Aconitine is probably the best-known of the sodium channel openers and is found in monkshood or wolfsbane (Aconitum napellus). Other sodium channel openers include veratridine from false or green hellebore (Veratrum genus), grayanotoxins from azalea and rhododendron (Rhododendron species), death camas (Zigadenus), and mountain laurel (Kalmia latifolia),
Aconitine has been found in a number of Chinese herbal remedies, most notably chuanwu and caowu. Most cases of acute poisoning result from the ingestion of herbs containing aconitine. Grayanotoxins have largely been reported to cause intoxication in regions where honey is produced from Rhododendron species. Veratridine has historically been used in both insecticides and medicinals.
Symptoms of sodium channel opener poisoning include numbness, tingling of the lips and tongue, bradycardia or irregular pulse, gastroenteritis, respiratory failure, and vagus nerve stimulation. The paramount concern in managing acute poisoning is the management of lethal arrhythmias.
Mechanism of toxicity
These toxins primarily activate voltage-gated sodium channels. They are lipid-soluble diterpenoid alkaloids, which allows them access to the sodium channel–binding site embedded within the plasma membrane, where they preferentially bind to the open state of the sodium channel. They exert their action on nerve and muscle membranes by persistent activation of channel at the resting membrane potential.
Sodium channel openers cause early and delayed after-depolarizations in ventricular myocytes, which may be due to increased intracellular calcium and sodium. This may explain the reports of biventricular tachycardia and torsade de pointes in patients with aconitine intoxication.
The amount and composition of plant alkaloids are the main factors determining the severity of intoxication, and these vary greatly with different species, the time of harvesting, and the method of processing. The lethal dose of aconitine is 0.22 mg/kg in mice and about 2 mg orally in humans.
Poisoning results in a combination of cardiovascular and neurologic toxicity. The onset of symptoms is 3 minutes to 2 hours, but typically within 10–20 minutes. Initial symptoms may include sneezing, diaphoresis, chills, weakness, perioral and limb numbness, and paresthesias, which are followed by vomiting, diarrhea, bradycardia with first-degree heart block or junctional bradycardia, dysrhythmias (including torsade de pointes), hypotension, CNS and respiratory depression, and seizures.
Death is usually due to ventricular arrhythmias. A characteristic but uncommon electrocardiographic finding is bidirectional ventricular tachycardia, similar to that seen with digoxin and other cardiac steroids.
In a retrospective review of 17 patients who had ingested herbal aconitine, the recovery time was from 1.5 to 2 days in mildly intoxicated patients, whereas patients with cardiovascular complications, including ventricular tachycardia, recovered in 7 to 9 days.
Hyperventilation resulting in respiratory alkalosis may be seen as a consequence of the central effect of aconitine on the medullary center.
Diagnosis of sodium channel opener poisoning should be considered in anyone with the rapid onset of paresthesias, weakness, and ventricular tachycardia.
Specific levels. Diagnosis is based on a history of exposure. Routine laboratory testing is ...