Pharmacological treatment of cardiac glycoside poisoning

Abstract

Cardiac glycosides are an important cause of poisoning, reflecting their widespread clinical usage and presence in natural sources. Poisoning can manifest as varying degrees of toxicity. Predominant clinical features include gastrointestinal signs, bradycardia and heart block. Death occurs from ventricular fibrillation or tachycardia. A wide range of treatments have been used, the more common including activated charcoal, atropine, β-adrenoceptor agonists, temporary pacing, anti-digoxin Fab and magnesium, and more novel agents include fructose-1,6-diphosphate (clinical trial in progress) and anticalin. However, even in the case of those treatments that have been in use for decades, there is debate regarding their efficacy, the indications and dosage that optimizes outcomes. This contributes to variability in use across the world. Another factor influencing usage is access. Barriers to access include the requirement for transfer to a specialized centre (for example, to receive temporary pacing) or financial resources (for example, anti-digoxin Fab in resource poor countries). Recent data suggest that existing methods for calculating the dose of anti-digoxin Fab in digoxin poisoning overstate the dose required, and that its efficacy may be minimal in patients with chronic digoxin poisoning. Cheaper and effective medicines are required, in particular for the treatment of yellow oleander poisoning which is problematic in resource poor countries.

Toxicarioside H induces drug-resistant mitophagy via promoting expression of sirtuin-3 in lung cancer cells

“…Lesch (Moraceae) [15] and structural analysis with MS and NMR confirmed that ToxH is a cardiac glycoside with a special cardenolide structure ( Figure 1A). Recent studies suggest that cardenolides derive anticancer activities via the induction of cancer apoptosis [16][17][18]. Since ToxH is a new cardenolide structure, its cytotoxicity was confirmed using an MTT assay [15].…”

“…Structural analysis by MS and NMR spectral data and chemical evidence show that ToxH is a cardiac glycoside with a special cardenolide structure ( Figure 1A) [15]. Recent research results indicate that cardenolides extracted from natural sources can have anticancer activity and can block tumor cell proliferation and induce tumor apoptosis via the regulation of several cell signaling pathways and sodium pump inhibition [16][17][18][19], and even through the induction of immunogenic cell death [20][21][22]. At this time, the anticancer activity of cardenolides has not been linked to mitophagy.…”

Comprehensive review of cardiovascular toxicity of drugs and related agents

“…Activated charcoal is used to avoid further absorption of the cardiac glycoside and interrupt the enterohepatic circulation. Atropine is preferred for bradycardia or AV blocks and temporal pacing can also be used . The digoxin‐specific antibody fragments are very important in the treatment of moderate or severe intoxication.…”

“…Atropine is preferred for bradycardia or AV blocks and temporal pacing can also be used. 305 The digoxin-specific antibody fragments are very important in the treatment of moderate or severe intoxication. As a result of their use, the mortality from digoxin intoxication dropped from 20-30% to 5-8%.…”

Who gets antidotes? choosing the chosen few

“…Titration to the desired effect is also generally used for atropine (titrated to cholinergic signs in cholinesterase inhibitor poisoning) , flumazenil (coma) , vitamin K (prothrombin time) , protamine (activated partial thromboplastin time), octreotide (blood glucose) , methylene blue (methaemoglobinaemia), calcium (blood pressure) , insulin (blood pressure), physostigmine (coma or delirium) , sodium bicarbonate (blood or urine pH), ethanol (ethanol concentration) and digoxin‐Fab (rate and rhythm) . The dose of an antidote can be far higher than the doses required when these drugs are used for other indications (Table ).…”