Cardiac glycosides – types, indications and contraindications

Author Ольга Кияница


Cardiac improvement can be corrected by taking cardiac glycosides. These drugs can increase cardiac output, but there is a risk of serious side effects. Therefore, before taking drugs from this pharmacological group, it is advisable to become familiar with their mechanism of action and possible toxicity.

Cardiac glycosides (SG) are a class of organic compounds that increase cardiac output and reduce the rate of contractions of the myocardium. The main effect is directed to the cellular sodium-potassium ATP-azny pump.Medical prescription is the treatment of heart failure and cardiac arrhythmias.The relative toxicity of SG does not allow them to be widely used.

The ancient Egyptians and Romans first used plants containing cardiac glycosides as medicines to help with heart diseases. Toxicity from herbal cardiac glycosides was well known by 1785, when William Whiting published his classic work describing the therapeutic use and toxicity of digitalis D purpurea. [1 - Bessen HA. Therapeutic and toxic effects of digitalis: William Withering, 1785. J Emerg Med. 1986; 4 (3): 243-8]

Cardiac glycosides, most commonly found as secondary metabolites in several plants, such as digitalis, have a diverse biochemical effect on the function of heart cells. As a result of recent studies, SG has also been proposed for the integrated treatment of cancer.

Video: Basic pharmacology of cardiotonic agents

General structure

The general structure of cardiac glycosides consists of a steroid molecule attached to a sugar (glycoside) and an R-group. The steroid core consists of five condensed rings, to which other functional groups can be attached, such as methyl, hydroxyl and aldehyde groups, affecting the biological activity of the entire molecule.

Cardiac glycosides vary in groups attached at both ends of the steroid. In particular, various sugar groups with a steroid sugar attached at the end can alter the solubility and kinetics of the molecule; however, the lactonic fragment at the end of the R-group is only needed to perform the structural function.

The structure of the ring attached to the R-end of the molecule, allows us to classify cardiac glycosides into two classes:

  1. Cardenolides.
  2. Bufadienolide.

Cardenolides are distinguished from bufadienolides by the presence of an “enolide,” a five-membered ring with one double bond at the end of the lactone. On the other hand, bufadienolide contain “dienolide” - a six-membered ring with two double bonds at the end of the lactone.

Although the compounds of both groups can be used to influence the cardiac output of the heart, cardenolides are more commonly used in medicine. This is mainly due to the availability of the raw material from which they are produced.


Cardiac glycosides can be more specifically classified based on the plants from which they are produced. A similar distribution is presented in the list below. For example, cardenolides were mainly obtained from digitalis purpurea and Digitalis lanata digitalis plants, whereas boufadienolides are derived from the venom of cane Bufo marinus. From the name of the reptile, they get part of their medical definition. The following is a complete list of plants from which cardiac glycosides can be obtained.

Plants from which cardenolides are produced:

  • Convalia vulgaris or Convallaria majalis (plant): convallotoxin.
  • Anchar or Antiaris toxicaria (evergreen trees and shrubs): antiarin.
  • Strofant Combe or Strophanthus kombe (Strophanthus vine): ouabain (g-strophanthin) and other strophanthins.
  • Digitalis lanata and digitalis purpurea or Digitalis lanata and Digitalis purpurea: digoxin, digitoxin.
  • Oleander normal or Nerium oleander: oleandrin.
  • Butcher or Asclepias: Oleandrin.
  • Spring Adonis or Adonis vernalis: adonitoxin
  • Kalanchoe Degremona or Kalanchoe daigremontiana and other types of Kalanchoe.
  • Heartwort or Leonurus cardiaca: Scylarenin.
  • Scallion or Drimia maritima: Proscillaridin A.

The organisms from which bufadienolidy :

  • Bufo marinus (cane toad): various boufadienolides

Mechanism of action

  1. Cardiac glycosides inhibit the action of the sodium-potassium pump in cardiomyocytic sarcolem. Thus, they increase the intracellular concentration of sodium and calcium, thereby exerting a positive inotropic effect, increasing the strength of contractions. The effect on the vessels and the heart is direct and indirect, while the control is carried out by the sympathetic and parasympathetic nervous system.
  2. Cardiac glycosides affect the parasympathetic system, activating it. Stimulation of the vagus nerve has a suppressive effect on the sinus node and atrio-ventricular node (negative dromotropic effect), thereby reducing the heart rate (negative chronotropic effect). The indirect effect of the activation of the vagus nerve also leads to a decrease in atrial myocardial contractility, a reduction in the refractory period and an acceleration of the conduction of impulses in the atria.Glycosides increase atrial muscle contractility, prolonging the refractory period and promoting the conduction of impulses.In addition, hypertension increases atrial automatics.
  3. An increase in the secretion of norepinephrine reduces the period of refraction of Purkinje fibers and increases their automatism. The same direct effect on Purkinje fibers is exerted by glycosides. The effect of noradrenaline and glycosides on the muscles of the ventricle is the same - the contractility of the heart increases, the period of refraction of the muscle fibers is shortened and the automatism of the heart muscle increases.
  4. Cardiac glycosides increase the sensitivity of baroreceptors.
  5. Cardiac glycosides reduce the activity of the sympathetic nervous system, reducing the resistance of peripheral arterioles. The direct effect of glycosides is opposite and increases resistance.

Estimated mechanism of action of SG, where ab are the stages of their action; minus - depressing effect; (↑) - increase in the content of ions; (↓) - reduction of the ion content.


Digoxin and digitoxin can be prescribed for administration in the form of tablets. Digoxin is excreted through the kidneys with a half-life of 1.5 days, and digitoxin mainly by the liver and bile, followed by excretion through the intestines (enterohepatic circulation), which causes a half-life of 7 days. Therefore, in view of potential toxicity, digoxin is usually preferred.

Digoxin should not be used for renal insufficiency, while digitoxin is contraindicated only for combined hepatic and renal insufficiency.

Strofantin is administered intravenously due to poor absorption in the intestines, but currently has no clinical / therapeutic significance. It is also excreted through the kidneys. The long half-life leads to the fact that a higher initial dose is required for saturation than a subsequent daily maintenance dose.

Pharmacokinetic parameters

A drug The half-life of the drug, in hours Absorption rate,% Protein binding, in% LD50 in mg / kg KG
Digitoxin 170 100 90 0.45
Digoxin 35 75 thirty 0.25
Strofantin 15 <5 ten 0.15

Note: LD50 KG = lethal dose, for a cat, intravenous.

Since many narcotic substances can affect the activity of cardiac glycosides, fluctuations in the concentration of the electrolyte, they also have only a limited therapeutic range, their use should be carried out in individual doses with careful monitoring of blood count. This applies in particular to digitalis glycosides (digoxin, digitoxin), in which the therapeutic and toxic areas can sometimes overlap.

Clinical significance

Cardiac glycosides have long been the main treatment for congestive heart failure and cardiac arrhythmias. This is due to the effect of these diseases on the force of contraction of the myocardium while reducing the heart rate.

Heart failure is characterized by the inability to pump a sufficient amount of blood to maintain the body. This may be due to a decrease in blood volume or a decrease in myocardial contractile force. The treatment of this condition focuses on lowering blood pressure so that the heart does not need to put a lot of effort to pump the required amount of blood. The contractile force of the heart can also be directly increased, which allows it to overcome the resulting load.

Cardiac glycosides, such as digoxin and digitoxin, help to increase the contractile capacity of the heart due to their positive inotropic activity.

Cardiac arrhythmia is a change in the heart rate towards an increase (tachycardia) or slowdown (bradycardia). The treatment tactics of this condition are primarily aimed at eliminating tachycardia or atrial fibrillation by slowing the heart rhythm, as cardiac glycosides do.

However, due to toxicity and dosage issues, cardiac glycosides have been replaced by synthetic drugs, such as ACE inhibitors and beta-blockers. They are no longer used as primary medical care for arrhythmias and heart failure.However, depending on the severity of the condition, they can still be administered in combination with other types of drugs.

Indications and contraindications


  • Chronic heart failure with atrial fibrillation or flutter and fast ventricular rhythm (the drug of choice).
  • Patients with chronic heart failure, sinus rhythm, NYHA class III class.
  • Patients with heart failure are, respectively, Grade II NYHA with sinus rhythm, in which their condition has improved and they have switched to the lower NYHA class after treatment with glycosides.


  • Arrhythmias with bradycardia.
  • Atrioventricular block II and III.
  • Sick sinus syndrome.
  • Ventricular tachycardia.
  • WPW syndrome.
  • Acute myocardial infarction.
  • Hypertrophic cardiomyopathy.
  • Syndrome of a carotid sine.
  • Amyloidosis of the heart.

Cardiac glycoside toxicity

Cardiac glycosides are most often used for therapeutic purposes, but their toxicity is widely recognized. For example, American poison control centers reported 2,632 cases of digoxin toxicity and 17 deaths from digoxin in 2008. [1 - Bronstein, Alvin C .; Spyker, Daniel OiA .; Cantilena, Louis R .; Green, Jody L .; Rumack, Barry H .; Giffin, Sandra L. (2009-12-01). "2008 Annual Report of the American Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report." Clinical Toxicology. 47 (10): 911–1084]

Cardiac glycosides affect the cardiovascular, nervous and gastrointestinal systems, so they can be used to determine the effects of toxicity. The effect of these compounds on the cardiovascular system can be a cause for concern, since they directly affect heart function by providing an inotropic and chronotropic effect.

  • Due to inotropic activity, an excessive dose of cardiac glycoside leads to an increase in heart rate, since calcium is released from cardiac muscle cells.
  • Toxicity also leads to changes in cardiac chronotropic activity, which causes multiple types of arrhythmias and potentially fatal ventricular tachycardia. These arrhythmias are a consequence of the influx of sodium and a decrease in the resting threshold of the membrane potential in the cells of the heart muscle. When they go beyond the narrow dosage characteristic of each cardiac glycoside, these compounds can quickly become dangerous.

In general, the intake of cardiac glycosides can interfere with the fundamental processes that regulate the membrane potential. SG is toxic to the heart, brain, and intestines in doses that can be reached very quickly.

On the part of the heart, the most common side effect is premature ventricular contraction.

Symptoms of glycosidic intoxication

Although acute and chronic toxicity due to inadequate intake of cardiac glycosides is treated equally, their non-cardiological (non-cardiac) clinical manifestations vary.

In acute intoxication, symptoms usually develop within a few minutes to a few hours, are non-specific and include nausea, vomiting, and abdominal pain.

Neurological symptoms are often non-specific and include weakness and altered mental status (for example, disorientation, confusion, lethargy).

With chronic intoxication, the symptoms are rather deceptive, making diagnosis difficult. Symptoms of glycosidic toxicity are not specific and include the following:

  • Anorexia.
  • Nausea.
  • Vomiting.
  • Diarrhea.
  • Abdominal pain
  • Weight loss.

Neurological symptoms include the following:

  • Confusion
  • Drowsiness.
  • Disorientation.
  • State of delirium.
  • Headache.
  • Hallucinations

Visual disturbances are manifested as follows:

  • Photophobia.
  • Blurry vision.
  • Scotomas.
  • Decreased visual acuity.
  • Aberrations of color vision (for example, chromopsy, xanthopsia).

Cardiac symptoms are similar in both acute and chronic toxicity and include the following:

  • Palpitations.
  • Chest pressure.
  • Dyspnea.
  • Dizziness.
  • Weakness.

Objective signs

The physical examination focuses on the cardiovascular, neurological and digestive systems. For vital signs, bradycardia or tachycardia is observed. In the absence of ingestion of alcohol and other drugs, environmental exposure, thyroid disorders, or the main infection, the patient is usually normothermic (the temperature is not elevated).

The results of an objective examination of specific systems are as follows :

  • Lightweight Most often, there are no pathological changes, although wheezing can be registered.
  • Heart - bradyarrhythmia or tachyarrhythmia can occur, as a rule, against the background of increased automatism and low conductivity; impulses can be weak, sometimes irregular.
  • The abdomen - the abdominal wall is usually soft; vomiting and diarrhea may occur; vomiting may contain vegetable components.
  • Skin - may be pale, with sweating and cool.
  • Neurological manifestations are usually non-local, while pupillary reflexes, most often, are not impaired. In abnormal cases, the following symptoms of glycosidic intoxication can be determined:
    • Altered level of consciousness.
    • Muscular hypotonia.
    • Hyporeflexia.
    • Dysarthria.
    • Ataxia.
    • Horizontal nystagmus.
    • General cramps.

In rare cases, the symptoms are so minor that after a while they pass on their own.

On an electrocardiogram, there may be changes characteristic of digitalis intoxication:

  1. T tooth two-phase or asymmetric negative.
  2. The RS-T segment is shifted below the contour and takes the form of a trough.
  3. Extrasystole or ventricular tachycardia, ventricular fibrillation or supraventricular tachycardia.
  4. Sinus bradycardia.
  5. AV node blockade or conduction delay through the AV node.

Prognosis and complications

Thousands of deaths due to intake of cardiac glycosides are reported each year, so the incidence of mortally ill patients ranges from 5% to 10%. These indicators can be significantly higher in countries or communities where folk or medicinal herbs are often used, which have cardiac glycosides in their composition.

Statistics of glycosidic intoxication by age

Data from the American Association of Centers for the Control of Poisons (ATSBC) for 2015 show the following age-related disorders due to exposure to cardiac glycosides:

  • Infants and children under 6 years old - 57%.
  • Children aged 6 to 19 years old - 18%.
  • Patients older than 19 years old - 22%.


Use without the secret intent of plants containing SG, rarely leads to death. However, other plants causing the development of a similar cardiac toxicity syndrome (for example, aconite) result in death after consumption. Fatal outcomes are most often associated with severe arrhythmias and refractory hyperkalemia. The severity of hyperkalemia predicts the overall outcome and severity of complications.

Complications of toxicity when using plant cardiac glycoside are secondary to disorders of tissue perfusion caused by hypotension, fever. Most often occurs:

  • Seizures hypoxemia.
  • Ischemic stroke.
  • Myocardial ischemia.
  • Encephalopathy.
  • Acute tubular necrosis.

Mortality / Morbidity

Factors contributing to an increase in morbidity and mortality are similar to those affecting patients with digoxin poisoning. They are generally divided into categories that are specific to humans and plants.

Predisposing factors associated with a person:

  • Old age.
  • The presence of a concomitant disease, such as renal failure, myocardial ischemia, hypothyroidism, hypoxia and electrolyte disturbance (for example, hypokalemia, hyperkalemia, hypomagnesaemia, hypercalcemia).

Predisposing factors specific to plants:

  • Type of plant containing cardiac glycoside.
  • The part that got into the body.
  • The specificity of the type of glycosidic component contained in the plant.
  • Concentration of cardiac glycosides.

Mortality is rare, but cases of illness indicating deaths from oleander, foxglove, squall and other related plants exist. In 2015, despite the fact that the AECSA reported about 2 deaths out of 1,370 cases involving glycoside-containing plants, 18 out of 1,253 cases of exposure to pharmaceutical cardiac glycosides were reported during the same period.

The AECSB noted a moderately significant incidence of less than 2% of plant cardioglycosides. In contrast, moderate and serious morbidity was observed in 48% of the pharmaceutical cardiac glycosides. In part, this may reflect lower concentrations of bioactive cardiac glycosides in plants. In addition, the pharmaceutical effects are usually most often seen in the older population (after 60 years) and mainly due to deliberate ingestion.

Most plant exposures occur in children under the age of 6 years and are usually unintentional and not associated with significant toxicity. More serious toxicity occurs during intentional administration in adolescents and adults.

Antidotes of cardiac glycosides

Therapeutic treatment options for cardiac glycoside toxicity are based on the following actions:

  • The use of pharmacological antagonists of bradycardia.
  • Reversing inhibition of Na + -K + -ATPases.
  • Enhanced removal of cardiac glycosides.

In 40% of patients with severe cardiotoxicity during treatment with yellow oleander, the sinus rhythm can recover in a few hours without special treatment, but it is impossible to determine with certainty who it will probably happen.

Spontaneous resolution due to acute digoxin poisoning has been reported less frequently, since such data are limited.The role of the antidote for the treatment of chronic digoxin poisoning is not fully understood. Key antidotes are presented in the table below.

Indications Treatment Dose
Known or potential toxicity Several tablets of activated carbon 50 g for the first time, then 25 g every 2-4 hours for 24 hours, but other modes are also used.
Hyperkalemia, renal failure, bradycardia, not responding to atropine, with ventricular arrhythmias. Anti-digoxin Fab
  • Two vials (80 mg each) in accordance with the clinical response to acute digoxin poisoning.
  • One vial (40 mg) for chronic digoxin poisoning can be repeated, if necessary, after 1 hour.
  • 20-30 vials (800-1200 mg) for poisoning with acute yellow oleander.
Hyperkalemia Intravenous Insulin and Dextrose 50 ml of 50% dextrose and then 10 units of short-acting insulin iv
Bradycardia Intravenous atropine 0.5-1 mg.
Bradycardia (and possibly hyperkalemia) Intravenous isoproterenol (isoprenaline) or oral salbutamol
Bradycardia and conduction block Temporary cardiac stimulation According to the usual rules.

Key points

  • Cardiac glycosides are drugs of organic origin, which, due to the peculiarities of their structure, can increase the strength of cardiac output without increasing the heart rate.
  • The most widely used digoxin, digitoxin, relatively often - strophanthin, other glycosidic drugs are less accessible to a wide circle of the population.
  • The therapeutic window of cardiac glycosides is very narrow, sometimes intersects with toxicity, which is why they are increasingly being replaced by synthetic agents like adrenergic blockers.
  • When determining the symptoms of an overdose, antidote treatment is required (atropine, anti-digoxin Fab, isoproterenol), although in some cases the manifestations of intoxication pass on their own.
  • In severe cases, the reception of cardiac glycosides can trigger the development of encephalopathy, myocardial infarction, stroke, acute tubular necrosis.

Video: Why cardiologists do not like not to prescribe glycosides

Source 1. Bessen HA. Therapeutic and toxic effects of digitalis: William Withering, 1785. J Emerg Med. 1986; 4(3):243-8 2. Сердечные гликозиды - Википедия - свободная энциклопедия 3. Bronstein, Alvin C.; Spyker, Daniel OiA.; Cantilena, Louis R.; Green, Jody L.; Rumack, Barry H.; Giffin, Sandra L. (2009-12-01). ""2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report"". Clinical Toxicology. 47 (10): 911–1084 4. Под ред. проф. Р.Н. Аляутдина. Фармакология: учебник. — 4-е изд., перераб. и доп.. — Москва: “ГЭОТАР-Медиа”, 2010. — С. 377, 423-431. — 832 с.

4.67 avg. rating (91% score) - 3 votes - votes

Similar articles

Heart failure

In cardiology, there is such a term as heart failure. What threatens this pathology is important to know all patients with severe cardiovascular disease. The timely provision of medical care helps to alleviate the patient's condition with this pathology, and in some cases prevent a sudden cardiac arrest.

Myocarditis cardiosclerosis: symptoms and treatment

Myocarditis cardiosclerosis is a pathology in which parts of the myocardium involved in inflammation die and are replaced by connective tissue. It is considered the most common form of cardiosclerosis. The fuller name that is used in professional medical sources is postmiocardic cardiosclerosis.


Among all cardiovascular pathologies, the most frequent complication of infectious diseases is myocarditis. Its prevalence is difficult to assess, since much depends on the occurrence of the underlying disease. If diphtheria accounts for an average of 25%, then ARVI rarely reaches 15%.


Leave a Reply

Your email address will not be published.