NMJ & AChE
This reversible acetylcholinesterase inhibitor increases acetylcholine availability at the neuromuscular junction, improving skeletal muscle contraction.
It is commonly prescribed for long-term symptomatic treatment of myasthenia gravis.
Pyridostigmine
This depolarizing neuromuscular blocking agent acts as an agonist at nicotinic Nm receptors, producing sustained depolarization of the motor end plate.
Succinylcholine
This medication rapidly reverses neuromuscular blockade caused by rocuronium and vecuronium by directly encapsulating the drugs, rather than increasing acetylcholine at the NMJ.
Sugammadex
This centrally acting skeletal muscle relaxant is a GABA-B receptor agonist used to treat spasticity in patients with multiple sclerosis or spinal cord injuries. Abrupt withdrawal can cause seizures and severe rebound spasticity.
Baclofen
These compounds irreversibly inhibit acetylcholinesterase, causing acetylcholine to accumulate at muscarinic and nicotinic receptors.
Exposure can produce excessive salivation, lacrimation, urination, diarrhea, muscle fasciculations, and respiratory failure.
Organophosphates
This reversible acetylcholinesterase inhibitor is unique because it can cross the blood-brain barrier.
physostigmine
This nondepolarizing neuromuscular blocker competitively antagonizes Nm receptors and can be rapidly reversed by sugammadex. It is commonly used for intubation.
Rocuronium/ vecuronium
During surgery, a patient receives a nondepolarizing neuromuscular blocker. To reverse the paralysis, the anesthesiologist administers neostigmine along with this medication to prevent bradycardia, excessive salivation, and other muscarinic effects.
Glycopyrrolate
This centrally acting muscle relaxant is an α₂-adrenergic receptor agonist that decreases excitatory neurotransmitter release in the spinal cord.
It is used to treat spasticity, but can cause hypotension, sedation, and dry mouth.
Tizanidine
A farmworker develops bradycardia, excessive salivation, diarrhea, pinpoint pupils, and muscle fasciculations after pesticide exposure.
These symptoms result from excess acetylcholine stimulating two major classes of cholinergic receptors.
Nicotinic and muscarinic receptors
A 62-year-old patient undergoes surgery under general anesthesia and receives rocuronium for skeletal muscle relaxation.
At the end of the procedure, the anesthesiologist administers a reversible acetylcholinesterase inhibitor to help restore neuromuscular function.
Because this medication also increases acetylcholine at muscarinic receptors, glycopyrrolate is administered alongside it to prevent bradycardia and excessive secretions.
Neostigmine
This nondepolarizing neuromuscular blocker undergoes Hofmann elimination, making its breakdown relatively independent of renal and hepatic function. Compared with a closely related agent, it is more likely to cause histamine release and hypotension.
Atracurium
A patient develops malignant hyperthermia after receiving succinylcholine during anesthesia.
This medication treats the condition by inhibiting calcium release from the skeletal muscle sarcoplasmic reticulum through the ryanodine receptor (RyR1).
Dantrolene
This centrally acting skeletal muscle relaxant is used for short-term treatment of acute musculoskeletal spasms, such as those associated with back injuries.
It has a tricyclic structure and commonly causes sedation and anticholinergic effects. It should be avoided with MAO inhibitors because of the risk of serious drug interactions.
Cyclobenzaprine
A patient presents with flushed skin, dry mucous membranes, dilated pupils, urinary retention, tachycardia, and confusion after ingesting an unknown medication.
These findings are caused by excessive blockade of muscarinic acetylcholine receptors.
anticholinergic (antimuscarinic) toxidrome
A 55-year-old farmer is brought to the emergency department after accidental exposure to an organophosphate pesticide.
He presents with excessive salivation, lacrimation, diarrhea, bronchorrhea, muscle fasciculations, and bradycardia.
He receives atropine to reverse the muscarinic manifestations.
The physician administers a second medication that restores acetylcholinesterase activity by removing the phosphate group from the inhibited enzyme, provided the enzyme has not undergone aging.
Pralidoxime
This nondepolarizing neuromuscular blocker has vagolytic properties, which can produce tachycardia during anesthesia.
Pancuronium
A patient develops severe muscle weakness, bronchorrhea, bradycardia, and pinpoint pupils after exposure to an organophosphate insecticide.
This medication competitively blocks muscarinic receptors, reversing the dangerous secretions and bradycardia, but does not reverse nicotinic-mediated muscle weakness.
Atropine
A patient with multiple sclerosis is prescribed a centrally acting muscle relaxant that activates Gi-coupled receptors in the spinal cord.
This drug decreases presynaptic calcium influx and increases postsynaptic potassium conductance, reducing excitatory neurotransmission.
baclofen
A patient presents with profuse sweating, salivation, diarrhea, bronchorrhea, and muscle fasciculations after organophosphate exposure.
The physician administers pralidoxime early to restore acetylcholinesterase activity.
However, after a period of time, the phosphorylated enzyme undergoes a chemical change that makes its inhibition effectively irreversible, even with pralidoxime.
Aging or dealkylation
This medication that blocks presynaptic voltage-gated potassium channels, prolonging depolarization and increasing calcium entry into the nerve terminal.
This increases acetylcholine release at the neuromuscular junction.
Amifampridine (3,4-diaminopyridine or 3,4-DAP)
A patient with severe renal and hepatic dysfunction requires neuromuscular blockade during surgery.
This medication is preferred because it undergoes organ-independent Hofmann elimination and produces minimal histamine release compared with its closely related drug.
Cisatracurium
A patient receives an acetylcholinesterase inhibitor to reverse a nondepolarizing neuromuscular blockade.
However, the anesthesiologist explains that this reversal strategy becomes unreliable when the patient has profound neuromuscular blockade, because the medication requires some spontaneous recovery of neuromuscular transmission.
Competitive antagonism
A patient receiving long-term intrathecal baclofen therapy experiences an interruption in drug delivery due to a malfunctioning infusion pump.
Within hours, the patient develops severe rebound spasticity, hyperthermia, agitation, and seizures.
This potentially life-threatening syndrome results from the abrupt discontinuation of a centrally acting GABA-B agonist.
Baclofen withdrawal
A patient presents with severe agitation, hyperthermia, tachycardia, dilated pupils, and altered mental status after ingesting an unknown medication.
The physician suspects anticholinergic toxicity, but the ECG demonstrates a widened QRS complex.
Although this acetylcholinesterase inhibitor can reverse central antimuscarinic toxicity because it crosses the blood-brain barrier, it should be avoided in this patient because of the risk of serious cardiac complications.
Physostigmine