Dr Akash C Chudasama
Abstract:
Digitalis is one of the most important Remedy for cardiovascular disease. this article provides the action of cardiac glycosides of digitalis purpurea on different parts of heart. The biochemical and electrical activity of cardiac glycosides is mention. Digitalis is not just a cardiac remedy but it is life saving drug in disease such as congestive cardiac failure, rhythmic disorder supraventricular tachycardia.
Key words: Digitalis purpurea, cardiac glycosides, congestive cardiac failure, supraventricular tachycardia, digoxin, foxglove.
Name of cardiac glycosides of digitalis
- Digoxin
- Acetyldigitoxin
- Digitoxin
- Metildigoxin
- Lanatoside C
- Gitoformate
- Acetyldigoxin
Introduction:
The term digitalis is used generally to refer to any of the cardioactive steroid or steroid glycoside com- pounds that have characteristic positive inotropic and electrophysiologic effects on the heart. Most of the drugs of this class currently in common use in the Unit- ed States are steroid glycosides derived from the leaves of the common flowering plant known as foxglove or Digitalis purpurea (digitoxin, gitalin, digitalis lead, or from D. lanata (digoxin, lanatoside C, deslanoside). An exception is ouabain, which is obtained from the seed of Strophanthus grams. All cardiac glycosides contain a steroid nucleus to which an n, Q-unsaturated lactone ring is attached at the C-1 7 position. This portion of the molecule without attached sugars is called the genin (or aglyeone), and is generally more transient and less potent in its myocardial effects than the parent glycoside. digitoxin differs only in the absence of the C- 1 2 hydroxyl group. Other cardiac glycosides differ in substituent groups on the steroid nucleus as well as in the structure and number of sugars attached at the C-3 position. Molecular requirements.
Cellular effect
The best defined action of cardiac glycosides at the cellular level is the ability to inhibit sodium and potassium transport across the plasma membrane by inhibition of the transport enzyme known as Na, K -activated ATPase.’ This action is apparent in some tissues at 10 ” M glycoside concentrations, and there is growing circumstantial evidence implicating Na, K – ATPase as a receptor that mediates at least some of the actions of these drugs. It is inhibition of this transport mechanism that accounts for the substantial efflux of K’ from the myocardium that occurs with digitalization.
Cardiac glycosides are thought to have no important direct effects on contractile proteins, intermediary metabolism, or substrate availability in heart muscle. Sustained contractile effects are not secondary to catecholamine release from cardiac sympathetic nerve endings, although this mechanism may be involved in some digitalis-induced arrhythmias. Current evidence indicates that cardiac glycosides increase the amount of calcium released to the contractile element at the time of excitation-contraction coupling, quite possibly related to interaction with the cell membrane Na, K-ATPase. Although details of the mechanism re- main uncertain, this increased calcium availability to the contractile element appears to be a crucial step in the chain of events leading to increased myocardial contractility.
Cellular events leading to the electrophysiologic changes that underlie digitalis-toxic cardiac rhythm disturbances probably involve inhibition of active transmembrane Na and K transport as well as changes in autonomic-nervous-system influences. In the presence of toxic concentrations of digitalis, marked changes in transmembrane action potentials of specialized cardiac conduction cells occur.’ Purkinje cells develop diminished action potential amplitude and duration, with a shift in the resting potential toward less negative values. Decreased upstroke (phase 0) velocity also occurs and is closely correlated with de- creased conduction velocity in specialized conducting tissues. In addition to these changes, the slope of spontaneous diastolic depolarization toward threshold becomes steeper, resulting in increased automaticity of ectopic pacemaker foci. Finally, there is increased het- erogeneity of refractory periods in different cells, pre- disposing to re-entrant rhythm disturbances.
Effects on intact heart
These can also be divided into mechanical and electrophysiologic effects, with the response of the individual patient depending to an important extent on his status before administration of the drug. It is now clear that the major salutary effect of digitalis in congestive heart failure derives from its ability to increase the force of myocardial contraction. Both velocity and force of contraction are increased, whereas the duration of systole is shortened slightly. Although cardiac glycosides can be shown to decrease renal tubular sodium reabsorption under experimental circumstances, improved hemodynamics rather than a direct effect on the kidney account for the diuretic effects of digitalis in patients with congestive heart failure. Increased con- tractility occurs in the normal as well as the failing heart. The increased cardiac output resulting from digitalization of the failing heart is not seen in normal subjects, however, owing to adjustments of the peripheral circulation.
Increased myocardial contractility brought about by cardiac glycosides tends to exact a price in increased myocardial oxygen consumption. This may be counter balanced, however, if the size of the failing heart is reduced. Tension within the ventricular wall is a prime determinant of oxygen consumption, and wall tension at any given pressure will be decreased with reduction in ventricular radius according to the LaPlace relation. This may well underlie the clinical observation that angina pectoris is often ameliorated by digitalization of patients with cardiac enlargement related to congestive heart failure, whereas anginal symptoms may in- crease with digitalization of a patient without cardiomegaly.
The electrophysiologic effects of digitalis on the intact heart are complex, and are mediated by both autonomic and direct mechanisms. The initial effects on atrioventricular conduction when digitalis is given are due to vagal stimulation, whereas direct effects become appreciable at full digitalization. Thus, within the atrioventricular node the refractory period is increased and conduction velocity is diminished, which may result in prolongation of the PR interval or overt toxicity in the form of second-degree atrioventricular block (al- most always of Wenckebach or Mobitz Type 1 variety) or third-degree block. In ventricular muscle cells, on the other hand, the action potential tends to be shortened, and the more rapid recovery time is reflected in a shortening of the QT interval of the electrocardiogram
Digitalis-induced slowing of atrioventricular con- duction provides a therapeutically beneficial decrease in the ventricular response to supraventricular tachy- arrhythmias such as atrial fibrillation and atrial flut- ter. It is important to recognize, however, that slowing of sinus tachycardia with digitalization of patients in congestive heart failure occurs by an entirely different mechanism. Sinus tachycardia in this clinical setting is due in large part to the high intrinsic sympathetic tone that characterizes the state of congestive heart failure. Withdrawal of this sympathetic drive with compensation of failure is the major factor in slowing of the sinus rate, rather than any direct effect of digitalis on the sinoatrial-node pacemaker. An important corollary of this observation is that sinus tachycardia due to fever, hypovolemia, thyrotoxicosis and other such stimuli must be controlled by appropriate management of the underlying cause, rather than by administration of large and potentially toxic doses of digitalis.
Recent studies have shown that centrally mediated sympathetic-nervous-system discharge occurs at the point of appearance of digitalis-toxic arrhythmias in laboratory animals, with increased nerve traffic on the cardiac sympathetic as well as vagus nerve trunks.’ It is also known that experimental sympathectomy increases resistance to development of digitalis-induced ectopic rhythm disturbances. Although controversy in this area persists, it may be that centrally mediated mechanisms play a more important part in digitalis toxic arrhythmias than has been generally recognized.
Peripheral vascular effect
In normal subjects, digitalis tends to increase tone of peripheral-resistance vessels, resulting in an increase in total peripheral resistance. In the presence of untreated congestive heart failure, however, peripheral resistance is already high because of increased sympathetic tone, and successful treatment with digitalis may result in no change or even a fall in peripheral resistance as failure improves. In certain experimental animal models, digitalis induced rises in resistance are particularly marked in the splanchnic bed, and a clinical impression exists that acute digitalization of patients with marginal mesenteric perfusion may occasionally precipitate is- chemic necrosis of the bowel.
Clinical application
Congestive heart failure. Cardiac glycosides are of potential value in most patients with symptoms and signs of congestive heart failure due to ischemic, valvular, hypertensive and congenital heart disease, cardiomyopathies and cor pulmonale. Improvement in de pressed myocardial contractility will tend to increase cardiac output, promote diuresis, and reduce the filling pressure of the failing left or right ventricle (or both), with consequent reduction of pulmonary vascular con gestion and central venous pressure. Digitalis is of no demonstrable benefit, however, in mitral stenosis with normal sinus rhythm unless right ventricular failure has supervened. Here, the problem is mechanical obstruction to blood flow rather than impaired myocardial contractility. Similarly, little benefit may result in patients with constrictive pericarditis or pericardia! tamponade. Idiopathic hypertrophic subaortic stenosis represents another process in which digitalis is often of little value, and may actually be deleterious because it can increase left ventricular outlet obstruction by augmenting the contractility of the hypertrophied out flow-tract segment. In the later stages of the process, in which congestive problems predominate over obstructive ones, cardiac glycosides may be beneficial as in other cardiomyopathies.
“Prophylactic” digitalization of the patient with diminished cardiac reserve about to undergo a major stress such as surgery is also controversial. I the absence of obvious cardiomegaly or other evidence of overt congestive heart failure, most clinicians prefer to withhold digitalis until a specific indication arises.
The availability of reliable per venous catheter endocardial pacing technics has helped to resolve the problem of digitalis use in patients with marginal atrioventricular conduction or established atrioventricular block. One can now carry out pacemaker implantation at minimal risk even in severely ill patients, and then give digitalis without fear of aggravating conduction problems.
Cardiac-rhythm disturbances. Digitalis is of potential use in the management of four types of supraventricular tachyarrhythmias.
The first, paroxysmal supraventricular tachycardia, whether of atrial or atrioventricular junctional (nodal) origin, usually responds to digitalization when simpler measures such as carotid-sinus pressure alone have failed. This vagal-stimulatory maneuver should be re peated during the course of digitalization, since_ the combination of partial digitalization and carot1d-smus pressure will often succeed when neither measure alone suffices. Maintenance digitalization usually abolishes or reduces the frequency of recurrent attacks. Use of digitalis in the setting of paroxysmal supraventricular tachycardia demands that digitalis intoxication has been excluded as a cause of the arrhythmia.
The second arrhythmia, atrial fibrillation with a rapid ventricular response, is one of the most common indications for the use of digitalis. Both vagal and direct mechanisms result in increased blockade of impulses arriving at the atrioventricular junction, with slowing of the ventricular rate. Conversion to normal sinus rhythm may occur in the course of digitalization. Addition of propranolol may be useful in circumstances (e.g., untreated thyrotoxicosis) in which the ventricular rate is difficult to control without emergence of toxic symptoms, and congestive heart failure is absent or minimal.
The third type, atrial flutter, usually accompanied by 2: I atrioventricular block in untreated cases, can often be managed with digitalis in doses sufficient to produce a degree of atrio ventricular blockade resulting in a ventricular rate in the range of 70 to 100 per minute. This effect may require doses considerably in excess of the usual range. As in atrial fibrillation, when the arrhythmia is poorly tolerated by the patient it is often advisable to attempt direct-current cardioversion before administration of dose of digitalis that would render the procedure hazardous.
Finally, Wolff-Parkinson-White syndrome tachyarrhythmias may be terminated or prevented by digitalis in cases in which preferential effects on conduction or refractoriness in the normal or anomalous conduction pathways result in interruption of the re-entrant circus movement. Quinidine or procainamide may be more effective in other cases, however, and an empirical approach is usually necessary.
Although ventricular premature beats are widely recognized as a manifestation of digitalis excess, they are also seen in coil, junction with congestive heart failure and may disappear when failure is effectively treat ed with digitalis.
Materia medica
Comes into play in all diseases where the heart is primarily involved, where the pulse is weak, irregular, intermittent, abnormally slow, and dropsy of external and internal parts. Weakness and dilatation of the myocardium. Its greatest indication is in failure of compensation and especially when auricular fibrillation has set in. Slow pulse in recumbent posture, but irregular and dicrotic on sitting up. Auricular flutter and fibrillation especially when subsequent to rheumatic fever. Heart block, very slow pulse. Other symptoms of organic heart disease, such as great weakness and sinking of strength, faintness, coldness of skin, and irregular respiration; cardiac irritability and ocular troubles after tobacco; jaundice from induration and hypertrophy of the liver, frequently call for Digitalis. Bluish appearance of face. Cardiac muscular failure when asystole is present. Stimulates the heart’s muscles, increases force of systole, increases length. Prostration from slight exertion. Collapse. Irregular heart especially of mitral disease.
References
- https://go.drugbank.com/categories/DBCAT000820
- The New England journal of medicine, Medical Intelligence, Drug therapy, Digitalis glycosides (first of two parts) Thomas. Smith, D.
- The New England journal of medicine, Medical Intelligence, drug therapy digitalis glycosides (second of two parts), Smith, M.D.
- Boericke W. BOERICKE’S New Manual of Homoeopathic MATERIA MEDICA With REPERTORY. Third Revised & Augmented Edition Based on Ninth Edition ed. Noida: B. JAIN PUBLISHERS (P) LTD.; 2021.
Dr. Akash C. Chudasama
PG Scholar Part 2 (Practice of Medicine)
C.D. Pachchigar College of Homoeopathic Medicine and Hospital, Surat, Gujarat.
