Summer 25 - NMBA Flashcards
(95 cards)
What is the mechanism of action of NMBAs?
Magnesium potentiates NMBAs by inhibiting calcium influx at the presynaptic terminal. NMBAs act on both presynaptic and postsynaptic nicotinic receptors to reduce acetylcholine availability and receptor activation.
What are the characteristics of mature and immature postsynaptic receptors?
Mature receptors are long-lived (2 weeks) and less easily depolarized. Immature receptors are short-lived (24 hours) and more sensitive to depolarization, important in denervation or burn injuries.
Where do NMBAs primarily act?
At the neuromuscular junction for muscle relaxation and at autonomic ganglia/CNS for potential off-target effects.
What is a competitive (non-depolarizing) block?
A competitive block reversibly competes with acetylcholine. Typical agents include rocuronium and vecuronium.
What happens during a non-competitive (depolarizing) block - Phase I?
Succinylcholine mimics acetylcholine and binds irreversibly at first, causing initial fasciculations followed by flaccid paralysis.
What is Phase II block?
Occurs with high or repeated doses of succinylcholine and clinically mimics non-depolarizing block. It is reversible with acetylcholinesterase inhibitors.
What is desensitization block?
The receptor is occupied but unresponsive to acetylcholine, triggered by excess agonists, AChE inhibitors, or multiple drug classes.
What is the critical concept of channel block?
Non-competitive block of ACh receptor channel prevents opening/closing and is irreversible by AChE inhibitors.
What are the clinical takeaways regarding Phase II and channel blocks?
Phase II and channel blocks mimic non-depolarizers with TOF fade and tetany without sustained response. Only Phase II block responds to reversal agents.
What is the role of acetylcholinesterase?
It hydrolyzes acetylcholine at the neuromuscular junction into choline and acetic acid, and is involved in managing bradycardia and salivation.
What are the structure-activity relationships of NMBAs?
All NMBAs have at least one quaternary amine, limiting CNS penetration. Most have two amine groups, affecting their risk for histamine release.
What are the mechanisms of histamine release?
Histamine release can be IgE-mediated (true anaphylaxis), IgG/IgM mediated (complement activation), or through direct mast cell degranulation.
How can histamine-mediated effects be prevented?
Slower or titrated dosing decreases release, and premedication with H1 or H2 blockers can be used.
What are the pharmacologic variables of NMBAs?
ED₉₅/ED₅₀ indicates the dose required to block twitch response. Onset time varies between agents, with rocuronium being fast and vecuronium slower.
What is the preferred route of administration for NMBAs?
IV route is preferred for rapid onset and predictable distribution; IM/SQ is less predictable.
What factors influence pharmacokinetics of NMBAs?
Factors include quaternary ammonium structure, protein binding, receptor affinity, injection speed, perfusion, obesity, and age.
What are the clinical implications of pregnancy on NMBA use?
Pregnancy increases potency and duration with magnesium sulfate, but NMBAs have minimal placental transfer.
What is the metabolism of succinylcholine?
Succinylcholine is rapidly metabolized by plasma cholinesterase, with a typical onset of 20-40 seconds and duration of 5-10 minutes.
What are the absolute contraindications for succinylcholine?
Contraindications include hyperkalemia risk, malignant hyperthermia susceptibility, allergy to succinylcholine, and homozygous atypical plasma cholinesterase.
What cardiovascular side effects can succinylcholine cause?
It may cause bradycardia, idioventricular rhythms, and ventricular arrhythmias, especially in pediatrics or with vagal stimulation.
What are the characteristics of non-depolarizing NMBAs?
They are classified into benzylisoquinolines and aminosteroids, with varying durations of action.
What is the onset and duration of rocuronium?
Rocuronium has an onset of 1-1.5 minutes and a duration of 35-50 minutes.
What is the caution associated with mivacurium?
Mivacurium is hydrolyzed by plasma cholinesterase, so caution is advised in cases of deficiency.
What is the class of succinylcholine?
Aminosteroid
