Toxicology - Strychnine / strychnos nux-vomica poisoning

Toxicology of Strychnine poisoning with properties, active principles, uses, metabolites, actions, signs, symptoms, tetanus vs strychnine poisoning, treatment, postmortem findings and medico-legal importance

1. Strychnine poisoning Adhavan. M 2nd year MBBS IGMC&RI Puducherry

2. Introduction Properties Active principles Uses Action Metabolism Signs & symptoms Tetanus vs strychnine poisoning Treatment Post-mortem findings Medico-legal importance

3. Introduction Strychnos nux-vomica (family loganiaceae) is evergreen tree native to south-east Asia especially India and Myanmar One of the oldest poisons known to man Also called nux-vomica, poison nut, quaker buttons Seeds of ripe fruit are poisonous Unbroken seeds are not poisonous

4. Identification of seeds: Flat, circular discs, 2.5×0.6 cm, concavo-convex, ash grey in colour, have a shiny surface, covered with silky hair Properties of Strychnine: Colourless, odourless, bitter, rhombic prism shaped crystals; dissolves sparingly in water & ether, dissolves well in alcohol & benzene

5. Active principles The seeds contain mainly 2 alkaloids: Strychnine Brucine Seeds also contain glucoside & loganin Alkaloids are mostly in seeds; but can also be isolated from all other parts including bark, leaves, roots Barks, leaves and roots contain Brucine, not Strychnine

6. Uses Respiratory stimulant, rodenticide, to kill stray dogs Available as herbal remedies as purgative, appetite suppressant, nerve tonics Adulterant in street drugs such as cocaine, heroin, amphetamines

7. Action Strychnine competitively antagonises the inhibitory neurotransmitter glycine by blocking its post-synaptic uptake by brain stem & spinal cord receptors Inhibitory effect of glycine is reduced, nerve impulses are triggered even with low levels of neurotransmitters Without inhibitory effect the motor neurons give continuous stimuli causing constant muscle contraction called release excitation High action in anterior horn cells/ Renshaw cells of spinal cord GABA is not affected

8. Metabolism All mucous membranes absorb Strychnine Taken up by liver and muscles Released later that causes convulsions on 2nd or 3rd day 80% metabolised by liver; hepatotoxic 20% excreted in urine and bile Found in cadaver for 4 years

9. Signs and symptoms Seen within 15 - 30 mins of ingestion of crushed seeds Bitter taste, choking sensation in throat, stiffness of neck, face Prodromal symptoms: restlessness, increased rigidity of muscles, muscular twitching, increased acquity of perception Face: cyanosed, looks anxious, staring eyes, prominent eyeballs, pupils dilated, mouth filled with bloodstained froth Risus sardonius - scornful laughter, Risus caninus - dog like laughter: seen due to raised eyebrows, bulging of eyes and contraction of jaw and facial muscles

10. Convulsions: initially clonic later becomes tonic Even slight impulses lead to high intensity convulsions Marked convulsions of anti-gravity muscles causing Opisthotonus posture Patient remains awake during convulsions as Strychnine doesn’t cross BBB Spasm of abdominal muscles cause Emprosthotonus (forward bending) or Pleurosthotonus (sideways)

11. Risus sardonius Opisthotonus posture

12. Convulsions cause lactic acidosis, rhabdomyolysis and hyperthermia Death occurs within 4-5 convulsions as patient cannot breathe Consciousness is lost and mind is clear until death During death, body freezes in middle of convulsions causing Cadaveric spasm

13. Cause of death: Death due to medullary paralysis Asphyxia due to spasm of respiratory muscles Exhaustion from convulsions Fatal dose: 15-50 mg or 1 crushed seed Fatal period: 1-2 hours

14. S. No. Features Strychnine  poisoning Tetanus 1 History of injury None Present 2 Onset Sudden in hours Gradual (days) 3 Site of action Post synaptic membrane Pre synaptic membrane 4 Trismus or lock jaw Does not start in nor especially affect jaw Starts in and affects lower jaw 5 Muscular condition Relaxed in between convulsions Rigid throughout 6 Fatal period 1-2 hrs >24 hrs 7 Chemical analysis Strychnine found No poison Strychnine poisoning Vs Tetanus

15. Treatment There is no specific antidote Supportive care with reducing external stimulus, prevention of convulsions Control of convulsions: Put patient in dark, noise-free room. Diazepam 0.1-0.5 mg/kg I.V. If ineffective GA like Galamine is given Barbiturates like Phenobarbital sodium, Amytal are antidotes Stomach wash with warm water and dil. KMnO₄. Then suspension of activated charcoal given I.V. fluid to maintain urine output to prevent renal failure due to metabolic acidosis Haemodialysis is ineffective

16. Autopsy findings Findings are not characteristic Rigor mortis appears early but is not necessarily prolonged Signs of asphyxia Extravasated blood may be found in muscles Viscera are congested Haemorrhages may be found in stomach, duodenum Strychnine can be easily detected in blood, urine, gastric fluid, bile, liver and kidney samples

17. Medico-legal importance Death is usually accidental due to overdose, exposure to rodenticide or children eating seeds Suicide and homicide are rare due to its bitter taste and painful death Used as aphrodisiac, cattle, arrow, dog and rat poison Tolerance develops on repeated consumption Can be detected easily even in decomposed bodies

18. References Biswas G. Spinal and peripheral nerve poisons-Strychnos Nux-vomica. In: Review of Forensic Medicine and Toxicology. Third edition. Jaypee Brothers Medical Publishers (P) Ltd; 2015.p.572-574. K.S.N. Reddy, O.P.Murthy. Spinal poisons. In: The Essentials of Forensic Medicine & Toxicology. 33rd edition. Jaypee Brothers Medical Publishers (P) Ltd. 2014.p.612-614.