Strychnine is an alkaloid derived from the seeds of the tree Strychnos nux-vomica. Brucine, a similar but weaker alkaloid, comes from the same seeds. Strychnine can be found in other plants (eg, Strychnos ignatii [Saint Ignatius bean], Lignum colubrinum [Snakewood]). It is odorless and colorless, with a bitter taste. At one time, strychnine was an ingredient in a variety of over-the-counter tonics and laxatives, and was used clinically in the treatment of cardiac arrest and snake envenomation and as an analeptic. Although strychnine is no longer found in pharmaceuticals, it is still available as a pesticide and rodenticide. It is also sometimes found as an adulterant in illicit drugs (eg, cocaine, heroin).

1. Strychnine competitively antagonizes glycine, an inhibitory neurotransmitter released by postsynaptic inhibitory neurons in the spinal cord. Strychnine binds to the chloride ion channel, causing increased neuronal excitability and exaggerated reflex arcs. This results in generalized seizure-like contraction of skeletal muscles. Simultaneous contraction of opposing flexor and extensor muscles causes severe muscle injury, with rhabdomyolysis, myoglobinuria, and, in some cases, acute renal failure.
2. Pharmacokinetics. Strychnine is absorbed rapidly after ingestion or nasal inhalation and distributed rapidly into the tissues. It has low plasma protein binding and a large volume of distribution (estimated at 13 L/kg in one case report). Strychnine is metabolized by the hepatic cytochrome P450 microsome system to a major metabolite, strychnine N-oxide, by first-order kinetics. Elimination is predominantly extrarenal, with an elimination half-life of about 10-16 hours.

A toxic threshold dose is difficult to establish. The potentially fatal dose is approximately 50-100 mg (1 mg/kg), although death was reported in an adult who had ingested 16 mg. Signs of toxicity can occur rapidly, and because management decisions should be based on clinical findings rather than the reported amount ingested, any dose of strychnine should be considered potentially life-threatening.

Signs and symptoms usually develop within 15-30 minutes of ingestion and may last up to 12-24 hours.

1. Muscular stiffness and painful cramps precede generalized muscle contractions, extensor muscle spasms, and opisthotonus. The face may be drawn into a forced grimace (risus sardonicus, “sardonic grin”). Muscle contractions are intermittent and easily triggered by emotional, auditory, or minimal physical stimuli. Repeated and prolonged muscle contractions often result in hypoxia, hypoventilation, hyperthermia, rhabdomyolysis, myoglobinuria, and renal failure.
2. Muscle spasms may resemble the tonic phase of a grand mal seizure, but strychnine does not cause true convulsions, as its target area is the spinal cord, not the brain. The patient is usually awake and painfully aware of the contractions, described as “conscious seizures.” Profound metabolic acidosis from increased lactic acid production is common.
3. Victims may also experience hyperacusis, hyperalgesia, and increased visual stimulation. Sudden noises or other sensory input may trigger muscle contractions. Rarely, anterior tibial compartment syndrome can be seen.
4. Death usually is caused by respiratory arrest that results from intense contraction of the respiratory muscles. Death may also be secondary to hyperthermia or rhabdomyolysis and renal failure.

Is based on a history of ingestion (eg, rodenticide or recent IV drug use) and the presence of seizure-like generalized muscle contractions, often accompanied by hyperthermia, lactic acidosis, and rhabdomyolysis (with myoglobinuria and elevated creatine kinase [CK]). In the differential diagnosis (see Table I-16, consider other causes of generalized muscle rigidity, such as tetanus, Latrodectus envenomation, and neuroleptic malignant syndrome.

1. Specific levels. Strychnine can be measured in the gastric fluid, urine, or blood by various analytic techniques, such as HPLC, GC/MS, and LC/MS. The toxic serum concentration is reported to be 1 mg/L, although blood levels do not correlate well with the severity of toxicity. Mortality has been reported with levels of 0.29-61 mg/L.
2. Other useful laboratory studies include electrolytes, BUN, creatinine, hepatic aminotransferases, CK, arterial blood gases or oximetry, lactate, and urine test for occult blood (positive in the presence of urine myoglobinuria).

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary.
   2. Treat hyperthermia, metabolic acidosis, and rhabdomyolysis if they occur.
   3. Limit external stimuli such as noise, light, and touch.
   4. Treat muscle spasms aggressively.
      1. Administer diazepam, 0.1-0.2 mg/kg IV, lorazepam, 0.05-0.1 mg/kg IV, or midazolam, 0.05-0.1 mg/Kg IV, to patients with mild muscle contractions. Consider opioids for pain relief. Note: These agents may impair respiratory drive.
      2. In more severe cases, use rocuronium, 0.6-1 mg/kg, or another nondepolarizing neuromuscular blocker (eg, vecuronium, pancuronium) to produce complete neuromuscular paralysis. Depolarizing agents (eg, succinylcholine) should be avoided due to potential unknown presence of hyperkalemia. Caution: Neuromuscular paralysis will cause respiratory arrest; patients will need endotracheal intubation and assisted ventilation.
2. Specific drugs and antidotes. There is no specific antidote.
3. Decontamination . Administer activated charcoal orally or by nasogastric tube if conditions are appropriate (see Table I-37,). Do not induce vomiting because of the risk for aggravating muscle spasms. Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
4. Enhanced elimination. Symptoms usually abate within several hours and can be managed effectively with intensive supportive care. Hemodialysis and hemoperfusion have not been beneficial for enhancing the clearance of strychnine. The use of repeat-dose activated charcoal has not been studied.