to an inhibition of the long-chain acyl CoA synthetase. In HepG2 cells, benzbromarone disrupted the mitochondrial network, leading to mitochondrial fragmentation and a decreased mitochondrial volume per cell. Cell death occurred by both apoptosis and necrosis. The study demonstrates that benzbromarone not only affects the function of mitochondria in HepG2 cells and human hepatocytes, but is also associated with profound changes in mitochondrial

  10. Ablation of atrial fibrillation with the Epicor system: a prospective observational trial to evaluate safety and efficacy and predictors of success

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    Diez Claudius

    2010-05-01

    Full Text Available Abstract Background High intensity focused ultrasound (HIFU energy has evolved as a new surgical tool to treat atrial fibrillation (AF. We evaluated safety and efficacy of AF ablation with HIFU and analyzed predictors of success in a prospective clinical study. Methods From January 2007 to June 2008, 110 patients with AF and concomitant open heart surgery were enrolled into the study. Main underlying heart diseases were aortic valve disease (50%, ischemic heart disease (48%, and mitral valve disease (18%. AF was paroxysmal in 29%, persistent in 31%, and long standing persistent in 40% of patients, lasting for 1 to 240 months (mean 24 months. Mean left atrial diameter was 50 ± 7 mm. Each patient underwent left atrial ablation with the Epicor system prior to open heart surgery. After surgery, the patients were treated with amiodarone and coumadin for 6 months. Follow-up studies including resting ECG, 24 h Holter ECG, and echocardiography were obtained at 6 and 12 months. Results All patients had successful application of the system on the beating heart prior to initiation of extracorporeal circulation. On average, 11 ± 1 ultrasound transducer elements were used to create the box lesion. The hand-held probe for additional linear lesions was employed in 83 cases. No device-related deaths occurred. Postoperative pacemaker insertion was necessary in 4 patients. At 6 months, 62% of patients presented with sinus rhythm. No significant changes were noted at 12 months. Type of AF and a left atrial diameter > 50 mm were predictors for failure of AF ablation. Conclusion AF ablation with the Epicor system as a concomitant procedure during open heart surgery is safe and acceptably effective. Our overall conversion rate was lower than in previously published reports, which may be related to the lower proportion of isolated mitral valve disease in our study population. Left atrial size may be useful to determine patients who are most likely to benefit from

  11. Prediction and prognosis of ventricular tachycardia recurrence after catheter ablation with remote magnetic navigation for electrical storm in patients with ischemic cardiomyopathy.

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    Jin, Qi; Jacobsen, Peter Karl; Pehrson, Steen; Chen, Xu

    2017-11-01

    Ventricular tachycardia (VT) recurrence after catheter ablation for electrical storm is commonly seen in patients with ischemic cardiomyopathy (ICM). We hypothesized that VT recurrence can be predicted and be related to the all-cause death after VT storm ablation guided by remote magnetic navigation (RMN) in patients with ICM. A total of 54 ICM patients (87% male; mean age, 65 ± 7.1 years) presenting with VT storm undergoing acute ablation using RMN were enrolled. Acute complete ablation success was defined as noninducibility of any sustained monomorphic VT at the end of the procedure. Early VT recurrence was defined as the occurrence of sustained VT within 1 month after the first ablation. After a mean follow-up of 17.1 months, 27 patients (50%) had freedom from VT recurrence. Sustained VT recurred in 12 patients (22%) within 1 month following the first ablation. In univariate analysis, VT recurrence was associated with incomplete procedural success (hazard ratio [HR]: 6.25, 95% confidence interval [CI]: 1.20-32.47, P = 0.029), lack of amiodarone usage before ablation (HR: 4.71, 95% CI: 1.12-19.7, P = 0.034), and a longer procedural time (HR: 1.023, 95% CI: 1.00-1.05, P = 0.05). The mortality of patients with early VT recurrence was higher than that of patients without recurrence (P storm guided by RMN is the strongest predictor of VT recurrence. ICM patients who have early recurrences after VT storm ablation are at high risk of all-cause death. © 2017 Wiley Periodicals, Inc.

  12. Insights into Pathophysiology from Medication-induced Tremor

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    John C. Morgan

    2017-10-01

    Full Text Available Background: Medication-induced tremor (MIT is common in clinical practice and there are many medications/drugs that can cause or exacerbate tremors. MIT typically occurs by enhancement of physiological tremor (EPT, but not all drugs cause tremor in this way. In this manuscript, we review how some common examples of MIT have informed us about the pathophysiology of tremor.Methods: We performed a PubMed literature search for published articles dealing with MIT and attempted to identify articles that especially dealt with the medication’s mechanism of inducing tremor.Results: There is a paucity of literature that deals with the mechanisms of MIT, with most manuscripts only describing the frequency and clinical settings where MIT is observed. That being said, MIT emanates from multiple mechanisms depending on the drug and it often takes an individualized approach to manage MIT in a given patient.Discussion: MIT has provided some insight into the mechanisms of tremors we see in clinical practice. The exact mechanism of MIT is unknown for most medications that cause tremor, but it is assumed that in most cases physiological tremor is influenced by these medications. Some medications (epinephrine that cause EPT likely lead to tremor by peripheral mechanisms in the muscle (β-adrenergic agonists, but others may influence the central component (amitriptyline. Other drugs can cause tremor, presumably by blockade of dopamine receptors in the basal ganglia (dopamine-blocking agents, by secondary effects such as causing hyperthyroidism (amiodarone, or by other mechanisms. We will attempt to discuss what is known and unknown about the pathophysiology of the most common MITs.

  13. Safety and efficacy of vernakalant for acute cardioversion of atrial fibrillation: an update

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    Dobrev D

    2013-04-01

    Full Text Available Yukiomi Tsuji,1 Dobromir Dobrev1–3 1Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, 2Division of Experimental Cardiology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 3Deutsches Zentrum für Herz-Kreislauf-Forshcung [German Center for Cardiovascular Research], partner site Heidelberg/Mannheim, Mannheim, Germany Abstract: Intravenous vernakalant has recently been approved in Europe as an atrial-selective antiarrhythmic drug for the conversion of recent-onset atrial fibrillation (AF. It inhibits atrial-selective K+ currents (IK,ACh and IKur and causes rate-dependent atrial-predominant Na+ channel block, with only a small inhibitory effect on the rapid delayed rectifier K+ current (IKr in the ventricle. Due to its atrial-selective properties, vernakalant prolongs the effective refractory period of the atria with minimal effects on the ventricles, being associated with a low proarrhythmic risk for torsades de pointes arrhythmias. Five pivotal clinical trials consistently demonstrated that vernakalant rapidly terminates AF with stable maintenance of sinus rhythm for up to 24 hours. A head-to-head comparative trial showed that the 90-minute conversion rate of vernakalant was substantially higher than that of amiodarone. Initially, a longer-acting oral formulation of vernakalant was shown to be effective and safe in preventing AF recurrence after cardioversion in a Phase IIb study. However, the clinical studies testing oral vernakalant for maintenance of sinus rhythm after AF cardioversion were prematurely halted for undisclosed reasons. This review article provides an update on the safety and efficacy of intravenous vernakalant for the rapid cardioversion of AF. Keywords: atrial fibrillation, antiarrhythmic drug, atrial-selective K+ currents, Na+ channel block, ventricles

  14. Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement.

    Science.gov (United States)

    D'Arcy, R; McDonnell, M; Spence, K; Courtney, C H

    2017-01-01

    A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T 4 ). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T 3 ) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging ( 123 I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T 3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. Free tri-iodothyronine (T 3 ) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T 4 ) or T 3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

  15. The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients.

    Science.gov (United States)

    Wattanachai, Nitsupa; Kaewmoongkun, Sutthida; Pussadhamma, Burabha; Makarawate, Pattarapong; Wongvipaporn, Chaiyasith; Kiatchoosakun, Songsak; Vannaprasaht, Suda; Tassaneeyakul, Wichittra

    2017-08-01

    The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays. The patients with variant genotypes of VKORC1 - 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability. VKORC1 - 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability.

  16. Adverse drug events associated with vitamin K antagonists: factors of therapeutic imbalance

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    El-Helou N

    2013-03-01

    Full Text Available Nancy El-Helou, Amal Al-Hajje, Rola Ajrouche, Sanaa Awada, Samar Rachidi, Salam Zein, Pascale SalamehClinical and Epidemiological Research Laboratory, Faculty of Pharmacy, Lebanese University, Beirut, LebanonBackground: Adverse drug events (ADE occur frequently during treatment with vitamin K antagonists (AVK and contribute to increase hemorrhagic risks.Methods: A retrospective study was conducted over a period of 2 years. Patients treated with AVK and admitted to the emergency room of a tertiary care hospital in Beirut were included. The aim of the study was to identify ADE characterized by a high international normalized ratio (INR and to determine the predictive factors responsible for these events. Statistical analysis was performed with the SPSS statistical package.Results: We included 148 patients. Sixty-seven patients (47.3% with an INR above the therapeutic range were identified as cases. The control group consisted of 81 patients (54.7% with an INR within the therapeutic range. Hemorrhagic complications were observed in 53.7% of cases versus 6.2% of controls (P < 0.0001. No significant difference was noticed between cases and controls regarding the indication and the dose of AVK. Patients aged over 75 years were more likely to present an INR above the therapeutic range (58.2%, P = 0.049. Recent infection was present in 40.3% of cases versus 6.2% of controls (P < 0.0001 and hypoalbuminemia in 37.3% of cases versus 6.1% of controls (P < 0.0001. Treatment with antibiotics, amiodarone, and anti-inflammatory drugs were also factors of imbalance (P < 0.0001.Conclusion: Many factors may be associated with ADE related to AVK. Monitoring of INR and its stabilization in the therapeutic range are important for preventing these events.Keywords: adverse drug events, vitamin K antagonists, bleeding risks, therapeutic imbalance

  17. Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events—European Registry in Atrial Fibrillation (PREFER in AF)

    Science.gov (United States)

    Kirchhof, Paulus; Ammentorp, Bettina; Darius, Harald; De Caterina, Raffaele; Le Heuzey, Jean-Yves; Schilling, Richard John; Schmitt, Josef; Zamorano, Jose Luis

    2014-01-01

    Aims We sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology. Methods and results The PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard deviation). Thirty per cent patients had paroxysmal, 24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent AF. Oral anticoagulation was used in the majority of patients: 4799 patients (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate 60–100 bpm). Half of the patients (50.7%) received rhythm control therapy by electrical cardioversion (18.1%), pharmacological cardioversion (19.5%), antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol 5.5%, dronedarone 4.0%), and catheter ablation (5.0%). Conclusion The management of AF patients in 2012 has adapted to recent evidence and guideline recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given to over 80% of eligible patients, including those at risk for bleeding. Rate is often adequately controlled, and rhythm control therapy is widely used. PMID:24084680

  18. The management of ventricular dysrhythmia in aconite poisoning.

    Science.gov (United States)

    Coulson, James M; Caparrotta, Thomas M; Thompson, John P

    2017-06-01

    directly correlated with the concentration of aconite alkaloids in the plasma. 54 of 65 cases developed ventricular tachycardia, six developed torsades des pointes, 15 patients developed ventricular fibrillation, 10 developed ventricular ectopics and one developed a broad complex tachycardia not otherwise specified; each dysrhythmia was regarded as separate and patients may have had more than one dysrhythmia. 10 patients died, giving a mortality of 15%. In total, 147 treatments were administered to 65 patients. 46 of the interventions were assessed by the authors as having been associated with successful restoration of sinus rhythm. Flecainide administration was accompanied by dysrhythmia termination in six of seven cases. Mexiletine was connected with correcting dysrhythmias in 3 of 3 cases. Procainamide administration was associated with return to sinus rhythm in 2 of 2 cases. Prolonged cardio-pulmonary resuscitation was administered to 15 patients where it was associated with a return to sinus rhythm in nine of these. Amiodarone was linked to success in correcting dysrhythmias in 11 of 20 cases. Cardiopulmonary bypass use was associated with a return to sinus rhythm in four out of six cases. Epinephrine was documented as being employed on four occasions, and was associated with a restoration of sinus rhythm on two of these. Magnesium sulphate administration was accompanied by dysrhythmia termination in two of nine cases. Direct cardioversion was associated with a return of sinus rhythm in 5 of 30 cases. However, it is not certain whether the drug treatment influenced the course of the dysrhythmia. Based on the evidence available from human case reports, flecainaide or amiodarone appear to be more associated with a return to sinus rhythm than lidocaine and/or cardioversion, although it is not established whether the administration of treatment caused reversion to normal sinus rhythm. The potential beneficial effects of amiodarone were not observed in animal studies. This

  19. Lysosomotropic cationic drugs induce cytostatic and cytotoxic effects: Role of liposolubility and autophagic flux and antagonism by cholesterol ablation

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    Parks, Alexandre; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

    2016-08-15

    Cation trapping in acidic cell compartments determines an antiproliferative effect that has a potential interest in oncology, as shown by clinical data and trials involving chloroquine and hydroxychloroquine. To further characterize the mechanism of this effect, we studied a series of 6 substituted triethylamine (s-Et{sub 3}N) drugs that encompasses a wide range of liposolubility (amiodarone, quinacrine, chloroquine, hydroxychloroquine, lidocaine, and procainamide). Three tumor cell lines and primary human endothelial cells were exploited in proliferation assays (48 h, cell counts). Accumulation of the autophagic effector LC3 II and the apoptotic marker cleaved PARP1 (immunoblots), cytotoxicity, cell cycle analysis and endocytic function were further tested in the p53-null histiocytic lymphoma U937 line. A profound and desynchronized antiproliferative effect was observed in response to all s-Et{sub 3}Ns with essentially no cell type specificity. Predictors of s-Et{sub 3}N potency were liposolubility and the acute accumulation of the autophagic effector LC3 II (6 h-treatments). For each s-Et{sub 3}N, there was an antiproliferative concentration range where cytotoxicity and apoptosis were not triggered in U937 cells (24–48 h-treatments). Quinacrine was the most potent cytostatic drug (1–5 μM). Co-treatment of cells with inhibitors of cholesterol, β-cyclodextrin or lovastatin, partially reversed the antiproliferative effect of each s-Et{sub 3}N. The cytopathology induced by cationic drug accumulation includes a cytostatic effect. Its intensity is cell type- and p53-independent, but predicted by the inhibition of autophagic flux and by the liposolubility of individual drugs and alleviated by cholesterol ablation. The superiority of quinacrine, biomarker value of LC3 II and antagonism by a statin may be clinically relevant. - Highlights: • Cation trapping in acidic cell compartments induces a cytostatic effect. • A series of substituted triethylamines has been

  20. Tachyarrhythmias, bradyarrhythmias and acute coronary syndromes

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    Trappe Hans-Joachim

    2010-01-01

    Full Text Available The incidence of bradyarrhythmias in patients with acute coronary syndrome (ACS is 0.3% to 18%. It is caused by sinus node dysfunction (SND, high-degree atrioventricular (AV block, or bundle branch blocks. SND presents as sinus bradycardia or sinus arrest. First-degree AV block occurs in 4% to 13% of patients with ACS and is caused by rhythm disturbances in the atrium, AV node, bundle of His, or the Tawara system. First- or second-degree AV block is seen very frequently within 24 h of the beginning of ACS; these arrhythmias are frequently transient and usually disappear after 72 h. Third-degree AV blocks are also frequently transient in patients with infero-posterior myocardial infarction (MI and permanent in anterior MI patients. Left anterior fascicular block occurs in 5% of ACS; left posterior fascicular block is observed less frequently (incidence < 0.5%. Complete bundle branch block is present in 10% to 15% of ACS patients; right bundle branch block is more common (2/3 than left bundle branch block (1/3. In patients with bradyarrhythmia, intravenous (IV atropine (1-3 mg is helpful in 70% to 80% of ACS patients and will lead to an increased heart rate. The need for pacemaker stimulation (PS is different in patients with inferior MI (IMI and anterior MI (AMI. Whereas bradyarrhythmias are frequently transient in patients with IMI and therefore do not need permanent PS, there is usually a need for permanent PS in patients with AMI. In these patients bradyarrhythmias are mainly caused by septal necrosis. In patients with ACS and ventricular arrhythmias (VTA amiodarone is the drug of choice; this drug is highly effective even in patients with defibrillation-resistant out-of-hospital cardiac arrest. There is general agreement that defibrillation and advanced life support is essential and is the treatment of choice for patients with ventricular flutter/fibrillation. If defibrillation is not available in patients with cardiac arrest due to VTA

  1. Beta-blocker use and risk of symptomatic bradyarrhythmias: a hospital-based case-control study

    Science.gov (United States)

    Lu, Hou Tee; Kam, Jiyen; Nordin, Rusli Bin; Khelae, Surinder Kaur; Wang, Jing Mein; Choy, Chun Ngok; Lee, Chuey Yan

    2016-01-01

    Objective To investigate the risk factors of symptomatic bradyarrhythmias in relation to β-blockers use. Methods A hospital-based case-control study [228 patients: 108 with symptomatic bradyarrhythmias (cases) and 120 controls] was conducted in Sultanah Aminah Hospital, Malaysia between January 2011 and January 2014. Results The mean age was 61.1 ± 13.3 years with a majority of men (68.9%). Cases were likely than control to be older, hypertensive, lower body mass index and concomitant use of rate-controlling drugs (such as digoxin, verapamil, diltiazem, ivabradine or amiodarone). Significantly higher level of serum potassium, urea, creatinine and lower level of estimated glomerular filtration rate (eGFR) were observed among cases as compared to controls. On univariate analysis among patients on β-blockers, older age (crude OR: 1.07; 95% CI: 1.03–1.11, P = 0.000), hypertension (crude OR: 5.6; 95% CI: 1.51–20.72, P = 0.010), lower sodium (crude OR: 0.04; 95% CI: 0.81–0.99, P = 0.036), higher potassium (crude OR: 2.36; 95% CI: 1.31–4.26, P = 0.004) and higher urea (crude OR: 1.23; 95% CI: 1.11–1.38, P = 0.000) were associated with increased risk of symptomatic bradyarrhythmias; eGFR was inversely and significantly associated with symptomatic bradyarrhythmias in both ‘β-blockers’ (crude OR: 0.97; 95% CI: 0.96–0.98, P = 0.000) and ‘non-β-blockers’ (crude OR: 0.99; 95% CI: 0.97–0.99, P = 0.023) arms. However, eGFR was not significantly associated with symptomatic bradyarrhythmias in the final model of both ‘β-blockers’ (adjusted OR: 0.98; 95% CI: 0.96–0.98, P = 0.103) and ‘non-β-blockers’ (adjusted OR: 0.99; 95% CI: 0.97–1.01, P = 0.328) arms. Importantly, older age was a significant predictor of symptomatic bradyarrhythmias in the ‘β-blockers’ as compared to the ‘non-β-blockers’ arms (adjusted OR: 1.09; 95% CI: 1.03–1.15, P = 0.003 vs. adjusted OR: 1.03; 95% CI: 0.98–1.09, P = 0.232, respectively). Conclusion Older

  2. The impact of cardiac rhythm on the mitral valve area and gradient in patients with mitral stenosis.

    Science.gov (United States)

    Arı, Hasan; Arı, Selma; Karakuş, Alper; Camcı, Sencer; Doğanay, Kübra; Tütüncü, Ahmet; Melek, Mehmet; Bozat, Tahsin

    2017-08-01

    The aim of this study was to evaluate the effect of cardiac rhythm on the echocardiographic mitral valve area (MVA) and transmitral gradient calculation in relation to net atrioventricular compliance (Cn). Patients (n=22) with mild or moderate pure rheumatic mitral stenosis (MS) (MVA 1 cm2) and atrial fibrillation (AF) were evaluated. All patients underwent transthoracic electrical DC cardioversion under amiodarone treatment. Nineteen of the 22 patients were successfully converted to sinus rhythm (SR). The patients were evaluated with transthoracic echocardiography before and two to three days after DC cardioversion. In order to deal with variable R-R intervals, the measurements were averaged on five to eight consecutive beats in AF. Cn was calculated with a previously validated equation [Cn (mL/mm Hg)=1.270 x MVA/E-wave downslope]. The Cn difference between AF and SR was calculated as follows: [(AF Cn-SR Cn)/AF Cn] x 100. The percentage gradient (mean or maximal) difference between AF and SR was calculated as follows: [AF gradient (mean or maximal) - SR gradient (mean or maximal)]/[AF gradient (mean or maximal)] x 100. The MVA was lower (MVA planimetric; 1.62±0.29 vs. 1.54±0.27; p=.003, MVA PHT; 1.66±0.30 vs. 1.59±0.26; p=0.01) but transmitral gradient (mean gradient; 6.49±2.51 vs. 8.89±3.52; p=0.001, maximal gradient: 16.94±5.11 vs. 18.57±4.54; p=0.01) and Cn values (5.37±0.77 vs. 6.26±0.64; pgradient difference (mean and maximal) (Cn difference-mean gradient difference; r=0.46; p=0.05; Cn difference-maximal gradient difference; r=0.72; p=0.001). Cardiac rhythm has a significant impact on echocardiographic evaluation of MVA, transmitral gradient, and Cn in patients with MS.

  3. TREATMENT OF PERIPARTUM CARDIOMYOPATHY (REVIEW

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    N. T. Vatutin

    2017-01-01

    Full Text Available The presented review concerns discussion about current insights into treatment of peripartum cardiomyopathy. The definition of peripartum cardiomyopathy and general issues about diagnosis and pathogenesis of the disorder are provided at the head of the review. Particularly, the role of the system «prolactin — cathepsin D — prolactin 16 kDa» in cardiomyopathy development is disclosed. The general approaches to management of the patients are highlighted. The review provides detailed data about indications, adverse effects and derived clinical experience concerning the main pharmacological drugs which had been used in peripartum cardiomyopathy treatment given their possible unfavorable influence on fetus maturation and maternal lactation. The detailed description is provided on diuretics including loop, thiazide and potassium-sparing drugs. It was noted relative safety and efficiency of nitrates and hydralazine in conditions of limited choice from vasodilator group and, particularly, angiotensinconverting-enzyme inhibitors and angiotensin-II receptor blockers which are contraindicated in pregnancy. A special attention is paid to the group of inotropic drugs: levosimendan, milrinone, and cardiac glycosides. The role of β-blockers and ivabradine is disclosed in heart failure treatment of peripartum cardiomyopathy. Anticoagulants were presented in details given that these drugs are justified in severe cardiac chambers dilation, decrease in ejection fraction, and in presence of intracardiac thrombosis. The place of antiarrhythmic drugs administrating in various cardiac rhythm disorders is discussed in the review. The data is given with account of potential influence on fetus in antenatal peripartum cardiomyopathy in which lidocaine and sotalol are the most preferable drugs; adenosine, quinidine, and flecainide are useful with caution, but amiodarone and dronedarone are absolutely contraindicated. Taking into account proposed pathogenic

  4. Indications, diagnostic yields and complications of transbronchial biopsy over 5 years in the State of Qatar

    International Nuclear Information System (INIS)

    Ibrahim, Abdulsalam S.; Allangawi, Mona H.; Sattar, Hisham A.; Mobyed, Hassan S.; Almohammed, Ahmed A.

    2005-01-01

    To review the indications, diagnostic yields and complications of transbronchial biopsy (TBB) in a tertiary hospital in the State of Qatar. A retrospective review of our records revealed 1006 adult flexible fibre optic bronchoscopies (FFB) at Hamad General Hospital, State of Qatar between January 1999 and December 2003. A total of 85 (8.4%) TBB were performed, but complete data were available for 71/85 (83.5%), which were reviewed for indications, diagnostic yields and complications. Adequate samples were obtained in 58/71 TBBs (81.7%), while 13/71 TBBs (18.3%) yielded mucosa. The main indications in 16/71 (22.5%) TBBs for radiographic localized pulmonary diseases were to rule out (TB) in 13 cases, and malignancy in 3 cases. Tuberculosis was verified in 3 (23%) of 13 cases with localized disease. 45 out of 71 (77.5%) TBBs were performed for radiographic diffuse pulmonary disease: 16/55 (29%) for miliary shadows, while 39/55 (70.9%) were carried out for reticular /reticulonodular infiltrates. Histopathology showed granulomatous lesions consistent with TB in 10/16 (62.5%) cases of miliary shadow. In other pattern of diffuse disease, the histopathological diagnosis were obtained in 25/39 (64%) cases. It showed non-specific pulmonary fibrosis in 13 cases, sarcoidosis in 4 cases, connective tissue disease associated interstitial fibrosis in 4 cases, bronchiolitis obliterans organizing pneumonia (BOOP) in one case, eosinophilic pneumonia in one case, amiodarone toxicity in one case and lymphangitis carcinomatosis in one case. The main complications were minor bleeding <50 cc in 17 cases (23.9%) pneumothorax in 7 cases (9.8%) and one case has sepsis. Our experience substantiates previous reports of the value and safety of transbronchial biopsy in rapid diagnosis smear-negative miliary TB. In diffuse lung diseases of a non-infectious nature, other than sarcoidosis, lymphangitis carcinomatosis and few other conditions, a pathological diagnosis are much less likely to be

  5. Mode of death on Chagas heart disease: comparison with other etiologies. a subanalysis of the REMADHE prospective trial.

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    Silvia M Ayub-Ferreira

    Full Text Available Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy.We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1% died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34-5.69; p = 0.006, LVEDD (left ventricular end diastolic diameter (HR 1.07; CI 1.04-1.10; p<0.001, creatinine clearance (HR 0.98; CI 0.97-0.99; p = 0.006 and use of amiodarone (HR 3.05; CI 1.47-6.34; p = 0.003 were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01-1.07; p = 0.005 and use of beta-blocker (HR 0.52; CI 0.34-0.94; p = 0.014 were independently associated with sudden death mortality.In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death.ClinicalTrials.gov NCT00505050 (REMADHE.

  6. Aluminum Phosphide; the Most Fatal Rodenticide and Fungicide

    International Nuclear Information System (INIS)

    Afshari, R.

    2007-01-01

    ; Chronic administration may lead to significant decreases in Na-K-ATPase activities in renal, hepatic and cardiac tissues, decreases of Ca-ATPase and Mg-ATPase in liver, and decreases in hematocrit, red blood cell count, hemoglobin and platelets. Prognosis: The mortality rate is high. The prognostic factors were shock, ECG abnormalities, using of vasoactive drugs, use of mechanical ventilation, and haemodynamic disturbances. Treatment: No specific antidote is known, but it is dose dependent and time dependent to stomach wash. In vitro, use of vegetable oils, coconut oil, and liquid paraffin and were effective in inhibiting release of phosphine from AP. Intravenous amiodarone/xylocard have successfully used to revert dangerous ventricular arrhythmias. Conclusion: Potential hazards associated with phosphide fumigants should be recognized. Minimizing the use of this fumigant improves worker safety, reduces both control costs and harm to the environment and potential duel use.(author)

  7. [Impact of metoprolol use in the treatment of patients with electrical-storm after cardioverter defibrillators implantation].

    Science.gov (United States)

    Yu, Jin-bo; Yang, Bing; Xu, Dong-jie; Chen, Ming-long; Shan, Qi-jun; Zou, Jian-gang; Chen, Chun; Zhang, Feng-xiang; Hou, Xiao-feng; Li, Wen-qi; Zhang, Rong; Cao, Ke-jiang

    2011-08-01

    To explore the effectiveness of the metoprolol dosage adjustment on reducing the incidence of electrical-storm (ES) in patients with Implantable Cardioverter Defibrillators (ICDs). Data from patients with ICD implantation between Jan, 2003 and Jun, 2006 in our hospital were retrospectively analyzed. ES was defined as either ≥ 3 times of ventricular tachyarrhythmias (VTAs) resulting in ICD therapy or VTAs lasting more than 30 s detected by ICD without any therapy within 24 hours. During a follow-up period of (27.5 ± 21.2) months, ES was recorded in 39 cases [34 males, average age (52.0 ± 13.1) years] out of 119 patients (32.8%) and 9 patients died after ES. During the period of storm attack, ES was successfully controlled in 25/30 patients by various interventions, including predisposing factors corrected in 5 cases, ICD reprogramming and antiarrhythmic drugs therapy optimized in 16 cases (one received intravenous injection of metoprolol), and VTAs eliminated by catheter ablation in 4 cases. ES was spontaneously resolved in the remaining 5 cases. In the chronic phase, 2 patients with Brugada syndrome were treated with Quinidine mono-therapy while the dosage of metoprolol was adjusted in the remaining 23 patients and the dosage of metoprolol was increased gradually from (26.8 ± 13.9) mg/d to (88.9 ± 53.5) mg/d without any adverse effects (9 patients received also oral amiodarone 200 mg/d). Post dosage adjustment, the total VTA episodes [(1.9 ± 1.7) times/month vs. (0.8 ± 0.6) times/month, P = 0.004], incidence of antitachycardia pacing therapies [(4.2 ± 3.8) runs/month vs. (2.3 ± 2.0) runs/month, P = 0.003], as well as electrical cardioversion or defibrillation [(1.1 ± 0.9) times/month vs. (0.4 ± 0.2) times/month, P = 0.001] were significantly decreased. ES was not controlled until a extremely high dosage [225 - 300 (255.3 ± 41.7) mg/d] of metoprolol was reached in the remaining 5 patients. Metoprolol use is essential and its dosage should be

  8. Hepatic toxicity of dronedarone in mice: Role of mitochondrial β-oxidation

    International Nuclear Information System (INIS)

    Felser, Andrea; Stoller, Andrea; Morand, Réjane; Schnell, Dominik; Donzelli, Massimiliano; Terracciano, Luigi; Bouitbir, Jamal; Krähenbühl, Stephan

    2014-01-01

    Highlights: • Dronedarone is not hepatotoxic to mice up to 200 mg/kg/day. • At 400 mg/kg/day dronedarone decreases food intake and inhibits hepatic fatty acid metabolism. • Impaired hepatic fatty acid metabolism is associated with increased hepatocyte apoptosis and serum transaminases. • Mice with subclinical impairment of β-oxidation are slightly more susceptible to dronaderone than wild type mice. - Abstract: Dronedarone is an amiodarone-like antiarrhythmic drug associated with severe liver injury. Since dronedarone inhibits mitochondrial respiration and β-oxidation in vitro, mitochondrial toxicity may also explain dronedarone-associated hepatotoxicity in vivo. We therefore studied hepatotoxicity of dronedarone (200 mg/kg/day for 2 weeks or 400 mg/kg/day for 1 week by intragastric gavage) in heterozygous juvenile visceral steatosis (jvs +/− ) and wild-type mice. Jvs +/− mice have reduced carnitine stores and are sensitive for mitochondrial β-oxidation inhibitors. Treatment with dronedarone 200 mg/kg/day had no effect on body weight, serum transaminases and bilirubin, and hepatic mitochondrial function in both wild-type and jvs +/− mice. In contrast, dronedarone 400 mg/kg/day was associated with a 10–15% drop in body weight, and a 3–5-fold increase in transaminases and bilirubin in wild-type mice and, more accentuated, in jvs +/− mice. In vivo metabolism of intraperitoneal 14 C-palmitate was impaired in wild-type, and, more accentuated, in jvs +/− mice treated with 400 mg/kg/day dronedarone compared to vehicle-treated mice. Impaired β-oxidation was also found in isolated mitochondria ex vivo. A likely explanation for these findings was a reduced activity of carnitine palmitoyltransferase 1a in liver mitochondria from dronedarone-treated mice. In contrast, dronedarone did not affect the activity of the respiratory chain ex vivo. We conclude that dronedarone inhibits mitochondrial β-oxidation in and ex vivo, but not the respiratory chain

  9. Appropriateness of administration of nasogastric medication and preliminary intervention

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    Zhou Q

    2012-11-01

    Full Text Available Ling-Ling Zhu,1 Ling-Cheng Xu,2 Hui-Qin Wang,3 Jing-Fen Jin,3 Hua-Fen Wang,3 Quan Zhou21Cadre Department, 2Department of Pharmacy, 3Division of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, ChinaAbstract: A utilization study was performed in a 2200-bed tertiary care teaching hospital. Data mining was performed on all nasogastric medication prescriptions for patients hospitalized in 2011. Nurses were interviewed by questionnaire. A PDCA (Plan-Do-Check-Act cycle was used for continuous quality improvement. The proportion of patients with nasogastric tubes (NGT was 3.2%. A large number of medical orders (n  6261 involved nasogastric medications with a package insert particularly noting that they should not be crushed or opened (group 1 or medications without a specific formulation recommendation in the package insert but having evidence discouraging NGT dosing (group 2. Of the nasogastrically administered sustained-release or controlled-release formulations, a sustained-release sodium valproate tablet formulation was the most prescribed drug and a sustained-release 2.5 mg felodipine tablet was prescribed with the highest proportion of NGT dosing [NGT/(NGT  oral  12.3%]. Among the nasogastrically administered enteric-coated formulations, a myrtol-standardized enteric-coated capsule formulation was the most prescribed drug and a pantoprazole tablet formulation was prescribed with the highest proportion of NGT dosing [NGT/(NGT  oral  19.3%]. Proportions of NGT dosing for amiodarone and carbamazepine (group 2 were 4.8% and 6.3%, respectively. The percentage of nurses with adequate knowledge about pharmaceutical dosage formulations was 60%. The rate of answering correctly as to whether medications in group 1 could be crushed or opened was only 30%. Awareness of evidence discouraging NGT dosing of medications in group 2 was zero. Most nurses (90% left physicians and

  10. Brugada syndrome in a patient with amyotrophic lateral sclerosis: a case report.

    Science.gov (United States)

    Battineni, Anusha; Gummi, Rohit; Mullaguri, Naresh; Govindarajan, Raghav

    2017-07-14

    Amyotrophic lateral sclerosis is a fatal neuromuscular disorder characterized by progressive death of the upper and lower motor neurons in the central nervous system. Patients with this disease die mostly as a result of respiratory failure; however, owing to prolonged survival through assisted ventilation, cardiovascular causes are increasingly responsible for mortality. We report what is to the best of our knowledge the first case of type 2 Brugada syndrome causing ventricular tachyarrhythmia and cardiac arrest in a patient with upper limb onset amyotrophic lateral sclerosis. A 48-year-old Caucasian woman with a significant past medical history of papillary thyroid carcinoma status postresection, pulmonary embolism on anticoagulation, and a recent diagnosis of right upper limb-onset amyotrophic lateral sclerosis presented to the emergency department of our hospital with acute on chronic shortness of breath. On further evaluation, she was found to have hypoxic and hypercapnic respiratory failure and was placed on bilevel positive airway pressure ventilation. Her 12-lead electrocardiogram showed sinus rhythm with J-point elevation, saddle-shaped ST segment elevation, predominantly in V1 and V2 with no significant QTc prolongation. No troponin elevation was noted in her laboratory workup. Because she was unable to protect her airway, a decision was made to intubate her. After 1 minute of induction with etomidate and succinylcholine, she went into pulseless ventricular tachycardia and fibrillation requiring three cycles of cardiopulmonary resuscitation with high-quality chest compressions, three doses of epinephrine, and a loading dose of amiodarone prior to return of spontaneous circulation. She was further evaluated by cardiology services and was diagnosed with type 2 Brugada syndrome, for which she was started on quinidine. Her respiratory failure and the drugs she received for intubation likely caused her ventricular tachycardia to occur in conjunction with an

  11. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany.

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    Sarganas, Giselle; Garbe, Edeltraut; Klimpel, Andreas; Hering, Rolf C; Bronder, Elisabeth; Haverkamp, Wilhelm

    2014-01-01

    Drug-induced long QT syndrome (diLQTS) leading to Torsade de Pointes (TdP) is a potentially lethal condition, which has led to several post-marketing drug withdrawals in the past decade. The true incidence of diLQTS/TdP is largely unknown. One explanation is under-reporting of this potentially life-threatening adverse event by physicians and other medical staff to pharmacovigilance agencies. To gain more insight into the incidence of diLQTS and TdP, the Berlin Pharmacovigilance Center (PVZ-FAKOS) has actively and prospectively identified patients who developed this particular type of drug-induced adverse event. Here, the basic characteristics of the affected patients are summarized and suspected drugs are discussed. Furthermore, an extrapolation of the Berlin incidence rates to the German Standard Population is presented. Using a Berlin-wide network of 51 collaborating hospitals (>180 clinical departments), adult patients presenting with long QT syndrome (LQTS/TdP) between 2008 and 2011 were identified by active surveillance of these hospitals. Drug exposures as well as other possible risk factors were obtained from the patient's files and in a face-to-face interview with the patient. One-hundred and seventy patients of possible LQTS/TdP were reported to the Pharmacovigilance Center of whom 58 cases were confirmed in a thorough validation process. The majority (66%) of these cases were female and 60% had developed LQTS/TdP in the outpatient setting. Thirty-five (60%) of 58 confirmed cases were assessed as drug-related based on a standardized causality assessment applying the criteria of the World Health Organization. Drugs assessed as related in more than two cases were metoclopramide, amiodarone, melperone, citalopram, and levomethadone. The age-standardized incidence of diLQTS/TdP in Berlin was estimated to be 2.5 per million per year for males and 4.0 per million per year for females. While European annual reporting rates based on spontaneous reports suggest an

  12. Lysosomotropic cationic drugs induce cytostatic and cytotoxic effects: Role of liposolubility and autophagic flux and antagonism by cholesterol ablation

    International Nuclear Information System (INIS)

    Parks, Alexandre; Marceau, François

    2016-01-01

    Cation trapping in acidic cell compartments determines an antiproliferative effect that has a potential interest in oncology, as shown by clinical data and trials involving chloroquine and hydroxychloroquine. To further characterize the mechanism of this effect, we studied a series of 6 substituted triethylamine (s-Et 3 N) drugs that encompasses a wide range of liposolubility (amiodarone, quinacrine, chloroquine, hydroxychloroquine, lidocaine, and procainamide). Three tumor cell lines and primary human endothelial cells were exploited in proliferation assays (48 h, cell counts). Accumulation of the autophagic effector LC3 II and the apoptotic marker cleaved PARP1 (immunoblots), cytotoxicity, cell cycle analysis and endocytic function were further tested in the p53-null histiocytic lymphoma U937 line. A profound and desynchronized antiproliferative effect was observed in response to all s-Et 3 Ns with essentially no cell type specificity. Predictors of s-Et 3 N potency were liposolubility and the acute accumulation of the autophagic effector LC3 II (6 h-treatments). For each s-Et 3 N, there was an antiproliferative concentration range where cytotoxicity and apoptosis were not triggered in U937 cells (24–48 h-treatments). Quinacrine was the most potent cytostatic drug (1–5 μM). Co-treatment of cells with inhibitors of cholesterol, β-cyclodextrin or lovastatin, partially reversed the antiproliferative effect of each s-Et 3 N. The cytopathology induced by cationic drug accumulation includes a cytostatic effect. Its intensity is cell type- and p53-independent, but predicted by the inhibition of autophagic flux and by the liposolubility of individual drugs and alleviated by cholesterol ablation. The superiority of quinacrine, biomarker value of LC3 II and antagonism by a statin may be clinically relevant. - Highlights: • Cation trapping in acidic cell compartments induces a cytostatic effect. • A series of substituted triethylamines has been studied in 4 cell

  13. SUBCLINICAL HYPOTHYROIDISM IN METABOLIC SYNDROME AND ROLE OF CRP IN 50 ADULT PATIENTS

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    Pratik Shah

    2017-04-01

    Full Text Available BACKGROUND Metabolic Syndrome (MetS is generally characterised as a clustering of the abnormal levels of blood lipids (low HDL and high triglycerides, impaired fasting glucose, elevated blood pressure, and excess abdominal obesity. The objectives of the study areTo evaluate presence of Subclinical Hypothyroidism in the study population of the patients with metabolic syndrome. To find out relation between Subclinical Hypothyroidism and different parameters of metabolic syndrome. To evaluate whether patients of metabolic syndrome with raised hs-CRP have an increased risk of having hypothyroidism. MATERIALS AND METHODS A total of 50 adult patients who met with inclusion criteria were selected. Patients with metabolic syndrome (MetS who fulfilled the NCEP-ATP III criteria: 3 out of 5 criteria positive. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions (e.g. lithium, amiodarone or γ-interferon were excluded from the study. RESULTS A total of 50 patients of metabolic syndrome were enrolled. Out of which 36 were euthyroid, 3 were overt hypothyroid and 11 were subclinical hypothyroid. Out of 11 patients of subclinical hypothyroidism, 9 were female and 2 were male patients. Out of 28 females, 9 (32% were SCH while out of 22 males, 2 (9% were SCH. Out of 50 patients, 3 were overt hypothyroid. All 3 patients had BP >130/85, waist circumference was >88 cm and HDL of 130/85, HDL 150 mg/dL and fasting blood glucose of >100 mg/dL were more associated with male patients. CONCLUSION Subclinical Hypothyroidism was present in 22% of study population and more so in females having metabolic syndrome (32%. Hence, it will be worthwhile to screen female metabolic syndrome patients for thyroid function abnormality. Abnormal blood pressure, triglycerides and HDL cholesterol levels were more associated with subclinical hypothyroidism

  14. National Characteristics of Emergency Medical Services Responses for Older Adults in the United States.

    Science.gov (United States)

    Duong, Hieu V; Herrera, Lauren Nicholas; Moore, Justin Xavier; Donnelly, John; Jacobson, Karen E; Carlson, Jestin N; Mann, N Clay; Wang, Henry E

    2018-01-01

    Older adults, those aged 65 and older, frequently require emergency care. However, only limited national data describe the Emergency Medical Services (EMS) care provided to older adults. We sought to determine the characteristics of EMS care provided to older adults in the United States. We used data from the 2014 National Emergency Medical Services Information System (NEMSIS), encompassing EMS response data from 46 States and territories. We excluded EMS responses for children older adults as age ≥65 years. We compared patient demographics (age, sex, race, primary payer), response characteristics (dispatch time, location type, time intervals), and clinical course (clinical impression, injury, procedures, medications) between older and younger adult EMS emergency 9-1-1 responses. During the study period there were 20,212,245 EMS emergency responses. Among the 16,116,219 adult EMS responses, there were 6,569,064 (40.76%) older and 9,547,155 (59.24%) younger adults. Older EMS patients were more likely to be white and the EMS incident to be located in healthcare facilities (clinic, hospital, nursing home). Compared with younger patients, older EMS patients were more likely to present with syncope (5.68% vs. 3.40%; OR 1.71; CI: 1.71-1.72), cardiac arrest/rhythm disturbance (3.27% vs. 1.69%; OR 1.97; CI: 1.96-1.98), stroke (2.18% vs. 0.74%; OR 2.99; CI: 2.96-3.02) and shock (0.77% vs. 0.38%; OR 2.02; CI: 2.00-2.04). Common EMS interventions performed on older persons included intravenous access (32.02%), 12-lead ECG (14.37%), CPR (0.87%), and intubation (2.00%). The most common EMS drugs administered to older persons included epinephrine, atropine, furosemide, amiodarone, and albuterol or ipratropium. One of every three U.S. EMS emergency responses involves older adults. EMS personnel must be prepared to care for the older patient.

  15. Effects of n-3 polyunsaturated fatty acids on cardiac ion channels

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    Cristina eMoreno

    2012-07-01

    Full Text Available Dietary n-3 polyunsaturated fatty acids (PUFAs have been reported to exhibit antiarrhythmic properties, attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on cardiac sodium channel (Nav1.5 and two potassium channels (Kv (Kv1.5 and Kv11.1. n-3 marine (docohexaenoic and eicohexapentaenoic acid and plant origin (alpha-linolenic acid PUFAs block Kv1.5 and Kv11.1 channels at physiological concentrations. Also, DHA and EPA decreased Nav1.5 and calcium channels. These effects on Na and Ca channels theoretically should shorten the cardiac APD, whereas the blocking actions of n-3 PUFAs of Kv channels should lengthen the cardiac action potential. Experiments performed in female rabbits fed with a diet rich in n-3 PUFAs show a longer cardiac action potential and effective refractory period. This study was performed to analyze if their antiarrhythmic effects are due to a reduction of triangulation, reverse use-dependence, instability and dispersion of the cardiac action potential (TRIaD as a measure of proarrhythmic effects. Dietary n-3 PUFAs supplementation markedly reduced dofetilide-induced TRIaD and abolished dofetilide-induced torsades de pointes (TdP. Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of dietary supplements of n-3 PUFAs against dofetilide induced proarrhythmia observed in this animal model. The cardiac effects of n-3 PUFAs resemble those of amiodarone: both block sodium, calcium and potassium channels, have anti-adrenergic properties, can prolong the cardiac action potential, reverse TRIaD and suppress TdP. The main difference is that sodium channel block by n-3 PUFAs has a much faster onset and offset kinetics. Therefore, the electrophysiological profile of n-3 PUFAs appears more desirable: the duration of reduced sodium current (facilitates re-entry is much shorter. The n-3 PUFAs appear as a safer alternative to other antiarrhythmic

  16. Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting.

    Science.gov (United States)

    Helmy, Sally A

    2015-01-01

    Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets. To (a) investigate the effect of tablet characteristics on weight and content uniformity of half tablets, resulting from splitting 16 commonly used medications in the outpatient setting and (b) provide recommendations for safe tablet-splitting prescribing practices. Ten random tablets from each of the selected medications were weighed and split by 5 volunteers (2 men and 3 women aged 25-44 years) using a knife. The selected medications were mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The resulting half tablets were evaluated for weight and drug content uniformity in accordance with proxy United States Pharmacopeia (USP) specification (95%-105% for digoxin and 90%-110% for the other 15 drugs). Weight and drug content uniformity were assessed by comparing weight or drug content of the half tablets with one-half of the mean weight or drug content for all whole tablets in the sample. The percentages by which the weight and drug content of each whole tablet or half tablet differed from sample mean values were calculated. Other relevant physical characteristics of the 16 products were measured. A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy USP specification for weight and drug content, respectively. Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test; however, the half tablets for the rest of the medications passed the test. Mean percent weight loss after

  17. Taquiarritmia fetal: Una revisión práctica Fetal tachyarrhythmia

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    Juan F Jaramillo D

    2009-02-01

    edema are common final outcomes before fetal death, that still at this point can be controlled and reverted. Although theoretically any type of arrhythmias could be developed in the fetus, 90% of fetal tachyarrhythmias correspond to supraventricular reciprocant tachycardia and flutter. Both types of arrhythmias may respond to digoxin, although some are refractory to this drug. Ultrasound application to the heart allows not only to rule out associated heart anomalies, but to realize treatment protocols. The measurement of the relation between ventricular-atrial and atrio-ventricular times allows to consider another type of arrhythmias such as junctional ectopic tachycardia, permanent junctional reprocicant tachycardia, etc., and to include other antiarrhythmics such as amiodarone, flecainide and sotalol among others. The main administration route of antiarrhythmics is the transplacental. Therefore not only the fetus but also the mother is exposed to drug side effects. A multidisciplinary group will confront this situation in order to offer both mother and fetus the best result.

  18. É a cardiomiopatia hipertrófica apical vista em uma amostra na cidade do Rio de Janeiro similar à encontrada no oriente? Is the apical hypertrophic cardiomyopathy seen in one population in Rio de Janeiro city similar to that found in the east?

    Directory of Open Access Journals (Sweden)

    Francisco Manes Albanesi Fº

    1997-08-01

    13 (8.34% with the apical form of the disease, whose clinical settings, diagnostic procedures and evolution were studied. RESULTS: There were 8 males and 5 females, between 19 and 75 years old, all white. Electrocardiogram (EKG showed giant T waves in precordial leads in 10 (76.92%, echocardiogram (ECHO demonstrated apical hypertrophy in all, 10 (76.92% had only in the left ventricle, 2 in right ventricle and one involving both. Cineangiography corroborated ECHO findings. Follow-up ranged from 6 to 294 months (x= 95.4. Two deaths occurred in patients with RV involvement, due to large atria, atrial fibrillation, tricuspid or mitral insufficiency and thromboembolism. Among the survivors, the patient with RV disease has diastolic restriction and the ones with LV involvement, 9 are asymptomatic using either propranolol (8 or amiodarone (1, and one uses no medication. CONCLUSION: A HCM seen in Rio de Janeiro is similar to that found in the Orient (Japan regarding presentation, diagnosis and evolution; but in 3 patients we have found RV disease, not described in Japan, characterizing a distinct group with a worse evolution.

  19. Medicamentos que podem induzir prolongamento do intervalo QT utilizados por idosos em domicílio

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    Josiane Macêdo Martins

    2015-10-01

    cardiac death. The objective of this study was to identify drugs used by elderly at home which may induce QTi prolongation. This is a quantitative, retrospective, descriptive, exploratory study conducted in a teaching hospital. A total of 190 elderly with information on the use of medications at home available in medical records were included in the study. The median age was 69.5 years, and 99 (52.1 % were female. The median number of medications used per patient at home was 4.0. A variety of 159 drugs were identified including 23(14.5% that may induce QTi prolongation. Among the 39 elderly (20.5% using drugs that may induce QTi prolongation, the most frequent were: amiodarone, amitriptyline, nortriptyline, citalopram and fluoxetine. Hypertension was the most frequent risk factor for QTi prolongation. The use of these drugs and the presence of risk factors place the elderly at increased risk for developing torsade de pointes. The identification of drugs that may induce QTi prolongation, drug-drug interactions and clinical conditions that may lead to this adverse effect reinforces the need for actions to ensure the drug safety in the elderly population and to avoid serious adverse events.Keywords: QT interval prolongation. Drugs. Elderly. Torsades de pointes.

  20. AL Amyloidosis

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    Desport Estelle

    2012-08-01

    /or immunofluorescence. Due to the systemic nature of the disease, non-invasive biopsies such as abdominal fat aspiration should be considered before taking biopsies from involved organs, in order to reduce the risk of bleeding complications. Differential diagnosis Systemic AL amyloidosis should be distinguished from other diseases related to deposition of monoclonal LC, and from other forms of systemic amyloidosis. When pathological studies have failed to identify the nature of amyloid deposits, genetic studies should be performed to diagnose hereditary amyloidosis. Management Treatment of AL amyloidosis is based on chemotherapy, aimed at controlling the underlying plasma clone that produces amyloidogenic LC. The hematological response should be carefully checked by serial measurements of serum free LC. The association of an alkylating agent with high-dose dexamethasone has proven to be effective in two thirds of patients and is considered as the current reference treatment. New agents used in the treatment of multiple myeloma are under investigation and appear to increase hematological response rates. Symptomatic measures and supportive care is necessary in patients with organ failure. Noticeably, usual treatments for cardiac failure (i.e. calcium inhibitors, β-blockers, angiotensin converting enzyme inhibitors are inefficient or even dangerous in patients with amyloid heart disease, that should be managed using diuretics. Amiodarone and pace maker implantation should be considered in patients with rhythm or conduction abnormalities. In selected cases, heart and kidney transplantation may be associated with prolonged patient and graft survival. Prognosis Survival in AL amyloidosis depends on the spectrum of organ involvement (amyloid heart disease being the main prognosis factor, the severity of individual organs involved and haematological response to treatment.

  1. Efficacy of posterior pericardiotomy in prevention of atrial fibrillation and pericardial effusion after aortic valve replacement: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    V. I. Kaleda

    2017-07-01

    Full Text Available Aim. Postoperative atrial fibrillation is one of the most frequent complications in cardiac surgery. The aim of this trial was to evaluate the effectiveness of posterior pericardiotomy in the prevention of postoperative atrial fibrillation and pericardial effusion in patients undergoing isolated primary aortic valve replacement.Methods. The trial was approved by the local ethics committee. It included adult patients under 70 y.o. who had signed the informed consent for participation in the study and who were planned to undergo isolated primary aortic valve replacement. Exclusion criteria were a history of atrial fibrillation, hyperthyroidism, amiodarone intake, severe chronic obstructive pulmonary disease, left ventricle ejection fraction less than 30%, the size of the left atrium exceeding 50 mm, active infective endocarditis, the presence of adhesions in the pericardium and/or left pleural cavity and mini-sternotomy. From October 2013 to April 2015 607 patients in our clinic underwent different aortic valve procedures. 507 patients were excluded from the study because of the inclusion and exclusion criteria. The remaining 100 patients were randomized into two groups: 49 patients underwent posterior pericardiotomy and 51 patients made up the control group. In both groups the frequency of postoperative atrial fibrillation, pericardial effusion greater than 5 mm, surgery-discharge time, as well as posterior-pericardiotomy-related complications were studied. Trial number: ISRCTN11129539.Results. There were no deaths, stroke or cardiac tamponade during the postoperative stay. Neither were there any complications associated with the performance of posterior pericardiotomy. The incidence of atrial fibrillation, pericardial effusion and average duration of the postoperative stay were similar in both groups: 16% in posterior pericardiotomy group vs 14% in the control group (p=0.71, 10% in posterior pericardiotomy group vs 12% in the control group (p=0

  2. Measurement of Regional and Global Pulmonary Clearance of 99mTc-DTPA (Demethylamitriptylene-Acetate): An Index of Alveolar Epithelial Permeability

    International Nuclear Information System (INIS)

    Vaskova, Olivija

    1996-01-01

    normals reported by many authors. Standardizing the procedures and establishing the normal range we started to use already proven method in different groups of subjects exposed to harmful agents supposed that alter epithelial integrity. Increased lung clearance of inhaled aerosols were obtained in non-symptomatic smokers, asbestosis suffering patients, and in non-smokers exposed to asbestos with normal lung ventilation studies. Faster clearance was also found in the patients with chronic renal failure on regular haemodialysis program using bio incompatible membrane, longer than 5 years. At the same time normal values were obtained in the group on short term haemodialysis. Abnormal clearance rate was shown in patients with malignant disease, exposed to external and internal lung radiation, and in subjects on long term amiodarone treatment, as well. In patients with cardiac heart failure and lung edema, and first stage of sarcoidosis, lung clearance was normal. It remains now as further challenge comparison of there values with some other investigations, expectantly it would contribute in elucidation of different mechanisms in pulmonary pathology. Assessment of 99m Tc-DTPA lung clearance is a very attractive method, non-invasive, cheap, and widely available. Until now there is no an other alternative procedure that would be able to give us more information about epithelial permeability. (Author)

  3. Tratamento cirúrgico da fibrilação atrial: procedimento do "labirinto": experiência inicial Surgical treatment of atrial fibrillation with "maze" procedure: initial experience

    Directory of Open Access Journals (Sweden)

    Adib D Jatene

    1992-06-01

    complicações infecciosas. Os pacientes restantes obtiveram alta hospitalar sem drogas antiarrítmicas. Em um período de um a dez meses (M = 5,4, os pacientes estão assintomáticos e o Holter mostra presença de ritmo atrial irregular permanente (com FC média de 70 a 80 bpm com condução AV preservada; o ecodoppler mostra presença de contração atrial eficiente. Não houve recorrências de FA e nenhum dos pacientes. Em conclusão, podemos admitir que, a curto prazo, a técnica do "labirinto" na FA em reumáticos restaurou a contração atrial organizada e controlou a FC. Assim, pode contribuir para redução de fenômenos trombo-embólicos. Maior número de pacientes deve ser observado durante tempo prolongado para avaliação da eficácia do procedimento.The "maze" procedure for surgical treatment of chronic atrial fibrillation (AF described by Cox was performed in 9 patients from July 91 to May 92; 7 were female and the ages range from 37 to 63y (51,4y. Eight patients had surgical rheumatic valve disfunction (mitral stenosis in 6; mitral double disfunction in 2 being 1 with associated tricuspid regurgitation and 1 had recurrent paroxicistic AF with no valve disfunction. Surgical treatment was performed following the technique described by Cox and the surgery was completed with 6 mitral comissurotomies and 2 mitral valve replacements. Three patients had left atrial thrombosis. There were no immediate deaths and 1 patient died in the 45th day with infeccious complications. The first patient required reoperation for bleeding review. Second and 3rd patients presented transitory atrial tachycardia in 3rd and 5th day, controlled with intravenous amiodarone. No other complications were observed. In a mean follow up period of 5,4m (1 to 10 m, all patients were in regular atrial rhythm without antiarrhythmic drugs. Effective atrial contraction was demonstrated by ECHO in all patients and no one returned to AF. In conclusion, this initial follow up showed good results in

  4. 2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients: pediatric basic life support.

    Science.gov (United States)

    2006-05-01

    providers. Cuffed endotracheal tubes may be used in infants (except newborns) and children in in-hospital settings provided that cuff inflation pressure is kept 20 kg who have a perfusing rhythm. Correct placement must be verified when the tube is inserted, during transport, and whenever the patient is moved. During CPR with an advanced airway in place, rescuers will no longer perform "cycles" of CPR. Instead, the rescuer performing chest compressions will perform them continuously at a rate of 100/minute without pauses for ventilation. The rescuer providing ventilation will deliver 8 to 10 breaths per minute (1 breath approximately every 6-8 seconds). Timing of 1 shock, CPR, and drug administration during pulseless arrest has changed and now is identical to that for advanced cardiac life support. Routine use of high-dose epinephrine is not recommended. Lidocaine is de-emphasized, but it can be used for treatment of ventricular fibrillation/pulseless ventricular tachycardia if amiodarone is not available. Induced hypothermia (32-34 degrees C for 12-24 hours) may be considered if the child remains comatose after resuscitation. Indications for the use of inodilators are mentioned in the postresuscitation section. Termination of resuscitative efforts is discussed. It is noted that intact survival has been reported following prolonged resuscitation and absence of spontaneous circulation despite 2 doses of epinephrine. The following are the major neonatal resuscitation changes in the 2005 guidelines: Supplementary oxygen is recommended whenever positive-pressure ventilation is indicated for resuscitation; free-flow oxygen should be administered to infants who are breathing but have central cyanosis. Although the standard approach to resuscitation is to use 100% oxygen, it is reasonable to begin resuscitation with an oxygen concentration of less than 100% or to start with no supplementary oxygen (ie, start with room air). If the clinician begins resuscitation with room air, it is

  5. Administração inadvertida de 4 mg de morfina por via subaracnóidea: relato de caso Administración inadvertida de 4 mg de morfina por vía subaracnoidea: relato de caso Accidental subarachnoid administration of 4 mg of morphine: case report

    Directory of Open Access Journals (Sweden)

    Bruno Salomé de Morais

    2008-04-01

    sus potenciales efectos adversos.BACKGROUND AND OBJECTIVES: The subarachnoid administration of morphine is a well-established anesthetic technique of postoperative analgesia due to its efficacy, safety and low cost. The objective of this paper was to report the accidental subarachnoid administration of 4 mg of morphine complicated by atrial fibrillation after administration of naloxone. CASE REPORT: A 45-year old male patient with 75 kg, 1.72 m, physical status ASA II, hypertensive, was scheduled for reconstruction of the anterior cruciate ligament of the left knee. After spinal anesthesia, it was noticed that the vial of morphine had been changed resulting in the accidental subarachnoid administration of 4 mg of morphine (0.4 mL of the 10 mg vial. Respiratory rate varied from 12 to 16 bpm and the patient remained hemodynamically stable without intraoperative complaints. Thirty minutes after admission to the post-anesthesia recovery unit the patient developed vomiting and diaphoresis being treated with 0.4 mg of naloxone followed by continuous infusion of 0.2 mg.h-1 until the symptoms had subsided. Continuous naloxone infusion was maintained in the Intensive Care Unit (ICU, where blood pressure, heart rate, respiratory rate and oxygen saturation were monitored as well as the presence of nausea, pruritus, vomiting, sedation, pain and urinary retention. Two hours after arriving at the ICU the patient developed acute atrial fibrillation without hemodynamic instability. Sinus rhythm was reestablished after the administration of 150 mg of amiodarone and discontinuation of the naloxone infusion. During the following 18 hours the patient remained hemodynamically stable and did not experience any other intercurrence until his discharge from the hospital. CONCLUSIONS: The present report is an alert for the risk of inadvertently switching of drugs during anesthesia, stressing the importance of referring patients being treated for opiate overdose to the ICU, due to the potential

  6. Knowledge about Ultraviolet Radiation Hazards and Tanning Behavior of Cosmetology and Medical Students.

    Science.gov (United States)

    Zuba, Ewelina Bogumiła; Francuzik, Wojciech; Malicki, Przemysław; Osmola-Mańkowska, Agnieszka; Jenerowicz, Dorota

    2016-04-01

    students reported lower incidence of sunscreen use (83.78% vs. 97.39%; P=0.0019). The age of the first tanning studio visit was also lower for cosmetology students (mean = 16.5 years) than medical students (mean = 17.2 years), (P=0.0290). Figure 1 illustrates the frequency of student tanning studio visits; the difference between groups was significant (P=0.0308). Skin cancers, dysplastic nevi syndrome, and precancerous lesions were reported in the family history by 19 students (10.00%). 12 of those students (63.16%) were also tanning salons users. 85 students (44.74%) reported a history of a sunburn in their childhood and over half of them continue visiting tanning salons. Some American (5) and French (6) studies assessed medical student knowledge and behaviors concerning sun risk and its prevention. The results of these studies indicated that medical school students did not have a satisfactory awareness about sun risk hazards. The French evaluation showed medical student knowledge was comparable to that of the French general population. Studies evaluating Polish student knowledge (7-9) showed ignorance of the term Fitzpatrick's skin phototype. We emphasize this because patients with phototype 1 and 2 are more susceptible to the development of skin cancers (10) and ignorance in this matter may be dangerous. UV rays may promote drug-induced photosensitivity reactions such as phototoxicity and photoallergy (1), with the most common causes being: non-steroidal anti-inflammatory agents (ketoprofen, ibuprofen, piroxicam, diclofenac), cardiovascular drugs (furosemid, amiodarone, thiazides), antibiotics (tetracyclines, ciprofloxacine, sulfonamides), psoralens, and oral contraceptives (11). Our study found deficient knowledge about drugs which may trigger photosensitivity reactions. Cosmetology students reported significantly more risky tanning behavior but did better in knowledge checking questions, which may be explained by their personal interest in this subject or by

  7. Proarrhythmic and antiarrhythmic effects of multiple ion channel inhibitors modulated by the late sodium current%多离子通道阻滞剂抗心律失常与致心律失常机制中晚钠电流的作用

    Institute of Scientific and Technical Information of China (English)

    任璐; 褚延鹏; 于善栋; 吴林

    2016-01-01

    rabbit hearts were isolated and perfused in Langendorff mode.Hearts were paced at a rate of 1 Hz after themo-ablation of AV node.Monophasic action potential(MAP)from the left ventricular epicardium and ECG signals were recorded in normal hearts and in hearts pretreated with an INaL enhancer ATX-Ⅱ before and after exposure of increasing concentrations of dronedarone(DRON,1 nmol/L-10 μmol/L),amiodarone(AMIO,1 nmol/L-10 μmol/L)and ranolazine(RAN,0.1-100 μmol/L)in cumulative concentration manners.Results DRON,AMIO and RAN caused concentrationdependent "monotonic" prolongations of MAPD90(n =8,P<0.05).AMIO alone prolonged MAPD90 at the concentration of 0.01 μmol/L and shortened MAPD90 at the concentration of 10 μmol/L(n =10,P<0.05).However,in the presence of 3 nmol/L ATX-Ⅱ,a stepwise increase in the concentrations of DRON and AMIO was associated with biphasic responses.DRON and AMIO significantly increased MAPD90 at concentrations of 0.1 μmoL/L and 0.03 μmol/L(n =4 and 12,P<0.05),inducing TdP in 75.0% and 83.3% hearts,respectively.But they decreased MAPD90 at higher concentrations and suppressed arrhythmias.When hearts were pretreated with 1 nmol/L ATX-Ⅱ,the prolongation of MAPD90 by RAN was only(43±14)ms(n=6,P<0.05),which was lower than that in hearts treated with RAN alone.When hearts were pretreated with 3 nmol/L ATX-Ⅱ,RANsignificantly shortened MAPD90(n=11,P<0.05).No arrhythmia was observed in hearts treated with RAN.Conclusions The effects of multichannel blocking drugs on MAPD depend on the relative concentration of suppressing IKr and late INa.These drugs prolong MAPD and may cause arrhythmias at lower concentration of inhibiting IKr,while shorten MAPD and eliminate arrhythmic activities at concentration when late INa was suppressed.