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Cholinergic + Organophosphate Poisonings, References, (National Center of…
Cholinergic + Organophosphate Poisonings
Pathophysiology
Organophosphate/Carbamate Poisoning
Organophosphorus compounds contain carbon + phosphorous acid derivates, which are absorbed through the skin, lungs, and gastrointestinal tract, binding to
acetylcholinesterase
(AChE), which makes the enzyme non-functional. AChE is an enzyme that hydrolyzes acetylcholine to choline and acetic acid, and the inhibition leads to an
excessive amount of acetylcholine
at the neuronal synapses and neuromuscular junction
Cholinergic Toxicity
Acetylcholinesterase inhibition leads to an
accumulation of acetylcholine
at synapse + neuromuscular junctions, which results in the
overstimulation of muscarinic and nicotine receptors
Differential Diagnoses
Other Conditions
Hypoglycemia
can present w/ sweating, altered mental status, and bradycardia
Brainstem Stroke
affects the vagal nuclei and can cause bradycardia, salivation, and miosis (pinpoint pupils)
Guillain-Barre Syndrome or Eaton-Lambert Syndrome Or Myasthenia Crisis
can present w/ autonomic dysfunction, i.e., excessive secretions and bradycardia, and weakness
Septic Shock
present w/ bradycardia, hypotension, & respiratory failure
Meningitis/Encephalitis
can lead to autonomic instability, excessive salivation, and altered mental status
Severe Asthma Exacerbation
presents with bronchoconstriction, dyspnea, tachypnea, wheezing and rhinorrhea
Other Poisionings
Organophosphate/Carbamate Poisoning
(diff dx for cholinergic ingestion) is indistinguishable from direct cholinergic toxicity (ask about recent pesticide exposure)
Nicotine Toxicity
(i.e., tobacco, c-cigarettes, nicotine patches) causes cholinergic and adrenergic effects
Mushroom Poisoning
(muscarinic-containing species, i.e., inocybe or clitocybe) present w/ similar "SLUDGE" sx
Opioid Overdose
d/t similar sx, including miosis, respiratory depression, and altered mental status (lacks salivation or diarrhea)
Beta-Blocker or Calcium Channel Blocker Overdoses
presents w/ bradycardia and hypotension, but lacks excessive secretions or miosis
Clonidine Overdose
presents w/ bradycardia, lethargy, and miosis, but lacks SLUDGE sx
Presentation
"DUMBELLS
+
SLUDGE"
D
iarrhea,
U
rination,
M
iosis,
B
ronchoconstriction,
B
radycardia,
E
mesis,
L
acrimation,
L
ethargy,
S
alivation,
S
weating
S
alivation,
L
acrimation,
U
rination,
D
efecation,
G
I
D
istress,
E
mesis
Management
ABCD's
If requiring intubation,
avoid succinylcholine
d/t lack of acetylcholinesterase caused by the poisoning will cause prolonged paralysis - rocuronium can be used
Adequate
volume resuscitation
w/ isotonic crystalloid (i.e., normal saline or lactated ringer solution)
Aggressive Decontamination
Remove clothing & discard, skin and eyes should be flushed to avoid further absorption of agent if appropriate + healthcare workers should wear PPE while treating patient
Activated charcoal
may be given to patients presenting within one hour of an organophosphate or carbamate ingestion
Medications
(atropine and pralidoxime)
IV administration of
atropine 0.05 mg/kg q5mins
first until respiratory sx resolve, then
pralidoxime,
which as as direct antidote by antagonizing the muscarinic receptor's actions & atropine can cross blood-brain-barrier to counteract the centrally acting acetylcholine.
If first dose of atropine is not effective, then dose should doubled q3-5m until pulmonary muscarinic s/sx are resolved
atropine does not treat neuromuscular dysfunction and will require
pralidoxime 25-50 mg/kg IV
infused slowly over 30 mins, which reactivates acetylcholinesterase, provides endogenous anticholinergic effects, and detoxifies unbound organophosphates & work on the nicotinic neuromuscular junction and should be given in setting of muscle weakness (i.e., respiratory muscle weakness)
Source of Poisoning
Organophosphates + carbamate pesticides, i.e.,
chlorpyrifos, diazinon, parathoin, fenthion, and matathion, methomyl, aldicarb
Muscarinic toxins, i.e., wild mushrooms or nerve agents (military-grade)
Neostigmine, physostigmine, bethanechol, donepezil, rivastigmine
Household products
, contaminated fruits, vegetables, or water
References
Henretig, F. M., Kirk, M. A., & McKay, C. A., Jr. (2019). Hazardous Chemical Emergencies and Poisonings.
The New England Journal of Medicine, 380
(17), 1638-1655.
https://doi.org/10.1056/NEJMra1504690
National Center for Biotechnology Information. (2019). Immune Responses in Infectious Diseases.
U.S. National Library of Medicine
.
https://www.ncbi.nlm.nih.gov/books/NBK539783/
Centers for Disease Control and Prevention. (n.d.). Diagnosis of cholinesterase inhibitor poisoning. Agency for Toxic Substances and Disease Registry. Retrieved March 29, 2025, from
https://archive.cdc.gov/www_atsdr_cdc_gov/csem/cholinesterase-inhibitors/diagnosis.html
UpToDate. (n.d.). Organophosphate and carbamate poisoning. Retrieved March 29, 2025, from
https://www.uptodate.com/contents/organophosphate-and-carbamate-poisoning#:~:text=Toxicity%20generally%20results%20from%20accidental,clothing%20%5B6%2D8%5D
.
(National Center of Biotechnology Information, 2019)
(Henretig et al., 2019)
(UpToDate, n.d.)
(UpToDate, n.d.)
(UpToDate, n.d.)