Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis / Eventos adversos associados à hidralazina: um relatório de dois casos de vasculite associada ao ANCA induzida por hidralazina

Abstract Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Resumo A hidralazina é um vasodilatador de ação direta, que vem sendo utilizado no tratamento da hipertensão arterial (HA) desde a década de 1950. Embora seja bem conhecido por causar lúpus induzido por drogas (LID), relatórios recentes estão indicando o surgimento da vasculite associada ao anticorpo citoplasmático anti-neutrófilo (ANCA), induzida por drogas (VID). Aqui, descrevemos dois pacientes (com idade entre 57 e 87 anos) que apresentaram lesão renal aguda grave (LRA), proteinúria e hematúria. Ambos estavam usando hidralazina para o tratamento da hipertensão. A sorologia para ANCA foi positiva em ambos os pacientes, juntamente com anticorpos anti-histona (comumente vistos na vasculite induzida por drogas). A biópsia renal revelou glomerulonefrite rapidamente progressiva clássica (pauci-imune) nestes pacientes e a hidralazina foi interrompida. Durante a internação hospitalar, o paciente de 57 anos necessitou de diálise e foi tratado com esteroides e rituximab para a doença do ANCA. A função renal melhorou e o paciente recebeu alta (fora da diálise) com creatinina sérica de 3,6 mg/dL (basal = 0,9 mg/dL). Em um seguimento de 2 anos, o paciente permaneceu fora da diálise com doença renal crônica avançada (DRC) (estágio IIIb). O paciente de 87 anos apresentava IRA grave com creatinina sérica em 10,41 mg/dL (valor basal de = 2,27 mg/dL). O paciente necessitou de hemodiálise e foi tratado com esteroides, rituximabe e plasmaferese. Infelizmente, o paciente desenvolveu bacteremia induzida por cateter e, posteriormente, evoluiu a óbito por sepse. A hidralazina pode causar IRA grave, resultando em DRC ou óbito. Dado este perfil de eventos adversos extremamente desfavorável e a disponibilidade generalizada de agentes anti-hipertensivos alternativos, o uso de hidralazina deve ser considerado com muita parcimônia.

Anti-TNF-α and hydralazine drug-induced lupus

Drug-induced lupus is a rare drug reaction featuring the same symptoms as idiopathic lupus erythematosus. Recently, with the introduction of new medicines in clinical practice, an increase in the number of illness-triggering implicated drugs has been reported, with special emphasis on anti-TNF-α drugs. In the up-to-date list, almost one hundred medications have been associated with the occurrence of drug-induced lupus. The authors present two case reports of the illness induced respectively by hydralazine and infliximab, addressing the clinical and laboratorial characteristics, diagnosis, and treatment.

study of the effect of hydralazine hydrochloride [apresoline] on the myocardium and renal cortex of the adult balady rabbits

In the present work, the effect of Apresoline on the myocardium and on the renal cortex of adult 18 male balady rabbits was reported. Administration of Apresoline in group 1: that received 5 mg / kg bw daily for 3 days produced sever effect on the heart in the form of wide separation between the muscle fivers, extravasated blood, wide areas of loss of striations and lysis of the myofibrils. When the drug was given in the therapeutic dose [0.5 mg / kg Bw] the effect of the drug increased progressively with the increase in the duration of intake. In group 2: that received the during for 2 weeks, some cardiac muscle fibers showed slight degeneration in the form of loss of striations, which were replaced by granular formation. Few mitochondria were degenerated. In group 3: that received Apresoline for 4 weeks, marked degeneration in the myofibrils in the form of wide areas of loss of striations that were replaced by granular formation were obvious. The sarcoplasm showed degenerated and elongated mitochondria, as well as autophagosomes and dense bodies. Also extravasted blood between the muscle fibers was apparent. The renal cortex suffered also from the treatment with Apresolin, but to a lesser degree than the heart. In group 1: Many proximal convoluted tubules were edematous with obliteration of their lumina and other were degenerated, but the distal tubules and the renal corpuscles appeared normal. In group 2: there were some inflammatory cells, little widening the capsular space and some proximal tubules were slightly dilated. In group 3: some renal corpuscles were degenerated with marked widening in the capsular spaces. Many proximal tubules were dilated with partial loss of their brush borders. Also, extravasated blood and degenerated mitochondria were prominent

Manejo de la preeclampsia severa/eclampia: comparación entre Nefidepina e Hidralazina como medicamentos antihipertensivos / Management of severe pre-eclampsia/eclampsia: comparison between Nifedipine and Hydralazine as antihypertensive drugs

Se compararon los efectos maternos y fetales entre la hidralazina parenteral y la infedipina sublingual, usados como antihipertensivos en el manejo de la preeclampsia severa. El diseño fue prospectivo, comparativo, longitudinal, de asignación clínica aleatoria. Se realizó en el Centro Médico Nacional IMSS Torreón, Coah., división de Gineco-Obstetricia. las pacientes fueron mujeres embarazadas con diagnóstico de preeclampsia severa, asignadas al azar para recibir hidralazin parenteral o nifedipina sublingual como manejo antihipertensivo. La única diferencia observada fue que los recién nacidos cuyas madres recibieron hidralazina, tuvieron calificación de Apgar significativamente menor que los que recibieron nifedipina. Ambos medicamentos son una buena alternativa como tratamiento antihipertensivo en casos de preeclampsia severa. Los hijos de madre tratada con nifedipina tuvieron calificación de Apgar más alta.

Manifestaçöes reumáticas induzidas por drogas: experiência pessoal e literatura; 1ª parte / Drug induced rheumatic disorders: personal experience and literature; Part 1

Os autores fazem uma revisäo da literatura quanto as manifestaçöes reumáticas induzidas por drogas. Salientam e questionam alguns dos mecanismos envolvidos nas reaçöes adversas as drogas e sua manifestaçöes clínico-laboratoriais, dando enfase ao lúpus-símile. Além disso, alertam sobre a importância em se detectar iatrogenia no curso de uma terapêutica medicamentosa

Efecto de la hidralazina en la vasoconstricción hipóxica: su estudio en un modelo canino de atelectasia lobar / Effects of hydralazine on the hipoxic pulmonnary vasoconstriction

Con el objetivo de conocer si la hidralazina (H) es capaz de inhibir la vasoconstricción hipóxica (VCH) se estudio su efecto sobre el cortocircuito intrapulmonar (Qs) en el modelo experimental de otelectasia regional (A). Se analizaron en siete perros los cambios circulatorios pulmonares y los del intercambio gaseoso en las siguientes condiciones: de control 1 (A y VCH), durante aumentos de flujo pulmonar alcanzando con la apertura de fístulas arteriovenosas (FA) (maniobra mecánica) y con el cierre de las mismas )control 2), después de la administración de hidralazina (0.33 mg/kg) y en el status y post sangrado controlado )control 3). Con la maniobra de FA se obtuvo un incremento significativo del gasto cardiaco (2.07 ñ 28 a 3.9 ñ 52 l. min, p <0.05), del Qs (de 13 ñ 1 a 23 ñ 3%, p <0.05) y de la pVO2 (38 ñ 2 a 48 ñ 1 mmHg p <0.05) con disminución en las resistencias pulmonares y sistémicas (Rs). Alcerrar las fístulas (C2) se alcanzó un estadio cardiopulmonar de equilibrio similar al de C1. Con el uso de H (intervención farmacológica) se observó en dirección y magnitud un cambio similar en el Qt (2.18 ñ 0.27 a 3.43 ñ 48 l. min. p <0.05); el Qs (14 ñ 1 a 23 ñ 3% p <0.05) y la pVO2: (40 ñ 2 a 48 ñ 3%, p <0.05) que con la maniobra mecánica de FA. Concluímos que la H es capaz de liberar la VCH pulmonar y que su mecanismo esta vinculado a las modificaciones de la pVO2 sin poder excluir su efecto farmacológico directo sobre la vasculatura pulmonar