Medical Pharmacology Chapter 6: Autonomic Pharmacology: Cholinergic Drugs
Edrophonium (Tensilon), neostigmine (Prostigmin), or pyridostigmine (Mestinon)-- effective by increasing acetylcholine availability of neuromuscular junction (secondary to acetylcholinesterase inhibition).
Physostigmine (Antilirium): not used because dosage requirement is excessive.
Anticholinesterase agents are usually administered during spontaneous neuromuscular-blockade recovery.
Recovery rate is the sum of:
(1) Spontaneous recovery from the blocking drug and
(2) The activity of the pharmacologic antagonist (anticholinesterase drugs).
Therefore: pharmacologic antagonism is more effective for short-or intermediate-acting neuromuscular-blocking drugs (undergoing plasma hydrolysis or Hoffmann elimination) compared to long-acting nondepolarizing neuromuscular-blocking agents
Special Considerations: use of muscarinic antagonists with anticholinesterases in reversal of neuromuscular blockade.
Reversal of nondepolarizing neuromuscular-blockade: necessitates only nicotinic cholinergic effects of anticholinesterases agents.
Minimizing muscarinic receptor-mediated effects of anticholinesterase drugs is beneficial an accomplished by a concurrent administration of atropine or glycopyrrolate (antimuscarinics).
The antimuscarinic agent should have a more rapid onset than the anticholinesterase drugs, reducing drug-induced bradycardia.
If edrophonium (Tensilon)(0.5 mg/kg) is used; atropine 7 µg/kg is appropriate.
A higher dose atropine (10-15 µg/kg) has been recommended, particularly if nonopioid-based maintenance anesthetic has been used.
If neostigmine is used (slower onset of action compared edrophonium (Tensilon)), then atropine or glycopyrrolate (Robinul) may be administered as the antimuscarinic agent;
Concurrent administration of these drugs results in an initial tachycardia because of atropine's more rapid onset.
Factors influencing the speed and extent of neuromuscular blockade reversal by anticholinesterase agents:
Intensity neuromuscular-blockade when reversal is initiated (train-of-four visible twitches)
Which nondepolarizing neuromuscular-blocking drug is being reversed
Edrophonium (Tensilon): less effective than neostigmine in reversing deep neuromuscular blockade (twitch height < 10% of control) produced by continuous atracurium (Tracrium), vecuronium (Norcuron), or pancuronium (Pavulon) infusions.
Edrophonium (Tensilon), probably better than neostigmine (Prostigmin)for reversing atracurium (Tracrium)blockade
Neostigmine (Prostigmin), probably better than edrophonium (Tensilon) for reversing vecuronium (Norcuron) blockade
Prevention/inhibition of anticholinesterase-mediated antagonism of neuromuscular-blockade.
Respiratory acidosis (PaCO2 >50 mm Hg.
Reversal of phase II block (following prolonged/repeated succinylcholine (Anectine)): may be reversed with edrophonium (Tensilon) or neostigmine (Prostigmin) in patients with normal plasma cholinesterase.
In patients with atypical plasma cholinesterase, phase II block reversal may not be reliable, requiring mechanical ventilation until blockade subsides.
Stoelting, R.K., "Anticholinesterase Drugs and Cholinergic Agonists", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 241-244