A review of cardiac glycosides: Structure, toxicokinetics, clinical signs, diagnosis and antineoplastic potential

Cardiac glycosides (CGs) are secondary compounds found in plants and amphibians and are widely distributed in nature with potential cardiovascular action. Their mechanism is based on the blockage of the heart's sodium potassium ATPase, with a positive inotropic effect. Some of the most well-known CGs are digoxin, ouabain, oleandrin, and bufalin. They have similar chemical structures: a lactone ring, steroid ring, and sugar moiety. Digoxin, ouabain, and oleandrin are classified as cardenolides, consisting of a lactone ring with five carbons, while bufalin is classified as bufodienolides, with a six-carbon ring. Small structural differences determine variations in the toxicokinetics and toxicodynamics of such substances. Most case reports of poisoning caused by CGs are associated with cardiovascular toxicity, causing a variety of arrhythmias and lesions in the heart tissue. Experimental studies also describe important similarities among different CGs, especially regarding species sensitivity. Recent studies furthermore focus on their antineoplastic potential, with controversial results. Data from research studies and case reports were reviewed to identify the main characteristics of the CGs, including toxicokinetics, toxicodynamics, clinical signs, electrocardiographic, pathological findings, antineoplastic potential and the main techniques used for diagnostic purposes.