
Understanding Cholinergic Crisis
A cholinergic crisis occurs when there is an excess of acetylcholine in the body, leading to overstimulation of the neuromuscular junction. This condition is also known as cholinergic syndrome or toxidrome in medical literature.
Common causes include acetylcholinesterase inhibitors, which are used in medications like Donepezil for dementia, and organophosphate insecticides such as diazinon.
Acetylcholinesterase is an enzyme that breaks down acetylcholine at the neuromuscular junction, and its high catalytic activity allows it to degrade 25,000 acetylcholine molecules per second.
The Neuromuscular Junction Explained
The neuromuscular junction is a chemical synapse where a motor neuron and muscle fiber meet. The motor neuron releases acetylcholine, which binds to receptors on the muscle fiber, causing it to contract. There are two types of acetylcholine receptors:
- Nicotinic Receptors: Found on skeletal muscles, their activation leads to muscle twitching and is crucial for breathing.
- Muscarinic Receptors: Located on visceral organs and glands, they modulate contractile activity and stimulate fluid secretion.
Causes of Cholinergic Crisis
The two primary causes are overdosing on cholinesterase inhibitors and exposure to organophosphate nerve agents.
Cholinesterase inhibitors are used to treat conditions like Myasthenia Gravis and to reverse muscle paralysis post-surgery. They are also used in dementia treatment.
Treatment Options for Cholinergic Crisis
Treatment includes anticholinergic drugs like atropine, oximes such as pralidoxime, and benzodiazepines like diazepam.
Edrophonium
Edrophonium helps differentiate between cholinergic and myasthenic crises. If paralysis worsens, it indicates a cholinergic crisis, while improvement suggests a myasthenic crisis.
Atropine
Atropine is used to manage cholinergic crisis by blocking muscarinic receptors, though it does not affect nicotinic receptors, so respiratory support may be needed.
Pralidoxime
Pralidoxime reactivates acetylcholinesterase inhibited by organophosphates and is used alongside atropine and diazepam in treatment.
Classification of Cholinergic Crisis
Cholinergic crisis can be sub-divided into:
- Nicotinic Crisis
- Arises from excessive activation of the nicotinic acetylcholine receptor system
- Associated with the following side effects: muscle weakness, involuntary muscle twitches, inability to swallow and cramping.
- Muscarinic Crisis
- Arises from excess activation of the muscarinic acetylcholine receptors
- Associated with: blurry vision, pain in the abdomen, vomiting, nausea, diarrhea and secretion of tears and mucus.
What are the Signs and Symptoms of a Cholinergic Crisis?
The signs and symptoms of cholinergic crisis result from excess activation of the muscarinic receptor system. The cluster of symptoms is best described with the acronym SLUDGE:
- Salivation: due to stimulation of the salivary glands
- Lacrimation: due to stimulation of the lacrimal glands
- Urination: due to relaxation of the internal sphincter muscle of urethra, and contraction of the detrusor muscles
- Diarrhea
- Gastrointestinal Distress: due to changes in smooth muscle tone of the gastrointestinal tract
- Emesis: vomiting
What are the Complications of a Cholinergic Crisis?
If left untreated cholinergic crisis can be life-threatening because muscles stop responding to Ach. This occurs as a protective, physiological response to excess Ach activity.
Specifically due to decreased nicotinic receptor activity, cholinergic crisis is associated with the following life-threatening events:
- Respiratory system failure as a result of insufficient gas exchange
- Decrease in muscle tone caused by paralysis or enfeeblement, also known as flaccid paralysis
Cholinergic Crisis vs Myasthenia Gravis
Cholinergic crisis can often be confused with another medical condition known as myasthenic crisis.
The distinction between these conditions is nebulous because they have a similar presentation.
But distinguishing cholinergic vs myasthenic crisis is crucial since the underlying pathology differs, in that they are exactly opposite, and administration of the wrong medication can be fatal.
Myasthenic crisis is a life-threatening form of myasthenia gravis where the muscles used for breathing become weak. If untreated, this can lead to breathing difficulties and ultimately lung failure.
While cholinergic crisis is associated with excess activity of the neurotransmitter Ach, myasthenic gravis is associated with declined Ach activity due to auto-reactive antibodies that ‘attack’ the nicotinic-Ach receptor system.
References
- Kaminski, Henry J. (2009) Myasthenia Gravis and Related Disorders. Springer Science & Business Media. ↩
- Levitan, Irwin. Kaczmarek, Leonard. (2015) Intercellular communication. The Neuron: Cell and Molecular Biology (4th ed.). New York, NY: Oxford University Press. pp. 153–328. ↩
- Itier V, Bertrand D. (2001) Neuronal nicotinic receptors: from protein structure to function. FEBS Letters. 504 (3): 118–25. ↩
- Eglen RM (July 2006). “Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function”. Auton Autacoid Pharmacol. 26 (3): 219–33. ↩
- Marx, John A. Marx (2014). Rosen’s emergency medicine: concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. 1441–1444. ↩
- Mary Jo Wagner; Susan B. Promes. (2007) Last Minute Emergency Medicine: A Concise Review for the Specialty Boards. McGraw Hill Professional. p. 12. ↩
- Hetherington KA, Losek JD. (2005) Myasthenia gravis: myasthenia vs. cholinergic crisis. Pediatr Emerg Care. 21 (8): 546-8. ↩