Origin and classification of drugs
The source of cardiac glycosides is medicinal plant materials. In modern medical practice, drugs isolated from plants of three main groups are used:
- Foxglove glycosides (Digitalis) — include digoxin, acetyldigoxin B, and lanatoside C.
- Strophanthus glycosides (Strophanthus) — represented by ouabain (strophanthin G).
- Lily of the valley glycosides (Convallaria) — contain corglycon and convallatoxin.
Digitoxin and lily of the valley preparations historically used are not included in the list of current modern therapy agents.
Molecular mechanism of action
The action of the drugs is based on influencing ion transport across the cardiomyocyte sarcolemma.
- Target: Blockade of the K+, Na+-ATPase enzyme (sodium-potassium pump).
- Ionic shifts: The cessation of sodium extrusion from the cell leads to its accumulation (hypernatriohystia) and a decrease in intracellular potassium (hypopotassthihystia).
- Calcium cascade: Sodium accumulation disrupts the functioning of the Na+, Ca2+ exchanger, which slows down calcium excretion and increases its concentration in the cytosol.
Excess calcium is deposited in the sarcoplasmic reticulum and released upon excitation, providing a powerful myocardial contraction.
Main pharmacological effects
The effect of cardiac glycosides on the heart muscle produces four main effects:
- Positive inotropic: increased force and shortening of systole.
- Negative chronotropic: reduction in heart rate (development of bradycardia) and prolongation of diastole, which ensures an economical mode of heart function.
- Negative dromotropic: slowing of conduction through the atrioventricular junction.
- Positive bathmotropic: increased myocardial excitability (in small doses).
The slowing of rhythm and conduction is due to vagotonia — an increase in vagus nerve tone.
Clinical use and side effects
Cardiac glycosides are prescribed for acute and chronic heart failure, as well as for the tachy-systolic form of atrial fibrillation.
The choice of drug depends on the speed of onset of the effect:
- Ouabain is administered only intravenously in acute conditions (effect occurs in 2–10 minutes).
- Digoxin is versatile: intravenously for acute failure, and orally for chronic conditions.
Overdose causes dangerous rhythm and conduction disorders (ventricular extrasystoles, AV blocks), as well as extra-cardiac symptoms: dyspepsia, visual disturbances in the form of xanthopsia, and neurological disorders.
Briefly: answers to topical questions
What specific rhythm and conduction disorders are characteristic of glycoside intoxication?
Glycoside intoxication is characterized by various rhythm and conduction disorders associated with altered automatism and suppression of impulse conduction.
- Ventricular extrasystoles — occur as a result of increased ventricular automatism.
- Atrioventricular block — develops as a consequence of the negative dromotropic effect.
- Ventricular paroxysmal tachycardia — sequential occurrence of 5 or more ventricular extrasystoles.
- Ventricular flutter and fibrillation — terminal rhythm disorders.
- Non-paroxysmal AV junctional tachycardia — occurs with prolonged use.
At high doses, atrial fibrillation can transition into flutter and the appearance of an autonomous (idioventricular) rhythm.
What specifically are the manifestations of dyspeptic and neurological symptoms in cardiac glycoside overdose?
Cardiac glycoside overdose presents with systemic extra-cardiac disorders:
- Dyspeptic disorders — nausea, vomiting, and diarrhea.
- Neurological and psychiatric disorders — headache, sleep disturbances, psychomotor agitation, and hallucinations.
- Visual disturbances — xanthopsia, i.e., impaired color perception with visible objects colored yellow and green.
What are the absolute and relative contraindications to the prescription of cardiac glycosides?
Sources do not provide a strict division into absolute and relative contraindications, however, the following conditions are listed where the prescription of cardiac glycosides is contraindicated or not recommended:
- Atrioventricular block (AV block).
- Hypertrophic cardiomyopathy — with a stable sinus rhythm, drugs are contraindicated due to aggravation of obstruction and proarrhythmic effect.
- WPW syndrome (ventricular pre-excitation) — when combined with atrial fibrillation or flutter, drugs are potentially dangerous as they can cause an increase in ventricular rate.
What drugs are used as antidotes for the treatment of cardiac glycoside poisoning?
Specific and antidote therapy drugs that bind the toxin or restore enzyme activity are used to treat cardiac glycoside poisoning.
- Digoxin antibody preparations (e.g., DigiFab/Digibind) — monoclonal antibodies that bind cardiac glycosides into inactive complexes.
- Unithiol — a donor of sulfhydryl groups that forms disulfide bridges with the glycoside molecule and releases its own thiol groups of $Na^+,K^+$-ATPase, restoring the transport function of the enzyme.
What ECG changes are caused by therapeutic doses of cardiac glycosides?
When taking cardiac glycosides, the following ECG findings are noted:
- ST segment — characteristic "scoop-like" depression.
- T wave — amplitude reduction.
- Q–T interval — shortening.
With prolonged use, ventricular extrasystole, non-paroxysmal AV junctional tachycardia, ventricular tachycardia, and conduction disturbances are possible.
F-K-K: Foxglove, Potassium down, Calcium up — strong contraction!
Class and exam questions
What is the main pharmacological effect characteristic of cardiac glycosides?
The primary effect is a positive inotropic effect, that is, an increase in myocardial contractility due to an elevation in cytosolic calcium ion concentration within cardiomyocytes.
What is the difference in the pharmacokinetic role of the glycone and aglycone?
The glycosidic part (glycone) determines the solubility, absorption, cumulation, and excretion of the drug, whereas the non-sugar part (aglycone) is responsible for the specific pharmacodynamic properties and mechanism of action.
What are the causes and manifestations of xanthopsia in overdose?
Xanthopsia is a specific symptom of intoxication in which color perception is impaired, and surrounding objects are colored yellow and green.
What else to study on this topic
- Structural differences between the aglycones of digitoxin, digoxin, and strophanthidin
- The role of secondary glycosides in the prolonged circulation of drugs in the bloodstream
- Mechanism of the diuretic action of cardiac glycosides
- Biological standardization of crude drugs and the frog unit (FU)
- Effect of cardiac glycosides on the automatism of various parts of the cardiac conduction system
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