Anticholinergic Poisoning
description
Transcript of Anticholinergic Poisoning
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Anticholinergic PoisoningAnticholinergic Poisoning
Andrew Dawson, Newcastle Mater Hospital
Robert Hoffman, New York Poison Centre
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
BelladonnaBelladonna
Atropa belladonna (Solanaceae)
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
KineticsKinetics Rapidly absorbed
– Prolonged absorbtion in overdose Large volume of distribution and rapid
distribution Low hepatic clearance
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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.
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Treatment OptionsTreatment Options Reassurance Physical Containment Sedation - benzodiazepines Physostigmine Close observation Risk of medical complications
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Efik PeopleEfik People
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PhysostigmPhysostigma venosuma venosum
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
“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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
? 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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
#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.
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
2:30 PM: – #4 was conscious, sitting up, able to answer
questions. Pupils still dilated– #3 unchanged
Next day– #4 Normal– #3 Still poisoned
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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%
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Pal in 1900 Pal in 1900 Reverses CurareReverses Curare
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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