Cao Wu

This record carries the Latin name Radix Aconiti Kusnezoffii Preparata, which names the processed drug, while the slug, the pinyin name Cao Wu and the parallel zhi-cao-wu record all identify this entry as the raw root. The two are pharmacologically different drugs. Raw Cao Wu carries its diester alkaloids intact; processing by prolonged steaming or boiling hydrolyses the C8 acetyl ester to the monoester alkaloids and, with further heating, the C14 benzoyl ester to the amine alcohols, a stepwise loss of toxicity of roughly two to three orders of magnitude that has been demonstrated directly by comparing unprocessed with processed aconite roots. A record in which the raw and the processed drug are indistinguishable invites a dispenser to supply raw root against a prescription written for the processed one, at doses set for the processed drug. Because the fatal dose is a few milligrams of alkaloid, that single substitution is lethal.

Decoction is not merely extraction; it is the last stage of detoxification. Mass-spectrometric studies of the aconite decoction process show diester alkaloids undergoing ester exchange and hydrolysis in the boiling pot, with diester content falling and monoester and amine alcohol content rising as boiling continues. A dose that is safe after the traditional prolonged pre-decoction of aconite is not safe if the herb is added late, boiled briefly, taken as a powder, infused rather than boiled, or extracted into alcohol. Duration of boiling is therefore a dosing variable of the same order of importance as the weight on the scale.

Aconite alkaloids are considerably more soluble in ethanol than in water, and steeping in spirit performs no hydrolysis, so a medicinal wine concentrates intact diester alkaloids rather than degrading them. Reviews of the causes of herb-induced aconite poisoning in Asia and of contributory factors in fatal cases repeatedly identify home-made or commercially prepared aconite-containing liquors, and consumption of a larger-than-intended volume, as a recurrent lethal pattern.

Aconitine and mesaconitine are absorbed through skin. Percutaneous absorption of both alkaloids has been measured directly from extracts of Radix Aconitum kusnezoffii, and systemic aconite poisoning following percutaneous absorption of Aconitum alkaloids is documented in the forensic literature. Broken skin, occlusive dressings, large treated areas, heat and prolonged contact all increase the absorbed dose, and the patient receives no warning taste or gastrointestinal signal.

Aconite alkaloids produce bidirectional ventricular tachycardia through persistent sodium-channel opening and consequent calcium overload; digitalis toxicity produces the same rhythm through sodium-potassium ATPase inhibition and calcium overload. The two mechanisms converge on the same arrhythmia, and bidirectional ventricular tachycardia is one of the very few rhythms in which either poison should be suspected. Case reports of herbal aconite poisoning presenting with bidirectional tachycardia establish the arrhythmogenic effect in humans.

Aconite poisoning presents with hypotension and bradycardia as well as with tachyarrhythmia, and both patterns are described in the clinical toxicology literature. Drugs that independently depress sinus node function, atrioventricular conduction or myocardial contractility add to that effect, and they also complicate recognition, because the bradycardia may be attributed to the prescribed drug rather than to the herb.

Aconite poisoning is not confined to overdose or mislabelling. Contamination of other herbs by aconite root during collection, drying, storage, cutting or grinding is a documented cause of Aconitum alkaloid poisoning, and poisoning has also followed the culinary use of aconite roots. Retrospective Hong Kong series covering 1989 to 2010 and 2008 to 2020 record cases arising in the course of ordinary practice, including from correctly labelled material, with the alkaloids confirmed analytically in patient samples.

Aconitine, mesaconitine and hypaconitine are cleared largely by oxidative and ester-hydrolytic metabolism, and their metabolites have been characterised in rat blood by sensitive chromatographic methods. Inhibiting that clearance raises plasma concentration of intact diester alkaloid. Direct human interaction studies have not been done, and given the lethality of the drug they are unlikely ever to be done, so this is mechanistic inference from established metabolic routes rather than a measured interaction.