Experiencia en el uso de propranolol para el tratamiento de la taquicardia supraventricular en pacientes menores de un año / Experience using propranolol for the management of supraventricular tachycardia in patients younger than 1 year

Objetivo. Evaluar los resultados y efectos adversos de la terapia con propranolol en menores de un año con taquicardia supraventricular. Población y métodos. Menores de 1 año con taquicardia supraventricular documentada, que recibieron tratamiento y prevención con propranolol por vía oral. Se analizaron sexo y edad, cardiopatía congénita asociada, pre excitación ventricular en el electrocardiograma basal, recurrencia intratratamiento y efectos adversos. Resultados. Se identificaron 107 pacientes. El primer episodio de taquicardia supraventricular ocurrió a una edad mediana de 190 días. En 10 pacientes, se observó cardiopatía congénita asociada. El 23,3 % presentó pre excitación ventricular en el electrocardiograma basal. El rango de la dosis de propranolol fue de 2 a 5 mg/kg/día. En el 30,8 %, se observó recurrencia intratratamiento. En 2 pacientes, se suspendió la medicación por efectos adversos graves. Conclusión. El propranolol evitó la recurrencia en el 70 % de los casos. En 2 pacientes, fue necesario suspenderlo por efectos adversos graves

Objective. To assess the results and adverse events of propranolol therapy in infants younger than 1 year with supraventricular tachycardia. Population and methods. Infants younger than 1 year with documented supraventricular tachycardia who received oral treatment and prophylaxis with propranolol. Sex and age, associated congenital heart disease, ventricular preexcitation in the base line electrocardiogram, on-treatment recurrence, and adverse events were analyzed. Results. A total of 107 patients were identified. The first supraventricular tachycardia event occurred at a median age of 190 days. Associated congenital heart disease was observed in 10 patients. Ventricular preexcitation in the baseline electrocardiogram was detected in 23.3 %. Propranolol dose ranged from 2 to 5 mg/kg/day. On-treatment recurrence was observed in 30.8 %. Medication was discontinued in 2 patients due to severe adverse events. Conclusion. Propranolol prevented recurrence in 70 % of cases. It was discontinued in 2 patients due to severe adverse events.

Propranolol en el tratamiento de los hemangiomas: una alternativa terapéutica / Propranolol in the treatment of hemangiomas: a therapeutic alternative

Introducción: los hemangiomas son los tumores benignos más frecuentes de la infancia. Generalmente involucionan espontáneamente después del año. Un porcentaje pequeño requiere tratamiento debido a complicaciones. Recientemente se ha comunicado beneficio del tratamiento con propranolol. Objetivo: describir la experiencia de tratamiento con propranolol en 6 niños con hemangiomas infantiles (HI) en dos centros asistenciales de Montevideo en el período 1/9/2010 – 31/12/2013. Metodología: se incluyeron los menores de 15 años portadores de hemangiomas asistidos en el Centro Hospitalario Pereira Rossell y en la Asociación Española tratados con propranolol. En todos los casos se realizó evaluación cardiológica previa. Se excluyeron aquellos con contraindicaciones absolutas al fármaco. En todos los casos se solicitó, previo al tratamiento, consentimiento informado. Se describe las características clínicas de los niños y la evolución. Resultados: se incluyeron 6 niños (5 niñas y un varón); rango 1 mes y 21 días a 20 meses. Las topografías fueron: labio superior con compromiso de narina 2, mejilla izquierda 1, raíz nasal e intraorbitario 1, intraocular 1, múltiple 1. En todos los casos la respuesta fue favorable con disminución progresiva de las lesiones en los primeros meses de tratamiento. Ninguno presentó complicaciones. Discusión: ésta es la primera comunicación de una serie de niños con hemangiomas tratados con propranolol en Uruguay. A pesar del escaso número de pacientes, se observó beneficio terapéutico sin complicaciones. El propranolol debe considerarse como una alternativa terapéutica al tratamiento con glucocorticoides sistémicos, cuya administración prolongada se asocia con serios efectos adversos.

Introduction: hemangiomas are the most common benign tumors of childhood. They usually regress spontaneously after the year of life. A small percentage require treatment due to complications. Recently it has been reported the benefit of treatment with propranolol. Objective: describe the experience of treatment with propranolol in 6 children with infantile hemangiomas (HI) in two centers of Montevideo in the period 1/9/2010-31/12/2013.Methodology: included infants under de age of 15 carriers of hemangiomas assisted in the Pereira Rossell hospital and the Spanish Association treated with propranolol. Cardiological assessment was previously performed in all cases. Those with absolute contraindications to the drug were excluded. Informed consent was requested prior to the treatment in all cases. The clinical features of children and evolution are described. Results: 6 children were included (5 girls and a male); range 1 month and 21 days to 20 months. The surveys were: upper lip with commitment of nostril 2, left cheek 1, nasal root and intraorbitary 1, intraocular 1, multiple 1. In all cases the response was favorable with progressive decrease in injuries in the first month of treatment. None of the patients presented complications. Discussion: this is the first communication of a series of children with hemangioma treated with propranolol in Uruguay. Despite the small number of patients therapeutic benefit without complications was observed. Propranolol should be considered as a therapeutic alternative to treatment with systemic glucocorticoids whose prolonged administration is associated with serious adverse effects.

A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine / Estudo controlado, randomizado e duplo cego do uso de baixas doses de propranolol, nortriptilina e a combinação destas duas drogas no tratamento preventivo da migrânea

Few trials have evaluated combination of two or more drugs in the preventive treatment of migraine. In this study three therapeutic regimens were compared: (a) propranolol, at a dose of 40 mg per day, (b) nortriptyline, at a dose of 20 mg per day, and (c) the combination of these two drugs in these dosages. The groups were matched according to age, gender, and frequency of migraine attacks prior to treatment. The period of treatment was two months and the frequency and intensity of headache attacks of the 30 days pre-treatment period were compared with the frequency of headaches in the treatment period. Fourteen patients in groups A and B and sixteen patients in group C have completed the study. Treatment with propranolol, alone or in combination, was shown to be effective. Treatment with nortriptyline alone was not effective. All three therapeutic regimens were safe and side effects were minimal. The frequency of discontinuation of the study was the same in the 3 groups but no patient left the study due to adverse reactions. The combined therapy proved to be as safe as the monotherapy. Further studies evaluating this and other possible combinations of drugs in higher doses and for longer periods, should more clearly elucidate the role of combined therapy in the treatment of migraine.

Poucos ensaios clínicos têm avaliado o tratamento preventivo da migrânea através da combinação de drogas. Neste estudo, três regimes terapêuticos foram comparados: (a) popranolol, na dose de 40 mg por dia, (b) nortriptilina, na dose de 20 mg por dia e (c) combinação destas duas drogas nestas dosagens. Os grupos foram pareados de acordo com idade, sexo e freqüência de crises previamente ao tratamento. O período de tratamento foi de dois meses e a frequência e a intensidade das crises de cefaléia do período pré-tratamento foram comparadas com as do período de tratamento. Concluíram o estudo 14 pacientes do grupo A, 14 do grupo B e 16 do grupo C. Os tratamentos com propranolol, isolado ou em associação mostraram-se eficazes. O tratamento com nortriptilina isolada não se mostrou eficaz para a redução do número de dias com cefaléia. Todos os três regimes terapêuticos foram seguros e os efeitos colaterais foram mínimos. A freqüência de abandono do estudo foi a mesma nos 3 grupos e nenhum paciente abandonou o estudo devido a reações adversas. A terapia combinada mostrou-se tão segura quanto a monoterapia. Estudos futuros avaliando esta e outras possíveis combinações de drogas, em doses maiores e por períodos mais longos, deverão elucidar mais claramente o papel da terapia combinada no tratamento da migrânea.

Nuestra experiencia con propranolol en el tratamiento de los hemangiomas / Our experience with propranolol in the treatment of hemangiomas

Introducción: Los hemangiomas son los tumores benignos más frecuentes de la infancia. La mayoría son lesiones tumorales localizadas, con bajo riesgo de complicaciones. Sin embargo, existe un grupo reducido de ellos (10 a 20%) que, durante la fase de crecimiento, puede ocasionar importante morbilidad, ya sea por ulceración, compromiso funcional por obstrucción de orificios naturales o porque producen una importante desfiguración cosmética. El tratamiento de primera línea para estos hemangiomas “complicados” son los corticoides sistémicos seguidos por vincristina o interferón alfa como drogas de segunda línea. El propranolol fue propuesto recientemente como una nueva opción terapéutica. Este trabajo describe nuestra experiencia en el tratamiento con propranolo de 33 pacientes con hemangiomas “complicados”, evaluados entre octubre de 2008 y octubre de 2009.Material y métodos: Fueron incluidos 33 pacientes (26 mujeres y 7 varones) con hemangiomas “complicados”, con edades entre 1 y 38 meses de vida. Se les administró propranolol oral a dosis de 2 mg/kg/día, dividido en 2-3 tomas. En todos los casos se obtuvo el consentimiento escrito de los padres. Al momento del ingreso en este protocolo fue realizada una evaluación clínica y cardiológica por un Pediatra y un Cardiólogo infantil. Durante el tratamiento se monitoreó la presión arterial y se hicieron electrocardiogramas repetidos. Resultados: Al inicio del tratamiento 27 pacientes eran menores de 1 año de vida, con edad media de 4,8 meses (rango: 1-11 meses). Los restantes 6 niños tenían 18, 20, 27, 36, 37 y 38 meses de edad. Treinta y uno de los 33 pacientes completaron el tratamiento, con una duración promedio de 4,5 meses (rango: 1 a 8 meses). Dos de ellos lo interrumpieron voluntariamente al no observar una respuesta significativa al mismo.

Introduction: Hemangiomas of infancy are the most common tumor of childhood. Although most children with hemangiomas have localized lesions with an uncomplicated course, a minority (10-20%) experience complications during the proliferative phase. Complications as ulceration, functional compromise due to obstruction of natural orifice or due to severe cosmetic desfigurement require treatment. The first line of treatment for these “complicated” hemangiomas is systemic corticosteroid and second line agents include vincristine or interferon alpha 2b. Propranolol was recently suggested as a therapeutic option for these hemangiomas. The present work reports our experience in the treatment of 33 patients with “complicated” hemangiomas with propranolol from October 2008 to October 2009. Materials and methods: Thirty-three patients (26 females and 7 males) with “complicated” hemangiomas, of 1 to 38 months of age, were included. Propranolol was given orally at a dose of 2 mg/kg/day, in 2-3 divided doses. In all cases informed consent was obtained from parents. At the moment of the inclusion in this protocol, a clinical and a cardiovascular evaluation was performed by a Pediatrician and a Pediatric Cardiologist. Electrocardiography and blood pressure were monitored during treatment. Results: Age at the beginning of treatment was less than 1 year old in 27 patients with an average age of 4.8 months (range: 1-11 months). The other 6 patients were 18, 20, 27, 36, 37 and 38 months old. Thirty-one of the 33 patients completed a 4.5 months average treatment (range: 1 to 8 months). Two of them voluntarily interrupted the treatment since they did not observe a significant response. Twenty-two patients showed quick response, with clinical evidence of regression during the first 2 weeks while the remaining 9 improved after 2 months of treatment. Just one patient showed an isolated episode of asymptomatic hypotension.

Influência da cirurgia de revascularização miocárdica com circulação extracorpórea sobre a farmacocinética do propranolol e do atenolol / Influence of Coronary Artery Bypass Grafting Surgery Employing Cardiopulmonary Bypass in the Pharmacokinetics of Propranolol and Atenolol

Níveis plasmáticos e farmacocinética de beta-bloqueadores podem ser alterados por hipotermia e circulação extracorpórea (H-CEC). Avaliou-se, em pacientes submetidos a revascularização miocárdica (RM) com H-CEC, a farmacocinética do propranolol (n=11) e do atenolol (n=8) nos períodos pré e pós-operatório. Observou-se aumento da meia vida biológica e volume de distribuição apenas para o propranolol. O clearance total permaneceu inalterado para os dois fármacos e ocorreu aumento da concentração plasmática de propranolol do início até o final da H-CEC. Os resultados mostram que a RM com H-CEC induz alterações farmacocinéticas diferentes para o propranolol e o atenolol / Plasma levels and pharmacokinetics of betablockers may be altered by hypothermic cardiopulmonary bypass (H-CPB). We evaluated the pharmacokinetics of propranolol (n=11) and atenolol (n=8) pre and postoperatively in patients submitted to coronary artery bypass grafting surgery (CABG) employing H-CPB. Increase of biological half-life and volume of distribution was observed only for propranolol. The total clearance remained unchanged for both drugs and an increase in plasma propranolol was observed from the beginning to the end of H-CPB. Data obtained show that CABG employing H-CPB influences the propranolol and atenolol pharmacokinetics in distinct ways.

Ansiedade social e abuso de propranolol: relato de caso / Social anxiety and propranolol abuse: a case study

Paciente com grave ansiedade social automedicou-se com propranolol durante seis anos, em doses de até 320 mg/d. Além do tratamento psicanalítico que já havia iniciado, foi tratada com tranilcipromina, apresentando melhora parcial do quadro fóbico e do abuso do betabloqueador. Após introdução de paroxetina, houve melhora ainda mais pronunciada. Apesar da automedicação com uma substância potencialmente eficaz em alguns casos, perpetuou-se durante anos um grave padrão fóbico de comportamento. O caso exemplifica as dificuldades de procura de tratamento específico pela população de fóbicos sociais. Levanta-se a hipótese da existência de uma prática crescente de automedicação com betabloqueadores entre fóbicos sociais e pessoas com ansiedade de desempenho, problema cuja relevância para a saúde pública ainda não foi pesquisada

Precipitation of hepatic encephalopathy by propranolol

Propranolol is used to prevent recurrent variceal bleeding in patients with periportal hypertension and cirrhosis. Though controversy still exist regarding its efficacy in these conditions, its potential to precipitate hepatic encephalopathy is rarely reported. In this case report, we describe a patient who developed severe hepatic encephalopathy shortly after porpanolol treatment and recurred on rechallenge with the drug

Morte após uso de antimonial pentavalente em leishmaniose tegumentar americana / Death after the use of pentavalent antimonial in american cutaneous leishmaniasis

Apresenta-se um caso de uma paciente feminina de 56 anos de idade, natural e procedente de André Fernandes (MG), com quadro clínico e histopatológico de Leishmaniose Tegumentar Americana (LTA), portadora de lesäo única na glabela. Foi medicada com antimoniato de N-metil-glucamina intravenoso na dose de 20mgSbV/Kg/dia, diluído em 250 ml de SGI (tempo de infusäo: 3-4 horas), por 30 dias seguidos. A pacientes era hígida, exceto por uma leve hipertensäo arterial sistêmica e durante todo o tratamento, apenas apresentou como efeito colateral a ocorrência de tremores que desapareceram com a continuiçäo da terapêutica. Três dias após o término do tratamento a paciente apresentou quadro convulsivo generalizado e perda de consciência de instalaçäo abrupta. Exames laboratoriais revelaram-se compatíveis com insuficiência hepática e renal graves. Sete dias após o início do quadro convulsivo, a paciente foi a óbito. Levando-se em conta o largo uso dos antimoniais pentavalentes na LTA, a ocorrência de insuficiências renal e hepática concomitantes é rara e deve ser relatada. Questionamos também se as manifestaçöes neurológicas observadas no caso näo seriam diretamente causadas pela droga

A study on withdrawal related haemodynamic response in chronic propranolol treated conscious rats.

Single dose of propranolol hydrochloride (5 mg/kg, i.p.) caused significant fall in heart rate (HR) but not in systolic blood pressure (SBP) in normotensive conscious rats. Multiple doses of propranolol (5 mg/kg, i.p., twice-a-day for 5 wk) caused significant fall in both HR and SBP at 2 wk and 4 wk in normotensive conscious rats. Sudden withdrawal of propranolol at 5 wk caused a significant blood pressure upswing and tachycardia between 12-24 h followed by normalization of both blood pressure and heart rate. The study documents a possible model of rebound hypertension in normotensive conscious rats.

Adverse reactions to propranolol, a non-selective beta-adrenergic blocking agent in hypertensive patients--a collaborative study.

Propranolol, a nonselective beta-adrenergic blocking agent, although prescribed frequently, has not been monitored for its adverse reactions in Indian population. A collaborative ADR monitoring study was planned in 2661 hypertensive patients. Exclusion criteria were associated circulatory insufficiency, heart block, left ventricular failure, diabetic mellitus and airway obstruction. The incidence of ADR was 2.1%, which is lower than reported incidence of 8.7 to 43.7 percent in other studies. This could be attributed to improper selection of patients, differences in methodology of monitoring, or to racial variation. In the present study ADR of fatigue (1.1%), dizziness (0.4%) and headache (0.2%) constituted the bulk. Additional reaction of pain in chest (0.2%), heart block (0.1%), hypoglycemia (0.1%), loss of libido (0.1%) and shock (0.03%), were also observed.

Uma análise do fosinopril: um novo inhibidor da ECA / Overview of fusinopril: a novel ACE inhibitor

O fosinopril - uma pró-droga do composto diácido ativo fosinoprilato é o precursor de uma nova classe química de inibidores da enzima conversora da angiotensina (ECA), os ácidos fosfínicos. É indicado, em administraçäo diária única, no tratamento da hipertensäo leve a moderada. Após a administraçäo oral, o fosinopril reduz eficazmente a pressäo arterial sistólica e diastólica durante 24 horas. Ensaios clínicos de curto prazo (oito a 12 semanas) constataram que a administraçäo diária de 10 a 40mg de fosinopril é significativamente mais eficaz que placebo e comparável a 40 a 80mg de propranolol duas vezes ao dia no tratamento de pacientes com hipertensäo essencial leve a moderada ou moderada severa que näo reagiam ao tratamento com diuréticos. Em um ensaio de 12 semanas, a administraçäo diária única de fosinopril ou de enalapril produziu efeitos anti-hipertensivo equivalentes em pacientes com hipertensäo essencial leve a moderada. Em pacientes idosos com hipertensäo leve a moderada, o fosinopril reduziu a pressäo arterial com eficácia equivalente à da nifedipina de liberaçäo prolongada (SR) e, aparentemente, com melhor tolerância. O fosinopril foi bem tolerado pelos pacientes estudados nos ensaios clínicos; a incidência de efeitos adversos foi semelhante à observada com placebo, propranolol ou enlapril. As ocorrências mais freqüentes foram cefaléia, tosse e tontura, mas estes sintomas säo

Possible alteration of some cardiovascular and hormonal parameters after abrupt withdrawal of propranolol or guanfacine following chronic mono-or combined therapy in spontaneous hypertensive rats

Spontaneous hypertensive rats [SHR] were given either propranolol [P], guanfacine [G] or combined treatment for four weeks, followed by sudden withdrawal of either [P] or [G] for 6 days. Results showed a significant decrease of the systolic blood pressure, heart rate and plasma renin activity after [P], [G] or combined treatment with a significant rebound increase after withdrawal. Concerning plasma aldosterone concentration, a significant decrease of this parameter was detected only after [G] treatment with a rebound significant increase after withdrawal. As regards angiotensin converting enzyme activity, there was a significant decrease of this parameter after [P] treatment with a significant rebound increase after withdrawal. Total daily urinary catecholamine exhibited a significant increase after [P] treatment and even after its withdrawal but there was a significant decrease after propranolol withdrawal in the group treated with both drugs. There was also a significant decrease of this parameter after [G] or combined treatment with a rebound significant increase after withdrawal of [G]. A significant increase of serum potassium was apparent after [P] or combined treatment with a significant decrease after withdrawal. These results indicated that propranolol and guanfacine are effective antihypertensive agents, besides, when a drug is to be withdrawn from the combination regimen, it is the beta- blocker rather than guanfacine

A cross-over trial comparing the effects of acebutolol and propranolol on the serum lipids and hypertension.

A two-way cross-over trial comparing the effects of acebutolol and propranolol on the lipid profile was conducted. 50 patients were evaluated. The primary objective was to determine whether treatment by certain classes of beta-blockers induced deleterious effects on the serum lipids which could partially or wholly negate the beneficial effect of controlling hypertension. Each patient served as his/her own control, and received 6 weeks of therapy with acebutolol and 6 weeks of therapy with propranolol. The analysis of the results revealed that acebutolol did not have any adverse effect on the lipid profile in contrast to reports which implicate other beta-blockers in inducing pro-atherogenic changes in the serum lipid profile; but acebutolol and propranolol were equi-effective in controlling hypertension.

Propranolol: indicaçöes, farmacocinética, efeitos adversos e interaçöes / Propranolol: therapeutic uses, pharmacokinetics, adverse effects and interactions

O propranolol é uma droga beta-bloqueadora que tem sua maior utilidade no tratamento de doença cardiovasculares, especialmente a hipertensäo arterial sistêmica e angina pectoris. A droga é bem absorvida pela via oral e tem importante metabolismo hepático de primeira passagem com grande variaçäo interindividual, o que pode levar a consideráveis variaçöes de doses dentro de uma mesma entidade clínica. É um fármaco geralmente bem tolerado, mas que pode ter entre seus efeitos adversos a descompensaçäo de insuficiência cardíaca e de asma; merece especial atençäo em pacientes diabéticos usando insulina e/ou hipoglicemiantes orais e cuidados especiais na descontinuaçäo do tratamento