Terapia de insulina y glucosa para el tratamiento de intoxicación grave con bloqueantes de canales de calcio en pediatría. Reporte de un caso / Insulin/glucose therapy for the treatment of severe calcium channel blocker poisoning in pediatrics. Case report

La intoxicación por bloqueantes de los canales de calcio es un cuadro poco frecuente en la población pediátrica. Los signos y síntomas pueden progresar de forma rápida y llevar al colapso cardiovascular y muerte. El sostén hemodinámico con inotrópicos y vasopresores no suele ser efectivo. La terapia con insulina y glucosa es un complemento eficaz del tratamiento inicial, que está ampliamente estudiado, y se utiliza en diferentes patologías con compromiso hemodinámico. Se presenta el caso de una paciente pediátrica con antecedente de ingestión de dosis altas de amlodipina con fines suicidas, con descompensación hemodinámica refractaria al tratamiento de soporte inotrópico habitual. A partir del tratamiento con insulina y glucosa, se logró la estabilidad hemodinámica, con evolución favorable de la paciente.

Calcium channel blocker poisoning is a rare condition in the pediatric population. Signs and symptoms can be rapidly progressive and lead to cardiovascular collapse and death. Hemodynamic support with inotropics and vasopressors is usually not effective. The insulin/glucose therapy is an effective complement to the initial treatment, which is widely studied and used in different pathologies with hemodynamic compromise. The case of a pediatric patient with a history of high-dose ingestion of amlodipine for suicidal purposes, with hemodynamic decompensation refractory to usual inotropic support treatment, is presented. From the insulin/glucose treatment, hemodynamic stability was achieved with a favorable evolution

Serie de Casos: Intoxicación por Amlodipino / Case Series: Amlodipine Intoxication

Resumen INTRODUCCIÓN: La intoxicación por distintas drogas es una importante causa de morbimortalidad en la edad pediátrica. No obstante, la intoxicación por amlodipino, que es un fármaco dihidropiridinico del grupo de calcioantagonistas ampliamente usado, no se encuentra bien documentada en Ecuador. El tratamiento se basa en implementar medidas para el shock clásico, en conjunto con medidas específicas para este tipo de intoxicación. CASOS CLÍNICOS: Presentamos dos reportes de casos clínicos de pacientes adolescentes ingresadas en unidad de cuidados intensivos pediátricos (UCIP), por intento autolítico mediante ingesta de amlodipino en conjunto con otros fármacos. EVOLUCIÓN: Durante su estancia hospitalaria presentaron cuadros evolutivos distintos. En ambos casos se necesitó manejo con drogas vasoactivas, modificando su dosis de acuerdo a respuesta clínica. En los dos casos se administró gluconato de calcio por horario y otras medidas de soporte descritas en el presente manuscrito. Finalmente, las dos pacientes presentaron buena evolución y fueron dadas de alta, con previa valoración y seguimiento de psicología y psiquiatría. CONCLUSIÓN: La intoxicación por amlodipino ha sido descrita escasamente debido a su baja frecuencia, a esto se añade el poco conocimiento basado en evidencia; motivos que la constituyen como un reto diagnóstico y terapéutico. Destacamos, en base a nuestra experiencia, la importancia de un alto índice de sospecha y de priorizar el inicio de vasopresores sobre la reanimación hídrica. Adicionalmente, recomendamos documentar la dosis exacta de ingesta e indagar sobre el consumo de otros fármacos para clasificar adecuadamente la gravedad de la intoxicación y establecer un plan de tratamiento. Finalmente, la monitorización y evaluación clínica constante y el apoyo de exámenes de laboratorio guiarán la conducta.(au)

BACKGROUND: Drug poisoning is an important cause of morbidity and mortality in pediatric patients. However, amlodipine poisoning, a widely used dihydropyridine calcium chanel blocker, is not fully documented in Ecuador. Treatment consists of classic measures for shock management and specific measures for this type of intoxication. CASE REPORTS: We present two case reports, both of teenage patients admitted into the pediatric intensive care unit for suicide attempt by taking amlodipine and some other drugs. EVOLUTION: During hospital stay, they presented a different evolutionary course. In both cases vasoactive drugs were needed, dosage was modified according to clinical course. Also in both patients, calcium gluconate was administered along with other support measures described in this paper. Finally, both patients presented a good outcome and were discharged after psychological and psychiatric assessment and follow up. CONCLUSION: The low frequency of amlodipine poisoning and the lack of evidence-based knowledge, constitute it as a diagnostic and therapeutic challenge. Based on our experience, we highlight the importance of early suspicion and prioritizing the use of vasopressors over fluid resuscitation. Additionally, we recommend documenting the exact dose of intake and inquiring about consumption of other drugs to properly classify the severity of the poisoning and stablish the treatment plan. Finally, constant clinical monitoring and support of laboratory tests will guide the conduct.(au)

Amlodipino y choque vasodilatado en una unidad de cuidados intensivos de un hospital general: Reporte de caso / Amlodipine and vasodilated shock in an intensive care unit of a general hospital: Case report

Los calcio antagonistas son fármacos usados para diferentes patologías médicas; sin embargo la intoxicación puede ser grave. Presentamos el caso de una mujer joven intoxicada por amlodipino quien cursó con choque vasodilatado y disfunción multiorgánica, en quien se usó vasopresores múltiples a dosis por encima de las habituales para estabilizarla. (AU)

Calcium antagonists are used in a number of medical conditions, but intoxication with these drugs may be lethal.We present the case of a young women intoxicated with amlodipine who presented with vasodilated shock and multi organ disfunction in whom multiple vasopressors at maximum allowed doses were used to estabilize the patient. (AU)

[New calcium channel blockers for the treatment of hypertension]. / Nuevos bloqueadores de los canales de calcio en el tratamiento de la hipertensión arterial.

L-type voltage-gated calcium channels play a key role in the regulation of arterial vascular smooth muscle tone and blood pressure levels and L-type calcium channel blockers (CCBs) are widely used antihypertensive drugs. Additionally, T-type channels regulate vascular tone in small-resistance vessels and renin and aldosterone secretion, and N-type channels, expressed in sympathetic nerve terminals, regulate the release of neurotransmitters. As compared with L-type CCBs, L/N-and L/T-type CCBs decreased intraglomerular pressure, improved renal hemodynamics and provided a greater decrease in proteinuria even in patients already treated with renin-angiotensin-aldosterone inhibitors. Thus, dual L/N-and L/T-type CCBs may exhibit therapeutic advantages over L-type blockers in hypertensive patients with chronic kidney disease. However, further large-scale, long-term comparative trials are needed to confirm that these differences translate into an improvement in clinical outcomes. © 2017 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

DIGOXINA E VERAPAMIL INDUZEM HIPERTROFIA EM CARDIOMIÓCITOS DE RATOS SEDENTÁRIOS E/OU TREINADOS / DIGOXIN AND VERAPAMIL PROMOTE CARDIOMYOCYTE HYPERTROPHY IN SEDENTARY AND/OR TRAINED RATS / DIGOXINA Y VERAPAMILO INDUCEN HIPERTROFIA DE CARDIOMIOCITOS EN RATAS SEDENTARIAS Y/O ENTRENADAS

RESUMO Introdução: Cardiotônicos e bloqueadores de canais de cálcio são fármacos que alteram o Ca2+ intracelular e afetam o coração. Objetivo: Avaliar os efeitos da administração de verapamil e digoxina sobre a morfologia cardíaca de ratos submetidos ao treinamento intervalado (TAI). Métodos: Ratos Wistar machos divididos em seis grupos (N = 8): Controle, Digoxina (30,0 µg.kg-1/dia), Verapamil (5,0 mg.kg-1/dia), Treinado, Treinado+digoxina e Treinado+verapamil. O TAI foi realizado em esteira rolante (60 min/dia/60 dias) concomitantemente com a administração dos fármacos. Fragmentos do ventrículo esquerdo (VE) foram coletados para análise histológica. Resultados: A digoxina e o verapamil aumentaram a área total do VE (p < 0,002), capilares/área VE (p < 0,01) e área de cardiomiócitos (p < 2,8e-10), sendo que, nesta última variável, o verapamil promoveu efeito ainda maior que a digoxina. O TAI aumentou VE/PC (p < 4e-05), o diâmetro interno do VE (p < 2,7e-6), a área de cardiomiócitos (p < 1,8e-6) e reduziu o [Lac] (p < 2,6e-5). Houve interação entre TAI e fármacos na área total (p < 9,8e-5), capilares (p < 0,04), células/área (p < 0,004) e área de cardiomiócitos (p < 2e-16). Conclusão: A digoxina promoveu hipertrofia de cardiomiócitos e, quando associada ao TAI, potencializou a hipertrofia. O verapamil foi mais eficiente em aumentar a área de cardiomiócitos em comparação com a digoxina, porém somente de forma isolada.

ABSTRACT Introduction: Cardiotonics and calcium channel blockers are drugs that alter intracellular Ca2+ and can affect the heart. Objective: To evaluate the effects of administration of verapamil and digoxin on heart morphology of rats subjected to interval training (IT). Methods: Male Wistar rats were divided into groups (n = 8): Control, Digoxin (30.0µg.kg-1/day), Verapamil (5.0 mg.kg-1/day), Trained, Trained+digoxin and Trained+verapamil. The IT was performed on a treadmill (60 min/day/60 days) concurrently with the drugs administration. Fragments of the left ventricle (LV) were collected for histological analysis. Results: Digoxin and verapamil increased the total area of the LV (p<0.002), capillary/LV area (p<0.01) and cardiomyocytes area (p<2.8e-10), and in the latter variable, verapamil promoted even greater effect than digoxin. The IT increased LV/BW (p<4e-05), the inner diameter of the LV (p<2.7e-6), the area of cardiomyocytes (p<1.8e-6), and reduced the [Lac] (p<2.6e-5). There was interaction between IT and drugs in the total area (p<9.8e-5), capillaries (p<0.04), cell/area (p<0.004) and cardiomyocytes area (p <2.0e-16). Conclusions: Digoxin promoted cardiomyocyte hypertrophy and when associated with IT, potentiated the hypertrophy. Verapamil was more efficient in increasing the cardiomyocytes area compared with digoxin, but only when isolated.

RESUMEN Introducción: Cardiotónicos y bloqueadores de los canales de calcio son fármacos que alteran el Ca2+ intracelular y afectan al corazón. Objetivo: Evaluar los efectos de la administración de verapamilo y digoxina sobre la morfología del corazón de ratas sometidas a entrenamiento a intervalos (EI). Métodos: Ratas Wistar macho, divididas en seis grupos (N = 8): Control, Digoxina (30,0 µg.kg-1/día), Verapamilo (5,0 mg.kg-1/día), Entrenado, Entrenado+digoxina y Entrenado+verapamilo. El entrenamiento a intervalos se realizó en una cinta de correr (60 min/día/60 días), con la administración concomitante de fármacos. Se recogieron fragmentos del ventrículo izquierdo (VI) para el análisis histológico. Resultados: La digoxina y el verapamilo aumentaron el área total del VI (p < 0,002), capilares/área VI (p < 0,01) y el área de los cardiomiocitos (p < 2,8e-10) y, en esta última variable, el verapamilo promovió un efecto aún mayor que la digoxina. EI entrenamiento a intervalos aumentó VI/PC (p < 4e-05), el diámetro interior del VI (p < 2,7e-6), el área de los cardiomiocitos (p < 1,8e-6) y redujo el [Lac] (p < 2,6e-5). Hubo una interacción entre fármacos y el EI en el área total (p < 9,8e-5), capilares (p<0,04), células/área (p < 0,004) y el área de los cardiomiocitos (p < 2e-16). Conclusión: La digoxina promovió la hipertrofia de los cardiomiocitos y, cuando al asociarse con el EI, potenció la hipertrofia. El verapamilo fue más eficiente en el aumento de la zona de los cardiomiocitos en comparación con la digoxina, pero sólo de forma aislada.

[Results of an intervention to reduce potentially inappropriate prescriptions of beta blockers and calcium channel blockers]. / Resultados de una intervención para disminuir prescripciones potencialmente inapropiadas de bloqueadores beta y calcioantagonistas.

OBJECTIVE: To determine the frequency of simultaneous prescription of ß-blockers and calcium channel blockers, notify the cardiovascular risk of these patients to the health care professionals in charge of them, and achieve a reduction in the number of those who use them. METHODS: Quasi-experimental, prospective study by developing an intervention on medical prescriptions of patients older than 65 years treated between January 1 and July 30, 2014, affiliated to the Health System in 101 cities in Colombia. A total of 43,180 patients received a ß-blocker each month, and 14,560 receiving a calcium channel blocker were identified. Educational interventions were performed and an evaluation was made, using sociodemographic and pharmacological variables, on the number of patients that stopped taking any of the two drugs in the following three months. RESULTS: A total of 535 patients, with a mean age 75.8±6.7 years received concomitant ß-blockers plus calcium channel blockers. Modification of therapy was achieved in 235 patients (43.9% of users) after 66 educational interventions. In 209 cases (88.9%) one of the two drugs was suspended, and 11.1% changed to other antihypertensive drugs. The variable of being more than 85 years old (OR: 1.93; 95% CI: 1.07-3.50), and receiving concomitant medication with inhibitors of the renin-angiotensin system (OR: 2.16; 95% CI: 1.28-3.65) were associated with increased risk of their doctor changing or stopping the prescription. CONCLUSIONS: An improved adherence to recommendations for appropriate use of ß-blockers and calcium channel blockers by health service providers was achieved. Intervention programs that reduce potentially inappropriate prescriptions for patients treated for cardiovascular disease should be used more frequently.

[The role of clevidipine in hypertension management: clinical results]. / El papel del clevidipino en el tratamiento antihipertensivo: resultados clínicos.

The prevalence of hypertension in general population is from 30% to 45%(.) Anesthesiologists frequently deal with the challenge of maintaining adequate control of perioperative blood pressure. On sudden elevations, a precise control is required to prevent end-organ damage. Recently, clevidipine, an ultra-short acting calcium antagonist has been approved by the FDA (www.accessdata.fda.gov), as a strategy for the intravenous treatment of hypertension; and by the Spanish Agency of Medicines and Medical Devices (www.aemps.gob.es) for the rapid reduction of arterial blood pressure in the perioperative setting. This medication has shown to have a rapid onset, easy titratability, and to exert a precise control of blood pressure. In addition, clevidipine has shown to be highly effective as monotherapy, and to have an excellent transition to oral antihypertensive therapy. For this article, an online search of the Medline literature was conducted up to February 2014 and "clevidipine" and "hypertension" used as keywords in order to analyze pharmacokinetics and pharmacodynamics of clevidipine. There are also clinical studies that provide evidence of the rapid and effective control that clevidipine has on blood pressure, especially in acute perioperative and emergency settings.

Manejo farmacológico de la amenaza de parto pretérmino / Pharmacological Management of Preterm Delivery Threat

Una vez instalado por completo el trabajo de parto pretérmino, los recursos para inhibirlos son poco eficaces, de ahí que las acciones preventivas desempeñan un papel fundamental en las estrategias para reducir la frecuencia y el impacto desfavorable del nacimiento pretérmino en la salud infantil. Los medicamentos que interrumpen o detienen la contractilidad uterina, llamados agentes tocolíticos, solo son eficaces cuando se administran antes del completo establecimiento del trabajo de parto. La hidratación puede reducir la contractilidad mediante el aumento del flujo sanguíneo uterino y una disminución de la secreción pituitaria de la hormona antidiurética y la oxitocina. Los medicamentos empleados para tocolisis incluyen los agentes betamiméticos (ritodrina, la terbutalina y la orciprenalina), los que inhiben la síntesis de prostaglandinas (anti-inflamatorios no esteroideos, indometacina), los que modifican la transmisión nerviosa en la placa neuromuscular (el sulfato de magnesio), y los inhibidores de los canales del calcio (la nifedipina). El nifedipino es considerado el tocolítico de primera elección y el más eficaz en la prevención del parto pretérmino (AU)

Once preterm labor is completely set up, the resources to restrain it are slightly effective; consequently preventive measures play an important role in the strategies to reduce the frequency and unfavorable impact of a preterm birth in neonatal health. The drugs to interrupt or stop uterine contractility, known as tocolytic agents, are only effective when administered before the full establishment of the delivery labor. Hydration can reduce contractility by increasing uterine blood flow and decreasing pituitary secretion of the antidiuretic hormone and the oxytocin. Drugs used as tocolytic agents include beta mimetic agents (ritodrine, terbutaline and orciprenaline), the ones inhibiting prostaglandin synthesis (nonsteroidal anti-inflammatory drugs, indomethacin), those modifying neural transmission at the neuromuscular plate (magnesium sulfate), and calcium channel blockers (nifedipine). Nifedipine is considered as a first choice tocolytic and the most effective one in the prevention of preterm delivery (AU)

Intoxicación grave con verapamilo / Severe intoxication with verapamil

Los calcioantagonistas, cada vez más usados en cardiología, son causas infrecuentes de intoxicaciones secundarias a intentos de suicidio o por mal uso de los mismos. Informamos de un caso con las manifestaciones clínicas clásicas descritas en la literatura y realizamos una investigación del tratamiento actual de dicha intoxicación.

Calcium channel blockers are currently widely used to treat many cardiological alterations; however, overdose and poisoning have been associated with morbidity and mortality mainly in those patients with suicidal attempts. We report a case and review the pathophysiology of overdose, treatment, and prognosis.