![]() ![]() However, there may be differences in action between individual cardiac glycosides 2 and this may influence toxicity or response to treatment. It is generally considered that cardiac glycosides have an identical mechanism of action, which has largely been described using digoxin and ouabain. There are limited pharmacokinetic data on other cardiac glycosides in humans. The number of seeds ingested correlates poorly with the area under the concentration–time curve or severity of cardiotoxicity, suggesting variability in bioavailability 8. ![]() The apparent terminal half‐life is also highly variable, with a median time of 42.9 h. ![]() For example, the mean elimination half‐life of digitoxin is long at 7.5 days which reflects extensive enterohepatic recirculation 10.Ĭompared with ingestion of yellow oleander extract, the pharmacokinetic profile of digoxin cross‐reacting substances following intentional ingestion of the seed is erratic with prolonged absorption (extending beyond 50 h post‐ingestion in some) which dominates the concentration–time profile. Digitalis cardiac glycosides are thought to undergo enterohepatic recycling, given that multiple doses of activated charcoal (MDAC) increase clearance (discussed later). In acute poisoning, the initial serum digoxin concentration may be very high and will not reflect the total body burden because full distribution has not occurred. The onset of digoxin's effect is delayed by approximately 6 h, which reflects the time for distribution to a peripheral compartment and/or time‐dependent binding to the Na +‐K +‐ATPase 11. The pharmacokinetics of digoxin vary, including absorption (can relate to the formulation 9), duration of distribution (2–6 h) and elimination half‐life (mean 40 h, range 20–50 h), and elimination is predominantly renal 10. Individual cardiac glycosides vary widely in their pharmacokinetic properties, despite similarities in structure 8. Treatment is complicated due to variability in toxic threshold, diagnostic tests, delayed onset of toxicity (particularly in the case of yellow oleander), requirement for hospital transfer and availability of efficacious and affordable treatments 5. Ingestion of seeds (yellow oleander) or oleander leaves can be associated with severe poisoning and death. Yellow oleander poisoning is a major public health issue in some regions of Sri Lanka and India 6, 7. Yellow oleander and common oleander are found throughout the tropics and subtropics 5. Digoxin poisoning may follow intercurrent illnesses and/or prescribing or dispensing errors, and accidental or intentional poisoning. For example, in the US alone, thousands of cases of cardiac glycoside poisoning were referred to US Poison Control Centers in 2013 and the majority were treated in a healthcare facility 4. This reflects the long‐standing and widespread therapeutic use of digitalis glycosides, particularly digoxin, but also epidemic and sporadic poisoning with oleander plants. Unfortunately, poisoning due to cardiac glycosides is a world‐wide phenomenon. Oleandrin, folineriin, adynerin, digitoxigeninīufalin, marinobufagenin, telocinobufagin Glucoscillarene A, proscillaridine A, scillarene A, scilliglaucoside and scilliphaeoside Thevetin A and B, peruvoside, neriifolin, thevetoxin, ruvoside, theveridosideĬonvallarin, convallamarin, convallatoxinĭigitalis sp (including D. Cheaper and effective medicines are required, in particular for the treatment of yellow oleander poisoning which is problematic in resource poor countries.Ĭascabela thevetia or Thevetia peruviana (previously T. 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. 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). Another factor influencing usage is access. This contributes to variability in use across the world. 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. 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. Death occurs from ventricular fibrillation or tachycardia. Predominant clinical features include gastrointestinal signs, bradycardia and heart block. Poisoning can manifest as varying degrees of toxicity. Cardiac glycosides are an important cause of poisoning, reflecting their widespread clinical usage and presence in natural sources. ![]()
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