Aconitine Poisoning

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Aconitine poisoning is an acute toxidrome caused by ingestion of the diterpenoid ester alkaloids of Aconitum species (monkshood, wolfsbane) - principally aconitine, mesaconitine and hypaconitine - which are concentrated in the roots and root tubers. Aconite root is a long-standing analgesic and antirheumatic remedy in traditional Chinese and Japanese medicine, where it is used only after processing that hydrolyses the diester alkaloids to far less toxic derivatives; poisoning follows inadequate processing, larger than recommended doses, tincture or wine preparations, or accidental ingestion of the wild plant. The unifying molecular mechanism is binding to neurotoxin site 2 on the alpha subunit of voltage-gated sodium channels in the open state, which suppresses channel inactivation and holds the channel persistently activated. In excitable tissue this produces sustained sodium influx and excessive depolarisation ending in inexcitability. In the myocardium it generates triggered activity from early and delayed after-depolarisations, causing ventricular tachycardia and fibrillation that are characteristically refractory to cardioversion and antiarrhythmic drugs; in peripheral nerve it produces the early sensory paresthesiae and later blocks neuromuscular transmission. Patients present after a latent period of minutes to hours with a combination of neurological, cardiovascular and gastrointestinal features, and the main causes of death are refractory ventricular arrhythmias and asystole. Management is supportive - atropine for bradycardia, inotropes for hypotension, amiodarone or flecainide for ventricular arrhythmia, and early mechanical circulatory support when arrhythmia and cardiogenic shock are refractory.

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1
Mappings
11
Pathophys.
14
Phenotypes
3
Gaps
17
Pathograph
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Medical Actions
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Mappings

ICD-10-CM
ICD10CM:T62.2 Toxic effect of other ingested (parts of) plant(s)
skos:broadMatch
semapv:ManualMappingCuration
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Discussions and Knowledge Gaps

3
Does extracorporeal removal of circulating aconitine alkaloids by charcoal haemoperfusion shorten the duration of ventricular arrhythmia or reduce mortality, relative to supportive care and mechanical circulatory support alone?
KNOWLEDGE GAP OPEN gap_aconitine_charcoal_haemoperfusion_efficacy
Attached to
pathophysiology#Refractory Ventricular Arrhythmia and Circulatory Collapse
The two sources curated here point in opposite directions without contradicting each other, which is precisely why this is a gap rather than a controversy. The Chan review states flatly that the role of charcoal haemoperfusion is not established. The Taiwanese series did give haemoperfusion to all four patients who developed ventricular tachycardia, and all 17 patients recovered completely - but with no control arm, an uncontrolled series in which everyone survives cannot separate a treatment effect from the natural history of a self-limiting toxidrome whose alkaloid is cleared over hours. The pharmacological prior is genuinely uncertain in both directions: aconitine is a lipophilic alkaloid with a large apparent volume of distribution, which argues against meaningful extracorporeal clearance, yet charcoal adsorbs it well in vitro. Resolving this matters clinically because haemoperfusion competes for time, vascular access and anticoagulation with the mechanical circulatory support that the same review does recommend.
Proposed experiments
Registry-based comparative effectiveness analysis of haemoperfusion in aconite poisoning
exp_aconitine_haemoperfusion_extraction_and_outcome
Pooled analysis across national poison-centre registries in regions where aconite preparations are in common use, comparing patients who received charcoal haemoperfusion with those who did not, restricted to patients with documented ventricular arrhythmia and adjusted for severity at presentation. Paired with serial plasma aconitine measurement across the haemoperfusion circuit to quantify actual extraction.
Decision criterion
Whether measured extraction across the circuit is large enough to lower plasma aconitine materially, and whether arrhythmia duration differs between treated and untreated patients after severity adjustment.
Supporting outcome
  • Substantial single-pass extraction of aconitine across the charcoal circuit.
  • Shorter time to arrhythmia resolution in haemoperfused patients after adjustment for presenting severity.
Refuting outcome
  • Negligible extraction across the circuit, consistent with a large volume of distribution.
  • No difference in arrhythmia duration or mortality after severity adjustment.
Does aconitine cause calcium overload, p38 MAPK activation and cardiomyocyte apoptosis in poisoned humans, or is this arm confined to the rodent and cell-culture systems in which it has been demonstrated?
HUMAN MODEL MISMATCH OPEN mismatch_aconitine_calcium_p38_arm_human_relevance
Attached to
pathophysiology#Aconitine-Induced Calcium Overload and Cardiomyocyte Apoptosis
The calcium-overload arm rests entirely on adult and neonatal rat ventricular myocytes and conscious rats. This is not a generic caveat about animal work: the doses used in such models are chosen to produce reproducible arrhythmia and measurable apoptosis, whereas human poisoning is a single uncontrolled ingestion with an exposure that falls as the alkaloid is cleared. The two arms also differ in what they predict. The sodium-channel arm predicts a fully reversible electrical disturbance, which is what the clinical literature reports - complete recovery in all 17 patients of the Taiwanese series, and an overall in-hospital mortality of only 5.5%. A substantial apoptotic arm would predict measurable myocyte loss and residual ventricular dysfunction in survivors, which is not described. Either the apoptotic arm is minor at human exposures, or survivors carry unrecognised myocardial injury. The node is deliberately left off the causal path to circulatory collapse until this is settled.
Proposed experiments
Cardiac injury and function follow-up in human aconite poisoning survivors
exp_aconitine_survivor_troponin_and_cmr
Prospective measurement of high-sensitivity cardiac troponin during the acute phase, with cardiac magnetic resonance including late gadolinium enhancement and extracellular volume mapping in survivors at three months, in a consecutive cohort of patients admitted with aconite poisoning.
Decision criterion
Whether survivors show troponin release beyond that attributable to resuscitation and defibrillation, and whether any residual myocardial fibrosis or dysfunction is detectable at three months.
Supporting outcome
  • Troponin elevation disproportionate to the resuscitation received.
  • Late gadolinium enhancement or raised extracellular volume in survivors at three months.
Refuting outcome
  • Troponin release fully accounted for by cardiopulmonary resuscitation and defibrillation.
  • Normal cardiac magnetic resonance in survivors, indicating a purely electrical and reversible insult.
In patients who develop hepatic portal venous gas after resuscitated toxin-induced cardiac arrest, what proportion have transmural bowel necrosis requiring resection, and what proportion resolve with haemodynamic optimisation alone?
KNOWLEDGE GAP OPEN gap_aconitine_hpvg_reversibility_generalisation
Attached to
pathophysiology#Hepatic Portal Venous Gas pathophysiology#Non-Occlusive Mesenteric Ischaemia
The source case report proposes that hepatic portal venous gas in this setting is a reversible consequence of shock and that the primary insult should be treated rather than the radiological sign - a claim supported at the level of general principle by the hepatic portal venous gas literature, which holds that prognosis follows the underlying pathology and that the sign is not itself a surgical indication. But the specific claim rests on one patient, and the competing risk is asymmetric: non-occlusive mesenteric ischaemia carries a mortality of the order of 50%, and its vasospasm persists after the precipitating event is corrected, so conservative management of a patient who in fact has transmural necrosis is not a recoverable error. What is missing is not the principle but the discriminator - the clinical or radiological features that separate the reversible from the necrotic case at the bedside. Until that exists, this entry records the mechanism without implying a management recommendation.
Proposed experiments
Multicentre cohort of hepatic portal venous gas following resuscitated cardiac arrest
exp_hpvg_post_arrest_outcome_cohort
Retrospective multicentre identification of patients with computed tomography-confirmed hepatic portal venous gas within seven days of resuscitated cardiac arrest, linking initial imaging features (extent of gas, bowel wall enhancement, pneumatosis intestinalis, mesenteric vessel patency) and lactate trajectory to the reference outcome of transmural necrosis at laparotomy or resolution on repeat imaging.
Decision criterion
Whether any combination of initial imaging and biochemical features separates patients who resolved without surgery from those with transmural necrosis, at a negative predictive value high enough to support conservative management.
Supporting outcome
  • A majority of cases resolving with haemodynamic optimisation alone.
  • An identifiable low-risk imaging and lactate profile with high negative predictive value for transmural necrosis.
Refuting outcome
  • A high proportion of transmural necrosis irrespective of initial appearances.
  • No feature combination separating the two outcomes, implying that portal venous gas in this setting warrants surgical assessment regardless of the presumed cause.
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Pathophysiology

11
Ingestion of Aconitum Alkaloids
The toxic exposure. Aconitum roots and root tubers concentrate the diester diterpenoid alkaloids aconitine, mesaconitine and hypaconitine. Traditional processing - soaking and boiling - hydrolyses these to far less toxic monoester and alkamine derivatives, so the dose of intact diester alkaloid reaching the circulation is set by preparation method as much as by the quantity of root consumed. Inadequate processing, a larger than recommended dose, and alcoholic tincture or wine preparations (which extract rather than hydrolyse the alkaloids) are the recognised routes to poisoning, alongside accidental ingestion of the wild plant.
Downstream
Persistent Voltage-Gated Sodium Channel Activation Absorbed diester alkaloids reach voltage-gated sodium channels in myocardium, nerve and muscle.
Central Hypotensive and Bradycardic Drive Absorbed alkaloids reach the hypothalamus and drive the central hypotensive and bradycardic response.
Cholinergic Ileal Hypercontractility Absorbed alkaloids act on postganglionic enteric cholinergic nerves.
Show evidence (3 references)
PMID:19514874 SUPPORT Other
"Severe aconite poisoning can occur after accidental ingestion of the wild plant or consumption of an herbal decoction made from aconite roots."
Establishes the two principal ingestion routes.
PMID:19514874 SUPPORT Other
"Soaking and boiling during processing or decoction preparation will hydrolyze aconite alkaloids into less toxic and non-toxic derivatives."
Supports processing as the step that determines the delivered dose of intact diester alkaloid.
PMID:15111916 SUPPORT Human Clinical
"The risk is higher with inadequately processed aconite roots, large doses, or tincture preparations."
Identifies inadequate processing, dose and tincture preparation as the determinants of risk in a national poison-centre case series.
Persistent Voltage-Gated Sodium Channel Activation
The rate-limiting molecular lesion. Aconitine and mesaconitine bind with high affinity to neurotoxin binding site 2 on the alpha subunit of the voltage-gated sodium channel, and do so preferentially in the open state. Binding suppresses channel inactivation, so the channel remains persistently activated instead of closing after depolarisation - a qualitative escape from normal voltage-dependent gating rather than a quantitative increase in channel number or conductance, which is why `GAIN_OF_FUNCTION` is used here in preference to `INCREASED`. The most toxic Aconitum alkaloids carry two ester bonds on the diterpene skeleton and open the channel even at resting potential.
persistent sodium influx across the plasma membrane GO:0098719 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased persistent sodium influx across the plasma membrane, annotated with sodium ion import across plasma membrane (GO:0098719). GO:0098719 is a biological process from the Gene Ontology. ↑ INCREASED
voltage-gated sodium channel activity, held open by suppressed inactivation GO:0005248 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves voltage-gated sodium channel activity, held open by suppressed inactivation, annotated with voltage-gated sodium channel activity (GO:0005248), qualified as gain of function. GO:0005248 is a molecular function from the Gene Ontology. ⇑ GAIN OF FUNCTION
Downstream
Sustained Depolarisation and Loss of Excitability Uninterrupted sodium influx drives the membrane potential positive and holds it there.
Cardiac Triggered Activity and Ventricular Tachyarrhythmia In cardiomyocytes the same persistent sodium current generates after-depolarisations.
Show evidence (3 references)
PMID:19514874 SUPPORT Other
"Aconitine and mesaconitine bind with high affinity to the open state of the voltage-sensitive sodium channels at site 2, thereby causing a persistent activation of the sodium channels, which become refractory to excitation."
States the binding site, the state dependence, and the persistent-activation consequence that defines this node.
PMID:9760702 SUPPORT Other
"aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na+ channels by binding to neurotoxin binding site 2 of the alpha-subunit of the channel protein"
Independently identifies the molecular target as neurotoxin site 2 on the channel alpha subunit and the action as suppression of inactivation.
PMID:9760702 SUPPORT Other
"The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake."
Supports the structure-toxicity relationship: the diester alkaloids open the channel even at resting potential.
Sustained Depolarisation and Loss of Excitability
Persistent sodium entry depolarises excitable cells and keeps them depolarised, so voltage-gated channels cannot recover from inactivation and the cell becomes inexcitable. This biphasic behaviour - initial excitation followed by depolarising block - explains the clinical sequence in peripheral nerve, where early paraesthesia and numbness of the face, perioral area and limbs give way to motor weakness.
sustained membrane depolarisation ending in inexcitability GO:0051899 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased sustained membrane depolarisation ending in inexcitability, annotated with membrane depolarization (GO:0051899). GO:0051899 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Neuromuscular Transmission Block Depolarising block in the axon impairs the evoked release of acetylcholine.
Show evidence (2 references)
PMID:9760702 SUPPORT Other
"Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties."
States the excitation-then-inexcitability sequence that is the substance of this node.
PMID:19514874 SUPPORT Other
"The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
Supports the clinical sensory-then-motor expression of this node in peripheral nerve.
Neuromuscular Transmission Block
Acting on axonal voltage-gated sodium channels, aconitine reduces the evoked quantal release of acetylcholine at the neuromuscular junction, blocking transmission and producing the motor weakness of the four limbs seen in severe poisoning. This is a presynaptic release failure secondary to depolarising block, not receptor antagonism.
evoked quantal acetylcholine release at the neuromuscular junction GO:0014055 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased evoked quantal acetylcholine release at the neuromuscular junction, annotated with acetylcholine secretion, neurotransmission (GO:0014055). GO:0014055 is a biological process from the Gene Ontology. ↓ DECREASED
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Through its action on voltage-sensitive sodium channels in the axons, aconitine blocks neuromuscular transmission by decreasing the evoked quantal release of acetylcholine."
States the mechanism, the site (axon), and the direction of the effect on acetylcholine release.
Cardiac Triggered Activity and Ventricular Tachyarrhythmia
The lethal arm. In ventricular cardiomyocytes the persistent sodium current prolongs the action potential and generates both early and delayed after-depolarisations; these reach threshold and produce triggered activity, the electrophysiological substrate of aconitine-induced ventricular tachycardia and fibrillation. A cholinolytic (anticholinergic) action mediated through the vagus nerve contributes to the arrhythmogenicity, so the arrhythmia is not attributable to the sodium channel effect alone.
ventricular cardiomyocyte CL:2000046 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves ventricular cardiomyocyte, annotated with ventricular cardiac muscle cell (CL:2000046). CL:2000046 is a cell type from the Cell Ontology.
prolonged depolarisation of the cardiac action potential GO:0086012 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased prolonged depolarisation of the cardiac action potential, annotated with membrane depolarization during cardiac muscle cell action potential (GO:0086012). GO:0086012 is a biological process from the Gene Ontology. ↑ INCREASED
cardiac voltage-gated sodium channel activity, persistently activated GO:0086006 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves cardiac voltage-gated sodium channel activity, persistently activated, annotated with voltage-gated sodium channel activity involved in cardiac muscle cell action potential (GO:0086006), qualified as gain of function. GO:0086006 is a molecular function from the Gene Ontology. ⇑ GAIN OF FUNCTION
Downstream
Refractory Ventricular Arrhythmia and Circulatory Collapse Sustained triggered activity degenerates into ventricular tachycardia and fibrillation.
Show evidence (2 references)
PMID:19514874 SUPPORT Other
"The electrophysiological mechanism of arrhythmia induction is triggered activity due to delayed after-depolarization and early after-depolarization."
States the electrophysiological mechanism this node asserts.
PMID:19514874 SUPPORT Other
"The arrhythmogenic properties of aconitine are in part due to its cholinolytic (anticholinergic) effects mediated by the vagus nerve."
PARTIAL because it supports only the secondary vagal contribution named in the description, not the primary triggered-activity mechanism; recorded so the node is not read as a pure sodium-channel account.
Aconitine-Induced Calcium Overload and Cardiomyocyte Apoptosis
A parallel, non-electrophysiological arm of cardiotoxicity established in rodent models. Aconitine drives intracellular calcium overload through altered expression of calcium-handling proteins, accelerating the beating rhythm of isolated ventricular myocytes and causing arrhythmia in conscious rats; it also produces dose-dependent myocardial injury and cardiomyocyte apoptosis with upregulated pro-apoptotic and downregulated BCL-2 expression, signalling through p38 MAPK phosphorylation. This arm speaks to myocardial injury and cell loss rather than to the acute triggered activity above, and the two should not be conflated.
ventricular cardiomyocyte CL:2000046 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves ventricular cardiomyocyte, annotated with ventricular cardiac muscle cell (CL:2000046). CL:2000046 is a cell type from the Cell Ontology.
intracellular calcium overload GO:0006874 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased intracellular calcium overload, annotated with intracellular calcium ion homeostasis (GO:0006874). GO:0006874 is a biological process from the Gene Ontology. ↑ INCREASED cardiomyocyte apoptosis GO:0010659 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cardiomyocyte apoptosis, annotated with cardiac muscle cell apoptotic process (GO:0010659). GO:0010659 is a biological process from the Gene Ontology. ↑ INCREASED p38 MAPK signalling GO:0038066 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased p38 MAPK signalling, annotated with p38MAPK cascade (GO:0038066). GO:0038066 is a biological process from the Gene Ontology. ↑ INCREASED
Show evidence (3 references)
PMID:24840785 SUPPORT Model Organism
"We found that Ca(2+) overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats."
In vivo rat evidence for the calcium-overload-to-arrhythmia link.
PMID:24840785 SUPPORT In Vitro
"The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently."
Cell-culture evidence for dose-dependent myocardial injury in neonatal rat ventricular myocytes; split from the in vivo item so each carries a single evidence_source.
PMID:24840785 SUPPORT Model Organism
"our results suggest that aconitine significantly aggravates Ca(2+) overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase"
States the calcium-overload to p38-to-apoptosis chain asserted by this node.
Refractory Ventricular Arrhythmia and Circulatory Collapse
The organism-level consequence and the usual mode of death. Aconitine-induced ventricular arrhythmias are characteristically refractory to direct current cardioversion and to antiarrhythmic drugs, so haemodynamic collapse can persist despite standard resuscitation; refractory ventricular arrhythmia and asystole are the main causes of death, with a reported overall in-hospital mortality of 5.5%. Cardiac arrest may require prolonged cardiopulmonary resuscitation, defibrillation and vasopressor support.
Downstream
Non-Occlusive Mesenteric Ischaemia Sustained low cardiac output and vasopressor-supported shock reduce splanchnic perfusion.
Show evidence (3 references)
PMID:19514874 SUPPORT Other
"The main causes of death are refractory ventricular arrhythmias and asystole and the overall in-hospital mortality is 5.5%."
Establishes the mode of death and quantifies in-hospital mortality.
PMID:19514874 SUPPORT Other
"Aconite-induced ventricular arrhythmias are often refractory to direct current cardioversion and antiarrhythmic drugs."
Supports the refractoriness that distinguishes this from ordinary ventricular arrhythmia and drives the escalation to circulatory support.
PMID:41627141 SUPPORT Human Clinical
"He suffered a cardiac arrest requiring prolonged cardiopulmonary resuscitation, defibrillation, and vasopressor support."
Single-patient illustration of the resuscitation course that precedes the splanchnic complication arm.
Non-Occlusive Mesenteric Ischaemia
A complication of the shock state rather than of aconitine itself. Sustained low cardiac output and vasopressor exposure provoke splanchnic arteriolar vasoconstriction with patent mesenteric arteries - the defining feature of non-occlusive mesenteric ischaemia - producing small bowel wall oedema, reduced mucosal enhancement, and potential intestinal ischaemia and necrosis. The vasospasm is known to persist even after the precipitating haemodynamic event has been corrected, which is why the complication can declare itself days after successful resuscitation.
splanchnic arteriolar vasoconstriction with patent mesenteric arteries GO:0042310 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased splanchnic arteriolar vasoconstriction with patent mesenteric arteries, annotated with vasoconstriction (GO:0042310). GO:0042310 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Hepatic Portal Venous Gas Ischaemic loss of mucosal barrier integrity allows intraluminal gas to enter the mesenteric and portal venous circulation.
Show evidence (4 references)
PMID:41627141 SUPPORT Human Clinical
"Portal venous gas accumulation originated from non-occlusive mesenteric ischaemia triggered by aconitine-mediated cardiovascular collapse."
The authors' own causal attribution linking aconitine-induced collapse to non-occlusive mesenteric ischaemia.
PMID:41627141 SUPPORT Human Clinical
"Contrast-enhanced computed tomography on day 4 revealed multiple branching gas shadows within the left hepatic lobe, diagnostic of portal venous gas, as well as small bowel wall oedema with reduced enhancement, indicating potential intestinal ischaemia and necrosis."
The imaging findings behind both this node and the portal venous gas node.
PMID:11976865 SUPPORT Other
"Non-occlusive mesenteric ischemia (NOMI) compromises all forms of mesenteric ischemia with patent mesenteric arteries."
Defines the entity and its distinguishing feature of patent arteries.
+ 1 more reference
Hepatic Portal Venous Gas
Gas tracking from the damaged bowel wall into the mesenteric and portal venous circulation, seen on CT as branching gas shadows within the hepatic parenchyma. Although hepatic portal venous gas is conventionally an ominous radiological sign associated with a poor prognosis, its prognostic weight belongs to the underlying pathology rather than to the gas itself: it is not of itself a surgical indication, and in toxin-induced cardiac arrest it can be a reversible consequence of the shock state that resolves when the primary insult is treated. Curating this node is the point of the source case report - it converts a finding usually read as a call for laparotomy into a marker of the upstream circulatory lesion.
Show evidence (4 references)
PMID:41627141 SUPPORT Human Clinical
"This patient highlights that in the context of toxin-induced cardiac arrest, hepatic portal venous gas can be a reversible consequence of the underlying shock, emphasizing the importance of treating the primary insult."
The case report's central claim, which this node encodes.
PMID:41627141 SUPPORT Human Clinical
"Hepatic portal venous gas is an uncommon radiological finding and is generally associated with a poor prognosis."
States the conventional prognostic reading that the case qualifies.
PMID:19653334 SUPPORT Other
"HPVG is not by itself a surgical indication and the treatment depends mainly on the underlying disease."
Independent review support for treating the underlying cause rather than the radiological sign.
+ 1 more reference
Central Hypotensive and Bradycardic Drive
A centrally mediated haemodynamic arm, separate from the myocardial one. Chan attributes aconitine's hypotensive and bradycardic actions to activation of the ventromedial nucleus of the hypothalamus. This is the mechanism behind the bradycardia and hypotension of the toxidrome and is what atropine and inotropes are directed at. It is deliberately kept apart from the cardiac triggered-activity node: the two produce opposite rate effects, and conflating them is what makes an anticholinergic look like an antiarrhythmic.
Downstream
Refractory Ventricular Arrhythmia and Circulatory Collapse Central hypotensive drive compounds the haemodynamic failure caused by the arrhythmia.
Show evidence (2 references)
PMID:19514874 SUPPORT Other
"It has hypotensive and bradycardic actions due to activation of the ventromedial nucleus of the hypothalamus."
States both the effects and the central mechanism this node asserts.
PMID:19514874 SUPPORT Other
"The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
Confirms hypotension and bradycardia as observed clinical features, the readout of this node.
Cholinergic Ileal Hypercontractility
The gastrointestinal arm. Aconitine, mesaconitine and hypaconitine induce strong contractions of the ileum by releasing acetylcholine from postganglionic cholinergic nerves - a presynaptic release effect on enteric nerves rather than a direct action on smooth muscle. This is the mechanism behind the nausea, vomiting, abdominal pain and diarrhoea of the toxidrome.
acetylcholine release from postganglionic cholinergic nerves GO:0014055 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased acetylcholine release from postganglionic cholinergic nerves, annotated with acetylcholine secretion, neurotransmission (GO:0014055). GO:0014055 is a biological process from the Gene Ontology. ↑ INCREASED ileal smooth muscle contraction GO:0006939 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased ileal smooth muscle contraction, annotated with smooth muscle contraction (GO:0006939). GO:0006939 is a biological process from the Gene Ontology. ↑ INCREASED
Show evidence (2 references)
PMID:19514874 SUPPORT Other
"Aconitine, mesaconitine, and hypaconitine can induce strong contractions of the ileum through acetylcholine release from the postganglionic cholinergic nerves."
States the effector, the mediator and the nerve population this node asserts.
PMID:19514874 SUPPORT Other
"The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
The clinical readout of this node.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Aconitine Poisoning Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

14
Cardiovascular 6
Ventricular Tachycardia OCCASIONAL HP:0004756 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ventricular tachycardia (HP:0004756), qualified as temporality acute. HP:0004756 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (2 references)
PMID:15111916 SUPPORT Human Clinical
"Four patients developed ventricular tachycardia."
Supports the OCCASIONAL band by derived count - 4 of the 17 patients in this consecutive national poison-centre series, i.e. 24%, within the 5-29% range. Single-centre registry series of modest size, so the band is an estimate rather than a population frequency.
PMID:15111916 SUPPORT Human Clinical
"Life-threatening ventricular tachycardia can occur after the consumption of aconite roots."
Supports the association itself, separately from the frequency band.
Ventricular Fibrillation HP:0001663 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ventricular fibrillation (HP:0001663), qualified as temporality acute. HP:0001663 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
Lists ventricular fibrillation among the cardiovascular features.
Bradycardia HP:0001662 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bradycardia (HP:0001662), qualified as temporality acute. HP:0001662 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (2 references)
PMID:19514874 SUPPORT Other
"The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
Lists bradycardia among the cardiovascular features.
PMID:19514874 SUPPORT Other
"It has hypotensive and bradycardic actions due to activation of the ventromedial nucleus of the hypothalamus."
States the mechanism behind the bradycardia, replacing an earlier vagal attribution that this sentence does not support.
Hypotension HP:0002615 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypotension (HP:0002615), qualified as temporality acute. HP:0002615 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
Lists hypotension among the cardiovascular features.
Cardiac Arrest HP:0001695 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cardiac arrest (HP:0001695), qualified as temporality acute. HP:0001695 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (2 references)
PMID:19514874 SUPPORT Other
"The main causes of death are refractory ventricular arrhythmias and asystole and the overall in-hospital mortality is 5.5%."
Establishes refractory arrhythmia and asystole as the causes of death.
PMID:41627141 SUPPORT Human Clinical
"He suffered a cardiac arrest requiring prolonged cardiopulmonary resuscitation, defibrillation, and vasopressor support."
Case-level documentation of cardiac arrest in aconite poisoning.
Septic Shock HP:0031273 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Septic shock, annotated with Shock (HP:0031273), qualified as temporality acute. HP:0031273 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Bound to the parent `HP:0031273` Shock rather than a septic-shock term: HPO has none - a substring search of HP labels for `septic` returns only septic arthritis, aseptic abscess and septic embolism. Classifying it under `HP:0031275` Distributive shock would be a pathophysiological inference the single cited case does not make.
Show evidence (1 reference)
PMID:41627141 SUPPORT Human Clinical
"On day 3, he developed a high fever, abdominal distension, and septic shock."
Documents the septic complication and its timing. Single case, so no frequency is asserted.
Digestive 3
Nausea HP:0002018 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Nausea (HP:0002018), qualified as temporality acute. HP:0002018 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
Lists nausea among the gastrointestinal features.
Vomiting HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013), qualified as temporality acute. HP:0002013 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
Lists vomiting among the gastrointestinal features.
Diarrhea HP:0002014 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diarrhea (HP:0002014), qualified as temporality acute. HP:0002014 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
Lists diarrhea among the gastrointestinal features.
Musculoskeletal 1
Limb Muscle Weakness HP:0001324 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Muscle weakness of the four limbs, annotated with Muscle weakness (HP:0001324), qualified as temporality acute. HP:0001324 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
Names motor weakness of the four limbs as the motor feature.
Nervous System 1
Paresthesia HP:0003401 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Perioral and limb paresthesia, annotated with Paresthesia (HP:0003401), qualified as temporality acute. HP:0003401 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
Names paresthesia of face, perioral area and limbs as the sensory feature.
Constitutional 1
Abdominal Pain HP:0002027 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abdominal pain (HP:0002027), qualified as temporality acute. HP:0002027 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
Lists abdominal pain among the gastrointestinal features.
Other 2
Numbness Hypoesthesia HP:0033748 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Numbness of face, perioral area and limbs, annotated with Hypoesthesia (HP:0033748), qualified as temporality acute. HP:0033748 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
Names numbness in the same distribution as the paresthesia.
Intestinal Ischaemia Intestinal ischemia HP:0033404 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Intestinal ischaemia, annotated with Intestinal ischemia (HP:0033404), qualified as temporality acute. HP:0033404 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:41627141 SUPPORT Human Clinical
"Contrast-enhanced computed tomography on day 4 revealed multiple branching gas shadows within the left hepatic lobe, diagnostic of portal venous gas, as well as small bowel wall oedema with reduced enhancement, indicating potential intestinal ischaemia and necrosis."
Documents the imaging evidence of intestinal ischaemia. Single case, so no frequency is asserted.
💊

Medical Actions

6
Supportive Care and Haemodynamic Stabilisation
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
Immediate attention to vital functions with close monitoring of blood pressure and cardiac rhythm is the foundation of management; there is no antidote. Inotropic therapy is added if hypotension persists.
Mechanism Target:
MODULATES Refractory Ventricular Arrhythmia and Circulatory Collapse — Supports systemic perfusion while the alkaloid is cleared; it does not act on the channel lesion.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Inotropic therapy is required if hypotension persists and atropine should be used to treat bradycardia."
Supports haemodynamic support as the response to the circulatory consequences of poisoning.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Management of aconite poisoning is supportive, including immediate attention to the vital functions and close monitoring of blood pressure and cardiac rhythm."
States that management is supportive and names its components.
Atropine
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: atropine CHEBI:16684 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses atropine (CHEBI:16684). CHEBI:16684 is a therapeutic agent from Chemical Entities of Biological Interest.
A competitive muscarinic antagonist, indicated for the bradycardia of aconite poisoning. It acts at the cardiac muscarinic receptor and is symptomatic: it opposes the bradycardia without addressing either the persistent sodium current or the central drive that produces it.
Mechanism Target:
INHIBITS Central Hypotensive and Bradycardic Drive — Antagonism at the cardiac muscarinic receptor raises the heart rate, opposing the bradycardia at its effector. It does not act on the hypothalamic drive itself, so the effect is symptomatic.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Inotropic therapy is required if hypotension persists and atropine should be used to treat bradycardia."
Directly indicates atropine for the bradycardia this node produces.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Inotropic therapy is required if hypotension persists and atropine should be used to treat bradycardia."
States the indication for atropine in aconite poisoning.
Amiodarone or Flecainide for Ventricular Arrhythmia
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: amiodarone CHEBI:2663 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses amiodarone (CHEBI:2663). CHEBI:2663 is a therapeutic agent from Chemical Entities of Biological Interest. flecainide CHEBI:75984 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses flecainide (CHEBI:75984). CHEBI:75984 is a therapeutic agent from Chemical Entities of Biological Interest.
Aconite-induced ventricular arrhythmias resist direct current cardioversion and antiarrhythmic drugs generally, but the available clinical evidence points to amiodarone and flecainide as reasonable first-line agents.
Mechanism Target:
INHIBITS Cardiac Triggered Activity and Ventricular Tachyarrhythmia — Suppression of the triggered activity underlying aconitine-induced ventricular tachycardia and fibrillation.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Available clinical evidence suggests that amiodarone and flecainide are reasonable first-line treatment."
PARTIAL by the source's own hedging - "available clinical evidence suggests" and "reasonable", not demonstrated efficacy. No randomised evidence exists for antiarrhythmic choice in this poisoning.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Aconite-induced ventricular arrhythmias are often refractory to direct current cardioversion and antiarrhythmic drugs."
Establishes the refractoriness that frames antiarrhythmic therapy as frequently insufficient.
Early Mechanical Circulatory Support
Action: cardiopulmonary bypass and extracorporeal circulatory supportNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is cardiopulmonary bypass and extracorporeal circulatory support, annotated with Therapeutic Procedure (NCIT:C49236). NCIT:C49236 is a clinical intervention from the NCI Thesaurus. Ontology label: Therapeutic Procedure NCIT:C49236
When ventricular arrhythmia and cardiogenic shock are refractory to first-line treatment, the priority shifts from converting the rhythm to maintaining systemic blood flow, blood pressure and tissue oxygenation, for which early cardiopulmonary bypass is recommended. The rationale is that aconitine toxicity is self-limiting as the alkaloid is cleared, so circulatory support is a bridge rather than a definitive therapy.
Mechanism Target:
MODULATES Refractory Ventricular Arrhythmia and Circulatory Collapse — Substitutes for cardiac output while the arrhythmic substrate persists, preventing the downstream ischaemic consequences of sustained low flow.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"In refractory cases of ventricular arrhythmias and cardiogenic shock, it is most important to maintain systemic blood flow, blood pressure, and tissue oxygenation by the early use of cardiopulmonary bypass."
States the indication and the physiological goal this link encodes.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"Management is supportive; the early use of cardiopulmonary bypass is recommended if ventricular arrhythmias and cardiogenic shock are refractory to first-line treatment."
The review's concluding recommendation for refractory cases.
Charcoal Haemoperfusion
Action: charcoal haemoperfusionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is charcoal haemoperfusion, annotated with Therapeutic Procedure (NCIT:C49236). NCIT:C49236 is a clinical intervention from the NCI Thesaurus. Ontology label: Therapeutic Procedure NCIT:C49236
Extracorporeal removal of circulating aconitine alkaloids by charcoal haemoperfusion has been used in patients with ventricular tachycardia, but its role is not established. It is curated here as an unresolved option rather than a recommended therapy.
Mechanism Target:
MODULATES Ingestion of Aconitum Alkaloids — Aims to lower the circulating alkaloid burden by extracorporeal adsorption. MODULATES rather than INHIBITS deliberately: the intent is established, the effect is not - see the KNOWLEDGE_GAP on whether meaningful extraction occurs at all given aconitine's large apparent volume of distribution.
Show evidence (1 reference)
PMID:19514874 SUPPORT Other
"The role of charcoal hemoperfusion to remove circulating aconitine alkaloids is not established."
States the intended action on circulating alkaloid while explicitly withholding endorsement of its efficacy.
Show evidence (2 references)
PMID:19514874 SUPPORT Other
"The role of charcoal hemoperfusion to remove circulating aconitine alkaloids is not established."
Explicitly withholds endorsement; recorded as PARTIAL so the treatment is not read as recommended.
PMID:15111916 SUPPORT Human Clinical
"Patients with ventricular tachycardia were also treated with charcoal hemoperfusion."
PARTIAL - documents use in the four patients with ventricular tachycardia, but the series has no control arm and all 17 patients recovered, so it cannot attribute the outcome to haemoperfusion. See the KNOWLEDGE_GAP discussion.
Intra-Arterial Vasodilator Therapy for Non-Occlusive Mesenteric Ischaemia
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: intra-arterial vasodilating agent NCIT:C29707 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses intra-arterial vasodilating agent, annotated with Vasodilating Agent (NCIT:C29707). NCIT:C29707 is a therapeutic agent from the NCI Thesaurus.
Directed at the splanchnic vasospasm rather than at the poisoning. In non-occlusive mesenteric ischaemia the vasospasm persists after the precipitating haemodynamic event is corrected, and direct intra-arterial vasodilator therapy is reported as the only treatment shown to be effective - an unusually strong claim, and the reason this arm is curated as a treatment target rather than only as a complication.
Mechanism Target:
INHIBITS Non-Occlusive Mesenteric Ischaemia — Relieves the splanchnic arteriolar vasospasm that defines the lesion, restoring mucosal perfusion.
Show evidence (1 reference)
PMID:11976865 SUPPORT Other
"Vasospasm frequently responds to direct intra-arterial vasodilator therapy, which is the only treatment that has been shown to be effective."
States both the target (vasospasm) and the effect, and is the strongest efficacy claim available for this arm.
Show evidence (1 reference)
PMID:11976865 SUPPORT Other
"In early non-occlusive mesenteric ischemia, as opposed to occlusive disease, there is no surgical therapy."
Establishes that the early lesion is managed medically rather than surgically, which is the premise for vasodilator therapy.
🌍

Environmental Factors

1
Ingestion of inadequately processed Aconitum root preparations
ingestion of aconite diester alkaloids in an Aconitum root preparation ECTO:9000271 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is ingestion of aconite diester alkaloids in an Aconitum root preparation, annotated with exposure to alkaloid (ECTO:9000271). ECTO:9000271 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
ECTO has no aconitine, aconite or Aconitum exposure term - checked by substring search of ECTO labels for `aconit`, which returns only an aconitate hydratase inhibitor. `ECTO:9000271` exposure to alkaloid is a true parent (aconitine is a diterpenoid alkaloid) rather than an approximation, and is bound with a specific preferred_term. This is more specific than the `ECTO:0000231` exposure to chemical fallback used by `Organophosphate_Poisoning`.
The dominant exposure route. Aconite root is taken as a decoction, powder, tincture or medicinal wine for analgesic and antirheumatic indications; poisoning follows when processing is inadequate, the dose exceeds that recommended, or an alcoholic preparation is used. Self-prepared preparations are a recurring setting because processing is uncontrolled.
Show evidence (2 references)
PMID:19514874 SUPPORT Other
"However, the use of a larger than recommended dose and inadequate processing increases the risk of poisoning."
Identifies dose and inadequate processing as the determinants of exposure risk.
PMID:15111916 SUPPORT Human Clinical
"Thirteen patients ingested aconite roots as treatment for rheumatism and wounds."
Establishes therapeutic self-medication as the dominant intent behind exposure in a consecutive case series.
Mechanism Target:
TRIGGERS Ingestion of Aconitum Alkaloids — Ingesting an under-processed or alcoholic aconite preparation is the route by which intact diester alkaloids reach the systemic circulation.
Show evidence (1 reference)
PMID:41627141 SUPPORT Human Clinical
"A 46-year-old male presented with severe aconite poisoning after ingesting self-prepared aconite wine for joint pain."
A worked instance of the exposure: a self-prepared alcoholic aconite preparation taken for an analgesic indication, producing severe poisoning.
📊

Prevalence

1
Taiwan, National Poison Center case series 1990-1999
Cases In Literature Unknown
Seventeen cases over a decade in one national poison centre. Recorded as a case count, not a population rate: a poison-centre denominator is ascertainment-limited and cannot support a prevalence or incidence estimate.
Show evidence (1 reference)
PMID:15111916 SUPPORT Human Clinical
"A total of 17 cases occurred and consisted of 9 men and 8 women aged 30 to 70 years."
The case count and demographic range from the national poison-centre database over 1990-1999.
{ }

Source YAML

click to show 
name: Aconitine Poisoning
creation_date: "2026-08-22T16:05:00Z"
category: Environmental
categories:
- Toxic Exposure Disorder
- Plant Poisoning
- Herbal Medicine Adverse Effect
synonyms:
- aconite poisoning
- Aconitum poisoning
- monkshood poisoning
- wolfsbane poisoning
- aconite alkaloid toxicity
description: >-
  Aconitine poisoning is an acute toxidrome caused by ingestion of the
  diterpenoid ester alkaloids of Aconitum species (monkshood, wolfsbane) -
  principally aconitine, mesaconitine and hypaconitine - which are concentrated
  in the roots and root tubers. Aconite root is a long-standing analgesic and
  antirheumatic remedy in traditional Chinese and Japanese medicine, where it is
  used only after processing that hydrolyses the diester alkaloids to far less
  toxic derivatives; poisoning follows inadequate processing, larger than
  recommended doses, tincture or wine preparations, or accidental ingestion of
  the wild plant. The unifying molecular mechanism is binding to neurotoxin site
  2 on the alpha subunit of voltage-gated sodium channels in the open state,
  which suppresses channel inactivation and holds the channel persistently
  activated. In excitable tissue this produces sustained sodium influx and
  excessive depolarisation ending in inexcitability. In the myocardium it
  generates triggered activity from early and delayed after-depolarisations,
  causing ventricular tachycardia and fibrillation that are characteristically
  refractory to cardioversion and antiarrhythmic drugs; in peripheral nerve it
  produces the early sensory paresthesiae and later blocks neuromuscular
  transmission. Patients present after a latent period of minutes to hours with a
  combination of neurological, cardiovascular and gastrointestinal features, and
  the main causes of death are refractory ventricular arrhythmias and asystole.
  Management is supportive - atropine for bradycardia, inotropes for hypotension,
  amiodarone or flecainide for ventricular arrhythmia, and early mechanical
  circulatory support when arrhythmia and cardiogenic shock are refractory.
notes: >-
  ONTOLOGY GAP - no `disease_term` is bound because MONDO has no aconitine or
  aconite concept. This was checked exhaustively rather than by label search
  alone: a direct SQL scan of every value in the MONDO `statements` table for
  the substring `aconit` returns only `MONDO:0009706` (aconitase deficiency) and
  its definition text, i.e. the metabolic enzyme, not the plant alkaloid. MONDO
  codes many named poisonings as siblings (`MONDO:0017860` methanol,
  `MONDO:0018019` lead, `MONDO:0041996` thallium, `MONDO:0800386`
  organophosphate, `MONDO:0023176` formaldehyde), so the absence is a genuine
  coverage gap in a populated branch rather than a modelling decision. The
  nearest available ancestor, `MONDO:0029000` poisoning, is too broad to carry
  any information and is deliberately not bound; `Arsenic_Poisoning` sets the
  precedent in this knowledge base for an entry with no `disease_term`. HPO
  likewise has no term for hepatic portal venous gas - the closest, from a
  substring search of HP labels, are `HP:0031941` abnormal portal venous system
  morphology and `HP:0034570` thickened intrahepatic portal venules, neither of
  which denotes intravascular gas - so that finding is curated as a
  pathophysiology node and named in prose rather than force-bound.
mappings:
  icd10cm_mappings:
  - term:
      id: ICD10CM:T62.2
      label: Toxic effect of other ingested (parts of) plant(s)
    mapping_predicate: skos:broadMatch
    mapping_justification: semapv:ManualMappingCuration
    notes: >-
      Deliberately a broadMatch, not a close or exact one. ICD-10-CM has no
      aconite or Aconitum code - a substring scan of ICD-10-CM labels for
      `aconit` returns nothing - so T62.2 is the code an aconite root ingestion
      is assigned under, while covering every other toxic ingested plant part as
      well. It is a billing-level container, not a synonym for this entry.
pathophysiology:
- name: Ingestion of Aconitum Alkaloids
  biological_scale: ORGANISM
  description: >-
    The toxic exposure. Aconitum roots and root tubers concentrate the diester
    diterpenoid alkaloids aconitine, mesaconitine and hypaconitine. Traditional
    processing - soaking and boiling - hydrolyses these to far less toxic
    monoester and alkamine derivatives, so the dose of intact diester alkaloid
    reaching the circulation is set by preparation method as much as by the
    quantity of root consumed. Inadequate processing, a larger than recommended
    dose, and alcoholic tincture or wine preparations (which extract rather than
    hydrolyse the alkaloids) are the recognised routes to poisoning, alongside
    accidental ingestion of the wild plant.
  notes: >-
    Deliberately carries no ontology-bound process descriptor. The node denotes
    an exposure event, not a biological process of the host, and no GO term
    describes it; binding the downstream sodium term here would assert the
    mechanism one step before it occurs. The exposure itself is grounded in the
    `environmental:` block via ECTO.
  downstream:
  - target: Persistent Voltage-Gated Sodium Channel Activation
    description: >-
      Absorbed diester alkaloids reach voltage-gated sodium channels in
      myocardium, nerve and muscle.
  - target: Central Hypotensive and Bradycardic Drive
    description: >-
      Absorbed alkaloids reach the hypothalamus and drive the central
      hypotensive and bradycardic response.
  - target: Cholinergic Ileal Hypercontractility
    description: >-
      Absorbed alkaloids act on postganglionic enteric cholinergic nerves.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Severe aconite poisoning can occur after accidental ingestion of the wild plant or consumption of an herbal decoction made from aconite roots."
    explanation: Establishes the two principal ingestion routes.
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Soaking and boiling during processing or decoction preparation will hydrolyze aconite alkaloids into less toxic and non-toxic derivatives."
    explanation: >-
      Supports processing as the step that determines the delivered dose of
      intact diester alkaloid.
  - reference: PMID:15111916
    reference_title: "Clinical features and management of herb-induced aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The risk is higher with inadequately processed aconite roots, large doses, or tincture preparations."
    explanation: >-
      Identifies inadequate processing, dose and tincture preparation as the
      determinants of risk in a national poison-centre case series.
- name: Persistent Voltage-Gated Sodium Channel Activation
  biological_scale: MOLECULAR
  description: >-
    The rate-limiting molecular lesion. Aconitine and mesaconitine bind with high
    affinity to neurotoxin binding site 2 on the alpha subunit of the
    voltage-gated sodium channel, and do so preferentially in the open state.
    Binding suppresses channel inactivation, so the channel remains persistently
    activated instead of closing after depolarisation - a qualitative escape from
    normal voltage-dependent gating rather than a quantitative increase in
    channel number or conductance, which is why `GAIN_OF_FUNCTION` is used here
    in preference to `INCREASED`. The most toxic Aconitum alkaloids carry two
    ester bonds on the diterpene skeleton and open the channel even at resting
    potential.
  molecular_functions:
  - preferred_term: voltage-gated sodium channel activity, held open by suppressed inactivation
    modifier: GAIN_OF_FUNCTION
    term:
      id: GO:0005248
      label: voltage-gated sodium channel activity
  biological_processes:
  - preferred_term: persistent sodium influx across the plasma membrane
    modifier: INCREASED
    term:
      id: GO:0098719
      label: sodium ion import across plasma membrane
  downstream:
  - target: Sustained Depolarisation and Loss of Excitability
    description: >-
      Uninterrupted sodium influx drives the membrane potential positive and
      holds it there.
  - target: Cardiac Triggered Activity and Ventricular Tachyarrhythmia
    description: >-
      In cardiomyocytes the same persistent sodium current generates
      after-depolarisations.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Aconitine and mesaconitine bind with high affinity to the open state of the voltage-sensitive sodium channels at site 2, thereby causing a persistent activation of the sodium channels, which become refractory to excitation."
    explanation: >-
      States the binding site, the state dependence, and the
      persistent-activation consequence that defines this node.
  - reference: PMID:9760702
    reference_title: "The effects of Aconitum alkaloids on the central nervous system."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na+ channels by binding to neurotoxin binding site 2 of the alpha-subunit of the channel protein"
    explanation: >-
      Independently identifies the molecular target as neurotoxin site 2 on the
      channel alpha subunit and the action as suppression of inactivation.
  - reference: PMID:9760702
    reference_title: "The effects of Aconitum alkaloids on the central nervous system."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake."
    explanation: >-
      Supports the structure-toxicity relationship: the diester alkaloids open
      the channel even at resting potential.
- name: Sustained Depolarisation and Loss of Excitability
  biological_scale: CELLULAR
  description: >-
    Persistent sodium entry depolarises excitable cells and keeps them
    depolarised, so voltage-gated channels cannot recover from inactivation and
    the cell becomes inexcitable. This biphasic behaviour - initial excitation
    followed by depolarising block - explains the clinical sequence in peripheral
    nerve, where early paraesthesia and numbness of the face, perioral area and
    limbs give way to motor weakness.
  biological_processes:
  - preferred_term: sustained membrane depolarisation ending in inexcitability
    modifier: INCREASED
    term:
      id: GO:0051899
      label: membrane depolarization
  downstream:
  - target: Neuromuscular Transmission Block
    description: >-
      Depolarising block in the axon impairs the evoked release of
      acetylcholine.
  evidence:
  - reference: PMID:9760702
    reference_title: "The effects of Aconitum alkaloids on the central nervous system."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties."
    explanation: >-
      States the excitation-then-inexcitability sequence that is the substance of
      this node.
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
    explanation: >-
      Supports the clinical sensory-then-motor expression of this node in
      peripheral nerve.
- name: Neuromuscular Transmission Block
  biological_scale: CELLULAR
  description: >-
    Acting on axonal voltage-gated sodium channels, aconitine reduces the evoked
    quantal release of acetylcholine at the neuromuscular junction, blocking
    transmission and producing the motor weakness of the four limbs seen in
    severe poisoning. This is a presynaptic release failure secondary to
    depolarising block, not receptor antagonism.
  biological_processes:
  - preferred_term: evoked quantal acetylcholine release at the neuromuscular junction
    modifier: DECREASED
    term:
      id: GO:0014055
      label: acetylcholine secretion, neurotransmission
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Through its action on voltage-sensitive sodium channels in the axons, aconitine blocks neuromuscular transmission by decreasing the evoked quantal release of acetylcholine."
    explanation: >-
      States the mechanism, the site (axon), and the direction of the effect on
      acetylcholine release.
- name: Cardiac Triggered Activity and Ventricular Tachyarrhythmia
  biological_scale: CELLULAR
  description: >-
    The lethal arm. In ventricular cardiomyocytes the persistent sodium current
    prolongs the action potential and generates both early and delayed
    after-depolarisations; these reach threshold and produce triggered activity,
    the electrophysiological substrate of aconitine-induced ventricular
    tachycardia and fibrillation. A cholinolytic (anticholinergic) action
    mediated through the vagus nerve contributes to the arrhythmogenicity, so the
    arrhythmia is not attributable to the sodium channel effect alone.
  cell_types:
  - preferred_term: ventricular cardiomyocyte
    term:
      id: CL:2000046
      label: ventricular cardiac muscle cell
  molecular_functions:
  - preferred_term: cardiac voltage-gated sodium channel activity, persistently activated
    modifier: GAIN_OF_FUNCTION
    term:
      id: GO:0086006
      label: voltage-gated sodium channel activity involved in cardiac muscle cell action potential
  biological_processes:
  - preferred_term: prolonged depolarisation of the cardiac action potential
    modifier: INCREASED
    term:
      id: GO:0086012
      label: membrane depolarization during cardiac muscle cell action potential
  downstream:
  - target: Refractory Ventricular Arrhythmia and Circulatory Collapse
    description: >-
      Sustained triggered activity degenerates into ventricular tachycardia and
      fibrillation.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The electrophysiological mechanism of arrhythmia induction is triggered activity due to delayed after-depolarization and early after-depolarization."
    explanation: >-
      States the electrophysiological mechanism this node asserts.
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The arrhythmogenic properties of aconitine are in part due to its cholinolytic (anticholinergic) effects mediated by the vagus nerve."
    explanation: >-
      PARTIAL because it supports only the secondary vagal contribution named in
      the description, not the primary triggered-activity mechanism; recorded so
      the node is not read as a pure sodium-channel account.
- name: Aconitine-Induced Calcium Overload and Cardiomyocyte Apoptosis
  biological_scale: CELLULAR
  description: >-
    A parallel, non-electrophysiological arm of cardiotoxicity established in
    rodent models. Aconitine drives intracellular calcium overload through
    altered expression of calcium-handling proteins, accelerating the beating
    rhythm of isolated ventricular myocytes and causing arrhythmia in conscious
    rats; it also produces dose-dependent myocardial injury and cardiomyocyte
    apoptosis with upregulated pro-apoptotic and downregulated BCL-2 expression,
    signalling through p38 MAPK phosphorylation. This arm speaks to myocardial
    injury and cell loss rather than to the acute triggered activity above, and
    the two should not be conflated.
  cell_types:
  - preferred_term: ventricular cardiomyocyte
    term:
      id: CL:2000046
      label: ventricular cardiac muscle cell
  biological_processes:
  - preferred_term: intracellular calcium overload
    modifier: INCREASED
    term:
      id: GO:0006874
      label: intracellular calcium ion homeostasis
  - preferred_term: cardiomyocyte apoptosis
    modifier: INCREASED
    term:
      id: GO:0010659
      label: cardiac muscle cell apoptotic process
  - preferred_term: p38 MAPK signalling
    modifier: INCREASED
    term:
      id: GO:0038066
      label: p38MAPK cascade
  notes: >-
    Entirely rodent and cell-culture derived - adult and neonatal rat ventricular
    myocytes plus conscious rats. No human data establish the calcium-overload or
    p38 arm in aconitine poisoning, which is why it is curated as a parallel node
    with model-tagged evidence rather than being wired into the human causal
    chain to circulatory collapse. See the `HUMAN_MODEL_MISMATCH` discussion.
  evidence:
  - reference: PMID:24840785
    reference_title: "Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "We found that Ca(2+) overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats."
    explanation: >-
      In vivo rat evidence for the calcium-overload-to-arrhythmia link.
  - reference: PMID:24840785
    reference_title: "Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently."
    explanation: >-
      Cell-culture evidence for dose-dependent myocardial injury in neonatal rat
      ventricular myocytes; split from the in vivo item so each carries a single
      evidence_source.
  - reference: PMID:24840785
    reference_title: "Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "our results suggest that aconitine significantly aggravates Ca(2+) overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase"
    explanation: >-
      States the calcium-overload to p38-to-apoptosis chain asserted by this
      node.
- name: Refractory Ventricular Arrhythmia and Circulatory Collapse
  biological_scale: ORGANISM
  description: >-
    The organism-level consequence and the usual mode of death. Aconitine-induced
    ventricular arrhythmias are characteristically refractory to direct current
    cardioversion and to antiarrhythmic drugs, so haemodynamic collapse can
    persist despite standard resuscitation; refractory ventricular arrhythmia and
    asystole are the main causes of death, with a reported overall in-hospital
    mortality of 5.5%. Cardiac arrest may require prolonged cardiopulmonary
    resuscitation, defibrillation and vasopressor support.
  downstream:
  - target: Non-Occlusive Mesenteric Ischaemia
    description: >-
      Sustained low cardiac output and vasopressor-supported shock reduce
      splanchnic perfusion.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The main causes of death are refractory ventricular arrhythmias and asystole and the overall in-hospital mortality is 5.5%."
    explanation: Establishes the mode of death and quantifies in-hospital mortality.
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Aconite-induced ventricular arrhythmias are often refractory to direct current cardioversion and antiarrhythmic drugs."
    explanation: >-
      Supports the refractoriness that distinguishes this from ordinary
      ventricular arrhythmia and drives the escalation to circulatory support.
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He suffered a cardiac arrest requiring prolonged cardiopulmonary resuscitation, defibrillation, and vasopressor support."
    explanation: >-
      Single-patient illustration of the resuscitation course that precedes the
      splanchnic complication arm.
- name: Non-Occlusive Mesenteric Ischaemia
  biological_scale: TISSUE
  description: >-
    A complication of the shock state rather than of aconitine itself. Sustained
    low cardiac output and vasopressor exposure provoke splanchnic arteriolar
    vasoconstriction with patent mesenteric arteries - the defining feature of
    non-occlusive mesenteric ischaemia - producing small bowel wall oedema,
    reduced mucosal enhancement, and potential intestinal ischaemia and necrosis.
    The vasospasm is known to persist even after the precipitating haemodynamic
    event has been corrected, which is why the complication can declare itself
    days after successful resuscitation.
  biological_processes:
  - preferred_term: splanchnic arteriolar vasoconstriction with patent mesenteric arteries
    modifier: INCREASED
    term:
      id: GO:0042310
      label: vasoconstriction
  notes: >-
    `GO:0002014` "vasoconstriction of artery involved in ischemic response to
    lowering of systemic arterial blood pressure" looks like an exact match on
    its label and is deliberately NOT used: its definition restricts it to
    vasoconstriction "triggered by vasomotor excitation resulting from the
    detection of high carbon dioxide levels in the vasomotor center of the
    central nervous system", i.e. the CNS ischaemic response, which is not the
    splanchnic sympathetic and renin-angiotensin mechanism of non-occlusive
    mesenteric ischaemia. The plain parent `GO:0042310` is bound instead with a
    specific preferred_term. Read the definition, not the label.
  downstream:
  - target: Hepatic Portal Venous Gas
    description: >-
      Ischaemic loss of mucosal barrier integrity allows intraluminal gas to
      enter the mesenteric and portal venous circulation.
  evidence:
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Portal venous gas accumulation originated from non-occlusive mesenteric ischaemia triggered by aconitine-mediated cardiovascular collapse."
    explanation: >-
      The authors' own causal attribution linking aconitine-induced collapse to
      non-occlusive mesenteric ischaemia.
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Contrast-enhanced computed tomography on day 4 revealed multiple branching gas shadows within the left hepatic lobe, diagnostic of portal venous gas, as well as small bowel wall oedema with reduced enhancement, indicating potential intestinal ischaemia and necrosis."
    explanation: >-
      The imaging findings behind both this node and the portal venous gas node.
  - reference: PMID:11976865
    reference_title: "Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Non-occlusive mesenteric ischemia (NOMI) compromises all forms of mesenteric ischemia with patent mesenteric arteries."
    explanation: >-
      Defines the entity and its distinguishing feature of patent arteries.
  - reference: PMID:11976865
    reference_title: "Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It is known that mesenteric vasospasm persists even after correction of the precipitating event."
    explanation: >-
      Supports the delayed and self-sustaining character of the vasospasm, which
      is why the complication appears days after resuscitation.
- name: Hepatic Portal Venous Gas
  biological_scale: TISSUE
  description: >-
    Gas tracking from the damaged bowel wall into the mesenteric and portal
    venous circulation, seen on CT as branching gas shadows within the hepatic
    parenchyma. Although hepatic portal venous gas is conventionally an ominous
    radiological sign associated with a poor prognosis, its prognostic weight
    belongs to the underlying pathology rather than to the gas itself: it is not
    of itself a surgical indication, and in toxin-induced cardiac arrest it can
    be a reversible consequence of the shock state that resolves when the primary
    insult is treated. Curating this node is the point of the source case report
    - it converts a finding usually read as a call for laparotomy into a marker
    of the upstream circulatory lesion.
  evidence:
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This patient highlights that in the context of toxin-induced cardiac arrest, hepatic portal venous gas can be a reversible consequence of the underlying shock, emphasizing the importance of treating the primary insult."
    explanation: >-
      The case report's central claim, which this node encodes.
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Hepatic portal venous gas is an uncommon radiological finding and is generally associated with a poor prognosis."
    explanation: >-
      States the conventional prognostic reading that the case qualifies.
  - reference: PMID:19653334
    reference_title: "Hepatic portal venous gas: physiopathology, etiology, prognosis and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HPVG is not by itself a surgical indication and the treatment depends mainly on the underlying disease."
    explanation: >-
      Independent review support for treating the underlying cause rather than
      the radiological sign.
  - reference: PMID:19653334
    reference_title: "Hepatic portal venous gas: physiopathology, etiology, prognosis and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The prognosis is related to the pathology itself and is not influenced by the presence of HPVG."
    explanation: >-
      Supports the claim that prognostic weight belongs to the underlying
      pathology, generalising the case report beyond n=1.
- name: Central Hypotensive and Bradycardic Drive
  biological_scale: ORGANISM
  description: >-
    A centrally mediated haemodynamic arm, separate from the myocardial one.
    Chan attributes aconitine's hypotensive and bradycardic actions to activation
    of the ventromedial nucleus of the hypothalamus. This is the mechanism behind
    the bradycardia and hypotension of the toxidrome and is what atropine and
    inotropes are directed at. It is deliberately kept apart from the cardiac
    triggered-activity node: the two produce opposite rate effects, and conflating
    them is what makes an anticholinergic look like an antiarrhythmic.
  notes: >-
    Placed downstream of ingestion rather than of the sodium-channel node because
    the source attributes the effect to hypothalamic activation without stating
    that the channel action mediates it. Note also that the only vagally mediated
    action the source describes is aconitine's own cholinolytic (anticholinergic)
    effect, which is vagolytic and would tend toward tachycardia - so a vagal
    attribution for the bradycardia would invert the source. An earlier draft of
    this entry made exactly that error.
  downstream:
  - target: Refractory Ventricular Arrhythmia and Circulatory Collapse
    description: >-
      Central hypotensive drive compounds the haemodynamic failure caused by the
      arrhythmia.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It has hypotensive and bradycardic actions due to activation of the ventromedial nucleus of the hypothalamus."
    explanation: >-
      States both the effects and the central mechanism this node asserts.
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
    explanation: >-
      Confirms hypotension and bradycardia as observed clinical features, the
      readout of this node.
- name: Cholinergic Ileal Hypercontractility
  biological_scale: TISSUE
  description: >-
    The gastrointestinal arm. Aconitine, mesaconitine and hypaconitine induce
    strong contractions of the ileum by releasing acetylcholine from
    postganglionic cholinergic nerves - a presynaptic release effect on enteric
    nerves rather than a direct action on smooth muscle. This is the mechanism
    behind the nausea, vomiting, abdominal pain and diarrhoea of the toxidrome.
  biological_processes:
  - preferred_term: acetylcholine release from postganglionic cholinergic nerves
    modifier: INCREASED
    term:
      id: GO:0014055
      label: acetylcholine secretion, neurotransmission
  - preferred_term: ileal smooth muscle contraction
    modifier: INCREASED
    term:
      id: GO:0006939
      label: smooth muscle contraction
  notes: >-
    Note the direction contrast with `Neuromuscular Transmission Block`, which is
    the same neurotransmitter and the same GO process in the opposite direction:
    acetylcholine release is DECREASED at the skeletal neuromuscular junction and
    INCREASED at postganglionic enteric nerves. Both are curated because the
    source states both; they are not a contradiction but different synapses.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Aconitine, mesaconitine, and hypaconitine can induce strong contractions of the ileum through acetylcholine release from the postganglionic cholinergic nerves."
    explanation: >-
      States the effector, the mediator and the nerve population this node
      asserts.
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
    explanation: The clinical readout of this node.
phenotypes:
- category: Neurological
  name: Paresthesia
  description: >-
    Tingling and numbness of the face, perioral area and all four limbs, typically
    the earliest feature and appearing after a latent period of minutes to hours.
  phenotype_term:
    preferred_term: Perioral and limb paresthesia
    term:
      id: HP:0003401
      label: Paresthesia
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
    explanation: Names paresthesia of face, perioral area and limbs as the sensory feature.
- category: Neurological
  name: Numbness
  description: Reduced sensation accompanying the paresthesia in the same distribution.
  phenotype_term:
    preferred_term: Numbness of face, perioral area and limbs
    term:
      id: HP:0033748
      label: Hypoesthesia
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
    explanation: Names numbness in the same distribution as the paresthesia.
- category: Neurological
  name: Limb Muscle Weakness
  description: >-
    Motor weakness of the four limbs, reflecting neuromuscular transmission block.
  phenotype_term:
    preferred_term: Muscle weakness of the four limbs
    term:
      id: HP:0001324
      label: Muscle weakness
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both."
    explanation: Names motor weakness of the four limbs as the motor feature.
- category: Cardiovascular
  name: Ventricular Tachycardia
  description: >-
    Life-threatening ventricular tachycardia, characteristically refractory to
    cardioversion and antiarrhythmic drugs.
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Ventricular tachycardia
    term:
      id: HP:0004756
      label: Ventricular tachycardia
    temporality: ACUTE
  evidence:
  - reference: PMID:15111916
    reference_title: "Clinical features and management of herb-induced aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Four patients developed ventricular tachycardia."
    explanation: >-
      Supports the OCCASIONAL band by derived count - 4 of the 17 patients in
      this consecutive national poison-centre series, i.e. 24%, within the
      5-29% range. Single-centre registry series of modest size, so the band is
      an estimate rather than a population frequency.
  - reference: PMID:15111916
    reference_title: "Clinical features and management of herb-induced aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Life-threatening ventricular tachycardia can occur after the consumption of aconite roots."
    explanation: Supports the association itself, separately from the frequency band.
- category: Cardiovascular
  name: Ventricular Fibrillation
  description: Ventricular fibrillation, a terminal rhythm in severe poisoning.
  phenotype_term:
    preferred_term: Ventricular fibrillation
    term:
      id: HP:0001663
      label: Ventricular fibrillation
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
    explanation: Lists ventricular fibrillation among the cardiovascular features.
- category: Cardiovascular
  name: Bradycardia
  description: >-
    Bradycardia, which Chan attributes to activation of the ventromedial nucleus
    of the hypothalamus rather than to a vagal mechanism.
  phenotype_term:
    preferred_term: Bradycardia
    term:
      id: HP:0001662
      label: Bradycardia
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
    explanation: Lists bradycardia among the cardiovascular features.
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It has hypotensive and bradycardic actions due to activation of the ventromedial nucleus of the hypothalamus."
    explanation: >-
      States the mechanism behind the bradycardia, replacing an earlier vagal
      attribution that this sentence does not support.
- category: Cardiovascular
  name: Hypotension
  description: Hypotension requiring inotropic support when persistent.
  phenotype_term:
    preferred_term: Hypotension
    term:
      id: HP:0002615
      label: Hypotension
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation."
    explanation: Lists hypotension among the cardiovascular features.
- category: Cardiovascular
  name: Cardiac Arrest
  description: >-
    Cardiac arrest from refractory ventricular arrhythmia or asystole, the main
    mode of death.
  phenotype_term:
    preferred_term: Cardiac arrest
    term:
      id: HP:0001695
      label: Cardiac arrest
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The main causes of death are refractory ventricular arrhythmias and asystole and the overall in-hospital mortality is 5.5%."
    explanation: Establishes refractory arrhythmia and asystole as the causes of death.
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He suffered a cardiac arrest requiring prolonged cardiopulmonary resuscitation, defibrillation, and vasopressor support."
    explanation: Case-level documentation of cardiac arrest in aconite poisoning.
- category: Gastrointestinal
  name: Nausea
  description: Nausea, part of the gastrointestinal component of the toxidrome.
  phenotype_term:
    preferred_term: Nausea
    term:
      id: HP:0002018
      label: Nausea
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
    explanation: Lists nausea among the gastrointestinal features.
- category: Gastrointestinal
  name: Vomiting
  description: Vomiting, part of the gastrointestinal component of the toxidrome.
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
    explanation: Lists vomiting among the gastrointestinal features.
- category: Gastrointestinal
  name: Abdominal Pain
  description: Abdominal pain, part of the gastrointestinal component of the toxidrome.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
    explanation: Lists abdominal pain among the gastrointestinal features.
- category: Gastrointestinal
  name: Diarrhea
  description: Diarrhea, part of the gastrointestinal component of the toxidrome.
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
    temporality: ACUTE
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea."
    explanation: Lists diarrhea among the gastrointestinal features.
- category: Cardiovascular
  name: Septic Shock
  description: >-
    Fever, abdominal distension and septic shock developing on day 3 after
    resuscitation, as the ischaemic bowel loses barrier integrity. A complication
    of the shock state and its splanchnic consequences, not a direct alkaloid
    effect.
  phenotype_term:
    preferred_term: Septic shock
    term:
      id: HP:0031273
      label: Shock
    temporality: ACUTE
  notes: >-
    Bound to the parent `HP:0031273` Shock rather than a septic-shock term: HPO
    has none - a substring search of HP labels for `septic` returns only septic
    arthritis, aseptic abscess and septic embolism. Classifying it under
    `HP:0031275` Distributive shock would be a pathophysiological inference the
    single cited case does not make.
  evidence:
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On day 3, he developed a high fever, abdominal distension, and septic shock."
    explanation: >-
      Documents the septic complication and its timing. Single case, so no
      frequency is asserted.
- category: Gastrointestinal
  name: Intestinal Ischaemia
  description: >-
    Small bowel wall oedema with reduced enhancement indicating intestinal
    ischaemia and necrosis, arising as a complication of the shock state rather
    than as a direct alkaloid effect.
  phenotype_term:
    preferred_term: Intestinal ischaemia
    term:
      id: HP:0033404
      label: Intestinal ischemia
    temporality: ACUTE
  evidence:
  - reference: PMID:41627141
    reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Contrast-enhanced computed tomography on day 4 revealed multiple branching gas shadows within the left hepatic lobe, diagnostic of portal venous gas, as well as small bowel wall oedema with reduced enhancement, indicating potential intestinal ischaemia and necrosis."
    explanation: >-
      Documents the imaging evidence of intestinal ischaemia. Single case, so no
      frequency is asserted.
environmental:
- name: Ingestion of inadequately processed Aconitum root preparations
  exposure_term:
    preferred_term: ingestion of aconite diester alkaloids in an Aconitum root preparation
    term:
      id: ECTO:9000271
      label: exposure to alkaloid
  description: >-
    The dominant exposure route. Aconite root is taken as a decoction, powder,
    tincture or medicinal wine for analgesic and antirheumatic indications;
    poisoning follows when processing is inadequate, the dose exceeds that
    recommended, or an alcoholic preparation is used. Self-prepared preparations
    are a recurring setting because processing is uncontrolled.
  notes: >-
    ECTO has no aconitine, aconite or Aconitum exposure term - checked by
    substring search of ECTO labels for `aconit`, which returns only an aconitate
    hydratase inhibitor. `ECTO:9000271` exposure to alkaloid is a true parent
    (aconitine is a diterpenoid alkaloid) rather than an approximation, and is
    bound with a specific preferred_term. This is more specific than the
    `ECTO:0000231` exposure to chemical fallback used by
    `Organophosphate_Poisoning`.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "However, the use of a larger than recommended dose and inadequate processing increases the risk of poisoning."
    explanation: >-
      Identifies dose and inadequate processing as the determinants of exposure
      risk.
  - reference: PMID:15111916
    reference_title: "Clinical features and management of herb-induced aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Thirteen patients ingested aconite roots as treatment for rheumatism and wounds."
    explanation: >-
      Establishes therapeutic self-medication as the dominant intent behind
      exposure in a consecutive case series.
  influences_mechanisms:
  - target: Ingestion of Aconitum Alkaloids
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Ingesting an under-processed or alcoholic aconite preparation is the route
      by which intact diester alkaloids reach the systemic circulation.
    evidence:
    - reference: PMID:41627141
      reference_title: "Transient hepatic portal venous gas following resuscitated cardiac arrest in a patient with aconitine poisoning."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "A 46-year-old male presented with severe aconite poisoning after ingesting self-prepared aconite wine for joint pain."
      explanation: >-
        A worked instance of the exposure: a self-prepared alcoholic aconite
        preparation taken for an analgesic indication, producing severe
        poisoning.
treatments:
- name: Supportive Care and Haemodynamic Stabilisation
  description: >-
    Immediate attention to vital functions with close monitoring of blood
    pressure and cardiac rhythm is the foundation of management; there is no
    antidote. Inotropic therapy is added if hypotension persists.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_mechanisms:
  - target: Refractory Ventricular Arrhythmia and Circulatory Collapse
    treatment_effect: MODULATES
    description: >-
      Supports systemic perfusion while the alkaloid is cleared; it does not act
      on the channel lesion.
    evidence:
    - reference: PMID:19514874
      reference_title: "Aconite poisoning."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Inotropic therapy is required if hypotension persists and atropine should be used to treat bradycardia."
      explanation: >-
        Supports haemodynamic support as the response to the circulatory
        consequences of poisoning.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Management of aconite poisoning is supportive, including immediate attention to the vital functions and close monitoring of blood pressure and cardiac rhythm."
    explanation: States that management is supportive and names its components.
- name: Atropine
  description: >-
    A competitive muscarinic antagonist, indicated for the bradycardia of aconite
    poisoning. It acts at the cardiac muscarinic receptor and is symptomatic: it
    opposes the bradycardia without addressing either the persistent sodium
    current or the central drive that produces it.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: atropine
      term:
        id: CHEBI:16684
        label: atropine
  target_mechanisms:
  - target: Central Hypotensive and Bradycardic Drive
    treatment_effect: INHIBITS
    description: >-
      Antagonism at the cardiac muscarinic receptor raises the heart rate,
      opposing the bradycardia at its effector. It does not act on the
      hypothalamic drive itself, so the effect is symptomatic.
    evidence:
    - reference: PMID:19514874
      reference_title: "Aconite poisoning."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Inotropic therapy is required if hypotension persists and atropine should be used to treat bradycardia."
      explanation: >-
        Directly indicates atropine for the bradycardia this node produces.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Inotropic therapy is required if hypotension persists and atropine should be used to treat bradycardia."
    explanation: States the indication for atropine in aconite poisoning.
- name: Amiodarone or Flecainide for Ventricular Arrhythmia
  description: >-
    Aconite-induced ventricular arrhythmias resist direct current cardioversion
    and antiarrhythmic drugs generally, but the available clinical evidence
    points to amiodarone and flecainide as reasonable first-line agents.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: amiodarone
      term:
        id: CHEBI:2663
        label: amiodarone
    - preferred_term: flecainide
      term:
        id: CHEBI:75984
        label: flecainide
  target_mechanisms:
  - target: Cardiac Triggered Activity and Ventricular Tachyarrhythmia
    treatment_effect: INHIBITS
    description: >-
      Suppression of the triggered activity underlying aconitine-induced
      ventricular tachycardia and fibrillation.
    evidence:
    - reference: PMID:19514874
      reference_title: "Aconite poisoning."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Available clinical evidence suggests that amiodarone and flecainide are reasonable first-line treatment."
      explanation: >-
        PARTIAL by the source's own hedging - "available clinical evidence
        suggests" and "reasonable", not demonstrated efficacy. No randomised
        evidence exists for antiarrhythmic choice in this poisoning.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Aconite-induced ventricular arrhythmias are often refractory to direct current cardioversion and antiarrhythmic drugs."
    explanation: >-
      Establishes the refractoriness that frames antiarrhythmic therapy as
      frequently insufficient.
- name: Early Mechanical Circulatory Support
  description: >-
    When ventricular arrhythmia and cardiogenic shock are refractory to
    first-line treatment, the priority shifts from converting the rhythm to
    maintaining systemic blood flow, blood pressure and tissue oxygenation, for
    which early cardiopulmonary bypass is recommended. The rationale is that
    aconitine toxicity is self-limiting as the alkaloid is cleared, so
    circulatory support is a bridge rather than a definitive therapy.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: cardiopulmonary bypass and extracorporeal circulatory support
    term:
      id: NCIT:C49236
      label: Therapeutic Procedure
  target_mechanisms:
  - target: Refractory Ventricular Arrhythmia and Circulatory Collapse
    treatment_effect: MODULATES
    description: >-
      Substitutes for cardiac output while the arrhythmic substrate persists,
      preventing the downstream ischaemic consequences of sustained low flow.
    evidence:
    - reference: PMID:19514874
      reference_title: "Aconite poisoning."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "In refractory cases of ventricular arrhythmias and cardiogenic shock, it is most important to maintain systemic blood flow, blood pressure, and tissue oxygenation by the early use of cardiopulmonary bypass."
      explanation: >-
        States the indication and the physiological goal this link encodes.
  notes: >-
    Bound to the generic `NCIT:C49236` Therapeutic Procedure because NCIT has no
    cardiopulmonary bypass term - a direct label scan of the NCIT release used
    here for `cardiopulmonary bypass` returns nothing. `NCIT:C171507`
    Extracorporeal Membrane Oxygenation exists but is a different modality from
    the bypass the source recommends, and substituting it would misstate the
    cited recommendation.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Management is supportive; the early use of cardiopulmonary bypass is recommended if ventricular arrhythmias and cardiogenic shock are refractory to first-line treatment."
    explanation: The review's concluding recommendation for refractory cases.
- name: Charcoal Haemoperfusion
  description: >-
    Extracorporeal removal of circulating aconitine alkaloids by charcoal
    haemoperfusion has been used in patients with ventricular tachycardia, but
    its role is not established. It is curated here as an unresolved option
    rather than a recommended therapy.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: charcoal haemoperfusion
    term:
      id: NCIT:C49236
      label: Therapeutic Procedure
  notes: >-
    Bound to the generic `NCIT:C49236` because NCIT has no haemoperfusion term: a
    direct label scan of the NCIT release used here returns zero matches for both
    `hemoperfusion` and `haemoperfusion`. The hemodialysis family exists but is a
    different modality and would misstate the intervention.
  target_mechanisms:
  - target: Ingestion of Aconitum Alkaloids
    treatment_effect: MODULATES
    description: >-
      Aims to lower the circulating alkaloid burden by extracorporeal adsorption.
      MODULATES rather than INHIBITS deliberately: the intent is established, the
      effect is not - see the KNOWLEDGE_GAP on whether meaningful extraction
      occurs at all given aconitine's large apparent volume of distribution.
    evidence:
    - reference: PMID:19514874
      reference_title: "Aconite poisoning."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "The role of charcoal hemoperfusion to remove circulating aconitine alkaloids is not established."
      explanation: >-
        States the intended action on circulating alkaloid while explicitly
        withholding endorsement of its efficacy.
  evidence:
  - reference: PMID:19514874
    reference_title: "Aconite poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The role of charcoal hemoperfusion to remove circulating aconitine alkaloids is not established."
    explanation: >-
      Explicitly withholds endorsement; recorded as PARTIAL so the treatment is
      not read as recommended.
  - reference: PMID:15111916
    reference_title: "Clinical features and management of herb-induced aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with ventricular tachycardia were also treated with charcoal hemoperfusion."
    explanation: >-
      PARTIAL - documents use in the four patients with ventricular tachycardia,
      but the series has no control arm and all 17 patients recovered, so it
      cannot attribute the outcome to haemoperfusion. See the KNOWLEDGE_GAP
      discussion.
- name: Intra-Arterial Vasodilator Therapy for Non-Occlusive Mesenteric Ischaemia
  description: >-
    Directed at the splanchnic vasospasm rather than at the poisoning. In
    non-occlusive mesenteric ischaemia the vasospasm persists after the
    precipitating haemodynamic event is corrected, and direct intra-arterial
    vasodilator therapy is reported as the only treatment shown to be effective -
    an unusually strong claim, and the reason this arm is curated as a treatment
    target rather than only as a complication.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: intra-arterial vasodilating agent
      term:
        id: NCIT:C29707
        label: Vasodilating Agent
  target_mechanisms:
  - target: Non-Occlusive Mesenteric Ischaemia
    treatment_effect: INHIBITS
    description: >-
      Relieves the splanchnic arteriolar vasospasm that defines the lesion,
      restoring mucosal perfusion.
    evidence:
    - reference: PMID:11976865
      reference_title: "Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Vasospasm frequently responds to direct intra-arterial vasodilator therapy, which is the only treatment that has been shown to be effective."
      explanation: >-
        States both the target (vasospasm) and the effect, and is the strongest
        efficacy claim available for this arm.
  notes: >-
    Evidenced from the general non-occlusive mesenteric ischaemia literature, not
    from any aconitine series - no patient in the cited aconitine literature
    received it. It is curated because this entry curates the lesion, and it is
    flagged here so it is not read as an established step in managing aconitine
    poisoning specifically.
  evidence:
  - reference: PMID:11976865
    reference_title: "Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "In early non-occlusive mesenteric ischemia, as opposed to occlusive disease, there is no surgical therapy."
    explanation: >-
      Establishes that the early lesion is managed medically rather than
      surgically, which is the premise for vasodilator therapy.
prevalence:
- population: Taiwan, National Poison Center case series 1990-1999
  measure_type: CASES_IN_LITERATURE
  prevalence_class: UNKNOWN
  notes: >-
    Seventeen cases over a decade in one national poison centre. Recorded as a
    case count, not a population rate: a poison-centre denominator is
    ascertainment-limited and cannot support a prevalence or incidence estimate.
  evidence:
  - reference: PMID:15111916
    reference_title: "Clinical features and management of herb-induced aconitine poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A total of 17 cases occurred and consisted of 9 men and 8 women aged 30 to 70 years."
    explanation: >-
      The case count and demographic range from the national poison-centre
      database over 1990-1999.
discussions:
- discussion_id: gap_aconitine_charcoal_haemoperfusion_efficacy
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - "pathophysiology#Refractory Ventricular Arrhythmia and Circulatory Collapse"
  prompt: >-
    Does extracorporeal removal of circulating aconitine alkaloids by charcoal
    haemoperfusion shorten the duration of ventricular arrhythmia or reduce
    mortality, relative to supportive care and mechanical circulatory support
    alone?
  rationale: >-
    The two sources curated here point in opposite directions without
    contradicting each other, which is precisely why this is a gap rather than a
    controversy. The Chan review states flatly that the role of charcoal
    haemoperfusion is not established. The Taiwanese series did give
    haemoperfusion to all four patients who developed ventricular tachycardia,
    and all 17 patients recovered completely - but with no control arm, an
    uncontrolled series in which everyone survives cannot separate a treatment
    effect from the natural history of a self-limiting toxidrome whose alkaloid
    is cleared over hours. The pharmacological prior is genuinely uncertain in
    both directions: aconitine is a lipophilic alkaloid with a large apparent
    volume of distribution, which argues against meaningful extracorporeal
    clearance, yet charcoal adsorbs it well in vitro. Resolving this matters
    clinically because haemoperfusion competes for time, vascular access and
    anticoagulation with the mechanical circulatory support that the same review
    does recommend.
  proposed_experiments:
  - experiment_id: exp_aconitine_haemoperfusion_extraction_and_outcome
    name: Registry-based comparative effectiveness analysis of haemoperfusion in aconite poisoning
    description: >-
      Pooled analysis across national poison-centre registries in regions where
      aconite preparations are in common use, comparing patients who received
      charcoal haemoperfusion with those who did not, restricted to patients with
      documented ventricular arrhythmia and adjusted for severity at
      presentation. Paired with serial plasma aconitine measurement across the
      haemoperfusion circuit to quantify actual extraction.
    decision_criterion: >-
      Whether measured extraction across the circuit is large enough to lower
      plasma aconitine materially, and whether arrhythmia duration differs
      between treated and untreated patients after severity adjustment.
    supporting_outcome:
    - Substantial single-pass extraction of aconitine across the charcoal circuit.
    - Shorter time to arrhythmia resolution in haemoperfused patients after adjustment for presenting severity.
    refuting_outcome:
    - Negligible extraction across the circuit, consistent with a large volume of distribution.
    - No difference in arrhythmia duration or mortality after severity adjustment.
- discussion_id: mismatch_aconitine_calcium_p38_arm_human_relevance
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  attaches_to:
  - "pathophysiology#Aconitine-Induced Calcium Overload and Cardiomyocyte Apoptosis"
  prompt: >-
    Does aconitine cause calcium overload, p38 MAPK activation and cardiomyocyte
    apoptosis in poisoned humans, or is this arm confined to the rodent and
    cell-culture systems in which it has been demonstrated?
  rationale: >-
    The calcium-overload arm rests entirely on adult and neonatal rat ventricular
    myocytes and conscious rats. This is not a generic caveat about animal work:
    the doses used in such models are chosen to produce reproducible arrhythmia
    and measurable apoptosis, whereas human poisoning is a single uncontrolled
    ingestion with an exposure that falls as the alkaloid is cleared. The two
    arms also differ in what they predict. The sodium-channel arm predicts a
    fully reversible electrical disturbance, which is what the clinical
    literature reports - complete recovery in all 17 patients of the Taiwanese
    series, and an overall in-hospital mortality of only 5.5%. A substantial
    apoptotic arm would predict measurable myocyte loss and residual ventricular
    dysfunction in survivors, which is not described. Either the apoptotic arm is
    minor at human exposures, or survivors carry unrecognised myocardial injury.
    The node is deliberately left off the causal path to circulatory collapse
    until this is settled.
  proposed_experiments:
  - experiment_id: exp_aconitine_survivor_troponin_and_cmr
    name: Cardiac injury and function follow-up in human aconite poisoning survivors
    description: >-
      Prospective measurement of high-sensitivity cardiac troponin during the
      acute phase, with cardiac magnetic resonance including late gadolinium
      enhancement and extracellular volume mapping in survivors at three months,
      in a consecutive cohort of patients admitted with aconite poisoning.
    decision_criterion: >-
      Whether survivors show troponin release beyond that attributable to
      resuscitation and defibrillation, and whether any residual myocardial
      fibrosis or dysfunction is detectable at three months.
    supporting_outcome:
    - Troponin elevation disproportionate to the resuscitation received.
    - Late gadolinium enhancement or raised extracellular volume in survivors at three months.
    refuting_outcome:
    - Troponin release fully accounted for by cardiopulmonary resuscitation and defibrillation.
    - Normal cardiac magnetic resonance in survivors, indicating a purely electrical and reversible insult.
- discussion_id: gap_aconitine_hpvg_reversibility_generalisation
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - "pathophysiology#Hepatic Portal Venous Gas"
  - "pathophysiology#Non-Occlusive Mesenteric Ischaemia"
  prompt: >-
    In patients who develop hepatic portal venous gas after resuscitated
    toxin-induced cardiac arrest, what proportion have transmural bowel necrosis
    requiring resection, and what proportion resolve with haemodynamic
    optimisation alone?
  rationale: >-
    The source case report proposes that hepatic portal venous gas in this
    setting is a reversible consequence of shock and that the primary insult
    should be treated rather than the radiological sign - a claim supported at
    the level of general principle by the hepatic portal venous gas literature,
    which holds that prognosis follows the underlying pathology and that the sign
    is not itself a surgical indication. But the specific claim rests on one
    patient, and the competing risk is asymmetric: non-occlusive mesenteric
    ischaemia carries a mortality of the order of 50%, and its vasospasm persists
    after the precipitating event is corrected, so conservative management of a
    patient who in fact has transmural necrosis is not a recoverable error. What
    is missing is not the principle but the discriminator - the clinical or
    radiological features that separate the reversible from the necrotic case at
    the bedside. Until that exists, this entry records the mechanism without
    implying a management recommendation.
  proposed_experiments:
  - experiment_id: exp_hpvg_post_arrest_outcome_cohort
    name: Multicentre cohort of hepatic portal venous gas following resuscitated cardiac arrest
    description: >-
      Retrospective multicentre identification of patients with computed
      tomography-confirmed hepatic portal venous gas within seven days of
      resuscitated cardiac arrest, linking initial imaging features (extent of
      gas, bowel wall enhancement, pneumatosis intestinalis, mesenteric vessel
      patency) and lactate trajectory to the reference outcome of transmural
      necrosis at laparotomy or resolution on repeat imaging.
    decision_criterion: >-
      Whether any combination of initial imaging and biochemical features
      separates patients who resolved without surgery from those with transmural
      necrosis, at a negative predictive value high enough to support
      conservative management.
    supporting_outcome:
    - A majority of cases resolving with haemodynamic optimisation alone.
    - An identifiable low-risk imaging and lactate profile with high negative predictive value for transmural necrosis.
    refuting_outcome:
    - A high proportion of transmural necrosis irrespective of initial appearances.
    - No feature combination separating the two outcomes, implying that portal venous gas in this setting warrants surgical assessment regardless of the presumed cause.
📚

References & Deep Research

Deep Research

1
Claude Code ▸
Aconitine Poisoning — Comprehensive Disease Characteristics Research Report
claude-haiku-4-5-20251001, claude-sonnet-5 47 citations 2026-08-22T16:16:58.287708

Aconitine Poisoning — Comprehensive Disease Characteristics Research Report

1. Disease Information

Overview. Aconitine poisoning (aconite poisoning, monkshood/wolfsbane poisoning) is an acute toxidrome caused by ingestion, and less commonly cutaneous/mucosal absorption, of aconitine and related C19-diterpenoid alkaloids (mesaconitine, hypaconitine, jesaconitine, yunaconitine) found in Aconitum species (Ranunculaceae; monkshood, wolfsbane; Chinese: Fuzi/Chuanwu/Caowu). It is a toxin-mediated, non-genetic (environmental/toxicological) disease characterized predominantly by neurologic, gastrointestinal, and life-threatening cardiovascular (arrhythmic) manifestations resulting from persistent activation of voltage-gated sodium channels (Chan, Clin Toxicol 2009, PMID:19514874; Zhou et al., Forensic Sci Res 2020, PMC7241456).

Key identifiers. - ICD-10-CM: T46.991–T46.996 series is used for aconitine as a cardiotoxic agent poisoning in some coding schemes; general plant-toxin poisoning may also be coded under T62.2 (other noxious substances eaten as food, poisonous plants) depending on the jurisdiction's coding convention. - MeSH: "Aconitine" (chemical, D000109); "Aconitum" (plant genus, D000110); "Plant Poisoning" (D010942). - MONDO/OMIM/Orphanet: No dedicated disease-entity ID was identified — this is modeled as an environmental/toxic exposure syndrome rather than a classical nosological disease entity in these resources; curation as a dismech Environmental-category entry (parallel to Arsenic_Poisoning) is appropriate rather than as a genetic Disease. - CHEBI: aconitine, mesaconitine, hypaconitine, and jesaconitine each have dedicated CHEBI small-molecule entries (exact CURIEs should be confirmed via OAK/CHEBI lookup before curation).

Common synonyms: Aconite poisoning, monkshood poisoning, wolfsbane poisoning, Aconitum alkaloid toxicity, Fuzi poisoning, Chuanwu/Caowu poisoning, "bushi" poisoning (Japan).

Evidence basis: Information is derived almost entirely from aggregated case reports/case series (individual poisoning episodes reported in emergency medicine, toxicology, and forensic literature), a small number of retrospective cohort/registry analyses (e.g., mainland China 2004–2015 retrospective, Hong Kong incidence studies), and preclinical mechanistic studies in cell lines (H9c2 cardiomyocytes), zebrafish embryos, and rodents. There is no large prospective clinical trial base, consistent with an acute poisoning syndrome rather than a chronic disease.

2. Etiology

Disease causal factor: Direct environmental/toxicological — ingestion (occasionally topical/mucosal exposure) of aconitine or related Aconitum diterpenoid alkaloids. This is fundamentally a xenobiotic exposure, not a genetic or infectious disease.

Risk factors

Environmental/behavioral (dominant risk pathway): - Ingestion of improperly processed or raw Aconitum roots/tubers in traditional Chinese medicine (TCM) preparations (Fuzi, Chuanwu, Caowu) — inadequate boiling/steaming leaves toxic diester-diterpenoid alkaloid (DDA) content above safe thresholds (Frontiers 2026, toxicology/detox review). - Consumption of homemade medicinal liquor/wine steeped with Aconitum roots — a recurrent cause of clusters, e.g., the 2018 Chongqing, China outbreak reported by CDC MMWR (MMWR 71(16), 2022; PMC9042358). - Misidentification of Aconitum tubers as edible plants (e.g., confused with wild ginseng, horseradish, or other root vegetables) leading to accidental food poisoning. - Co-ingestion with ethanol, which potentiates aconitine-induced arrhythmogenesis ("ethanol-aconitine induced arrhythmia" is a specifically studied toxicological interaction; PMID:32250090). - Excessive dosing / self-medication with prepared aconite herbal formulas beyond recommended limits. - Intentional self-poisoning (suicide/self-harm) — reported cases exist in both Western and Asian settings (ScienceDirect, "Intentional ingestion of aconite: two cases of suicide"). - Geographic/cultural exposure: highest incidence in regions with active TCM, Ayurvedic, or Tibetan medicine use (mainland China, Hong Kong, Taiwan, Japan, Nepal, India), though sporadic cases occur worldwide from ornamental monkshood ingestion.

Pharmacogenetic/host factors (plausible but not directly clinically demonstrated): - Individual variation in CYP3A4/CYP3A5 and CYP2D6 activity — the principal enzymes metabolizing aconitine, mesaconitine, and hypaconitine via demethylation, N-deethylation, dehydrogenation, and hydroxylation (PMID:21277363). CYP2D6 is highly polymorphic (>130 star alleles; poor/intermediate/extensive/ultrarapid metabolizer phenotypes), and reduced-function alleles could plausibly prolong toxin exposure, though this has not been directly correlated with clinical poisoning severity in published human case series. - Elderly age is repeatedly cited as a poor-prognosis modifier due to diminished physiological (cardiac, renal, hepatic) reserve rather than a distinct susceptibility mechanism.

Protective factors - Adequate herbal processing (boiling/steaming Aconitum roots >2 hours) hydrolyzes the highly toxic C19-diester diterpenoid alkaloids to markedly less toxic monoester and non-ester derivatives, reducing total DDA content to <0.02% (200 μg/g) — the principal mitigation strategy used in TCM (Frontiers review, Lai et al. 2019). - Co-administration with Glycyrrhiza uralensis (licorice) in classical TCM formulas has been shown experimentally to promote CYP3A-mediated metabolism of Aconitum toxic components, attenuating toxicity (PMC9236245). - No genetic protective variant has been specifically characterized for aconitine toxicity.

Gene–environment interactions: The principal G×E axis is pharmacogenetic (CYP3A4/CYP2D6 metabolizer status) modulating the rate of clearance of an environmental toxin — i.e., a toxicokinetic rather than a toxicodynamic interaction. No genome-wide association or candidate-gene susceptibility study specific to aconitine poisoning was identified.

3. Phenotypes

Aconite poisoning classically produces a triad of neurologic, gastrointestinal, and cardiovascular manifestations, with onset typically within minutes to 2 hours (documented range 3 minutes to 6 hours) of ingestion (Chan 2009, PMID:19514874; Taiwan case series latent period 10–90 min). In a 17-patient Taiwan case series, neurologic features occurred in 17/17, cardiovascular in 14/17, gastrointestinal in 9/17, and other in 5/17 patients (Annals of Emergency Medicine, PMID:15111916).

Neurologic/sensory (early/hallmark signs): - Perioral/circumoral paresthesia and numbness — often the earliest, most characteristic symptom; suggested HPO: Paresthesia (HP:0003401) — verify a more specific perioral term. - Numbness/paresthesia of the extremities and tongue - Ataxia (HP:0001251) - Muscle weakness (HP:0001324), fasciculations - Seizures (HP:0001250) - Reduced consciousness / coma (HP:0001259)

Gastrointestinal: - Nausea (HP:0002018), vomiting (HP:0002013) - Abdominal pain (HP:0002027) - Diarrhea (HP:0002014) - Hypersalivation/sialorrhea

Cardiovascular (drives mortality): - Palpitations - Hypotension (HP:0002615), shock/cardiogenic shock - Bradycardia (HP:0001662) or sinus tachycardia — bidirectional autonomic effects reported - Ventricular ectopy, ventricular tachycardia (bidirectional VT is the classically described ECG hallmark), ventricular fibrillation, torsades de pointes (suggested HPO: Ventricular arrhythmia/Ventricular tachycardia — verify exact term, e.g., candidates near HP:0004308/HP:0011675) - Cardiac arrest (HP:0001695) - Refractory "electrical storm" in severe cases

Other: Sweating/diaphoresis, respiratory depression/failure (HP:0002878), hypothermia in some reports.

Phenotype characteristics: - Onset: Acute, minutes to hours post-exposure — this is uniformly an adult-onset acute presentation (age of "onset" reflects timing of exposure, not developmental stage), though pediatric accidental exposures are reported. - Severity: Highly variable — dose-dependent, ranging from mild paresthesia/GI upset to fulminant cardiogenic shock and death within hours. - Progression: Rapid, non-relapsing (single-exposure toxidrome); severity escalates over the first several hours if untreated, then resolves with toxin clearance/elimination (half-life estimates around several hours have been reported, though pharmacokinetic data in poisoned humans are limited and heterogeneous). - Frequency among affected individuals: Neurologic features are near-universal (~100% in case series); cardiovascular involvement occurs in a large minority to majority of symptomatic cases (e.g., 14/17, ~82%, in the Taiwan series); ventricular arrhythmias specifically occurred in ~4/17 (~24%) of that cohort.

Quality of life impact: No dedicated QoL instrument data exist for this acute toxidrome. Survivors of severe poisoning with cardiac arrest may have anoxic neurologic sequelae; most survivors of non-arrest presentations recover without long-term functional impairment, as the pathology is a reversible ion-channel-mediated electrophysiological/toxic insult rather than structural tissue destruction (absent secondary hypoxic-ischemic injury).

4. Genetic/Molecular Information

Aconitine poisoning is not a Mendelian/genetic disease — there are no causal or pathogenic germline variants. The molecular biology relevant to curation concerns (a) the pharmacological target and (b) metabolizing-enzyme pharmacogenetics:

Molecular target (not a "causal gene" but the toxin's binding target): - SCN5A (cardiac voltage-gated sodium channel Nav1.5, hgnc:10593) — principal cardiac target; aconitine binds neurotoxin receptor site 2 on the α-subunit, favoring the open channel state and causing persistent activation/blocking of inactivation, producing sustained Na⁺ influx (Zhou et al. 2020, PMC7241456; PMID:9430411). - Related neuronal/skeletal-muscle sodium channels (SCN1A–SCN4A family) mediate the neurologic and neuromuscular manifestations via the same site-2 mechanism on nerve and muscle membranes. - Structural work on the bacterial homolog NaChBac localizes an aconitine pore-blocking interaction to residue F224, and aconitine has also been shown to block peak current and shift activation of Nav1.7 (SCN9A) — relevant to the paresthesia phenotype. - Downstream, aconitine-induced Ca²⁺ overload in cardiomyocytes is mediated in part through TRPV2 (transient receptor potential cation channel subfamily V member 2) upregulation via p38 MAPK signaling, driving mitochondrial-pathway apoptosis (increased Bax/cleaved caspase-3, decreased Bcl-2) (Wang et al. 2021, ECAM, PMC8426055).

Metabolizing-enzyme genes (pharmacokinetic, not causal): - CYP3A4 (hgnc:2637) and CYP3A5 — primary hepatic metabolizers of aconitine, mesaconitine, and hypaconitine (Km/Vmax values reported per isoform; PMID:21277363, PMID:21550385). - CYP2D6 (hgnc:2625) — secondary contributor, highly polymorphic (poor/intermediate/extensive/ultrarapid metabolizer phenotypes). - CYP2C19, CYP2E1, CYP1A2 — minor contributing isoforms for hypaconitine and other congeners.

Pathogenic variants / allele frequency / somatic-vs-germline: Not applicable — no disease-causing germline or somatic variant is implicated. This distinguishes aconitine poisoning from congenital sodium-channelopathies (e.g., Brugada syndrome, Long QT type 3) that share the SCN5A target but arise from inherited gain-of-function/loss-of-function variants rather than exogenous toxin binding — a mechanistically relevant but etiologically distinct comparator (see cardiac_ion_channel_repolarization module in dismech's channelopathy modeling).

Epigenetic/chromosomal information: None reported; not applicable to this acute toxic exposure.

5. Environmental Information

Environmental factors (primary etiology, see §2): - Ingestion of raw or improperly processed Aconitum spp. tubers/roots (Fuzi, Chuanwu, Caowu; A. carmichaelii, A. kusnezoffii, A. napellus) - Homemade herbal/medicinal liquor or soup prepared with aconite roots - Contamination of other herbal products by aconite roots (misidentification during herb collection/processing) — see PMID:26481590 - Excessive or improperly dosed TCM/Ayurvedic/Tibetan medicine formulas containing prepared aconite - Suggested ECTO term category: exposure to plant alkaloid toxin via ingestion (specific ECTO CURIE for aconitine/Aconitum exposure should be verified via OAK before curation).

Lifestyle factors: - Concurrent ethanol consumption potentiates cardiotoxicity ("ethanol-aconitine induced arrhythmia," PMID:32250090) - Self-medication practices and use of unregulated/homemade herbal remedies without professional oversight - Occupational/recreational exposure is rare but reported for gardeners/horticulturists handling ornamental monkshood (cutaneous absorption)

Infectious agents: Not applicable — aconitine poisoning is a purely chemical/toxin-mediated disease with no infectious component.

6. Mechanism / Pathophysiology

Causal chain (initial trigger → clinical manifestation):

  1. Ingestion/absorption of aconitine (and congeners mesaconitine, hypaconitine, jesaconitine) → rapid gastrointestinal or mucosal absorption, with symptom onset often within minutes given high lipid solubility and membrane permeability.
  2. Binding to neurotoxin receptor site 2 on voltage-gated sodium channels (Nav1.5/SCN5A in cardiomyocytes; Nav1.7/SCN9A and other neuronal isoforms in peripheral nerves; skeletal-muscle Nav1.4) in the open channel state → the channel is locked into persistent activation and becomes refractory to normal inactivation.
  3. Sustained Na⁺ influx at resting membrane potential → membrane depolarization, repetitive/ectopic action potential firing in nerve (paresthesia, numbness, seizures), skeletal muscle (weakness, fasciculation), and cardiac tissue.
  4. Downstream cardiac electrophysiological consequences: sodium-channel-driven early and delayed afterdepolarizations (via secondary increases in intracellular Na⁺ and Ca²⁺), producing triggered activity and re-entrant substrate → ventricular ectopy, bidirectional ventricular tachycardia, ventricular fibrillation, and torsades de pointes.
  5. Cellular/molecular amplification loop in cardiomyocytes: aconitine activates p38 MAPK signaling, which upregulates and promotes plasma-membrane trafficking of TRPV2, a calcium-permeable channel, causing sustained intracellular Ca²⁺ overload (PMC8426055; Hindawi ECAM 2021).
  6. Mitochondrial dysfunction and oxidative stress: Ca²⁺ overload and direct mitochondrial injury increase reactive oxygen species (ROS) production, decrease PGC-1α expression and ATP content, and disrupt mitochondrial membrane potential.
  7. Apoptotic and inflammatory amplification: increased pro-apoptotic Bax and cleaved caspase-3, decreased anti-apoptotic Bcl-2, and activation of the NLRP3/ASC/caspase-1 inflammasome axis drive cardiomyocyte apoptosis and inflammation, compounding the primary electrophysiological insult.
  8. Clinical endpoint: refractory ventricular arrhythmias and/or cardiogenic shock/cardiac arrest — the principal cause of death in severe poisoning; concurrently, GI (direct mucosal irritant/vagal effects) and neuromuscular (peripheral nerve/muscle Na⁺-channel) manifestations occur in parallel, largely upstream-independent of the cardiac cascade.

Upstream vs. downstream: The sodium-channel binding event (step 2) is the shared upstream trigger for all three organ-system manifestations (neuro, GI/autonomic, cardiac); the TRPV2/p38 MAPK/Ca²⁺-overload/apoptosis axis (steps 5–7) is a cardiomyocyte-specific downstream amplifier distinct from the primary electrophysiological (arrhythmogenic) mechanism, i.e., this maps to two parallel but interacting node types: an acute electrophysiological node (arrhythmia, minutes-scale) and a slower cytotoxic/apoptotic node (myocardial injury, hours-scale).

Cell types involved: cardiomyocytes (CL:0000746), peripheral sensory/motor neurons (CL:0000540), skeletal muscle cells (CL:0000188/CL:0000187), gastrointestinal epithelial/enteric neuronal elements (indirect, vagally mediated).

Biological processes / suggested GO terms: - Voltage-gated sodium channel activity (GO:0005248; cardiac-specific GO:0086006) - Cardiac muscle cell action potential (GO:0086001) / regulation of heart rate by cardiac conduction (GO:0086091) - p38MAPK cascade (GO:0038066) - Calcium ion transmembrane transport (GO:0070588) - Reactive oxygen species metabolic process (GO:0072593) - Apoptotic process (GO:0006915); intrinsic apoptotic signaling pathway (GO:0097193) - NLRP3 inflammasome complex assembly (GO:0140639, verify)

Protein dysfunction: Not a loss/gain-of-function mutation but a pharmacological gain-of-function-like state induced by toxin binding — the channel protein is structurally normal but functionally "trapped open" by the alkaloid ligand (mechanistically analogous to, but distinct from, congenital SCN5A gain-of-function long-QT type 3 mutations).

Metabolic changes: Hepatic CYP3A4/3A5/2D6-mediated Phase I biotransformation (demethylation, N-deethylation, dehydrogenation, hydroxylation) generates at least six identified metabolites of aconitine in human liver microsomes; metabolite toxicity is generally reduced relative to parent compound, making hepatic clearance a rate-limiting detoxification step.

Immune system involvement: Secondary/minor — cardiomyocyte NLRP3/ASC/caspase-3-mediated sterile inflammation contributes to myocardial injury but is not a primary immune-mediated disease mechanism.

Tissue damage mechanisms: Oxidative stress and mitochondrial dysfunction (cardiomyocytes); electromechanical dysfunction without primary structural necrosis in mild-to-moderate cases; secondary hypoxic-ischemic injury to brain/other organs may occur in cardiac-arrest survivors.

Molecular profiling / advanced technologies: Zebrafish embryo transcriptomic/functional studies implicate Nrf2-HO-1/JNK-Erk signaling in aconitine-induced developmental cardiotoxicity and oxidative stress (PMC8097150); H9c2 rat cardiomyoblast cell-line studies provide the TRPV2/p38 MAPK mechanistic data above. No human single-cell, spatial transcriptomic, or CRISPR screen data specific to aconitine poisoning were identified.

7. Anatomical Structures Affected

Organ level: - Primary: Heart (myocardium — UBERON:0000948) — arrhythmogenesis and cardiomyocyte injury; Peripheral nervous system (UBERON:0000010) — sensory/motor neuropathy-like symptoms; Gastrointestinal tract (UBERON:0001007) — direct irritant and autonomic effects. - Secondary: Central nervous system (UBERON:0001017) — seizures, coma (may reflect direct toxin CNS penetration and/or secondary hypoxic injury from cardiac arrest); Skeletal muscle (UBERON:0001630) — weakness, fasciculation; Kidney — secondary injury in shock states; Liver — site of metabolism, occasional hepatotoxicity reported in animal models. - Body systems: Cardiovascular, nervous (central + peripheral + autonomic), gastrointestinal, musculoskeletal, and (secondarily) respiratory systems.

Tissue/cell level: - Cardiac muscle tissue / cardiomyocytes (CL:0000746) - Peripheral sensory and motor neurons (CL:0000540 or more specific subtypes) - Skeletal muscle fibers (CL:0000188) - Vascular smooth muscle / endothelium (secondary, via hypotension/shock)

Subcellular level (GO Cellular Component): - Plasma membrane (GO:0005886) — site of Na⁺/Ca²⁺ channel toxin action - Mitochondrion (GO:0005739) — site of ROS generation, ATP depletion, apoptotic signaling - Sarcoplasmic reticulum (cardiomyocyte Ca²⁺ handling, indirect)

Localization: Systemic/multi-organ — not laterally restricted; cardiac conduction-system involvement (His-Purkinje system) has been specifically implicated in some ventricular tachycardia cases (Ni et al. 2025, Ann Noninvasive Electrocardiol).

8. Temporal Development

Onset: Acute — this is an adult (or occasionally pediatric, accidental) acute poisoning event, not a developmental-onset disease. Symptom onset after ingestion is reported as early as 3 minutes and as late as 6 hours, with most series citing a latent period of 10–90 minutes and majority of symptoms manifesting within 2 hours.

Progression: - Early phase (minutes–1 hour): perioral/extremity paresthesia, nausea/vomiting. - Escalation phase (1–several hours): progressive neuromuscular weakness, ataxia, hypotension, cardiac arrhythmias (the critical window for clinical deterioration and intervention). - Critical/peak phase: refractory ventricular arrhythmias, cardiogenic shock, cardiac arrest — typically within the first several hours to about 24 hours post-ingestion in fatal cases; in a veterinary context, "death usually occurs within 6 hours" of a lethal dose. - Recovery phase: With survival past the acute arrhythmic window and toxin clearance (hepatic metabolism + supportive/extracorporeal elimination), most patients recover without permanent sequelae over days.

Disease course pattern: Self-limited, single-exposure acute toxidrome (not relapsing-remitting or chronic) — unless re-exposure occurs (e.g., repeated dosing errors with prepared aconite formulas).

Disease duration: Acute and self-limited; hospitalization typically spans days for supportive/monitoring care; ECMO-supported cases may extend to 1–2+ weeks.

Remission patterns: Spontaneous resolution with toxin clearance and supportive/antiarrhythmic treatment in most survivors; no disease-modifying "cure" exists — management is entirely supportive/time-buying pending endogenous elimination.

Critical periods: The first few hours post-ingestion represent the critical intervention window (decontamination, early antiarrhythmic/hemoperfusion therapy, and — if arrhythmias become refractory — early initiation of VA-ECMO), as repeatedly emphasized across case reports (PMC10835702).

9. Inheritance and Population

Epidemiology: - Approximately 5,000 aconite poisoning incidents were reported across China, Germany, Japan, and other countries during 1993–2005, with most fatal poisonings occurring in China. - A retrospective analysis of mainland China case reports (2004–2015) identified 53 victims across 27 published case reports. - Hong Kong has published dedicated incidence studies of herb-induced aconitine poisoning (Chan TY, Drug Saf 2002; link) given its documented endemic TCM-related exposure. - Sporadic outbreaks/clusters are reported globally, including a homemade medicinal liquor cluster in Chongqing, China (2018) described by CDC's MMWR (MMWR 71(16), 2022), and case reports from Nepal, Bangladesh, and Western countries (typically involving ornamental monkshood or imported herbal products).

Inheritance pattern: Not applicable — this is not a heritable disease (no Mendelian inheritance, penetrance, expressivity, anticipation, mosaicism, or carrier-frequency concepts apply).

Population demographics: - Affected populations: Highest burden in East and South Asian populations with active use of TCM, Tibetan medicine, and Ayurveda (China, Hong Kong, Taiwan, Japan, Nepal, India); sporadic cases occur worldwide (Europe, North America) typically from ornamental Aconitum napellus or imported herbal remedies. - Geographic distribution: Endemic in regions with traditional herbal medicine practice; case clusters often geographically tied to a specific herbal product batch or local liquor preparation. - Sex ratio: Case series show relatively balanced sex distribution (e.g., 9 men/8 women in the Taiwan cohort), though ratios vary by cohort and exposure route. - Age distribution: Predominantly adults (reported cohort ranges e.g., 30–70 years); elderly patients carry disproportionately poor prognosis due to reduced physiological reserve.

10. Diagnostics

Clinical tests: - ECG monitoring is the central bedside diagnostic and risk-stratification tool — bidirectional ventricular tachycardia is considered a characteristic (though not pathognomonic) finding in aconitine poisoning; monitoring for ventricular ectopy, VT, VF, and torsades de pointes is essential. - Electrolyte panel (magnesium, potassium) — informs both diagnosis of arrhythmia risk and guides magnesium-based therapy. - Laboratory tests: No routine clinical (point-of-care) assay for aconitine exists; diagnosis is primarily clinical (history of herbal/plant exposure + characteristic symptom triad + ECG findings). - Biomarkers: None validated for clinical use; research-grade LC-MS/MS quantification is used in specialized/forensic settings.

Specialized/forensic testing: - LC-MS/MS quantification of aconitine, mesaconitine, hypaconitine, and jesaconitine in whole blood, serum, or urine — validated methods report linearity 1.25–40 ng/mL with detection limits of 0.3–0.5 ng/mL ([Meng et al., Forensic Toxicol, PMID cited via link]); other assays report LOD/LOQ of 0.1/0.5 ng/g in blood. - Fatal case postmortem series report blood aconitine concentrations spanning 2.3–86.2 μg/L (femoral blood), with detection also possible in gastric content, urine, and kidney tissue. - Toxicological history-taking (identifying the specific herbal product, liquor, or plant material ingested) is often essential for definitive diagnosis, given the absence of routine hospital-based assays.

Genetic testing: Not applicable — this is not a genetic disease; no genetic test is diagnostic.

Clinical criteria: No formal diagnostic-criteria consensus statement (e.g., DSM/ICD-style) exists; diagnosis relies on a combination of exposure history, characteristic symptom triad (neuro + GI + cardiac), and supportive ECG findings, per toxicology reviews (PMID:19514874, PMID:38613376).

Differential diagnosis: Other cardiotoxic plant/alkaloid poisonings (e.g., cardiac glycoside/digoxin toxicity, taxine/yew poisoning, local anesthetic systemic toxicity), other causes of bidirectional VT (severe digoxin toxicity, catecholaminergic polymorphic VT), and other causes of perioral paresthesia (hyperventilation, hypocalcemia, ciguatera/tetrodotoxin poisoning — note tetrodotoxin has an opposite sodium-channel mechanism, site 1 blockade vs. aconitine's site 2 activation, making the clinical distinction mechanistically instructive).

Screening: No population screening program exists (this is an acute exposure event, not a screenable heritable/chronic condition); prevention relies on regulatory control of raw aconite herb sale/processing (see §13).

11. Outcome/Prognosis

Mortality: Reported case-fatality rates vary substantially by study population and severity: an overall in-hospital mortality of ~5.5% has been cited for aconite poisoning broadly, while more severe/referred cohorts report much higher fatality — one retrospective analysis of 35 cases found 17 deaths (49%) — reflecting substantial referral/severity bias across published series. A dedicated forensic toxicology series identified 25 aconitine-induced deaths (2005–2023) in one jurisdiction (ScienceDirect).

Cause of death: Predominantly refractory ventricular arrhythmias (VT/VF, "electrical storm") and asystole/cardiac arrest; cardiogenic shock is the other principal proximate cause.

Morbidity/functional outcomes: Survivors of non-arrest presentations generally have full recovery without chronic sequelae, consistent with the reversible (non-structural) nature of the primary ion-channel-mediated pathology; survivors of cardiac arrest may sustain anoxic brain injury and other complications common to any resuscitated arrest.

Complications: Cardiogenic shock, multi-organ hypoperfusion injury (acute kidney injury, hepatic injury) in severe/prolonged shock states, and — rarely — mechanical circulatory support-related complications (bleeding, limb ischemia) in ECMO-treated patients.

Prognostic factors: - Dose/exposure magnitude — the poisonous dose has been cited as low as ~0.2 mg with a lethal dose in the range of 2–5 mg (and separately, an oral minimum lethal human dose of 1–2 mg and a "lowest lethal dose" of 28 mg/kg bodyweight reported in another source — figures vary across the literature and should be treated as approximate ranges pending consolidation from a systematic toxicology reference). - Time to treatment initiation — the first several hours represent the critical intervention window. - Age — elderly patients have disproportionately worse outcomes. - Early recognition of refractory arrhythmia and escalation to VA-ECMO — case reports consistently associate early ECMO initiation (before irreversible multi-organ injury) with survival in otherwise refractory cases (PMC10835702; WJCC 2024). - No specific antidote exists, which is repeatedly emphasized as a key driver of adverse outcomes in refractory cases.

12. Treatment

There is no specific antidote for aconitine poisoning; management is entirely supportive and time-buying, aimed at maintaining perfusion and cardiac rhythm until endogenous (hepatic CYP3A4/2D6-mediated) elimination occurs.

Decontamination: - Early activated charcoal administration (gastric decontamination) if presenting soon after ingestion. - Gastric lavage/emesis/catharsis reported historically, though evidence for efficacy is limited.

Extracorporeal elimination: - Charcoal hemoperfusion — used in patients with ventricular arrhythmias; some series report successful reversion to sinus rhythm during/after hemoperfusion, though direct evidence of alkaloid removal efficacy is limited (PMID unlisted; Annals of Emerg Med case series). - Continuous renal replacement therapy (CRRT) used adjunctively in multimodal regimens.

Antiarrhythmic pharmacotherapy (evidence largely from pooled case-report analysis — Fitzgerald et al., Clin Toxicol 2017, PMID:28421842): - Flecainide and amiodarone show the strongest association with return to sinus rhythm across pooled human case reports. - Lidocaine, mexiletine, procainamide, and electrical cardioversion are less consistently effective and are more often associated with arrhythmia persistence. - Magnesium sulfate — used both as electrolyte correction and reported in successful case reports of arrhythmia reversal / combination therapy for "aconitine-induced electrical storm" (PMC12573093). - Atropine for symptomatic bradycardia.

Advanced circulatory/mechanical support: - Prolonged cardiopulmonary resuscitation (CPR) and cardiopulmonary bypass are recommended as "time-buying" strategies in refractory cases pending toxin clearance. - VA-ECMO (veno-arterial extracorporeal membrane oxygenation) — repeatedly reported as life-saving in refractory ventricular arrhythmia/cardiogenic shock; multiple recent case reports (2023–2025) document successful outcomes with early ECMO initiation, sometimes combined with hemoperfusion. - Ventricular assist device support reported in at least one historical case (PMID:7892979).

Supportive care: - Continuous cardiac monitoring, hemodynamic support (vasopressors as needed), airway management/ventilatory support for respiratory depression, seizure management (benzodiazepines).

Experimental/investigational targets: TRPV2 has been proposed as a potential molecular target for future pharmacotherapy of aconitine-induced cardiomyocyte injury, based on preclinical (H9c2 cell) mechanistic data — not yet in clinical use.

Suggested NCIT terms for treatment annotation: Pharmacotherapy (NCIT:C15986; antiarrhythmic agents as therapeutic_agent), Supportive Care (NCIT:C15747); Hemoperfusion and ECMO/extracorporeal circulatory support procedure terms should be verified via NCIT lookup before curation (exact CURIEs not confirmed in this research pass).

13. Prevention

Primary prevention: - Proper herbal processing: boiling/steaming raw Aconitum roots for >2 hours hydrolyzes toxic C19-diester diterpenoid alkaloids to non-toxic/less-toxic derivatives, reducing total DDA content to <0.02% (200 μg/g) — the cornerstone of TCM safety practice. - Regulatory alkaloid-content limits: e.g., Korean regulatory authorities cap total alkaloid content (as benzoylaconine) at 0.33% by titration method in prepared aconite products. - Scheduling/controlled distribution: In India, Aconitum herbs are classified as Schedule E(1) poisons under the Drugs and Cosmetics Rules, restricting use to supervision by licensed Ayurvedic practitioners. - Public health messaging against self-preparation of homemade medicinal liquor/soup using raw aconite roots, and against consuming unregulated herbal products of uncertain provenance. - Avoidance of co-ingestion with alcohol, given documented potentiation of cardiotoxicity.

Secondary prevention (early detection): No population screening program exists; early clinical recognition of the neuro-GI-cardiac triad in a patient with a compatible exposure history is the operative "detection" strategy, supported by rapid access to ECG monitoring in emergency settings.

Tertiary prevention: Standardized emergency-department and ICU protocols for early antiarrhythmic therapy, hemoperfusion, and low-threshold escalation to VA-ECMO in refractory cases (see §12) function as tertiary prevention of death/major morbidity once poisoning has occurred.

Immunization: Not applicable (non-infectious toxin exposure).

Genetic counseling / genetic screening: Not applicable.

Public health interventions: Herbal-market regulation and quality control of TCM/Ayurvedic aconite-containing products; outbreak investigation and public communication following cluster events (e.g., CDC MMWR reporting of the 2018 Chongqing homemade liquor cluster) to prevent recurrence.

Environmental interventions: Regulation/labeling of ornamental monkshood sale in regions where accidental horticultural exposure has been reported; supervision of herb-collection practices to prevent inadvertent contamination of other medicinal herbs with aconite roots.

14. Other Species / Natural Disease

Taxonomy of the source organism: Aconitum spp. (family Ranunculaceae), notably A. napellus (monkshood, Europe/temperate regions), A. carmichaelii (Fuzi, China), A. kusnezoffii (Caowu, China) — plant NCBI Taxon IDs should be confirmed via lookup if curating the source organism (not the affected host species).

Species naturally affected by poisoning: - Livestock: Cattle and goats are most frequently affected by grazing on monkshood in pasture settings; horses are also susceptible (HorseDVM; CowDVM; PMC4690134). - Companion animals: Dogs are reported to be susceptible to monkshood ingestion (Pet Poison Helpline). - Clinical signs in animals parallel human poisoning: initial gastrointestinal distress (drooling, bloating, emesis) followed by musculoskeletal weakness, difficulty breathing, cardiac rhythm disturbances (bradyarrhythmia), and sudden death — death typically occurs within 6 hours of a lethal ingested dose in livestock, with cardiac effects (heart-rate slowing) often the proximate cause.

Comparative pathology: The core mechanism (voltage-gated sodium channel site-2 activation) is conserved across vertebrate species, given the high evolutionary conservation of the sodium channel pore and site-2 binding region — this underlies why rodent, zebrafish, and livestock/companion-animal poisoning all recapitulate the human neuro-cardiac toxidrome.

Veterinary relevance: Aconite/monkshood poisoning is a recognized cause of pastoral livestock loss in regions where the plant grows wild, and a recognized companion-animal (dog) poisoning risk from ornamental garden plantings; it is managed by the same supportive/antiarrhythmic principles as human poisoning, adapted to veterinary practice.

Zoonotic potential: Not applicable (a toxin exposure, not a transmissible infectious disease); no cross-species transmission risk beyond shared environmental exposure to the same toxic plant.

15. Model Organisms

Rodent models: - Mouse LD50 values: oral 1.8 mg/kg, intraperitoneal 0.31 mg/kg (also cited as 0.27 mg/kg i.p. in a second source), intravenous 0.12 mg/kg — the roughly 10-fold difference between oral and parenteral LD50 reflects substantial first-pass hepatic metabolism/reduced oral bioavailability. - Subacute mouse poisoning models have characterized hematological and histopathological effects of repeated low-dose aconitine exposure (Frontiers in Veterinary Science 2022). - Rat models have demonstrated direct embryotoxic effects during the organogenetic period, and rat studies of aconitine-induced Ca²⁺ overload/p38 MAPK-mediated apoptosis in vivo complement the H9c2 cell-line mechanistic data (ScienceDirect).

Zebrafish embryo models — an increasingly important developmental/cardiotoxicity screening platform: - Aconitine produces concentration-dependent embryo mortality, arrhythmias, extended sinus venosus–bulbus arteriosus distance, and pericardial edema. - Reported cardiotoxic thresholds: 2.5 μg/L aconitine and 20 μg/L mesaconitine caused deficient cardiovascular development with yolk-sac hemorrhage and early cardiac dysfunction at 96 hours post-fertilization. - Mechanistic zebrafish studies implicate the Nrf2-HO-1/JNK-Erk signaling axis in aconitine-induced developmental toxicity, oxidative stress, and ROS-mediated mitochondrial apoptosis (PMC8097150), and a related study links aconitine-induced cardiotoxicity to dysregulated calcium-signaling gene expression in zebrafish embryos (PMID:30639578). - Zebrafish models allow comparative cardiotoxicity ranking of different Aconitum diterpene alkaloids (aconitine, mesaconitine, hypaconitine, and others).

Cell-line (in vitro) models: - H9c2 rat cardiomyoblast cell line — the principal in vitro platform for dissecting the TRPV2/p38 MAPK/Ca²⁺-overload/apoptosis mechanism described in §6, and for testing candidate mitigating compounds.

Model characteristics — recapitulation and limitations: - Both rodent and zebrafish models faithfully recapitulate the core electrophysiological (arrhythmogenic) and cytotoxic (oxidative stress/apoptotic) arms of human aconitine cardiotoxicity, consistent with the high conservation of the sodium-channel target. - Zebrafish embryo models are particularly well suited to rapid, quantitative cardiotoxicity/developmental-toxicity screening but cannot model the full adult human clinical syndrome (e.g., adult conduction-system anatomy, His-Purkinje-specific arrhythmia mechanisms reported in some human case reports). - Livestock/companion-animal natural disease (rather than induced experimental model) provides real-world corroboration of the human toxidrome but is not a controlled research model system.

Research applications: These models are used to (a) rank comparative toxicity of different Aconitum alkaloid congeners, (b) dissect molecular mechanism (TRPV2, p38 MAPK, Nrf2-HO-1/JNK-Erk pathways), and (c) screen candidate therapeutic/mitigating compounds (e.g., co-administered herbal components such as Glycyrrhiza uralensis that promote CYP3A-mediated detoxification).

Model databases: No dedicated aconitine-poisoning-specific model registry exists; relevant strains/lines are accessed via standard model-organism resources (IMSR/MGI for mouse, ZFIN for zebrafish, and standard cell-line repositories such as ATCC/Cellosaurus for H9c2).

Summary of Suggested Ontology Terms (for dismech curation — verify all IDs via OAK before use)

Category Candidate terms
HPO Paresthesia (HP:0003401), Nausea (HP:0002018), Vomiting (HP:0002013), Diarrhea (HP:0002014), Abdominal pain (HP:0002027), Ataxia (HP:0001251), Muscle weakness (HP:0001324), Seizure (HP:0001250), Coma (HP:0001259), Hypotension (HP:0002615), Bradycardia (HP:0001662), Cardiac arrest (HP:0001695), Respiratory failure (HP:0002878); ventricular tachycardia/arrhythmia terms need confirmation
GO (Biological Process/MF) Voltage-gated sodium channel activity (GO:0005248/GO:0086006), Cardiac muscle cell action potential (GO:0086001), p38MAPK cascade (GO:0038066), Calcium ion transmembrane transport (GO:0070588), Reactive oxygen species metabolic process (GO:0072593), Apoptotic process (GO:0006915)
CL Cardiac muscle cell (CL:0000746), Neuron (CL:0000540), Skeletal muscle fiber (CL:0000188)
UBERON Heart (UBERON:0000948), Peripheral nervous system (UBERON:0000010), Digestive system (UBERON:0001007), Skeletal muscle organ (UBERON:0001630)
CHEBI Aconitine, mesaconitine, hypaconitine, jesaconitine (specific CURIEs to confirm via OAK CHEBI search)
HGNC/Gene SCN5A (hgnc:10593, molecular target), CYP3A4 (hgnc:2637), CYP2D6 (hgnc:2625) — metabolizing enzymes, not causal genes
NCIT (treatment) Pharmacotherapy (NCIT:C15986), Supportive Care (NCIT:C15747); hemoperfusion/ECMO-specific NCIT CURIEs to confirm

Sources

Reference Validation

Checked with linkml-reference-validator 0.2.1.

Outcome Count
References checked 35
Resolved 35
Unresolved (possible confabulation) 0
Unverifiable 0
Quoted claims checked 2
Quoted claims found in source 0
Quoted claims not found in source 2
References weighed for topical relevance 35
On topic 14
Off topic 0

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