what is the function of cardiac glycosides

Full Answer

What are cardiac glycosides?

Cardiac glycosides are a class of organic compounds that increase the output force of the heart and increase its rate of contractions by acting on the cellular sodium-potassium ATPase pump.59 They are selective steroidal glycosides and are important drugs for the treatment of heart failure and cardiac rhythm disorders.

What is the mechanism of action of glycoside?

Mechanism of actionEdit. Cardiac glycosides affect the sodium-potassium ATPase pump in cardiac muscle cells to alter their function. Normally, these sodium-potassium pumps move potassium ions in and sodium ions out.

Do cardiac glycosides increase or decrease heart rate?

Do cardiac glycosides decrease heart rate? At low therapeutic doses, cardiac glycosides can have the effect of reducing heart rate and increasing gastrointestinal activity for individuals, as they act on the parasympathetic nervous system.

What is the best cardiac glycoside for heart failure?

In addition, cardiac glycosides can be prescribed for congestive heart failure when other medications fail. Now, the most commonly used cardiac glycoside is digoxin, which can be given orally, intravenously, and intramuscularly.

What is the mechanism of action for cardiac glycosides?

Mechanism of action and toxicity Cardiac glycosides inhibit the Na+‐K+‐ATPase on cardiac and other tissues, causing intracellular retention of Na+, followed by increased intracellular Ca2+ concentrations through the effect of the Na+‐Ca2+ exchanger.

Which cardiac glycoside is used in heart failure?

Introduction. The two types of glycosides used to treat CHF are digoxin and digitoxin, the primary being digoxin. Cardiac glycosides, including digitalis and digoxin, have long-standing use in clinical practice.

What is the function of sugar part in cardiac glycoside?

These results suggest that the sugar moiety of the cardiac glycosides is important for the inhibitory effect on the K+ release induced by PTX and that the inhibition is not related to their inhibitory potency on the (Na+ + K+)-ATPase activity.

What is an example of cardiac glycoside?

Cardiac glycosides include: Digoxin (Lanoxicaps, Lanoxin, Digibind) Digitoxin (Crystodigin)

Do cardiac glycosides decrease heart rate?

At low therapeutic doses, cardiac glycosides can have the effect of reducing heart rate and increasing gastrointestinal activity for individuals, as they act on the parasympathetic nervous system.

How do cardiac glycosides treat heart failure?

Cardiac glycosides are a class of organic compounds that increase the output force of the heart and increase its rate of contractions by acting on the cellular sodium-potassium ATPase pump. They are selective steroidal glycosides and are important drugs for the treatment of heart failure and cardiac rhythm disorders.

Do cardiac glycosides increase blood pressure?

Background: For the past two decades, it has generally been accepted ('Blaustein hypothesis') that cardiac glycosides such as ouabain and digoxin increase the sodium and calcium content of smooth muscle cells, so inducing arterial vasoconstriction and a rise in blood pressure.

What are the indications of cardiac glycosides?

Today glycosides have 3 indications: manifest and chronic cardiac insufficiency, arrhythmia absoluta and paroxysmal supraventricular tachycardia. Glycosides are no longer important in the therapy of acute cardiac insufficiency.

How does cardiac glycosides treat heart failure?

Cardiac glycosides are a class of organic compounds that increase the output force of the heart and increase its rate of contractions by acting on the cellular sodium-potassium ATPase pump. They are selective steroidal glycosides and are important drugs for the treatment of heart failure and cardiac rhythm disorders.

Why is digoxin used in heart failure?

Digoxin, also called digitalis, helps an injured or weakened heart pump more efficiently. It strengthens the force of the heart muscle's contractions, helps restore a normal, steady heart rhythm, and improves blood circulation. Digoxin is one of several medications used to treat the symptoms of heart failure.

What drug is used for congestive heart failure?

Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Prinivil, Zestril) Perindopril (Aceon)

Is digoxin and digitoxin same?

Digitoxin is a cardiac glycoside used for the treatment of heart failure and certain kinds of heart arrhythmia. It is a phytosteroid and is similar in structure and effects to digoxin, though the effects are longer-lasting....Digitoxin.Clinical dataPubChem CID441207IUPHAR/BPS6782DrugBankDB01396ChemSpider38998728 more rows

What are cardiac glycosides?

Cardiac glycosides are a class of medications commonly derived from foxglove plants, such as Digitalis lanata and Digitalis purpurea. The most comm...

What are cardiac glycosides used for?

Cardiac glycosides are used to treat patients with atrial fibrillation and atrial flutter. In addition, they can be prescribed for congestive heart...

How do cardiac glycosides work?

The mechanism of action of cardiac glycosides involves inhibiting the Na+ K+ ATPase enzyme, also known as the sodium-potassium pump. This causes so...

Which receptor does the cardiac glycoside digoxin bind to?

Digoxin reversibly binds to a receptor site on the Na+ K+ ATPase enzyme, inhibiting its function of exchanging sodium and potassium across the cell...

What are potential side effects of cardiac glycosides?

Cardiac glycosides can have some potential side effects, and can also be an important cause of poisoning and toxicity. The most frequent side effec...

Do cardiac glycosides decrease heart rate?

At low therapeutic doses, cardiac glycosides can have the effect of reducing heart rate and increasing gastrointestinal activity for individuals, a...

Are cardiac glycosides still used?

Cardiac glycosides are still in use. However, they can cause severe side effects and toxicity, so they’ve been replaced with other medications as f...

What are the most important facts to know about cardiac glycosides?

Cardiac glycosides are a class of medications that inhibit the Na+ K+ ATPase enzyme, increasing the force of heart contractions. The most commonly...

What are the structures of cardiac glycosides?

The cardiac glycosides consist of a C23 steroid body, a conserved C-14 β–OH, an α,β- unsaturated five-membered lactone ring linked to position 17, and a β O-linked carbohydrate at position 3 ( Fig. 22). Cardiac glycosides differ from each other by defined substitutions on the conserved steroid moiety of the cardenolide, particularly at the 12 and 16 positions and the A and B rings, at the 3 position, and at the lactone ring. Digoxin is a relatively rigid hydrophobic hapten, free of charge groups, with rotation possible at the C-17–lactone bond and at the C-3–sugar and sugar–sugar bonds. Many (17) cardiac glycoside and aglycone structures were determined by X-ray crystallography (summarized in Schildbach et al., 1993a ). Hundreds of natural and synthetic analogs of digoxin have been described that serve as fine specificity probes of antidigoxin antibody structures.

How does digoxin work?

Digoxin is a cardiac glycoside produced by foxgloves, and it has been used for over two centuries to treat heart failure because it enhances myocardial power. It achieves this by increasing the level of intracellular calcium, as illustrated in Figure 3.12. Its immediate pharmacological action, however, is to slow down the sarcolemmal Na + –K + exchange pump, by inhibiting the membrane ATPase that powers it. This produces a rise in intracellular sodium concentration and a fall in the sodium gradient across the cell membrane. Since the Ca2+ –Na + exchange pump is itself driven by the sodium gradient ( Figure 3.5 ), calcium expulsion is slowed and calcium accumulates in the cell.

What is digoxin used for?

Over the 230 years since this first description, digoxin is still used in the management of cardiovascular diseases, including heart failure. Specifically, digoxin is recommended by the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) and the European Society of Cardiology (ESC) to decrease hospitalizations for heart failure , as multiple trials have shown its ability to improve symptoms, quality of life, and exercise tolerance (Dobbs et al., 1977; The Digitalis Investigation Group, 1997; Lee et al., 1982; The Captopril-Digoxin Multicenter Research Group, 1988; Guyatt et al., 1988; DiBianco et al., 1989; Uretsky et al., 1993; Packer et al., 1993; Yancy et al., 2013; McMurray et al., 2012). However, unlike beta-blockers and renin–angiotensin inhibitors, digoxin has not been shown to reduce mortality. This has likely been a contributing factor in the reduction of digoxin use in the management of heart failure, where it is currently reserved for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite the use of disease-modifying therapies (Patel et al., 2016; Hussain et al., 2006; Yancy et al., 2013; Goldberger and Alexander, 2014 ).

How long does digoxin take to work?

The onset of action after an oral dose occurs within 30 to 120 minutes and peaks at approximately 6 to 8 hours. The effects of IV digoxin begin after 5 to 30 minutes. The elimination half-life in adult patients with normal renal function is between 36 and 48 hours and prolonged in renal dysfunction. In preterm neonates and full-term neonates the half-life is 60 to 170 hours and 35 to 45 hours, respectively. In toddlers and younger children the half life is 18 to 35 hours (Table 19.4 ).

Does digoxin help with heart failure?

Digoxin is currently indicated (as a second- or third-line therapy) for ventricular rate control in atrial fibrillation and in the treatment of systolic heart failure.95,96 Although it is effective in providing symptomatic relief for heart failure, it does so with a significant increase in mortality and its use should essentially be considered palliative. 97 It is likewise associated with increased mortality in patients with atrial fibrillation, and although it is effective in decreasing ventricular rate at rest, it does not prevent exercise induced tachycardia, does not aid in conversion to sinus rhythm, and may be associated with conversion from sinus rhythm back to atrial fibrillation.98

Does digoxin cause endocrine changes?

This cardiac glycoside may produce endocrine changes. Raised levels of oestradiol and lowered levels of T and luteinizing hormone have been reported in men taking digoxin (Stoffer et al 1973; Neri et al 1987 ). In one study, 14 men on long-term digoxin therapy were compared with 12 men of similar age and cardiac functional capacity. The digoxin users had significantly raised oestradiol and lowered T and luteinizing hormone and also reported significantly greater reduction in sexual interest and sexual activity ( Neri et al 1980 ). This was replicated in a further study ( Neri et al 1987 ).

Is digoxin a parasympathomimetic drug?

This is a cardiac glycoside that is useful for rate control in patients with atrial fibrillation and as a supplementary treatment for heart failure. At therapeut ic doses, digoxin has a parasympathomimetic effect, which causes increased refractoriness of the AV node and a slowing of the ventricular response rate in atrial fibrillation. However, at toxic doses digoxin has a sympathomimetic effect and causes delayed after-depolarizations; both of these effects cause arrhythmias. Many different arrhythmias are seen with digoxin toxicity. Common types include junctional tachycardia, bigeminy, and second-degree AV block. Cardiac toxicity is exacerbated by hypokalemia, hypercalcemia, and hypomagnesemia. Noncardiac signs of toxicity include nausea, vomiting, diarrhea, delirium, agitation, and visual disturbances. Serum levels of digoxin are increased in patients taking amiodarone and, to a lesser extent, diltiazem. The maintenance dose of digoxin should be halved in patients receiving amiodarone.

Why do people use cardiac glycosides?

From ancient times, humans have used cardiac-glycoside-containing plants and their crude extracts as arrow coatings, homicidal or suicidal aids, rat poisons, heart tonics, diuretics and emetics, primarily due to the toxic nature of these compounds.

What are the structures of cardiac glycosides?

The general structure of a cardiac glycoside consists of a steroid molecule attached to a sugar ( glycoside) and an R group. The steroid nucleus consists of four fused rings to which other functional groups such as methyl, hydroxyl, and aldehyde groups can be attached to influence the overall molecule's biological activity. Cardiac glycosides also vary in the groups attached at either end of the steroid. Specifically, different sugar groups attached at the sugar end of the steroid can alter the molecule's solubility and kinetics; however, the lactone moiety at the R group end only serves a structural function.

How do glycosides help with heart failure?

Cardiac glycosides have long served as the main medical treatment to congestive heart failure and cardiac arrhythmia, due to their effects of increasing the force of muscle contraction while reducing heart rate. Heart failure is characterized by an inability to pump enough blood to support the body, possibly due to a decrease in the volume of the blood or its contractile force. Treatments for the condition thus focus on lowering blood pressure, so that the heart does not have to exert as much force to pump the blood, or directly increasing the heart's contractile force, so that the heart can overcome the higher blood pressure. Cardiac glycosides, such as the commonly used digoxin and digitoxin, deal with the latter, due to their positive inotropic activity. On the other hand, cardiac arrhythmia are changes in heart rate, whether faster ( tachycardia) or slower ( bradycardia ). Medicinal treatments for this condition work primarily to counteract tachycardia or atrial fibrillation by slowing down heart rate, as done by cardiac glycosides.

How does digoxin affect heart rate?

The disrupted calcium homeostasis and increased cytoplasmic calcium concentrations cause increased calcium uptake into the sarcoplasmic reticulum (SR) via the SERCA2 transporter. Raised calcium stores in the SR allow for greater calcium release on stimulation, so the myocyte can achieve faster and more powerful contraction by cross-bridge cycling. The refractory period of the AV node is increased, so cardiac glycosides also function to decrease heart rate. For example, the ingestion of digoxin leads to increased cardiac output and decreased heart rate without significant changes in blood pressure; this quality allows it to be widely used medicinally in the treatment of cardiac arrhythmias.

How do cardiac glycosides affect the ATPase pump?

Cardiac glycosides affect the sodium-potassium ATPase pump in cardiac muscle cells to alter their function. Normally, these sodium-potassium pumps move potassium ions in and sodium ions out. Cardiac glycosides, however, inhibit this pump by stabilizing it in the E2-P transition state, so that sodium cannot be extruded: intracellular sodium concentration therefore increases. With regard to potassium ion movement, because both cardiac glycosides and potassium compete for binding to the ATPase pump, changes in extracellular potassium concentration can potentially lead to altered drug efficacy. Nevertheless, by carefully controlling the dosage, such adverse effects can be avoided. Continuing on with the mechanism, raised intracellular sodium levels inhibit the function of a second membrane ion exchanger, NCX, which is responsible for pumping calcium ions out of the cell and sodium ions in at a ratio of 3Na+#N#/ Ca2+#N#. Thus, calcium ions are also not extruded and will begin to build up inside the cell as well.

What is the difference between a bufadienolide and a cardenolide?

Cardenolides differ from bufadienolides due to the presence of an “enolide,” a five-membered ring with a single double bond, at the lactone end. Bufadienolides, on the other hand, contain a “dienolide,” a six-membered ring with two double bonds, at the lactone end. While compounds of both groups can be used to influence the cardiac output of the heart, cardenolides are more commonly used medicinally, primarily due to the widespread availability of the plants from which they are derived.

Where do cardiac glycosides come from?

For example, cardenolides have been primarily derived from the foxglove plants Digitalis purpurea and Digitalis lanata, while bufadienolides have been derived from the venom of the cane toad Bufo marinus, from which they receive the “bufo” portion of their name. Below is a list of organisms from which cardiac glycosides can be derived.

How long does digoxin stay in the body?

Digoxin has a half-life of 36 hours, is 60% to 85% absorbed by the gastrointestinal tract, and has a duration of action of approximately 3 to 6 days. It is eliminated primarily by the kidney. Digoxin exerts its inotropic action by binding to and inhibiting the function of a cell membrane enzymatic receptor, Na+ /K + -ATPase (the Na + /K + “pump”). The function of this enzyme is to move sodium out of the cell and potassium into the cell. When it is deactivated, the intracellular concentration of sodium increases. This in turn stimulates another transport system that exchanges intracellular sodium for extracellular calcium. As a result, more calcium is available intracellularly to interact with the myocardial contractile proteins; hence, it augments contractility.

How do vasopressors affect the cardiovascular system?

Cardiovascular toxicities that have been observed with use of vasopressors stem from their receptor-mediated effects. The β agonism of the sympathomimetics produces palpitations, ectopic heartbeats, sinus tachycardia, and ventricular arrhythmias. 96 The direct effect on myocardial tissues may be manifested as electrocardiographic (ECG) changes, such as a reduction in T-wave amplitude, reported during epinephrine infusions in normal individuals. Increased myocardial oxygen demand may precipitate an infarction, especially in individuals with underlying cardiac disease. A dramatic rise in heart rate and peripheral vascular resistance may produce severe hypertension, which could lead to cerebral hemorrhage or hemiplegia. Excessive α-adrenergic stimulation may produce vasoconstriction so severe in the extremities, kidneys, or liver that tissues become ischemic or necrotic. Gangrene of the extremities is reported with high doses of dopamine in patients with underlying occlusive vascular disease. Extravasation of a sympathomimetic agent may lead to tissue necrosis. 149

Is obesity a metabolic disorder?

Obesity is a metabolic disorder that is characterized by an excess accumulation of fat in the body, which may be as a result of excess daily energy intake that surpasses daily energy expenditure [68]. Obesity is an independent risk factor for metabolic syndrome, hypertension, type 2 diabetes (T2DM), dyslipidemia, sleep apnea, respiratory disorders, stroke, and certain types of cancer [69].

What are the Mechanisms of action of cardiac glycosides?

When looking at the mechanism of action we need to consider two modes of action by which digoxin works.

What is the name of the glycosides in the heart?

Cardiac Glycosides: Digoxin, Mechanism of Action, Dosage and Toxicity. Digoxin belongs to a class of drugs known as cardiac glycosides. These are organic compounds derived from a plant known as foxglove and used in the treatment of heart conditions. These compounds are known to have positive inotropy meaning that they have ...

How does digoxin work in heart failure?

For a better understanding of how digoxin works in heart failur e, we shall look at the basic physiology of how the heart muscle contracts and how heart failure occurs.

What is digoxin used for?

Arrhythmias are of various types but digoxin is used in arrhythmias affecting the atria. Atria are the upper chambers of the heart. Examples of arrhythmias affecting the atria are atrial fibrillation and atrial flutter. Digoxin is also used to treat heart failure (HF).

How long does digoxin stay in the body?

The long half-life of digitalis compounds necessitates special considerations when dosing. With a half-life of 40 hours , digoxin would require several days of constant dosing to reach steady-state, therapeutic plasma levels.

Why does impaired renal function lead to enhanced plasma levels of digoxin?

Impaired renal function leads to enhanced plasma levels of digoxin because digoxin is eliminated by the kidneys.

What are some examples of cardiac glycosides?

Examples of cardiac glycosides. There are many drugs under the class of cardiac glycosides. The most common ones are. Digoxin. Digitoxin . Ouabain. But for this article, we shall be highly interested in the most commonly used drug among the cardiac glycosides; Digoxin. Digoxin is an antiarrhythmic drug.

What is digoxin used for?

An older adult client is on digoxin (Lanoxin), a cardiac glycoside, for the treatment of heart failure. What is important for the health care professional to assess prior to administering this medication?

What is adenosine given for?

Adenosine (Adenocard) is an antiarrhythmic agent given to clients in supraventricular tachycardia (SVT). Which of the following are common side effects of Adenocard?

Can cardiac glycosides raise Na+?

It has long been known that cardiac glycosides can inhibit the membrane sodium-potassium (Na+-K+) pump, raising intracellular Na+. However, at clinical concentrations of cardiac glycosides, a change in intracellular Na+ that correlates with a change in cardiac contraction has been very difficult to …

Can cardiac glycosides increase intracellular Na+?

It has long been known that cardiac glycosides can inhibit the membrane sodium-potassium (Na+-K+) pump, raising intracellular Na+. However, at clinical concentrations of cardiac glycosides, a change in intracellular Na+ that correlates with a change in cardiac contraction has been very difficult to demonstrate. The recent use of Na+-sensitive microelectrodes in the experimental laboratory has made intracellular Na+ measurements possible. A doubling of contraction strength in vitro is associated with a change of only approximately 1 mM intracellular Na+. Another membrane transport system, the Na+-Ca2+ exchange system, exchanges extracellular Na+ for intracellular Ca2+. If this system is responsible for regulating intracellular Ca2+, then it would be very sensitive to the transmembrane Na+ concentration gradient. This influence of intracellular Na+ on Na+-Ca2+ exchange is though to be the cellular basis of the positive inotropic action of digitalis. However, a number of issues remain unresolved, such as the extent of Na+-K+ pump inhibition by the level of cardiac glycoside achieved clinically.

Overview

Classification

Mechanism of action

Clinical significance

Toxicity

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