Cardiac glycosides

CARDIAC GLYCOSIDES

• Cardiac glycosides or digitalis essentially refer to a group of chemically and pharmacologically related drugs, that act on the heart by causing atrioventricular conduction and vagal tone.
• They are invariably employed to slow the heart rate in atrial fibrillation and also administered in congestive heart failure.
• A large number of ‘drug substances’ are able to enhance the force of contraction of the heart. It is, however, pertinent to state here that this ionotropic activity may be specifically of great utility and importance in the ultimate treatment of congestive heart failure

Cardiac Glycosides

• Drugs originally obtained from plant source, Digitalis purpurea and Digitalis lanata
• Digoxin and digitoxin are the only cardiac glycosides currently available
• Main pharmacologic effect of cardiac glycosides is to increase the contractile force of myocardial contraction
• Cardiac glycosides also decrease heart rate and atrioventricular conduction

Digoxin

The side chain of digoxin is made up of three molecules of digitoxose in a glycosidic linkage, which upon hydrolysis yields the aglycone, digoxigenin (C23 H34 O5).

Digoxigenin is obtained from the leaves of Digitalis lanata Ehrh. (Family : Scrophulariaceae). Its cardiotonic actions are very much alike to those of digitalis. It is used in the treatment of congestive heart failure

Digitoxin

Digitoxin is obtained from Digitalis purpurea Linne, Digitalis lanata Ehrh, and other suitable species of Digitalis.

Its side chain is comprised of three molecules of digitoxose in a glycosidic linkage. Hydrolysis affects removal of the side chain to yield the aglycone, digitoxigenin (C23H34O4).

Digitoxin is the most potent of the digitalis glycosides besides possessing its inherent maximum cumulative action

Mechanism of Action

• Cardiac glycosides inhibit Na/K adenosine triphosphatase, the “sodium pump” which causes more Na to remain inside myocardial cells
• Increased intracellular Na stimulates Na/Ca exchange that brings more Ca inside heart cells to increase the force of contraction
• Cardiac glycosides also stimulate the vagus nerve which decreases heart rate

Pharmacokinetics and Dosing

• Digoxin is water soluble and eliminated mostly unmetabolized by the urinary tract
• Digitoxin is more lipid soluble, requires metabolism, and has a longer half-life
• In acute CHF, initial “digitalization” doses are administered to rapidly attain effective therapeutic concentration
• Lower daily maintenance doses are then given to maintain desired therapeutic concentrations

Electrolyte and Cardiac Glycoside Interactions

• Low serum potassium (K) levels “hypokalemia” increase drug toxicity and can cause cardiac arrhythmias
• High serum potassium levels “hyperkalemia” decrease the actions of the cardiac glycosides
• Increased serum calcium levels “hypercalcemia” can increase the actions and toxicity of the cardiac glycosides

Adverse Effects

• Common complaints include headache, dizziness, nausea, and vomiting
• Visual disturbances “halo effect” around lights often signals overdosage
• Bradycardia, ectopic beats, and a variety of other cardiac arrhythmias can occur and can be life-threatening

Diuretic Therapy of CHF

• Diuretic drugs are used to eliminate excess sodium and fluid retention
• Elimination of excess fluid allows the heart to function more efficiently
• Diuretics can be administered with cardiac glycosides and other drugs used to treat CHF

Vasodilator Therapy of CHF

• Vasodilator drugs relax and dilate blood vessels
• Vasodilation decreases peripheral resistance, allows more efficient blood flow, and usually increases cardiac output
• Angiotensin-converting enzyme inhibitors and angiotensin receptor blocking drugs are particularly useful in CHF