Revigorando os digitálicos / Reviving the digitalis

O tratamento farmacológico clássico da insuficiência cardíaca (IC) baseava-se somente no uso de digitálicos, diuréticos e vasodilatadores; entretanto, apesar da melhora sintomática inicial, a IC progredia independente do estado hemodinâmico do paciente. Com a descoberta da ativação do sistema neuro-hormonal na fisiopatologia da IC, iniciou-se uma nova era terapêutica com o uso dos inibidores da enzima conversora da angiotensina, bloqueadores dos receptores da angiotensina, betabloquedores e a espironolactona, tornando-se responsáveis pela redução de morbidade e mortalidade na IC e modificando a sua evolução. O papel dos medicamentos mais antigos, como digitálicos e os diuréticos, tornou-se cada vez menos certo na modificação da história natural da IC e, com isso, o digitálico passou a ser progressivamente menos prescrita pelos médicos. Neste artigo será feita uma análise da literatura sobre o uso dos digitálicos na IC, revisando os principais estudos, suas indicações e limitações no manuseio dessa síndrome, e destacando a importância de se rever a necessidade de voltar a prescrevê-los mais em pacientes com IC.

Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

Identification and estimation of endogenous digoxin in biological fluids and tissues by TLC and HPLC.

A procedure for estimation of digoxin in biological samples after adding a known quantity of digoxin followed by extraction, separation by TLC and HPLC is described. The identity of digoxin thus extracted from rat brain has been established by reaction with digoxin antibody and by its inhibition of Na(+)-K+ ATPase activity. The method could be a better substitute to the routine radioimmunoassay as interfering substances are removed by TLC and HPLC.

Digoxinemia / Digoxin

Se discute el uso de la digoxina como adyuvante en la terapia cardíaca; se hacer referencia a su mecanismo de acción y a los diferentes factores fisiológicos y medicamentos que afectan su biodisponibilidad, así como a algunos de los factores que pueden alterar su cuantificación en líquidos corporales. Se ofrecen recomendaciones para optimizar este determinación y se revisan los niveles terapéuticos recomendados

Estimation of serum digoxin in patients with heart failure

This study included 15 patients with rheumatic heart failure under the classic antifailure methods [digoxin and diuretics]. A good history and thorough clinical examination especially for manifestations of right and left sided heart failure were done. Laboratory investigations such as Hb level, ESR, CRP and ASOT were done. Serum digoxin level was 0.51-1.9 mg/ml, mean 1.039 in the controlled group, while it was 0.97-2 ng/ml, mean 1.30 in uncontrolled group. Comparing this to the therapeutic level 1.2 ng/ml most of the cases of controlled and uncontrolled groups showed low digoxin level and not showed toxic digoxin level

Serum Digoxin level, serum potassium and kidney function in congestive heart failure patients treated with and without captopril

30 patients with severe congestive heart failure of more than 2 months duration were studied, 26 patients had ischemic heart disease and 4 had dilated cardiomyopathy. All were receiving Digoxin and Furosemide and 6 patients had been on Amiodaron. The study was in 4 phases: [1] Before captopril, [2] All the patients received captopril, [3] Half of the patients continued on captopril, [4] Patients were crossed over in a double blind manner to the alternative therapy. All treatments other than captopril was maintained. Captopril caused a significant increase in serum Digoxin level. No patients developed evidences of Digoxin toxicity. Serum potassium rose and the frequency of ventricular arrhythmia showed a moderate decline. Creatine clearance and radioisotopically measured glomerular filtration rate fell, but there was a poor relationship between these and the increase in serum Digoxin

Utilization of digoxin and theophylline assays in the eastern province

The utilization of therapeutic drug monitoring [TDM] for serum digoxin and theophylline was assessed with respect to the indication, time of sample collection and contribution to patient care. A total of 585 serum drug level determinations of digoxin [275] and theophylline [328] were done in a four month period. Reasons for requests were subtherapeutic response [27.5%], suspected toxicity [3.8%], baseline data [26.7%], patients at risk for toxicity [7.7%], and for the remaining 34.4% of orders, no reason was stated. The highest number of requests 246 [42.1%] were from the inpatient ward [INP], followed by emergency room [ER] 32.6%, outpatient department [OPD] 13% and intensive care unit [ICU] 12.3%. Repeated assays accounted for 363 determinations of which 55.9% had levels similar to the previous ones. In this study, we found a high incidence of inappropriateness in patient selection [34.4%], time of serum sample collection [28.4%], and dosage adjustment [46.8%]. However, when these audit criteria were analyzed together, the overall appropriateness was as low as 33.5%. This indicated that serum drug monitoring was poorly utilized and did not contribute much to the patient's care. This results in an estimated financial loss per year [for inappropriate use of digoxin and theophylline levels] of about 37,344 Saudi Riyals [US $ 9,956.00]. Corrective educational programs for the staff, based on standard guidelines for TDM, have been initiated and this study is a baseline for future prospective audits

Hemorragía sub-aracnoidea primaria y sustancias inmunoreactivas endogena similar a la digoxina / Subarachnoid hemorrage and endogenous immunoreactiva substance similar to digoxin

Se determinaron niveles de digoxina por un método de inmunoensayo fluorométrico enzimático en plasma de 15 pacientes con hemorragia subaracnoidea primera (HSA) por ruptura de aneurisma intracraneal, en 15 controles sanos (Control I) y 15 controles con afecciones neuroquirúrgicas distintas a la HSA (Control II). Ninguno de los 45 pacientes había recibido digoxina. En 11 de los 15 pacientes con HSA, el método determinó la presencia en plasma de substancia inmunoreactiva endógena similar a la digoxina (SIESD) en un rango de 0,13 a 0,42 ng/ml (promedio: 0,28 ng/ml) días antes del tiempo promedio (8 días) de aparición de vasoespasmo clínico. Los mayores niveles se observaron en pacientes que se complicaron posteriormente con trastornos del sensorial y disfunción neurológica. De los 15 controles sanos solo dos mostraron niveles de SIESD de 0,11 y 0,17 ng/ml. De los 15 controles II solo tres (prolactinosa, meningismos múltiples y malformación arteriovenosa cerebelosa) presentaron valores de 0,10 y 0,21 ng/ml. La diferencia de los valores de SIESD entre los pacientes con HSA y cada uno de los grupos controles fue estadísticamente significativo (p < 0,001). La SIESD se encuentra con frecuencia en pacientes con HSA y pudiera ser utilizado como factor predictivo de vasoespasmo clínico

Identificaçäo cromatográfica de glicosídeos cardiotônicos em comprimidos e injetáveis / Chromatographic identifications of cardiac glycosides in tablets and injections

Os princípios ativos de comprimidos e injetáveis contendo glicosídeos cardiotônicos (digitoxina, digoxina e lanatosídeo C) foram identificados por Cromatografia em Camada Delgada

Inmunoensayoenzimático homogéneo para la determinación de digoxina plasmática: experiencia clínica y correlación con el radioinmunoensayo / Homogeneus enzimatic immune-assay (H.E.I.A.) for determination of blood levels of digoxin: clinical experience and comparison with radioinmune - assay (RIA)

En el presente trabajo presentamos nuestra experiencia clínica con la determinación de niveles plasmáticos (NP) de Digoxina utilizando el método de Inmunoensayo enzimático homogéneo, EMIT, en muestras de plasma de 50 pacientes hospitalizados en el Hospital Clínico de la Universidad de Chile. El método EMIT se ha señalado como uno de utilidad similar al Radioinmunoensayo (RIA) para Digoxina pero no encontramos información en la literatura que fundamente esta aseveración. En 47 pacientes con función renal normal y sin evidencias de toxicidad el NP encontrado fue de 1,6 ñ 0,5 ng/ml (X ñ DS) con una dosis de 0,23 ñ 0,04 mg/día. Sólo un paciente presentó signos de intoxicación digitálica con un NP de 2,8 ng/ml. Los otros dos pacientes tenían alterada su función renal y presentaron NP de 1,0 y 1,3 ng/ml con dosis de 0,12 mg/día en cada caso. Estos valores son similares a aquellos descritos por la literatura científica en los cuales se utilizó el RIA en la determinación. Utilizando el plasma de doce de los pacientes, se realizó un estudio de correlación midiendo las concentraciones de la droga por ambas técnicas, encontrándose un índice de correlación r = 0,91 (p <0,05). Nuestros resultados aportan evidencias de que el método EMIT es de similar utilidad al RIA con las ventajas de ser más rápido, simple en su ejecución y con un menor costo de instalación