Chan Su

Bufadienolides inhibit the cardiac Na+/K+-ATPase by the same mechanism as digoxin and act at the same site. There is no separation of effect, so the combination is straightforward pharmacodynamic addition on a target with a narrow therapeutic index. Fatal Chan Su poisoning has been documented in the West after ingestion of a Chinese herbal tea containing the drug, and the clinical course of toad venom poisoning is described in the literature as resembling acute digitalis overdose. Any other cardioactive glycoside-containing herb carries the same additive risk.

This is a diagnostic interaction that must appear on every toad-derived record. Bufadienolides are structurally close enough to digoxin to cross-react with the antibodies used in digoxin immunoassays, producing apparent serum digoxin concentrations in patients who have never taken digoxin. Datta and Dasgupta showed that Chan Su produces marked digoxin-like immunoreactivity on EMIT 2000 and Randox assays, with the magnitude of interference varying widely between different commercial brands of the same product; Reyes and colleagues examined the newer Digoxin III assay with Chan Su and Lu-Shen-Wan. Monoclonal-antibody-based methods generally cross-react less than polyclonal ones, but no assay can be assumed clean. Depending on the assay format, the interference can bias results either upward or downward, so a normal digoxin level does not exclude bufadienolide exposure either.

The same antibody cross-reactivity that ruins the immunoassay is therapeutically useful. Brubacher and colleagues reported successful treatment of toad venom poisoning with digoxin-specific Fab fragments in a clinical case and then demonstrated efficacy experimentally, showing that Fab binds bufadienolides and reverses their cardiac effects. Because the Fab is raised against digoxin, the binding is cross-reactive rather than exact, so dosing cannot be calculated from a serum level in the way it is for digoxin and empirical dosing is required.

Potassium competes with cardiac glycosides for binding to the Na+/K+-ATPase. Lowering serum potassium therefore increases glycoside binding and toxicity at any given drug concentration; this is a firmly established principle for digoxin and applies identically to bufadienolides, which occupy the same site. Conversely, established bufadienolide poisoning itself causes hyperkalaemia through pump inhibition, so the electrolyte picture may swing.

Bufadienolides slow AV conduction and sinus rate through both direct and vagally mediated effects, exactly as digoxin does. Rate-limiting calcium channel blockers, beta-blockade and amiodarone act on the same nodal tissue. The combination risks symptomatic bradycardia and complete heart block. Amiodarone and verapamil additionally raise digoxin levels by transporter inhibition; whether they do the same for bufadienolides is not established, but the pharmacodynamic addition alone is sufficient reason to avoid the combination.

Bufadienolide poisoning produces hyperkalaemia, and the reflex in hyperkalaemia is to give intravenous calcium for membrane stabilisation. In digitalis toxicity this has historically been avoided on the grounds that glycoside-poisoned myocardium is already calcium-overloaded and further calcium may provoke intractable arrhythmia. The evidence for that concern is contested and largely historical, but the underlying calcium overload from Na+/K+-ATPase inhibition is the same for bufadienolides.

Toad venom is sold as a hard topical preparation intended to be applied to the penis to delay ejaculation, and users have swallowed it. Fatalities from this route are documented, and Ko and colleagues separately reported a death from a Chinese herbal tea containing ch'an su. The hazard is that the product is not recognised as a cardiac glycoside by the user or, initially, by the clinician, so the presentation is investigated as an unexplained arrhythmia.