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 is also found in a number of Chinese herbal remedies, most notably chuanwu and caowu and the Tibetan medicine Manquin. 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.

1. These lipid soluble toxins bind with high affinity to the open state of voltage-sensitive sodium channels resulting in persistent activation of the channel. With sustained depolarization, the sodium channels become refractory to excitation.
2. 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.

1. 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. In traditional Chinese medicine, aconite roots are used only after processing to reduce the toxic alkaloid content. The lethal dose of aconitine is 0.1 mg/kg in mice and approximately 2 mg orally in humans.

1. Poisoning results in a combination of neurologic, cardiovascular, and gastrointestinal features. The onset of symptoms ranges from 3 minutes to 2 hours, but typically occurs within 10-20 minutes. Initial symptoms may include sneezing, diaphoresis, chills, weakness, perioral and limb numbness, and paresthesias, 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.
2. Death is usually due to ventricular arrhythmias. A characteristic but uncommon electrocardiographic finding is bidirectional ventricular tachycardia, similar to that seen with digitalis and other cardiac steroids.
3. In a retrospective review of 17 patients who ingested herbal aconitine, the recovery time varied from 1.5 to 2 days in mildly intoxicated patients, whereas patients with cardiovascular complications, including ventricular tachycardia, recovered in 7-9 days.
4. Hyperventilation resulting in respiratory alkalosis may be seen as a consequence of the central effect of aconitine on the medullary center.

Of sodium channel opener poisoning should be considered in anyone with the rapid onset of paresthesias, weakness, and ventricular tachycardia. Signs and symptoms resemble that of cardiac steroid poisoning with the addition of neurologic features.

1. Specific levels. Diagnosis is based on a history of exposure, with careful consideration of any herbal medicine use. Routine laboratory testing is unlikely to be helpful. Blood and urine aconitine, veratridine, and grayanotoxins can be obtained by using liquid and gas chromatography with mass spectrometry but only through specialized toxicology reference laboratories.
2. Other useful studies include electrocardiogram, electrolytes, and glucose.

1. Emergency and supportive measures. Treatment is therapeutically challenging and based primarily on case report data. Patients who have ingested plants with aconitine alkaloids should be admitted to a monitored setting, even if initially asymptomatic.
   1. Protect the airway and assist ventilation if necessary.
   2. Treat bradycardia, hypotension, coma, and seizures if they occur.
   3. Amiodarone and flecainide are reasonable first-line agents for ventricular tachycardia.
   4. Magnesium is recommended for prolonged QT interval and torsade de pointes.
   5. Early use of extracorporeal membrane oxygenation (ECMO) is recommended if ventricular arrhythmias and cardiogenic shock are refractory to first-line treatment.
2. Specific drugs and antidotes. None.
3. Decontamination
   1. Single-dose activated charcoal should be considered in patients who present within 1 hour of ingestion and have an intact or protected airway. Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
   2. Whole-bowel irrigation has not been evaluated in the management of Aconitum or other sodium channel opener ingestions. Because of the rapid absorption of these diterpene alkaloids, it is not recommended.
4. Enhanced elimination. The lipophilicity of these compounds and their large volumes of distribution make them poor candidates for extracorporeal removal.