All Pharmacy Pearls

Introduction

    abundant in prescription and over the counter (OTCs)

  • 2. Their ease of access to anticholinergic drugs and lack of

    • concern by most patients for serious adverse effects

    make them potentially dangerous drugs

  • 3. Anticholinergic toxicity can lead to a complex toxidrome

    • characterized in the CNS by hallucinations, delirium,

    agitation and seizures

  • 4. Non-CNS effects can include dry mouth, mydriasis,

    • blurred vision, decreased/absent bowel sounds, urinary

    retention, dry and flushed skin, tachycardia, and

    hyperthermia.

  • 5. The earliest documented use of physostigmine to reverse

    • anticholinergic delirium was in 1864 by Kleinwachter who

    treated prisoners who had mistakenly consumed

    atropine

  • 6. Case reports from the 1980-90s showed an association

    • between physostigmine use and worsened patient

    outcomes, which has led to a drastic decline in its use for

    anticholinergic toxicity

  • 7. These case reports involved physostigmine administration

    • in the setting of TCA toxicity with prolonged QRS have

    been the most common situation which displayed

Pharmacology

Physostigmine
Dose
-
IV: 0.5 to 2 mg
-
Repeat every 5 min PRN to
reverse agitation
-
2 mg cumulative MAX
Administration
-
Slow IV Push ~3-5 min
Formulation
-
IV: 2mg/2mL vials
PK/PD
-
Onset ~1 min
-
Duration 30-60 mins
Adverse Effect
-
Bradycardia
-
Bronchospasm
-
Bronchorrhea
-
Diaphoresis
-
Muscle fasciculation
Warnings
-
Convulsions may occur with
overly rapid IV
administration
Contraindication
-
QRS > 100 msec
-
TCA toxicity
Pharmacy
Friday
Physostigmine
for
Anticholinergic
Toxidrome
Author,
Year
Design/ sample
size
Offending Agents
causing Toxicity
Outcome
Boley SP,
2018
Prospective
observational
analysis
n=154
Antihistamines (68%),
analgesics (19%), and
antipsychotics (19%)
Delirium control in 79% of patients who received
physostigmine versus 36% of those who did not
(OR 6.6)
No difference in adverse events with
physostigmine vs standard of care
Arenas,
2018
Retrospective
cohort study
n=191
Anticholinergic plant
(35.1%),
Diphenhydramine
(29.3 %), other
antihistamines (7.3%),
TCAs (1.6%), other
agents (26.7 %)

Evidence











Conclusions


anticholinergic toxidrome. Minimal adverse effects have been reported as long as there is no report of TCA


ingestion and QRS < 100 msec. However, patient’s delirium will return once the physostigmine wears off, so repeat


dosing may be needed.










References


1.
Physostigime. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from
http://www.micromedexsolutions.com/
2.
Boley SP, et al. Physostigmine is superior to non-antidote therapy in the management of antimuscarinic delirium: a prospective study
from a regional poison center. Clin Toxicol. 2018 Jun 29. Epub ahead of print. PMID 29956570
3.
Arens AM, et al. Safety and effectiveness of physostigmine: a 10-year retrospective review. Clin Toxicol (Phila). 2018 Feb;56(2):101-107.
4.
Rosenbaum C,et al. Timing and frequency of physostigmine redosing for antimuscarinic toxicity. J Med Toxicol. 2010 Dec;6(4):386-92
5.
Weizberg M, et al. Altered mental status from olanzapine overdose treated with physostigmine. Clin Toxicol (Phila). 2006;44(3):319-25.
6.
Burns MJ, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med.
2000 Apr;35(4):374-81
7.
Pentel P, et al. Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Annals of emergency medicine.
1980;9:588-90.









Tags:
0.5 to 2 mg anticholinergic delirium QRS





Source PDF

Physostigime for Anticholinergic Toxidrome- pharmacy friday-11302018.pdf