Therapeutic drug monitoring of digoxin–20 years of experience

Background

Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1–2 ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood.

米力农与洋地黄治疗充血性心力衰竭的疗效比较

目的探讨米力农与洋地黄治疗充血性心力衰竭的疗效。方法选择106例充血性心力衰竭患者，随机分为米力农组（38例）、洋地黄组（38例）和对照组（30例）。米力农组用米力农（10nag＋生理盐水250m1）5-10mg·kg^-1·min。静滴；洋地黄组口服洋地黄（地高辛0．125--0．25mg／d）；对照组仅口服和静注利尿剂和安慰剂，疗程均为10d。治疗前、后观察患者的心功能级别并做心脏超声心功能指数测定。结果米力农组心功能改善总有效率为89．47％，洋地黄组为81．58％，两组比较差异无统计学意义（P〉O．05），但米力农组明显高于对照组（36．67％）（P〈O．05）。两治疗组治疗后，心脏超声心功能指数有明显改善。结论米力农与洋地黄对治疗充血性心力衰竭有明显的疗效。     

Sugar transport in the perifused left atrium: effects of contraction frequency, digitalis and ionic alterations.

The activity of the sugar transport system in the rat left atrium was studied by measuring the distribution of 3-methylglucose. Sugar transport increased progressively with the rate of muscle contraction, from rest to 240 beat/min. This effect persisted for up to 15 min after contraction had ceased. Hyperosmolarity increased sugar transport in parallel with cell shrinkage, expansion of extracellular space and increase in intracellular Na⁺ and ionic strength; opposite changes were induced by hypo-osmolarity. Anoxia, uncouplers of oxidative phosphorylation, K⁺-free medium, as well as 10^?5 g/ml ouabain or 1.0 mm diphenylhydantoin (DPH) stimulated sugar transport and inhibited the Na⁺ pump. In contrast, 10^?9 g/ml ouabain or 0.5 mm DPH decreased sugar transport and intracellular Na⁺ and increased intracellular K⁺. In all these respects sugar transport in atria resembled that in skeletal muscle. The data are consistent with the proposed role of Ca²⁺ as regulator of sugar transport but exclude cytoplasmic Ca²⁺ from this function. The effect of 10^?9 g/ml ouabain appears not to be related to the inotropic effect of the drug.     

Digitoxin therapy partially restores cardiac catecholamine and brain serotonin metabolism in congestive heart failure

The effect of therapeutic doses of digitalis in modifying neural activity has been the subject of considerable controversy. In earlier studies we reported an increase both in serotonergic activity in the posterior hypothalamus and pons-medulla and in cardiac sympathetic tone in the failing cardiomyopathic hamster. In this study we examine the effects of doses of digitoxin, known to be therapeutic for hamster heart failure, on monoamine neurotransmitter metabolism in the brain and heart during the cardiomyopathy. Both digitoxin and ASI-222, a polar amino-glycoside which does not cross the blood-brain barrier, given either acutely (6 mg/kg ip) or chronically (2 mg/kg/day ip for 10 days), normalized the failure-induced increase in serotonin turnover in the pons-medulla but had no effect on the changes in the posterior hypothalamus. Digitoxin therapy also reduced cardiac and adrenal sympathetic activity partially restoring cardiac catecholamine stores. In order to more clearly define the pathways involved we measured serotonin (microgram/g protein) in 18 brain nuclei after 10 days of digitoxin or vehicle treatment. Heart failure was associated with an increase in serotonin in five nuclei: the mammillary; bodies, ventromedial, periventricular and paraventricular nuclei of the hypothalamus, and the centralis superior nucleus of the raphe. Digitoxin therapy completely normalized the changes in the centralis superior and ventromedialis nuclei; neither congestive heart failure nor digitoxin affected serotonin levels in other nuclei. We conclude that there is an increase in activity in specific brain serotonergic nuclei in congestive heart failure. Digitalis reduces cardiac sympathetic tone and restores the changes in two of these nuclei: the ventromedial and the centralis superior.+2     

Assessment of digoxin antibody use in patients with elevated serum digoxin following chronic or acute exposure

OBJECTIVE: To evaluate the use of antidotal therapy in patients with an elevated digitalis concentration following chronic or acute exposure. DESIGN AND SETTING: Retrospective review of patient records over 2 years in 20 city hospitals in France. PATIENTS: Overall 838 patients with an elevated serum digitalis concentration (digoxin[Symbol: see text]>[Symbol: see text]1.95[Symbol: see text]ng/ml or digitoxin[Symbol: see text]>[Symbol: see text]23[Symbol: see text]ng/ml) were included in the study. Of these, 67 (8%) had received antidotal therapy with Fab fragments. MEASUREMENTS AND RESULTS: The relationships between previously reported prognostic criteria and use of antidotal therapy were investigated. We identified five independent factors that were associated with the use of antidotal therapy: acute overdose (OR 15.74), Fab fragment availability in the hospital (11.06), serum potassium (1.81), and heart rate (0.96). Mortality was significantly lower in Fab-treated (6%, 4/67) than untreated patients (15%, 117/770). CONCLUSIONS: Antidotal therapy is underused in patients with an elevated digitalis concentration especially in patients with chronic digitalis exposure. These patients in our series presented a higher mortality rate than patients with acute poisoning. Although they were older and tended to have a history of cardiac disease, they did not differ from patients with acute poisoning with regard to the main severity criteria and prognostic factors. The use of identical criteria for antidotal treatment after acute and chronic poisoning should help optimize outcomes. Fab fragment availability is insufficient in France but ranks only second after type of poisoning (acute or chronic) in the multivariate association with Fab treatment.     

Alternans during fascicular ventricular tachycardia due to digitalis toxicity

This report describes a digitalis-induced regular fascicular ventricular tachycardia characterized by marked QRS alternans a manifestation not usually associated with this arrhythmia. The striking alternation of QRS configuration suggested alternating ventricular activation from either a single focus with two exits in distal branches of the left anterior fascicle or 2 different foci localized in the Purkinje-myocardial network of the left anterior fascicle.     

冠心病患者的EDF昼夜节律与健康人的比较

目的：了解冠心病人血中内生洋地黄因子（ＥＤＦ）水平是否存在２４ｈ节律性变化及这种变化的特征和意义；方法：用放免法对２０例冠心病人和９例“健康人”进行了２４ｈ血中ＥＤＦ的动态监测；结果：发现冠心病患者血清ＥＤＦ浓度有着与健康同龄人明显不同的昼夜节律性变化，其峰值在７：００，谷值在１９：００，两者差别悬殊；结论：在对冠心病患者应用洋地黄类药物和检测血清地高辛浓度时，必须考虑到其ＥＤＦ的这种特殊的变化规     

Digoxin intoxication: An old enemy in modern era

Objectives Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. Methods We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph (ECG) findings, and serum digoxin levels > 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. Results Thirty-eight of 71 patients (53.5%) had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females (64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively). The mortality rate during the hospital course was 7%. Conclusion This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population.     

心先安与洋地黄对比治疗慢性心衰120例观察

目的 比较心先安与洋地黄治疗慢性心力衰竭的疗效。方法 将120例心衰患者随机分成心先安组（n=60）和洋地黄组（n=60）。心先安组给予心先安120mg～150mg加入5％葡萄糖盐水250ml中静脉滴注，连续10日～14日；洋地黄组给予地高辛0．125mg或0．25mg口服，每日1次。结果 心力衰竭临床症状改善的有效率，心先安组为82％；洋地黄组为84％，两组间无显著差异（P〉0．05）。结论 心先安是一种疗效可靠，无明显毒副作用的强心、扩血管药物。