小儿地高辛代谢及合理临床应用研究进展

地高辛是儿科临床最常用的强心苷类药物.由于地高辛治疗窗窄,治疗剂量与中毒剂量接近,个体差异大,临床中有关地高辛中毒或者剂量不足的病例时有报道,其影响因素众多.有研究表明,年龄、体重、肝肾功能、肠道微生态及药物间相互作用等均可影响地高辛的代谢动力学.临床应用时除观察有无中毒的表现外,需综合各种影响因素,个体化调整用药,并严密监测地高辛血药浓度.     

维持量地高辛中毒的预防对策：附47例分析

分析了47例维持量地高辛中毒患者的临床表现,中毒发生时间平均为服药后11天,平均用药总量2.25mg。临床表现与常规剂量洋地黄中毒无明显差异。中毒易患因素为:重度缺氧,低钾血症,肾、肝功能不良;合并感染;充血性肝硬化以及风湿活动等。其中39例为两种或两种以上易患因素并存(83.0％)。结合有关文献对维持量地高辛中毒之易患因素进行了讨论,提出相应的预防对策。     

Digoxin toxicity in a premature infant: Treatment with Fab fragments of digoxin-specific antibodies

Summary The first use of Fab fragments to treat digoxin toxicity in a premature infant with renal failure, 18 h after the onset of severe arrhythmias, is reported with dramatic results. The development of digoxin toxicity in the context of accepted therapeutic dosing to treat heart failure due to a cerebral arteriovenous malformation is discussed.     

Enzyme Activities of Myocardial Energy Metabolism during Prolonged Digoxin Treatment in Rats

Abstract The effect of prolonged digoxin treatment (1 mg/kg day for 8 days) on the activity levels of some enzymes of energy metabolism (phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase) in rat myocardium was studied. In the control animals receiving the solvent mixture (glycerol: ethanol:water in 1:1:1) a transient decrease in the lactate dehydrogenase and citrate synthase activity levels was observed. In the hearts of digoxin treated rats the level of activity of phosphofructokinase was permanently lowered by the fourth day and the level of activity of citrate synthase permanently increased after the first day of treatment. A transient increase in the activity level of succinate dehydrogenase in the myocardium of digoxin treated animals was seen between days 1 and 6. In this study a permanent decrease in phosphofructokinase and an increase in citrate synthase activity levels in rat heart muscle was noted during prolonged digoxin treatment.     

The Foeto–Maternal Distribution of Digoxin in Early Human Pregnancy

Abstract The concentrations of digoxin in maternal and foetal serum and in foetal tissues were measured after two oral doses in 12–16 weeks pregnancies. In maternal serum a digoxin level of 1.3 ng/ml was found, while the foetal serum level was 0.7 ng/ml. The placenta had a concentration of 5.8 ng/g, but no measurable amounts of digoxin were found in amniotic fluid, foetal heart, kidney, liver or muscle.     

Effects of Digoxin on Isolated Human Mesenteric Vessels

Abstract Digoxin had contractant effects on isolated, human mesenteric arteries and veins. Veins were more sensitive to this action of the glycoside than arteries. The contractions were not affected by phentolamine or by washing with a digoxin-free solution. However, they were abolished by the calcium antagonist nifedipine, and by washing with a calcium-free medium. In the presence of digoxin, the maximum response to noradrenaline (1.8 × 10^-5 M) increased markedly in both arteries and veins, and the concentration-response curve for the amine was displaced to the left. Immersion of vein preparations in calcium-free solution for 30 min. abolished the digoxin contracture; an increase in extracellular calcium restored the response. Changes in extracellular potassium concentration caused changes in tension of the mesenteric veins similar to those previously demonstrated in peripheral veins - both in the presence and in the absence of digoxin. It is concluded that digoxin contracts mesenteric vessels by a direct action on the muscle cells, and potentiates the contractant effects of noradrenaline. These effects are dependent on the availability of extracellular calcium. Mesenteric vascular reactions caused by changes in extracellular potassium are influenced by digoxin.     

Steady state serum concentrations and renal clearance of digoxin in neonates,infants and children

Summary Steady state serum concentrations of digoxin were determined repeatedly in 34 infants with congenital heart disease. Simultaneous measurements of renal clearances of digoxin, creatinine and urea were obtained in 29 of the subjects. Serum digoxin concentrations were markedly higher in children under the age of 3 months than in those over this age, despite equal weight — adjusted 24 h doses. This finding was explained by a very rapid increase in renal digoxin clearance in the first 3 months — 32±7 ml/min/1.73m² at 1 week to 65.6±30 at 3 months. The subsequent increase in digoxin clearance was much slower, e.g. to 87.7±43 ml/min/1.73m² at 12 months. Renal clearance of digoxin was equally well correlated with creatinine clearance (r=0.87) as with urea clearance (r=0.83), but it exceeded that of creatinine in all age groups. The findings indicate that both glomerular and tubular function is involved in the renal elimination of digoxin in young children, and that development of renal elimination of the drug parallels that of the maturation of renal function in the early months of life. The neonate and infant with congestive heart failure display impaired ability to eliminate digoxin. The impairment lessens rapidly with the development of renal function over the first 3 months of life. Diminished doses of digoxin should be advocated in this age group if therapeutic serum concentrations of the drug are to be maintained and toxicity avoided.     

Digoxin elimination by exchange transfusion

The report covers four cases presenting simultaneous indications for digitalisation and exchange transfusions. Intravenous administration of digoxin was followed: 1. by monitoring of the behaviour of the plasma digoxin level; 2. by determination of the total amount of glycoside eliminated by the blood exchange. Particular attention was paid to the effect of the delay between injection and exchange transfusion on the amount of digoxin eliminated.All four cases showed moderate falls in plasma levels. The amounts of digoxin eliminated by exchange transfusion were in reverse relationship to the delay between administration of digoxin and the blood exchange. At no time did the eliminated fraction exceed 5% of the total amount present in the body.

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Zusammenfassung Es wird von vier Fällen berichtet, bei denen sich zugleich die Indikation zur Digitalisierung und zur Austauschtransfusion ergab. Nach vorhergehender, intravenöser Digoxingabe wurde einerseits das Verhalten der Digoxinkonzentration im Plasma gemessen, andererseits die gesamte durch den Blutaustausch eliminierte Glykosidmenge bestimmt. Besondere Beachtung galt einer Abhängigkeit des eliminierbaren Prozentsatzes von dem zeitlichen Abstand der Austauschtransfusion zur vorangehenden Injektion.In allen vier Fällen wurde ein mäßiges Absinken der Plasmakonzentration beobachtet. Die durch Austauschtransfusion eliminierte Digoxinmenge stand in einem verkehrt proportionalen Verhältnis zum Intervall zwischen Digoxingabe und Blutaustausch. In keinem Fall überstieg diese eliminierte Fraktion 5% der insgesamt im Körper enthaltenen Menge.

     

Biliary and urinary excretion of five cardiac glycosides and its correlation with their physical and chemical properties

Summary Biliary and urinary excretion of five tritiumlabelled cardiac glycosides, i.e. Ouabain, K-strophanthoside, Digoxin, Digitoxin and Deslanatoside C, were investigated in anaesthetized guinea-pigs 5 h after i.v. or enteral administration. Urinary excretion in the main route of elimination in the case of Ouabain and Deslanatoside C. Conversely, biliary excretion is predominant in the case of Digoxin and Digitoxin. K-strophanthoside is excreted both via bile and urine. In conscious guinea-pigs treated i.v. with the same cardiac glycosides the highest levels were observed in urine, bile, kidneys and liver. The relative values of those levels were in agreement with the excretion pattern observed in anaesthetized animals. An inverse linear relation (P<0.05) was encountered between biliary excretion rate and polarity of glycoside molecula. This correlation has been previously observed by ohter authors in other species, but not in the rabbit. This suggests that the correlation may not be considered generally applicable at present.