Cardioactive steroid poisoning: A comparison of plant- and animal-derived compounds

Abstract

Introduction: Cardioactive steroids (CASs) are found in plants, animals, and insects. Their affinity for Na+-K+ ATPase is attenuated by the type of lactone at carbon 17 (C17) of the steroid backbone: those with 5-membered lactone rings, or cardenolides, are derived mostly from plants with 6-membered rings or from animals with bufadienolides. A systematic review of CAS poisoning was performed to compare the mortality rate of cardenolides and bufadienolides.Methods: MEDLINE was searched for articles using commonly reported names of CASs, and keywords were limited to human cases only. We searched cases from 1982 to 2003, so that supportive care was similar and digoxin-specific Fab was available. Identified reports of CAS poisoning were read to exclude cases involving licensed pharmaceuticals. Inclusion criteria included hyperkalemia, gastrointestinal symptoms, electrocardiographic evidence of CAS toxicity, digoxin serum concentration, or history of exposure to a substance containing a CAS. Clinical data was collected, including information about treatment with digoxin-specific Fab and treatment outcome.Results: Fifty-nine articles, describing 924 patients, were identified. Eight hundred ninety-seven patients (97%) ingested a CAS with a 5-membered lactone ring, and mortality was 6% (n = 54). Twenty-seven patients (2.9%) ingested a CAS with a 6-membered lactone ring, and mortality was 29.6% (n = 8). The difference in mortality rates was statistically significant (p < 0.001, [X 2 ]). CASs with 6-member rings accounted for the highest percentage of nonsuicidal exposures.Conclusion: Although cardenolides accounted for the majority of exposures, bufadienolides were five times more lethal than cardenolides.

Independentlyevolved toad‐eating snakes exhibit sexually dimorphic enlargement of adrenal glands

“…They found distinct mutations in toads, suggesting that the bufadienolidebinding sites of NKA have been altered through evolution to confer resistance to cardiotonic steroids. Zhen et al (2012) reported that several independent lineages of insects that consume cardiotonic cardenolides, which are similar in chemical structure and pharmacological action to bufadienolides (Barrueto Jr et al, 2006), have evolved mutant forms of NKA that confer resistance to those toxins. A similar study by Feldman et al (2009) on tetrodotoxin (TTX)-resistant garter snakes (Thamnophis) found mutations in the genes coding for sodium channels (NA v1.4), which are the target molecules of TTX.…”

“…Zhen et al . () reported that several independent lineages of insects that consume cardiotonic cardenolides, which are similar in chemical structure and pharmacological action to bufadienolides (Barrueto Jr et al ., ), have evolved mutant forms of NKA that confer resistance to those toxins. A similar study by Feldman et al .…”

Native Medicines and Cardiovascular Toxicity

“…The effective substance in the plants are ephedrine and pseudoephedrine. 63 Cardiovascular toxic manifestations of Ephedra include arrhythmias (e.g., ventricular tachycardia/fibrillation), acute myocardial infarction, vasoconstriction, hypersensitivity myocarditis, coronary artery aneurysm, thrombosis, and vasculitis. 64À67 Pathogenesis include endothelial dysfunction, stimulation of alpha and beta receptor agonist with increased secretion of catecholamines, and promoting inflammatory process.…”

Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease

“…Ouabain belongs to a group of compounds, the cardiotonic steroids, which are composed of a steroidal backbone, the aglycone, or genin; a five-membered unsaturated lactone ring; and a sugar moiety, which varies depending on the type of cardenolide (15). Ouabain binds to the extracellular side of the Na-K-ATPase ␣-subunit, preferentially docking to the E2 phosphorylated conformation of the transporter.…”