Cholinesterase Inhibitors & Other Pharmacologic Antagonists to Neuromuscular Blocking Agents Flashcards
What is the primary clinical use of cholinesterase inhibitors (anticholinesterases)?
To reverse nondepolarizing muscle blockade.
Which systems does acetylcholine serve as the neurotransmitter for?
Acetylcholine is the neurotransmitter for the parasympathetic nervous system, parts of the sympathetic nervous system, CNS neurons, and somatic nerves innervating skeletal muscle.
How do cholinesterase inhibitors help in reversing neuromuscular blockade?
They increase the amount of acetylcholine available to compete with nondepolarizing muscle relaxants, reestablishing neuromuscular transmission.
What is a potential risk of excessive doses of acetylcholinesterase inhibitors?
They can paradoxically potentiate a nondepolarizing neuromuscular blockade and prolong the depolarization blockade of succinylcholine.
How does renal or hepatic insufficiency affect the duration of cholinesterase inhibitors?
Prolongation of nondepolarizing muscle relaxants from renal or hepatic insufficiency is likely to be accompanied by a corresponding increase in the duration of action of a cholinesterase inhibitor.
How long does it take to fully reverse a nondepolarizing block with cholinesterase inhibitors?
The time depends on the choice and dose of the cholinesterase inhibitor, the muscle relaxant used, and the extent of the blockade before reversal.
Should a reversal agent be routinely given to patients who received nondepolarizing muscle relaxants?
Yes, unless full reversal is demonstrated or the postoperative plan includes continued intubation and ventilation.
What are the suggested end points for monitoring recovery from neuromuscular blockade?
Sustained tetanus for 5 seconds in response to a 100-Hz stimulus in anesthetized patients, or sustained head lift in awake patients.
What is the mechanism of action of sugammadex?
Sugammadex forms tight 1:1 complexes with steroidal neuromuscular blocking agents, reversing their effects.
What effect does cysteine have on gantacurium?
Cysteine inactivates gantacurium via metabolic degradation and adduct formation.
What is the physical structure of neostigmine?
Neostigmine consists of a carbamate moiety and a quaternary ammonium group, making it lipid-insoluble and unable to cross the blood-brain barrier.
What is the maximum recommended dose of neostigmine?
The maximum recommended dose of neostigmine is 0.08 mg/kg, up to 5 mg in adults.
How long do the effects of neostigmine last?
The effects of neostigmine are usually apparent in 5 minutes, peak at 10 minutes, and last more than 1 hour.
What should be given alongside neostigmine to minimize muscarinic side effects?
An anticholinergic agent like glycopyrrolate (0.2 mg per 1 mg of neostigmine) or atropine (0.4 mg per 1 mg of neostigmine) should be given.
What is pyridostigmine’s potency compared to neostigmine?
Pyridostigmine is 20% as potent as neostigmine.
How does pyridostigmine’s onset and duration compare to neostigmine?
Pyridostigmine has a slower onset (10–15 minutes) and a slightly longer duration of action (>2 hours) than neostigmine.
Why should glycopyrrolate be preferred over atropine with pyridostigmine?
Glycopyrrolate’s slower onset of action better matches that of pyridostigmine, leading to less tachycardia.
What is the main use of edrophonium?
Edrophonium is primarily used for diagnosing myasthenia gravis and as a short-acting cholinesterase inhibitor for reversing neuromuscular blockade.
How does edrophonium differ from neostigmine and pyridostigmine?
Edrophonium relies on noncovalent bonding to acetylcholinesterase and has the shortest duration of action among cholinesterase inhibitors.
What is the usual dose of edrophonium?
The recommended dose of edrophonium is 0.5–1 mg/kg.
How does edrophonium compare to neostigmine in terms of muscarinic effects?
Edrophonium’s muscarinic effects are less pronounced than those of neostigmine, requiring only half the amount of an anticholinergic agent.
What are the clinical uses of physostigmine?
Physostigmine is effective in treating central anticholinergic toxicity, benzodiazepine-induced central nervous system depression, and postoperative shivering.
How does physostigmine differ from other cholinesterase inhibitors?
Physostigmine is the only cholinesterase inhibitor that passes the blood-brain barrier due to its lipid solubility.
How does the presence of other conditions affect the reversal of neuromuscular blockade?
Conditions like respiratory acidosis, electrolyte disturbances, hypothermia, and certain drug interactions can impair the reversal of neuromuscular blockade.
What are non-classic reversal agents for neuromuscular blockade?
Sugammadex and L-cysteine are two non-classic agents currently under investigation for reversing nondepolarizing neuromuscular blockade.
How does sugammadex work as a reversal agent?
Sugammadex forms a 1:1 complex with steroidal neuromuscular blocking agents, effectively reversing their effects.
What is the role of L-cysteine in neuromuscular blockade reversal?
L-cysteine can reverse the neuromuscular blocking effects of gantacurium and other fumarates by forming less active degradation products.
What is the recommended dose range for sugammadex?
Sugammadex is typically administered in doses of 4–8 mg/kg.
What concerns are there regarding the use of sugammadex?
Hypersensitivity and allergic reactions are concerns with sugammadex, which is why it has not yet been approved by the US Food and Drug Administration.
How does L-cysteine work in reversing gantacurium’s effects?
L-cysteine rapidly combines with gantacurium in vitro to form less active adducts, reversing its neuromuscular blocking effects.
