CRACKCast Episode 150 – Anticholinergics

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This episode of CRACKCast Covers Rosen’s Chapter 145, Anticholinergics. You will learn everything you need to know for the next hot and bothered patient that rolls in to the ED!

Shownotes: PDF HERE

Rosen’s In Perspective

Here we are usually talking about anticholinergic = antimuscarinic

But in general Muscarinic receptors are on smooth muscle and the autonomic nervous system (SLUDGE & BBB)

Nicotinic receptors are on skeletal muscle NMJ

 

Anticholinergic “Red as a beet

Dry as a bone

Blind as a bat

Mad as a hatter

Hot as hell

The bladder keeps its tone and the heart runs alone”

Antimuscarinic and antinicotinic properties – leading to a relative sympathomimetic (sympathetic overdrive because cholinergic tone is blocked)

 

Hyperthermia, cutaneous flushing, delirium, hallucinations, mydriasis, urinary retention, and dry skin and mucous membranes

Antihistamines, tricyclic antidepressants, cyclobenzaprine, orphenadrine, antiparkinson agents, antispasmodics, phenothiazines, atropine, scopolamine, belladonna alkaloids (eg, Jimson Weed) Supportive, based on the specific agent

Core Questions

[1] Describe the anticholinergic toxidrome

Box 145.1: Clinical Presentation of Antimuscarinic Toxicity

  1. Mydriasis: “Blind as a bat”
  2. Altered mental status: “Mad as a hatter”
  3. Dry mucous membranes: “Dry as a bone”
  4. Dry, flushed skin: “Red as a beet”
  5. Hyperthermia: “Hot as Hades”
  6. Urinary retention: “Full as a flask”
  7. Decreased bowel sounds/ileus
  8. Tachycardia

See Figure 145.1 In Rosen’s (9th)

[2] List 10 anticholinergic meds

In general the list you’ll see is:

  • Plants
    • Jimson weed
  • belladonna alkaloids
    • Atropine
    • Scopolamine
  • Antihistamines (H1 blockers)
    • Dimenhydrinate
    • Diphenhydramine
  • Antiparkinson agents
    • Benztropine (Cogentin)
    • Procyclidine
  • Tricyclic antidepressants
    • Cyclobenzaprine
    • Amitriptyline

 

Let’s break this down into common antimuscarinic and antinicotinic drugs

 

Antimuscarinic agents

  • Atropine
  • Benztropine (Cogentin)
  • Dimenhydrinate (Gravol, Dramamine)
  • Diphenhydramine (Benadryl, Nytol, Advil PM, etc.)
  • Doxylamine (Diclectin, Restavit, Unisom)
  • Glycopyrrolate (Robinul)
  • Ipratropium (Atrovent)
  • Oxybutynin (Ditropan, Driptane, Lyrinel XL)
  • Tiotropium (Spiriva)
  • Tricyclic antidepressants (28 compounds with numerous trade names)
  • Scopolamine
  • Tropicamide

Antinicotinic agents

  • Bupropion (Zyban, Wellbutrin) – Ganglion blocker
  • Dextromethorphan – Cough suppressant and ganglion blocker

Plants of the Solanaceae family contain various anticholinergic tropane alkaloids, such as scopolamine, atropine, and hyoscyamine

Plants = The most common plants containing anticholinergic alkaloids (including atropine, scopolamine, and hyoscyamine among others) are:

  • Atropa belladonna (deadly nightshade)
  • Brugmansia species
  • Datura species
  • Garrya species
  • Hyoscyamus niger (henbane)
  • Mandragora officinarum (mandrake)

List source seen here

See Table 145.1 in Rosen’s (9th)

Note: In Canada the usual place you will see Doxylamine is in combination w/ pyridoxine (vitamin B6) which makes Diclectin, which is used to prevent morning sickness.

[3] List 15 Differential Diagnoses for the “Hot & Bothered” Patient

Box 145.2: Common Differential Diagnosis Considerations With Overlapping Signs and Symptoms of Antimuscarinic Toxicity

Differential Diagnosis Considerations

Toxicological

  1. Sympathomimetic toxicity
  2. Serotonin toxicity
  3. Neuroleptic malignant syndrome
  4. Lithium toxicity
  5. Antidepressant toxicity
  6. Antipsychotic toxicity

Central Nervous System

  1. Intracranial hemorrhage (ICH)
  2. Seizure

Metabolic

  1. Hyperthyroid
  2. Encephalopathy

Infectious

  1. Sepsis
  2. Central nervous system (CNS) infections

[4] Describe the management of anticholinergic toxicity

Stabilization

  • Sodium bicarb for QRS widening (<100 in TCA, otherwise goal <110)
  • Supportive care
  • Fluid resuscitate
  • Tx seizures & agitation w/ Benzos
  • Aggressively treat temp (if evaporative cooling does not work, then go for intubation, deep sedation and paralysis)
  • Physostigmine controversial see below

 

Decontamination

  • Generally not needed
  • There is no role for gastric lavage, whole bowel irrigation, or hemodialysis.
  • Oral activated charcoalnot indicated UNLESS:
    • symptomatic patients w/ ingestion of a highly toxic quantity of antimuscarinic plant seeds
    • only if the patient presents early after ingestion (<2 hours) and
    • is anticipated to remain cooperative.
    • **** Administering AC is best made in consultation with a medical toxicologist or regional poison center. ***

Elimination

***In general no role***

Antidote – Physostigmine

  • reversibly inhibits cholinesterases in the both peripheral nervous system and CNS
  • allows for acetylcholine accumulation and subsequent com­petition with the antimuscarinic blocking agent occupying the receptor
  • short half­-life, approximately 20 minutes but clinical duration of physostigmine is 3 to 6 hours.
  • Far more effective than Benzos at treating agitation / delirium
  • Other cholinesterase inhibitors not used as they DO NOT CROSS BBB (eg pyridostigmine, neostigmine, edrophonium)

Classic indications are:

  • Delirium / Coma / Seizure
  • risk of harming themselves or staff
  • requiring ongoing physical restraint, or
  • interfering with effective treatment (eg, pulling out IV lines)

Contraindications:

  • TCA overdose
  • Wideined QRS >100
  • AV blocks
  • Bradycardia
  • Unknown co-ingestions

See Box 145.3, and see the shownotes for more goodies from FOAMCAST

This post was copyedited and uploaded by Owen Scheirer

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Adam Thomas

Adam Thomas

CRACKCast Co-founder and newly minted FRCPC emergency physician from the University of British Columbia. Currently spending his days between a fellowship in critical care and making sure his toddler survives past age 5.
Adam Thomas
- 2 hours ago
Chris Lipp
Chris Lipp is one of the founding Fathers for CrackCast. He currently divides his time as an EM Physician in Calgary (SHC/FMC) and in Sports Medicine. His interests are in endurance sports, exercise as medicine, and wilderness medical education. When he isn’t outdoors with his family, he's brewing a coffee or dreaming up an adventure…..