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PubMed1991

A note on the use of topical digitalis prior to William Withering.

Attention is called to the fact that, long before the systematization of oral digitalis therapy by Withering in the eighteenth century, the drug was applied to the skin by inunction, producing effects that can now be recognized as due to an overdosage of Digitalis glycosides. The history of digitalis is briefly reviewed: the drug appears not to have been known to Greek and Roman physicians, but by the Middle Ages was widely used in folk medicine. Contrary to current wisdom, there is a wealth of historical information suggesting that topically applied Digitalis glycosides are capable of exerting physiological activity. It is perhaps time to re-examine this feature, in view of the present-day general interest in transdermal medications.

Administration, Topical↗
PubMed1996

Quantitative determination of cardiac glycosides in Digitalis lanata leaves by reversed-phase thin-layer chromatography.

An analytical method for the determination of cardiac glycosides in Digitalis lanata leaves by reversed-phase thin-layer chromatography (RP-TLC) was developed. The procedure consisted of extraction of dry leaf powder with 50% methanol and clean-up by Sep-Pak cartridges prior to RP-TLC analysis. RP-TLC was performed on an octadecylsilyl bonded silica gel plate, using a developing solvent of acetonitrile-methanol-0.5 M NaCl (1:1:1) for primary glycosides and acetonitrile-methanol-0.5 M NaCl (12:7:9) for secondary glycosides. The plate was scanned with a reflectance densitometer at 225 nm. The quantitation was carried out by the internal standard method. The present method is reliable and relatively simple for the determination of cardiac glycosides in Digitalis lanata leaves.

Cardiac Glycosides↗
PubMed1986

Isolation and quantitative determination of some cardioactive glycosides from Digitalis lanata by high-performance liquid chromatography.

A rapid extraction method followed by high-performance liquid chromatographic assay was developed for the quantitative determination of the cardioactive glycosides of Digitalis lanata. The leaf samples were extracted with water or aqueous alcohols. The simple extraction method gives a better yield than the methods described previously. Lanatoside C and its metabolites have been separated on a reversed-phase column with various mixtures of acetonitrile, methanol, and water as mobile phases for isocratic elution. Extraction and quantitative determination of lanatoside C and digoxin from a leaf sample require not more than 30 min.

Chromatography, High Pressure Liquid↗
PubMed1993

[Digitalis for the treatment in patients with heart failure].

Digitalis glycosides are the first-choice drugs in the treatment of the patients with congestive heart failure and atrial fibrillation. Recently, it has been shown that digitalis glycosides have potentially beneficial neurohumoral modulating effects by decreasing excessive neurohumoral responses directly or by improving baroreflex mechanisms in congestive heart failure. Accordingly, there are many investigators who believe that digitalis glycosides are neurohormonal modulating agents in heart failure. There may be a dissociation between hemodynamic and neurohormonal effects in response to digitalis glycosides. The activation of the neurohormonal system may be present in patients with asymptomatic left ventricular dysfunction. Digitalis glycosides may therefore be used, not only to improve symptomatic congestive heart failure, but also to protect against the progressive deterioration of asymptomatic cardiac dysfunction.

Atrial Natriuretic Factor↗
PubMed2001

Digitalis for treatment of congestive heart failure in patients in sinus rhythm.

BACKGROUND: Digitalis glycosides have been in clinical use in the treatment of congestive heart failure for more than 200 years. In recent years several trials have been conducted to address concerns about efficacy and toxicity. Although a systematic review of the literature was recently published, an update is required to include more current trials. OBJECTIVES: To examine the effectiveness of digitalis glycosides in treating congestive heart failure in patients with normal sinus rhythm. To examine the effect of digitalis in patients taking diuretics, ACE inhibitors, and beta blockers; patients with varying severity and duration of disease; patients with prior exposure to digitalis vs. no prior exposure; and patients with diastolic vs. systolic dysfunction. SEARCH STRATEGY: Electronic databases were searched between 1966 and 2000. Dissertation Abstracts and annual meeting abstracts of the American Heart Association, American College of Cardiology, and European Society of Cardiology were searched from 1996-2000. In addition, reference lists provided by the pharmaceutical industry (Glaxo Wellcome Inc.) were searched. SELECTION CRITERIA: Included were randomized placebo-controlled trials of 20 or more adult patients of either sex with symptomatic congestive heart failure who were studied for seven weeks or more. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of heart failure such as acute ischemic heart disease or myocarditis was present. DATA COLLECTION AND ANALYSIS: Articles selected from the searches described above were reviewed by one of the coauthors, and validated by staff from the central office of the Heart Collaborative Review Group in Bristol, UK. MAIN RESULTS: Eleven articles meeting the defined criteria were identified, and major endpoints of mortality, hospitalization, and clinical status, based respectively upon on 8, 4, and 10 of these selected studies, were recorded and analyzed. The data show that there is no difference in mortality between treatment and control groups, whereas digitalis therapy is associated with a lower rate of hospitalization and of clinical deterioration. REVIEWER'S CONCLUSIONS: The literature indicates that digitalis has a useful role in the treatment of patients with congestive heart failure who are in normal sinus rhythm.

Cardiotonic Agents↗
PubMed1993

Newer concepts in the medical management of patients with congestive heart failure.

Congestive heart failure (CHF) remains a major cause of morbidity and mortality in the United States, especially among the elderly. Although an underlying disturbance in cardiac function can be identified in most patients, manifestations of the disease are greatly influenced by other factors, particularly neurohumoral and peripheral adaptive responses which occur secondary to impaired cardiac function. The renin-angiotensin system (RAS) is integrally involved in the pathophysiology of CHF. Originally considered a humoral system, the RAS is now known to exist and operate within cardiac and vascular tissues. The importance of tissue-specific renin-angiotensin systems in CHF is presently under investigation. Most patients with symptomatic CHF benefit from the administration of an ACE inhibitor. Certain asymptomatic patients, such as those with severe left ventricular (LV) dysfunction and those who are at high risk for LV remodeling after anterior wall myocardial infarction, may also benefit from ACE inhibitor therapy. Diuretics and nitrates improve symptoms and often cardiac output in many patients with CHF. Although many new inotropic agents have been tested in CHF patients, none appear clinically superior to digitalis glycosides. The efficacy of digitalis glycosides in CHF may in part result from sympathoinhibitory properties such as the activation of baroreceptor mechanisms. Despite the fact that many CHF patients die from arrhythmias, treatment of asymptomatic ventricular arrhythmias in these patients is not recommended. Patients with symptomatic or sustained ventricular arrhythmias are best treated by a physician experienced in cardiac electrophysiology. Therapy with beta-blocking drugs for CHF patients is controversial. Anticoagulants are recommended for selected patients with CHF. Finally, exercise therapy may improve functional capacity in some patients with CHF through its effects on peripheral blood vessels and skeletal muscle tissues.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Significance of skeletal muscle digitalis receptors for [3H]ouabain distribution in the guinea pig.

The importance of specific digitalis glycoside binding sites in skeletal muscle for the digitalis glycoside distribution in the guinea pig was evaluated using [3H]ouabain and [3H]digoxin binding assays. Measurements of [3H]ouabain binding capacity (EOmax) in gastrocnemius and heart muscles in vitro gave values of 474 +/- 15 and 1,092 +/- 39 pmol/g wet wt., respectively, in 4-week-old guinea pigs. Hence the total amount of [3H]ouabain binding sites in skeletal muscle and the heart was around 42,700 and 1,200 pmol, respectively. The apparent dissociation constants (Kd) for ouabain receptor interaction was 0.7 X 10(-7) and 1.5 X 10(-7) M for skeletal muscle and heart, respectively. Comparison of [3H]ouabain and [3H]digoxin binding revealed that these drugs are competitive. From birth to maturity the concentration of [3H]ouabain binding sites in guinea pigs decreased from 803 +/- 58 to 304 +/- 28 pmol/g wet wt. in gastrocnemius muscle and from 1,458 +/- 31 to 1,079 +/- 19 pmol/g wet wt. in the heart. After i.p. injection, measurements of the distribution of [3H]ouabain in plasma, skeletal muscle and the heart showed an almost equal relative specific occupancy of digitalis glycoside receptors in skeletal muscle and the heart: When 10% of the digitalis receptors in the heart were occupied by [3H]ouabain, 13% of those in the skeletal muscles were occupied. It was calculated that 1 hr after the i.p. administration of [3H]ouabain the amount of [3H]ouabain specifically bound to the skeletal muscles and the heart corresponded to 5 times and 1/10 the amount available in the extracellular pool, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1975

[Serum concentration of glycosides and digitalis intoxication(author's transl)].

Serum glycoside concentration was 2.3 ng/ml or more in 299 patients digitalised with digoxin or digoxin derivatives. Mean serum glycoside concentration was 3.4 +/- 1.3 ng/ml (range 2.3-11.00 ng per ml). Usually, high serum concentrations were associated with advanced den or digoxin-derivative overdosage occurred in only 10% of patients. Almost three quarters of those with intoxication had impaired renal function. There was some evidence that low body-weight increased the potential risk of intoxication.

Arrhythmias, Cardiac↗