Neurotoxic and Cardiac Poisons — Strychnine, Digitalis, Oleander and Aconite

Toxicology questions group poisons by the organ system they attack. Neurotoxic poisons act on the nervous system — here the spinal convulsant strychnine. Cardiac poisons act on the heart — digitalis (digoxin), oleander (Nerium oleander and Thevetia peruviana) and aconite (Aconitum species). All four are plant-derived alkaloids or glycosides, and all are common in exam stems because the clinical picture is highly specific.

The key to scoring is a four-part habit for each poison: source → mechanism → signature clinical sign → treatment. The table at the end of this page lists the answers side by side.

Strychnine is a highly toxic, white, odourless, bitter crystalline alkaloid from the seeds of *Strychnos nux-vomica*, a plant native to Southeast Asia, India and Australia. Sources of poisoning include rodenticides and pesticides, traditional herbal remedies containing nux vomica seeds, and street drugs (heroin or cocaine) adulterated with strychnine.

Mechanism. Strychnine is a competitive antagonist of glycine, the main inhibitory neurotransmitter, at postsynaptic glycine receptors in the spinal cord and brainstem. Loss of this inhibition lets motor neurons fire unopposed, so even trivial stimuli provoke generalised muscle contractions. Higher motor centres are unaffected, so consciousness is preserved.

• Onset: within about 15 to 30 minutes of ingestion; faster by inhalation or injection.
• Convulsions: typically 30 seconds to 2 minutes, with opisthotonic posturing — back arched, limbs extended, jaws clenched. Triggered by touch, noise or emotional stimuli.
• Risus sardonicus from facial muscle spasm; trismus; tachycardia, hypertension, abdominal cramps.
• Awake seizures — painful spasms with intact awareness and no postictal state.
• Complications: hyperthermia (up to about 43 °C), rhabdomyolysis with myoglobinuria and kidney injury, metabolic and lactic acidosis, hyperkalaemia. Death is usually from asphyxia due to respiratory muscle spasm, or from hyperthermia and rhabdomyolysis.

Diagnosis is clinical — episodic spasms with a clear sensorium and a plausible exposure. Strychnine can be measured in gastric fluid, urine or serum, but blood levels are not clinically useful because they correlate poorly with severity; urine and gastric measurements give the most reliable assessment of exposure. Laboratory work-up looks for hyperkalaemia, acidosis, rhabdomyolysis and renal failure.

Treatment is mainly supportive: a quiet, dark environment to reduce stimuli, airway protection, aggressive cooling for hyperthermia, and fluids to keep urine output above 1 mL/kg/h to protect the kidneys from rhabdomyolysis. Toxicity generally resolves within 24 hours, and patients who survive with prompt care usually recover without lasting sequelae.

Digoxin comes from the foxglove plant (Digitalis lanata) and has a narrow therapeutic window. Its main action is inhibition of the sodium-potassium ATPase pump in myocytes: intracellular sodium rises, calcium enters in exchange, and contractility increases. Digoxin also raises vagal tone, slowing conduction through the SA and AV nodes. At toxic concentrations, increased cell excitability and reduced resting potential produce afterdepolarisations and almost every type of arrhythmia.

• Extracardiac: anorexia, nausea, vomiting, headache, confusion, and visual disturbance — especially a yellow tinge to vision, photophobia and photopsia.
• Cardiac: premature ventricular complexes (commonest), AV block, bradycardia, ventricular tachycardia — and bidirectional ventricular tachycardia, which StatPearls calls pathognomonic. Arrhythmia is the leading cause of death.
• Electrolytes: hyperkalaemia in acute toxicity (a marker of severity); hypokalaemia, hypomagnesaemia and hypercalcaemia make toxicity more likely at any given level.
• ECG at therapeutic doses ('digitalis effect'): T-wave flattening or inversion, a scooped ST segment and ST depression — this alone is not toxicity.

Management: activated charcoal for acute ingestion (gastric lavage is not recommended because vagal stimulation can worsen bradycardia), continuous ECG monitoring, correction of electrolytes, and Fab fragments in severe cases. Fab treatment causes hypokalaemia, so potassium is monitored. Atropine is used for bradycardia and lidocaine or phenytoin for ventricular arrhythmias; cardioversion is not recommended because it can precipitate ventricular arrhythmias — defibrillation follows ACLS protocol if needed. Intravenous calcium is traditionally avoided in digoxin toxicity because of the theoretical 'stone heart' concern, although StatPearls notes that studies have not shown this to be a problem in practice.

Two plants are involved: common (pink) oleander, *Nerium oleander*, whose toxic glycoside is oleandrin, and yellow oleander, *Thevetia peruviana*, which contains thevetin. All parts of Nerium oleander are toxic — leaves, stems, roots, fruit and flowers. Oleander poisoning is described in tropical and subtropical regions where these plants grow abundantly; unintentional ingestion occurs in children, while intentional self-poisoning with seeds is more common in India and Sri Lanka.

The mechanism is identical to digoxin — sodium-potassium ATPase inhibition. The clinical picture is similar: nausea, vomiting and abdominal pain, followed by arrhythmias including sinus bradycardia, AV block and ventricular tachyarrhythmias, hyperkalaemia and sudden cardiac death. Ingestion of yellow oleander seeds has erratic and prolonged absorption. One study in a review found that crushed seeds caused more severe cardiac manifestations than whole seeds, and that serum potassium was a critical predictor of cardiotoxicity and outcome.

Treatment follows the cardiac glycoside pathway: supportive care, activated charcoal, atropine and temporary pacing for bradyarrhythmias, and digoxin-specific Fab fragments as the most effective antidote. Reviews note that access to Fab is limited by cost and logistics, and that treatment protocols are not standardised.

Aconite (monkshood) is derived from Aconitum species of the family Ranunculaceae; in India Aconitum ferox is known as Vatsanabha. Aconitum-containing preparations are used in traditional medicine across Asia and are classified as Schedule E(1) poisons under India's Drugs and Cosmetics Rules, 1945. Poisoning is usually accidental, from home-prepared decoctions or herbal liquors that have not been properly processed (the Ayurvedic Shodhana detoxification).

Mechanism. Aconitine binds neurotoxin site 2 of the α-subunit of voltage-gated sodium channels, locking them in an open state and preventing normal inactivation. Persistent sodium influx and prolonged depolarisation cause delayed afterdepolarisations and re-entrant ventricular arrhythmias. One review quotes poisoning at an aconitine dose of 0.2 mg, with 2 to 4 mg being fatal.

• Neurological: paraesthesia and numbness, classically perioral and in the limbs, dizziness and muscle weakness.
• Gastrointestinal: vomiting, diarrhoea.
• Cardiovascular: hypotension, bradycardia or tachyarrhythmia, ventricular ectopics, ventricular tachycardia, AV block, cardiogenic shock — the cause of death.
• Onset in case reports ranged from about 2 to 8 hours after ingestion.

Treatment. There is no specific antidote. Management relies on intensive cardiovascular support, inotropes if hypotension persists and atropine for bradycardia. For refractory ventricular arrhythmia or cardiogenic shock, venoarterial ECMO has been used as a bridge. A recent case report notes that beta-blockers lack a mechanistic rationale in aconitine toxicity, since the arrhythmia is driven by sodium-channel activation.

1. Read the sensorium. Convulsions with clear consciousness = strychnine.
2. Read the ECG. Bidirectional VT or AV block with hyperkalaemia = cardiac glycoside (digitalis or oleander). Ventricular arrhythmia with numbness = aconite.
3. Match mechanism to channel. Glycine receptor (strychnine), Na+/K+ ATPase (digitalis, oleander), voltage-gated Na+ channel (aconite).
4. Know which poison has an antidote. Digitalis and oleander have Fab; aconite and strychnine do not (supportive care only).
5. Watch the potassium. Hyperkalaemia in acute glycoside toxicity worsens arrhythmias; Fab then causes hypokalaemia.