Wan Nian Qing

This is a genuine digoxin-type interaction, not a theoretical one. The rhodexins are cardenolides acting at the identical molecular target as digoxin, the alpha subunit of the sodium-potassium ATPase, and one of them is a glycoside of digitoxigenin, the aglycone of digitoxin itself; small amounts of digitoxin are reported in the plant directly. Adding this herb to a digoxin regimen is pharmacologically the same as raising the digoxin dose by an unknown amount, at a target where the therapeutic window is already narrow. The margin is small in absolute terms: the minimum lethal intravenous dose of the extract is reported at 0.091 mg/kg in the cat and 0.29 mg/kg in the rabbit. A further problem is measurement - plant cardenolides cross-react with digoxin immunoassays, so a serum digoxin level taken while the patient is on this herb cannot be interpreted, and may be falsely reassuring or falsely alarming.

Cardenolide binding to the sodium-potassium ATPase competes with potassium at the extracellular potassium site, so a fall in serum potassium increases the degree of pump inhibition at any given glycoside concentration. Hypomagnesaemia has the same effect. This is the best characterised mechanism by which digitalis toxicity is precipitated in clinical practice, and it applies to plant cardenolides without modification. The risk is compounded here because the herb itself is diuretic and is traditionally prescribed for oedema and heart failure, exactly the patients who are also on loop diuretics.

The plant's glycosides slow the heart rate through vagal excitation and directly depress atrioventricular conduction; in overdose the recorded pattern is premature beats progressing to complete conduction block. Beta-blockers, the non-dihydropyridine calcium channel blockers and amiodarone depress AV conduction by separate mechanisms, so the effects are additive on the same node. Amiodarone and verapamil additionally raise circulating digoxin concentrations by inhibiting P-glycoprotein, and the rhodexins are structurally the kind of substrate that transporter handles.

Sodium-potassium ATPase inhibition raises intracellular sodium and, through the sodium-calcium exchanger, intracellular calcium; this is the mechanism of the positive inotropic effect and also of glycoside-induced afterdepolarisations. Giving intravenous calcium on top of a cardenolide load adds to an already elevated intracellular calcium and has long been regarded as hazardous in digitalis toxicity. The same reasoning applies to the rhodexins.

Several drugs in the Chinese materia medica are cardenolide-bearing, most importantly Xiang Jia Pi, the bark of Periploca sepium, which is cardioactive and is a well known point of confusion with the non-cardioactive Wu Jia Pi (Eleutherococcus). Combining any two cardenolide herbs stacks activity at the same target with no way to calculate the resulting dose, because neither is standardised. Periplogenin glycosides occur in Rohdea itself, underlining the chemical overlap.

Extracts of this plant stimulate the smooth muscle of the bladder and uterus in addition to their cardiac effects, and the Chinese materia medica record the drug as prohibited in pregnancy. The cardiac glycoside content would in any case make it unacceptable in pregnancy.