Strychnine
Strychnine is an alkaloid derived from the seeds of the tree Strychnos nux-vomica. It is odorless and colorless, with a bitter taste. Brucine, a similar but weaker alkaloid, comes from the same seeds. At one time, strychnine was an ingredient in a variety of over-the-counter tonics and laxatives, and it was used 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).
Mechanism of toxicity
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.
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 (Vd estimated at 13 L/kg in one case report). Strychnine is metabolized by the hepatic cytochrome P-450 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 (see also Table II–61).
Toxic dose.
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