Anticholinergic Poisoning

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Anticholinergic PoisoningAnticholinergic Poisoning

Andrew Dawson, Newcastle Mater Hospital

Robert Hoffman, New York Poison Centre


BelladonnaBelladonna

Atropa belladonna (Solanaceae)


KineticsKinetics Rapidly absorbed

– Prolonged absorbtion in overdose Large volume of distribution and rapid

distribution Low hepatic clearance


DynamicsDynamics 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


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.


Anticholinergic DeliriumAnticholinergic 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


Treatment OptionsTreatment Options Reassurance Physical Containment Sedation - benzodiazepines Physostigmine Close observation Risk of medical complications


Efik PeopleEfik People


PhysostigmPhysostigma venosuma venosum


Efik LawEfik 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


“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


Hydrolysis of AcetylcholineHydrolysis of Acetylcholine

CH3 C

O

O CH2 CH2 N CH3

CH3CH3

+

Cholinesterase

SerineAnionic

siteEsteratic

site

CH3 C

OH

O+

CH2 CH2 N CH3

CH3CH3


? Anticholinererases? Anticholinererases

Name Selectivity Site of action Tacrine BChase > AChase (x 4) Anionic g

Donepezil AChase >> BChase (x 188) Anionic gp

Rivastigmine AChase = BChase Anionic g & Esteratic g Physostigmine BChase > AChase (x 2) Esteratic Galantaminea AChase > BChase (x 9) Esteratic gp


First Use As An AntidoteFirst 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


#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.


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


2:30 PM: – #4 was conscious, sitting up, able to answer

questions. Pupils still dilated– #3 unchanged

Next day– #4 Normal– #3 Still poisoned


Comparison of Physo and BZsComparison of Physo and BZs Retrospective review of 52 patients with

anticholingeric symptoms Physostigmine

– Controlled agitation: 96%– Reversed delirium: 87%

Benzodiazepines– Controlled agitation: 24%– Reversed delirium:9%


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


Pal in 1900 Pal in 1900 Reverses CurareReverses Curare


Tacrine in anticholinergic Tacrine in anticholinergic deliriumdelirium

Unblinded Study: 26 patients

– 15 Retrospective chart review clinical toxicology database

– 11 Prospective pilot study safety & dose ranging

Safety primary outcome Efficacy secondary outcome


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

Rank Description

0 No delirium

1 Delirium no intervention

2 Delirium reassurance only

3 Delirium requires restraint


Response DurationResponse Duration The Mean duration of 1st response

Dosemg

Duration(hours)

15 1.48 ± 0.1030 4.21 ± 0.8945 3.19 ± 1.4560 5.58 ± 2.60

Any dose >15 4.20 ± 0.74

Anticholinergic Poisoning

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