Toxicidad pulmonar por amiodarona. No olvidemos lo aprendido / Pulmonary toxicity by amiodarone. Let's not forget what we learned

La toxicidad pulmonar es un efecto adverso poco frecuente de la amiodarona cuyo diagnóstico es una tarea complicada ya que debe tenerse una alta sospecha clínica y descartar otras patologías que pueden confundirse con este proceso. Es importante que el diagnóstico sea precoz para poder instaurar un tratamiento temprano y evitar la progresión a fibrosis pulmonar. Presentamos un caso que manifiesta la importancia de un diagnóstico preciso y la buena evolución del mismo tras la retirada del fármaco y la instauración de tratamiento. (AU)

Pulmonary toxicity is a rare adverse effect of amiodarone, the diagnosis of which is a complicated task since a high clinical suspicion must be maintained and other pathologies that may be confused with this process must be ruled out. It is important that the diagnosis is early to be able to establish early treatmentand avoid progression to pulmonary fibrosis. We present a case that shows the importance of an accurate diagnosis and its good evolution after drug withdrawal and treatment initiation. (AU)

Manejo anestésico de una tormenta tiroidea en un paciente afecto de ataxia de Friederich. A propósito de un caso / Anaesthetic management of thyroid storm in a patient with Friederich's ataxia. A case report

Paciente de 26 años afecto de ataxia de Friederich con una miocardiopatía hipertrófica no obstructiva sometido a una tiroidectomía total por una tirotoxicosis secundaria a amiodarona persistente (a pesar de elevadas dosis de antitiroideos y corticoides), que intraoperatoriamente presentó un episodio sugestivo de tormenta tiroidea.La tormenta tiroidea es una urgencia endocrinológica que asocia una elevada morbimortalidad. Para mejorar la supervivencia es de vital importancia un diagnóstico temprano y un tratamiento precoz que incluya: un tratamiento sintomático, el tratamiento de las manifestaciones cardiovasculares, neurológicas y/o hepáticas y de la tirotoxicosis, así como suprimir o evitar estímulos desencadenantes y practicar un tratamiento definitivo.(AU)

A 26-year-old patient with Friederich's ataxia with hypertrophic obstructive cardiomyopathy undergoing a total thyroidectomy due to persistent amiodarone-induced thyrotoxicosis (despite high doses of antithyroid drugs and corticosteroids), presented an intraoperative episode suggestive of thyroid storm.Thyroid storm is an endocrine emergency that is associated with high morbimortality. Early diagnosis and treatment, which is of vital importance to improve survival. Treatment includes: symptomatic treatment, treatment of cardiovascular, neurological, and/or hepatic manifestations and thyrotoxicosis, measures to suppress or avoid triggering stimuli, and definitive treatment.(AU)

Anaesthetic management of thyroid storm in a patient with Friederich's ataxia. A case report.

A 26-year-old patient with Friederich's ataxia with hypertrophic obstructive cardiomyopathy undergoing total thyroidectomy due to persistent amiodarone-induced thyrotoxicosis (despite high doses of antithyroid drugs and corticosteroids), presented an intraoperative episode suggestive of thyroid storm. Thyroid storm is an endocrine emergency that is associated with high morbidity and mortality. Early diagnosis and treatment, which is of vital importance to improve survival, includes symptomatic treatment, treatment of cardiovascular, neurological, and/or hepatic manifestations and thyrotoxicosis, measures to suppress or avoid triggering stimuli, and definitive treatment.

Resultados del programa de cribado de enfermedad de Fabry en pacientes con córnea verticillata en el Hospital Universitario de Navarra / Results of the screening program for Fabry disease in patients with cornea verticillata at the University Hospital of Navarre

Introducción La cornea verticillata (CV) o queratopatía vortex se caracteriza por la presencia de depósitos en forma de espiral en el epitelio corneal. Las causas más frecuentes son los fármacos antipalúdicos y la amiodarona, y dentro de las causas sistémicas la enfermedad de Fabry (EF). Material y métodos Se realiza un estudio descriptivo prospectivo multidisciplinar en un centro de tercer nivel y de referencia en la Comunidad Foral de Navarra, tras la implementación de un programa de despistaje de la EF en los pacientes atendidos en consultas del servicio de oftalmología que eran diagnosticados de CV y posteriormente fueron remitidos a la consulta de enfermedades minoritarias del servicio de Medicina Interna del Hospital Universitario de Navarra para la realización del estudio de la EF. Resultados Dos mujeres y 4 varones, con una edad media de 76,8 años, se diagnosticaron de CV, de un total de 17.280 pacientes valorados en consultas externas por 3 especialistas de oftalmología durante el periodo de abril de 2018 a abril de 2020. Una paciente falleció antes de realizar el estudio de despistaje y en ningún paciente se diagnosticó la EF. Conclusiones A pesar de que el programa de despistaje de la EF en pacientes con CV en el Hospital Universitario de Navarra no confirmó ningún caso con EF, los especialistas en oftalmología deben tener en cuenta el posible diagnóstico de la EF en aquellos pacientes con CV en sus consultas rutinarias (AU)

Introduction Cornea verticillata (CV) or vortex keratopathy is characterized by the presence of spiral-shaped deposits in the corneal epithelium. The most frequent causes are antimalarial drugs and amiodarone and, among systemic causes, Fabry disease (FD). Material and methods A multidisciplinary, prospective, descriptive study was conducted in a tertiary reference center in Spain's Autonomous Community of Navarre after the implementation of a FD screening program for patients attended to in the Ophthalmology Department. The study analyzed those diagnosed with CV, who were subsequently referred to the rare disease clinic of the University Hospital of Navarre's Internal Medicine Department for an FD study. Results Two women and four men with a mean age of 76.8 years were diagnosed with CV out of a total of 17,280 patients evaluated in outpatient consultations by three ophthalmology specialists during the period from April 2018 to April 2020. One patient died before performing the screening study and no patients were diagnosed with FD. Conclusions Despite the fact that the University Hospital of Navarre's FD screening program for patients with CV did not confirm any cases of FD, ophthalmology specialists should consider the possible diagnosis of FD in patients with CV in their routine consultations (AU)

Results of the screening program for Fabry disease in patients with cornea verticillata at the University Hospital of Navarre.

INTRODUCTION: Cornea verticillata (CV) or vortex keratopathy is characterized by the presence of spiral-shaped deposits in the corneal epithelium. The most frequent causes are antimalarial drugs and amiodarone and, among systemic causes, Fabry disease (FD). MATERIAL AND METHODS: A multidisciplinary, prospective, descriptive study was conducted in a tertiary reference center in Spain's Autonomous Community of Navarre after the implementation of a FD screening program for patients attended to in the Ophthalmology Department. The study analyzed those diagnosed with CV, who were subsequently referred to the rare disease clinic of the University Hospital of Navarre's Internal Medicine Department for an FD study. RESULTS: Two women and four men with a mean age of 76.8 years were diagnosed with CV out of a total of 17,280 patients evaluated in outpatient consultations by three ophthalmology specialists during the period from April 2018 to April 2020. One patient died before performing the screening study and no patients were diagnosed with FD. CONCLUSIONS: Despite the fact that the University Hospital of Navarre's FD screening program for patients with CV did not confirm any cases of FD, ophthalmology specialists should consider the possible diagnosis of FD in patients with CV in their routine consultations.

Is amiodarone still a reasonable therapeutic option for rhythm control in atrial fibrillation?

Amiodarone is the most potent antiarrhythmic drug available and is commonly prescribed to treat and prevent not only life-threatening ventricular arrhythmias but also atrial fibrillation (AF). The latest European Society of Cardiology AF guidelines state that amiodarone is recommended for long-term rhythm control in all AF patients but that other antiarrhythmic drugs should be considered first whenever possible, due to its extracardiac toxicity. In patients without significant or with only minimal structural heart disease, amiodarone is not listed as a possibility in their therapeutic scheme. Still, amiodarone is widely and liberally used, and is the most prescribed antiarrhythmic drug for patients with AF despite its high toxicity profile. Non-cardiovascular death was more frequent with amiodarone treatment than with a rate control strategy in AFFIRM, while meta-analyses suggest an association between amiodarone use in patients without structural heart disease and increased non-cardiovascular mortality. Severe or even fatal outcomes due to amiodarone may occur years after treatment initiation and are often not acknowledged by the prescribing physician, who may no longer be following the patient. The lack of widely accepted diagnostic criteria and symptom definitions may lead to underestimation of the incidence of severe side effects and of its toxicity. Unlike the underestimated risk of toxicity with amiodarone, severe complications associated with catheter ablation are usually directly ascribed to the treatment even by non-medical personnel, possibly resulting in overestimation of risks. This brief review will address the issue of amiodarone overuse and the frequent underestimation of its toxicity, while suggesting scenarios in which its use is entirely reasonable, and compare it with catheter ablation.

Prevalencia de medicamentos que prolongan el intervalo QT en salas de cardiología de un hospital de alta complejidad / Drug induced prolongation of Q-T interval in cardiology wards

Resumen: Antecedentes: La prevalencia del síndrome del QT largo (SQTL) producido por medicamentos es una de las reacciones adversas que en el último tiempo ha aumentado en prevalencia y mortalidad. No solamente ocurre con el uso de medicamentos para el tratamiento de cardiopatías, sino también en medicamentos con otra acción terapéutica. Objetivo: Evaluar la prevalencia del síndrome del SQTL inducido por medicamentos en salas de cardiología de un hospital de alta complejidad. Métodos: Estudio prospectivo, de tipo descriptivo y de corte transversal en 36 pacientes cardiópatas, que consistió en evaluar la frecuencia del uso de medicamentos que son capaces de producir un SQTL y la prevalencia de este efecto adverso. Los datos clínicos se recolectaron de la ficha clínica y de entrevistas con los pacientes. Se efectuó un seguimiento para detectar la aparición de prolongación del intervalo QT. Los resultados obtenidos fueron presentados por medio de estadística descriptiva (programa estadístico Statgraphics Centurion, versión XVI). No hubo estadística inferencial dada la ausencia de un grupo control. Resultados: 41,7%, de los 36 pacientes presentaron SQTL que en 86,7% de ellos fue asociado a un medicamento. Los medicamentos más frecuentemente asociados a este efecto adverso fueron Amiodarona (38,5%) y Ondansetrón (23,1%), y el factor de riesgo mayormente involucrado fue el sexo femenino (61,5%). Conclusión: Existió una alta prevalencia del uso de medicamentos que producen un SQTL, destacándose que existen medicamentos utilizados para otras patologías que también pueden producirlo.

Abstract: Background: The prevalence of the Long QT interval syndrome (LQTS) associated to drugs has increased en the last decades along with an increased mortality due to this condition. It occurs not only with drugs used to treat cardiac disease but also to other drugs. Aim: To evaluate the prevalence of drug induced LQTS in cardiology wards of a high complexity hospital. Method: This is a prospective, descriptive and cross sectional study in 36 patients with heart disease. The use of drugs known to affect the QT interval along with the frequency of LGTS were evaluated. Clincal data was obtained from clinical records and personal interviews. Patients were followed for the appearance of LQTS. Descriptive were used to present the results. No inferential statistics were used as no control group was involved (Statgraphics Centurion, version XVI). Results: 41.7% of the 36 patients developed LQTS and the association with drugs was present in 86.7% of them. The drugs most commonly identified were amiodarone (38.5%) and ondansetron (23.1%) of patients. Female geneder was the most common associated condition (61.5%). Conclusion: There was a frequent use of drugs known to produce LQTS, but other drugs may also be associated int this group of patients with heart disease admitted to intensive or intermediate care facilities.

Amiodarona: fortalezas y debilidades / Amiodarone strengths and weaknesses

Prescritos en la práctica clínica por su eficacia. En su inicio se utilizó para tratar la angina de pecho. hoy día es usado para el tratamiento de cualquier forma de taquicardia. Objetivo: Reconocer la prescripción de la Amiodarona y sus efectos adversos. Métodos: Se realizó una revisión descriptiva en las bases de datos de Lilacs donde se encontraron 18 artículos y en PubMed/Medline (Mesh) 206 artículos, de los cuales se le aplicaron los criterios de inclusión a 51 artículos. Conclusiones: La amiodarona es uno de los antiarrítmicos más utilizados para el tratamiento de las arritmias, su variedad de efectos adversos y toxicidad es conocida, por tanto, los pacientes en tratamiento ameritan un minucioso monitoreo(AU)

Introduction: Amiodarone is one of the most prescribed antiarrhythmic drugs in clinical practice due to its efficacy. Initially it was used to treat angina pectoris, however, today it is used to treat any form of tachycardia. Objective: To identify the prescription of amiodarone and its adverse effects. Methods: A descriptive review was carried out in Lilacs databases where 18 articles were found and in PubMed/Medline (Mesh) 206 articles were retrieved. The inclusion criteria were applied to 51 articles. Conclusions: Amiodarone is one of the most widely used antiarrhythmic drugs for the treatment of arrhythmias, its variety of adverse effects and toxicity is known, therefore, patients undergoing treatment justify careful monitoring(AU)

Tireotoxicose induzida pela amiodarona - revisão de literatura e atualização clínica / Amiodarone-induced thyrotoxicosis - literature review & clinical update

Resumo A amiodarona é amplamente utilizada no tratamento de arritmias atriais e ventriculares, porém devido sua alta concentração de iodo, o uso crônico da droga pode induzir distúrbios tireoidianos. A tireotoxicose induzida pela amiodarona (TIA) pode descompensar e exacerbar anormalidades cardíacas subjacentes, provocando aumento da morbidade e mortalidade, principalmente em pacientes com fração de ejeção do ventrículo esquerdo <30%. Os casos de TIA são classificados em dois subtipos que direcionam a conduta terapêutica. Os riscos e benefícios de manter a amiodarona devem ser avaliados de maneira individualizada, e a decisão de continuar ou suspender a droga deve ser tomada conjuntamente por cardiologistas e endocrinologistas. O tratamento de TIA tipo 1 é semelhante ao do hipertireoidismo espontâneo, sendo indicado o uso de drogas antitireoidianas (metimazol e propiltiouracil) em doses elevadas. A TIA tipo 1 mostra-se mais complicada, pois apresenta proporcionalmente maiores números de recorrências ou até mesmo a não remissão do quadro, sendo recomendado o tratamento definitivo (tireoidectomia total ou radioiodo). TIA tipo 2 é geralmente autolimitada, mas devido a elevada mortalidade associada a tireotoxicose em pacientes cardiopatas, o tratamento deve ser instituído para que o eutireoidismo seja atingido mais rapidamente. Em casos bem definidos de TIA tipo 2, o tratamento com corticosteroides é mais efetivo do que o tratamento com drogas antitireoidianas. Em casos graves, independentemente do subtipo, a restauração imediata do eutiroidismo por meio da tireoidectomia total deve ser considerada antes que o paciente evolua com piora clínica excessiva, pois a demora na indicação da cirurgia está associada ao aumento da mortalidade.

Abstract Amiodarone is widely used in treating atrial and ventricular arrhythmias; however, due to its high iodine concentration, the chronic use of the drug can induce thyroid disorders. Amiodarone-induced thyrotoxicosis (AIT) can decompensate and exacerbate underlying cardiac abnormalities, leading to increased morbidity and mortality, especially in patients with left ventricular ejection fraction <30%. AIT cases are classified into two subtypes that guide therapeutic management. The risks and benefits of maintaining the amiodarone must be evaluated individually, and the therapeutic decision should be taken jointly by cardiologists and endocrinologists. Type 1 AIT treatment is similar to that of spontaneous hyperthyroidism, using antithyroid drugs (methimazole and propylthiouracil) at high doses. Type 1 AIT is more complicated since it has proportionally higher recurrences or even non-remission, and definitive treatment is recommended (total thyroidectomy or radioiodine). Type 2 AIT is generally self-limited, yet due to the high mortality associated with thyrotoxicosis in cardiac patients, the treatment should be implemented for faster achievement of euthyroidism. Furthermore, in well-defined cases of type 2 AIT, the treatment with corticosteroids is more effective than treatment with antithyroid drugs. In severe cases, regardless of subtype, immediate restoration of euthyroidism through total thyroidectomy should be considered before the patient progresses to excessive clinical deterioration, as delayed surgery indication is associated with increased mortality.

Silymarin's defensive role against hepatotoxicity induced by amiodarone in albino rats / El efecto defensivo de silimarin contra la hepatotoxicidad inducida por amiodarona en ratas albinas

SUMMARY: Amiodarone (AMD), an orally powerful antidysrhythmic medication that has caused hepatotoxicity on long-term administration, is commonly used across the world. Silymarin ameliorative effects (SLM); this research elucidated the magnitude of the damage to the liver tissue in AMD. We divided 24 albino rats evenly into four groups given daily doses by gastric tube for eight weeks as follows; the 1st group acted as a control group; the 2nd group received SLM; the 3rd group received AMD; and the 4th group received AMD parallel to SLM. Liver tissues prepared for light, electron microscopic and serum samples screened for biomarkers (I)liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); (II) oxidative and antioxidant stress, malondialdehyde (MDA) and superoxide dismutase (SOD); and (III) inflammatory markers, tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6). The findings showed that AMD caused hepatic histological changes that included congestion of the blood vessels, leucocytic infiltration and cytoplasmic vacuolation. Ultrastructural degeneration of the mitochondria, endoplasmic reticulum swelling, nuclear pyknosis and increased fat droplets and lysosomes were observed. The biochemical findings showed an increase in the AMD group's ALT and AST activities. The group of rats treated with AMD and SLM, increased the improvements in histology and ultrastructure, while the ALT and AST levels were reduced. Our findings collectively agreed that SLM has a protective impact on AMD hepatotoxicity which can be due to its antioxidant properties.

RESUMEN: La amiodarona (AMD) es un fuerte medicamento antiarrítmico administrado por vía oral que ha causado hepatotoxicidad en la administración a largo plazo utilizado con frecuencia en todo el mundo. Efectos de mejora de la silimarina (SLM); esta investigación analizó la magnitud del daño al tejido hepático en la DMAE. Dividimos 24 ratas albinas de manera uniforme en cuatro grupos que recibieron dosis diarias por sonda gástrica durante ocho semanas de la siguiente manera; el primer grupo fue designado como grupo control; el segundo grupo recibió SLM; el tercer grupo recibió AMD; y el cuarto grupo recibió AMD en paralelo a SLM. Se prepararon tejidos hepáticos para muestras de suero, microscopía de luz y electrónica y se analizaron para biomarcadores (I) enzimas de daño hepático, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST); (II) estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (III) marcadores inflamatorios, factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6). Los hallazgos mostraron que la DMAE genera cambios histológicos hepáticos que incluyen congestión de los vasos sanguíneos, infiltración leucocítica y vacuolación citoplásmica. Se observó una degeneración ultraestructural de las mitocondrias, aumento del retículo endoplásmico, picnosis nuclear y aumento de gotitas de grasa y lisosomas. Los hallazgos bioquímicos mostraron un aumento en las actividades de ALT y AST del grupo AMD. El grupo de ratas tratadas con AMD y SLM, aumentó las mejoras en histología y ultraestructura, mientras que se redujeron los niveles de ALT y AST. Nuestros hallazgos coincidieron colectivamente en que SLM tiene un impacto protector sobre la hepatotoxicidad de AMD debido a sus propiedades antioxidantes.

Pathological thyroid findings in amiodarone-induced thyrotoxicosis.

Amiodarone (AMD) is a class III antiarrhythmic drug whose chronic or high dosage administration alters the tests of thyroid function. AMD is also associated with hypothyroidism or thyrotoxicosis. Total thyroidectomy is an efficient treatment of AMD-induced thyrotoxicosis in cases resistant to medical therapy, worsening of cardiac function and/or severe thyrotoxicosis. Although AMD is a widely used drug, its pathological consequences are not well known. We describe the pathological findings in the thyroid gland of a patient who underwent total thyroidectomy due to AMD-induced thyrotoxicosis. The surgical specimen was macroscopically normal, but histologically showed multiple follicles totally or partially invaded by clear vacuolated (foamy) histiocytes, sometimes multinucleated. Loss of thyrocytes, breaks in the follicular basal membrane and stromal fibrosis could also be appreciated but no lymphocytic infiltrates were found. An awareness of these histopathological features is particularly important for surgical pathologists, especially as there are very few published reports describing these alterations.

Falla hepática subaguda secundaria a hepatotoxicidad severa por medicamentos: reporte de caso / Subacute liver failure secondary to severe drug-related hepatotoxicity: case report

La falla hepática aguda es una patología rara con una mortalidad alta y causas variadas, entre ellas, la hepatotoxicidad secundaria al uso de medicamentos, con un diagnóstico diferencial difícil, en particular en presencia de polifarmacia. Esta patología se asocia con falla orgánica multisistémica que puede hacer necesario el trasplante hepático si no se logra la estabilización del paciente. Se presenta el caso de una mujer de 50 años con un cuadro de 6 semanas de evolución, consistente en dolor en hipocondrio derecho, náuseas e ictericia generalizada, quien presentó falla hepática aguda de tipo subagudo que finalmente requirió trasplante hepático. Se describe el abordaje diagnóstico hacia la identificación de una etiología medicamentosa probable por el uso de amiodarona, con la evolución positiva de la paciente después de 3 años de seguimiento postrasplante.

Acute liver failure is a rare disease with high mortality and a multitude of causes, including drug-induced liver injury, with a difficult differential diagnosis, particularly in the presence of polypharmacy. This pathology is associated with multisystemic organic failure which may require liver transplantation if patient stabilization is not achieved. We present the case of a 50-year-old woman with a 6-week history of right upper quadrant pain, nausea and generalized jaundice, who presented subacute liver failure which ultimately required liver transplantation. We describe the diagnostic approach towards the identification of a probable drug-related cause, due to the use of amiodarone, with a positive outcome for the patient after 3 years of post-transplant follow-up.

Pre-operative embolization of thyroid arteries in a case of refractory amiodarone-induced thyrotoxicosis. Case report / Embolización preoperatoria de las arterias tiroideas en un caso de tirotoxicosis refractaria por amiodarona. Reporte de caso

Abstract Introduction: Amiodarone has become one of the main antiarrhythmic drugs. However, it may cause a wide variety of adverse effects, sometimes severe. Amiodarone-induced thyroid dysfunction is one of the best known problems, resulting in either thyrotoxicosis or hypothyroidism. Case presentation: A patient who, after 2 years of using amiodarone for the control of atrial fibrillation, developed thyrotoxicosis, refractory to conventional medical treatment. To optimize the patient's clinical condition before total thyroidectomy, embolization of thyroid arteries was performed. Conclusion: Embolization of the thyroid arteries as bridge therapy to thyroidectomy is an uncommon alternative in patients with amiodarone-induced hyperthiroidism. However, this treatment was useful to improve our patient's symptoms and to optimize the anesthetic/surgical procedure.

Resumen Introducción: La amiodarona se ha convertido en uno de los principales fármacos empleados en el manejo de las arritmias cardiacas. Sin embargo, puede llegar a presentar una amplia variedad de efectos adversos, en ocasiones graves. La alteración de la función tiroidea es uno de sus problemas más conocidos, que puede causar tanto hipertiroidismo como hipotiroidismo. Presentación del caso: Se presenta el caso de un paciente que, después de recibir durante dos años amiodarona para el control de una fibrilación auricular, desarrolló una tirotoxicosis refractaria al tratamiento médico clásico, por lo que se decidió realizar una embolización de las arterias tiroideas previa a tiroidectomía total, para lograr una optimización preoperatoria de su situación clínica. Conclusión: La embolización de las arterias tiroideas como terapia puente a la tiroidectomía es una alternativa poco empleada en pacientes con hipertiroidismo, más aun si es debido a la administración de amiodarona, con escasos datos publicados en la literatura. En nuestro caso fue de utilidad para mejorar la sintomatología del paciente y optimizar el procedimiento anestésico-quirúrgico.

Amiodarone does not affect brain injury in a rat model of transient forebrain ischemia.

OBJECTIVES: Although amiodarone may cause neurotoxicity that can affect patient outcomes when used during cardiopulmonary resuscitation (CPR), it has been commonly prescribed during CPR. This study investigated the possible neurotoxic effects of amiodarone in a rat model of transient forebrain ischemia. DESIGN: A prospective laboratory animal study was carried out. SETTING: Animal laboratory. MATERIALS: Male Sprague-Dawley rats. INTERVENTION: Eight minutes of forebrain ischemia was induced in rats by bilateral carotid occlusion and hypotension (mean arterial pressure=35mmHg) under isoflurane (1.5%) anesthesia. Amiodarone (0, 50, 100 and 150mg/kg) with saline was injected intraperitoneally 10min after ischemia. Rats given 0mg/kg of amiodarone were used as saline-treated controls. Sham operated rats received no treatment. VARIABLES OF INTEREST: Animals were evaluated neurologically on postoperative days 4-7, and histologically after a one-week recovery period. RESULTS: The greatest improvement in water maze test performance corresponded to the sham operated group (p=0.015 vs. saline-treated controls). No differences in performance were seen in amiodarone-treated rats compared with saline-treated controls. In the control group, 45% of the CA1 hippocampal neurons survived, compared with 78% in the sham operated group (p=0.009). Neuron survival after ischemia in the amiodarone treatment groups (50, 100 and 150mg/kg) (58%, 40% and 36%, respectively) and in the control rats did not differ significantly. CONCLUSIONS: The administration of amiodarone immediately after transient forebrain ischemia did not worsen spatial cognitive function or neuronal survival in the hippocampal CA1 region in rats. The current results must be applied with caution in humans. However, they indicate that the potential neurotoxicity induced by amiodarone during resuscitation after cardiac arrest may be negligible.

Anaphylactic shock versus Kounis syndrome in cardiac surgery: Differential diagnosis. / Shock anafiláctico versus síndrome de Kounis durante el intraoperatorio de cirugía cardiaca: diagnóstico diferencial.

Although Kounis syndrome was described almost 3 decades ago, there has been a notable increase in the reports of cases of acute coronary syndromes developed in the context of allergic reactions, also known as Kounis syndrome. This article discusses the diagnostic possibility in the face of an acute biventricular failure in the course of an anaphylactic reaction during the intra-operative period of a cardiac valve surgery.

Alteraciones endocrinas asociadas al uso medicamentos en el Programa Distrital de Farmacovigilancia de Bogotá durante el periodo 2012 a 2016 / Medication-use related endocrine disruption reported to the local pharmacovigilance program in Bogota, during 2012- 2016 / Alterações endócrinas associadas ao uso de medicamentos no Programa Distrital de Vigilância farmacológica em Bogotá no período 2012-2016

Objetivos. Conocer las reacciones adversas tipo endocrino asociado al uso de medicamentos y reportado al Programa Distrital de Farmacovigilancia de Bogotá durante el periodo 2012 a 2016. Materiales y métodos. Los reportes analizados corresponden al periodo del 1º de enero de 2012 al 31 de diciembre de 2016 del Programa Distrital de Farmacovigilancia. Su análisis se hizo mediante algoritmos de causalidad y por tipo de evento. Resultados. Se analizaron 85 reportes. Uno de ellos relacionado con una sospecha de problema de calidad del medicamento, los otros 84 relaciona-dos con reacciones adversas sobre los cuales se centró la investigación. De los 84 reportes, 36 (42,9 %) corresponden a reacciones adversas a medicamento tipo A y 26 (31 %) a reportes de reacciones adversas a medicamentos de tipo fallo terapéutico. Los principales efectos secundarios a los medicamentos fueron el aumento de los niveles de hormona paratiroidea por uso de cinacalcet en 27 (34,1 %) reportes, seguidas por el síndrome de Cushing relacionado con la administración de prednisolona en 12 (14,1 %), bocio por uso de adalimumab en 12 (14,1 %), hiperprolactinemia por el uso de risperidona en 10 (11,8 %) e hipotiroidismo inducido por amiodarona en 3 (3,4 %). Conclusiones. El desarrollo de estos estudios permite conocer las principales reacciones adversas que se presentan durante el uso habitual de los medicamentos, así como su perfil de seguridad.

Objective. Becoming familiar with medication-use related endocrine disruption reported to the local pharmacovigilance program in Bogotá during 2012-2016.Tools and methods. Analyzed reports are dated between January 1st, 2012 and December 31st, 2016 and were gathered from the Pharmacovigilance Program in Bogotá. The analysis of the said reports was conducted through causality algorithms and event type.Results. Out of 87 analyzed reports, two were not included in the study due to lack of information for its classification in one case and, medication-related problems in another case. 36 reports (42.9 %) were found to have adverse reaction to type A medications, while 26 reports (34.1%) were found to have medication related problem type therapeutic failure. The main medication related problems were associated to the use of Cinacalcet with increased levels of parathormone in 27 out of 87 analyzed reports in this study. Other medication related problems found were: Cushing Syndrome, associated with the use of prednisolone in 12 reports; Goiter associated to the use of adalimumab in 12 reports; Hyperprolactinemia associated to the use of Risperidone in 10 reports and, Hypothyroidism associated to the use of Amiodarone in 3 reports. Conclusions: Carrying out such studies allows for the understanding of the main medication-use problems that are shown during common use of medications, as well as their safety profile.

Objetivo. O objetivo do artigo é conhecer as alterações endócrinas associadas ao uso de medicamentos reportadas pelo Programa Distrital de Vigilância farmacológica em Bogotá. Materiais e métodos. Os reportes analisados correspondem ao período de janeiro de 2012 a dezembro 2016 e a analise foi realizada com algoritmos de causalidade e por tipo de evento. Resultados. Foram analisados 87 reportes, embora no final dois deles foram desconsiderados, um por corresponder a um problema relacionado com o medicamento e o outro por falta de informações para classifica-lo. Encontraram-se 36 (42%) de reportes associados a reações adversas perante os medicamentos tipo A e 26 (31%) de reportes de RAM tipo falho terapêutico. As principais RAM foram por uso de cinacalcet com aumento dos níveis de parathormona em 27 reportes (34%), seguidas de Síndrome de Cushing relacionado com prednisolona em 12 reportes (14,1%), bócio por uso de adalimumab em outros 12 re-portes, hiperprolactinemia por uso de risperidona em 10 casos (11,8%) e hipotiroidismo induzido por amiodarona em 3 casos. Conclusoes. O desenvolvimento destes estudos, permite conhecer as principais reações adversas causadas pelo uso habitual dos medicamentos mesmo como seu perfil de segurança.

Tirotoxicosis inducida por amiodarona (TIA): un reto diagnóstico y terapéutico / Amiodarone-induced thyrotoxicosis (TIA): a diagnostic and therapeutic challenge

Resumen La tirotoxicosis inducida por amiodarona (TIA) se presenta en 5-12% de los pacientes tratados con ese medicamento, tiene el potencial de exacerbar una enfermedad cardiaca, lo que incrementa la morbilidad o mortalidad de los pacientes. Existen 2 tipos de TIA, con mecanismos fisiopatológicos diferentes; es importante distinguir entre ellos ya que el tratamiento es diferente. Sin embargo esta distinción en ocasiones es complicada. Se presenta el caso de una paciente de 81 años con antecedente de leucemia mieloide aguda, que cursó con aumento de volumen de cuello 48 h después de haber sido egresada por un cuadro de fibrilación auricular (FA) tratada con infusión de amiodarona. Bioquímicamente con tirotoxicosis y reaparición de la FA. Se sospechó de una TIA. Para enfocar el tratamiento es indispensable distinguir entre los 2 tipos de tirotoxicosis inducida por amiodarona. El ultrasonido Doppler y el gammagrama tiroideo pueden ser útiles para establecer el diagnóstico. Se deben considerar las comorbilidades de los pacientes, así como los efectos secundarios al momento de establecer el tratamiento.

Abstract Amiodarone induced thyrotoxicosis (AIT) appears on the 5-12% of patients, it potentially can exacerbate a cardiac illness, leading to an increase in the morbility/mortality of patients. Two types of AIT exist, each one with a different etiology. It is important to distinguish between them to be able to establish a treatment. However, sometimes it can be quite difficult. Case Report: An 81 year-old woman, with a history of acute myelod leukemia, showed up with thyroid enlargement at the ER. She was discharged 48 h earlier, after an atrial fibrillation (AF) episode which was controlled with amiodarone IV infusion. Because the biochemical diagnosis of thyrotoxicosis and reaparition of AF,an AIT was suspected. To be able of distinguishing between the two types of AIT is essential to establish a treatment. The use of a thyroid doppler sonography and a thyroid scintigraphy is helpful. The comorbidities of the patient and the possible side effects should be taken into account when deciding the treatment.

Long QT syndrome secondary to drug interaction between hydroxychloroquine and amiodarone / Síndrome de QT largo secundario a la interacción entre hidroxicloroquina y amiodarona

Abstract: A 67-year-old female patient with a diagnosis of heart failure with preserved ejection fraction secondary to severe mitral regurgitation in treatment with metoprolol, spironolactone, and digoxin. She was diagnosed systemic lupus erythematosus (SLE) because of the presence of arthritis, alopecia, thrombocytopenia, direct positive Coombs +++, positive ANAs 1:1,280 and positive lupus anticoagulant. The rheumatology service indicated hydroxychloroquine 200 mg every 24 hours. She presented atrial fibrillation, and amiodarone was initiated. Two weeks later the patient was admitted because of presyncope, electrocardiogram showed sinus bradycardia with long QT interval. A temporary pacemaker was placed, and hydroxychloroquine and amiodarone suspended. Twenty-four hours later, a new electrocardiogram was taken showing pacemaker rhythm with reduction of the QT interval. After 72 hours the temporary pacemaker was removed and on the fifth day the patient was discharged with an electrocardiogram in sinus rhythm with a corrected QT (Bazett) of 456 miliseconds. The hydroxychloroquine was reinitiated following discharge. She presented another episode of atrial fibrillation, and was treated with amiodarone, hydroxychloroquine was suspended previously, and she did not present prolongation of QT interval. The long QT syndrome was present when amiodarone and hydroxychloroquine interacted.(AU)

Resumen: Paciente femenina de 67 años, con diagnóstico de insuficiencia cardiaca con fracción de expulsión preservada, secundaria a insuficiencia mitral severa, en tratamiento con metoprolol, espironolactona y digoxina. Le fue diagnosticado lupus eritematoso sistémico, debido a la presencia de artritis, alopecia, trombocitopenia, Coombs directo positivo +++, anticuerpos antinucleares positivos 1:1,280 y anticoagulante lúpico positivo. El Servicio de Reumatología indicó hidroxicloroquina 200 mg cada 24 horas. Presentó fibrilación auricular, por lo que se le inició amiodarona. Dos semanas posteriores la paciente es ingresada debido a un episodio de presíncope, se le realizó electrocardiograma que demostró bradicardia sinusal con un intervalo QT prolongado. Se le colocó un marcapasos temporal, además de que se suspendió hidroxicloroquina y amiodarona. Después de 72 horas se retiró el marcapasos, y al quinto día se egresó con un electrocardiograma en ritmo sinusal con el intervalo QT corregido por Bazett de 456 milisegundos. La hidroxicloroquina fue reiniciada al egreso. La paciente presentó otro episodio de fibrilación auricular y fue tratada con amiodarona, previa suspensión de hidroxicloroquina, sin presentar prolongación del intervalo QT. El síndrome de QT largo sólo se presentó con la interacción de amiodarona con hidroxicloroquina.(AU)

LASIK and surface ablation in patients treated with amiodarone. / LASIK y ablación de superficie en pacientes tratados con amiodarona.

OBJECTIVE: To determine the anatomical and functional outcomes of corneal refractive surgery in patients on amiodarone, a drug listed as being contraindicated in patients undergoing this procedure. MATERIAL AND METHODS: A retrospective observational study was conducted on all consecutive patients who took amiodarone and who underwent LASIK or surface ablation from January 2003 to December 2014. Functional (visual and refractive) outcomes are described. RESULTS: A total of 20 patients (33 eyes) were included. No significant intraoperative or postoperative complications were found. CONCLUSIONS: In our experience, LASIK and surface ablation did not produce significant clinical complications in selected patients taking amiodarone. The absolute exclusion of certain systemic medications should be reconsidered.