Anticholinergic Poisoning

1. Anticholinergic Poisoning Andrew Dawson, Newcastle Mater Hospital Robert Hoffman, New York Poison Centre

2. Belladonna Atropa belladonna(Solanaceae)

3. Kinetics • Rapidly absorbed • Prolonged absorption in overdose • Large volume of distribution and rapid distribution • Low hepatic clearance

4. Dynamics • 5 muscarinic subtypes: • Different tissue distributions with some overlap • M1 receptors: CNS • M2 receptors:CNS and heart • M3 receptors: Salivary glands • M4 receptors: Brain and lungs • Different affinity at different receptors

6. Central Anticholinergic Syndrome • Delirium (Hyperactive or Hypoactive) • Seizures • Peripheral Anticholinergic Syndrome • thirst, dry mouth, dilated pupils, tachycardia, flushed face, slowed gastric emptying and decreased bowel sounds, dry skin, hyperthermia, urinary retention.

8. Anticholinergic Delirium • Acute confusional state • Blockade of cholinergic muscarinic receptors • Pure anticholinergic drugs • Many psychiatric drugs • Plants • 40-50 admissions per annum • Delirium doubles mean duration of stay to 56 hours • Increased levels of staffing

9. Treatment Options • Reassurance • Physical Containment • Sedation - benzodiazepines • Physostigmine • Close observation • Risk of medical complications

10. Efik People

11. Physostigma venosum

12. Efik Law • Trial by ordeal • Deadly esere • Administration of the Calabar bean • First observed by WF Daniell in 1840 • Later described by Freeman 1846 in a Communication to the Ethnological Society of Edinburgh

13. “A suspected person is given 8 beans ground and added to water as a drink. If he is guilty, his mouth shakes and mucus comes from his nose. His innocence is proved if he lifts his right hand and then regurgitates. If the poison continues to affect the suspect after he has established his innocence, he is given a concoction of excrement mixed in water which has been used to wash the external genitalia of a female.” Simmons 1952

14. Serine Esteratic site Anionic site Cholinesterase Hydrolysis of Acetylcholine O C H C H 3 3 C H C O C H C H N C H 3 2 2 3 +

15. ? Anticholinesterases

16. First Use As An Antidote • Kleinwächter 1864 • 4 prisoners drank atropine solution thinking it was liquor • 9AM estimated atropine dose 64 mg total • One patient was asymptomatic (spat it out) • Another had dilated pupils, with a normal pulse and temperature

17. #3: “extreme drunkenness”; laughing, delirious, unable to speak coherently, flushed, dilated pupils, temp 38.7 oC, pulse 70/min, ? movement disorder. • #4: Unable to stand, flushed, elevated temperature, tachypnea, very dilated pupils, dry mouth, coma alternating with agitation.

18. Tried ipecac, coffee, tannic acid and cinnamon • Unable to give beer with tartar emetic • Both patients deteriorated • Gave Calabar extract (about 1 mg physostigmine) to #4, keep #3 as a control

19. 2:30 PM: • #4 was conscious, sitting up, able to answer questions. Pupils still dilated • #3 unchanged • Next day • #4 Normal • #3 Still poisoned

20. Comparison of Physo and BZs • Retrospective review of 52 patients with anticholinergic symptoms • Physostigmine • Controlled agitation: 96% • Reversed delirium: 87% • Benzodiazepines • Controlled agitation: 24% • Reversed delirium: 9%

21. Physostigmine • Lower incidence of complications • 7% vs 46% • Shorter recovery time • 12 vs 24 hours • No difference in side effects • Burns et al: Ann Emerg Med 2000;35:374-381

22. Pal in 1900 Reverses Curare

23. Tacrine in anticholinergic delirium • Unblinded Study: • 26 patients • 15 Retrospective chart review clinical toxicology database • 11 Prospective pilot study safety & dose ranging • Safety primary outcome • Efficacy secondary outcome

24. Defining Success / Response • Documented clinical resolution of symptoms • Patient as being described as being lucid • Shift in 1 level of care

25. Response Duration • The Mean duration of 1st response