Muscle relaxants actin on the nMF Flashcards
Long acting direct NMJ inhibitors
Duration of inhibition
Doxacurium
Pancuronium
Pipecuronium
Duration 1-3 hours
-curonium suffix means they are steroid compounds
Medium acting NMJ inhibitors
Vecuronium, Rocuronium, Atracurium and Cisatracurium
Short acting NMJ inhibitors
Mivacurium
What are all of the direct muscle nicotinic receptor inhibitors derived from?
Tubocurare, the frog poison.
General/common kinetics of the NMJ inhibitors
Highly polar,
Administered parenterally
Rapid onset within 2-6 minutes.
Progression of the paralysis
centrally to peripherally, starting at the eyes, then the head, then extremeties, trunk, diaphragm last.
Which NMJ inhibitors are metabolized by liver
Vecuronium and Rocuronium
How are atracurium and cisatracurium metabolized
Spontaneous degradation in the plasma by ‘hofmann elimination’
Forms a Laudanosine intermediate which can cross the BBB and cause seizures.
Atracurium also has some liver metabolism and creates more laudanosine.
Cisatracurium is the ONLY NMJ antagonist that does not need to be dose adjusted in patients with renal deficiency or with multiorgan failure.
How is Mivacurium metabolized?
By plasma pseudocholinesterase, causing its very short duration, 10-15 minutes.
General side effects of NMJ antagonists
Hypotension - from some ANS inhibition at the ganglia.
Reflex tach
Weak M2 inhibition also, also generating tachycardia
Respiratory depression and possible asphyxia
Side effect of Tubocurarine and Atracurium
Histamine release
Bronchospasm
Pruritus
Hypotension
Side effect of Pancuronium
NE release, NE reuptake inhibition,
Tachycardia
How do you reverse the effects of any of the tubocurare derivatives?
AChE inhibitors, specifically Neostigmine, quaternary amine to stay peripheral.
plus Atropine to compensate for the excessive muscarinic stimulation caused by the AChE.
How to reverse the effects of the steroid NMJ inhibitors?
Sugammadex
hydrophobic pocket that binds the steroid structures directly.
What drugs potentiate the actions of the NMJ inhibitors?
The anesthetics
Elderly patients
Myasthenia gravis patients
Succinylcholine other name
Suxamethonium
Succinylcholine clinical uses
Short surgeries and procedures
Intubation, Bronchoscopy
Succinylcholine adverse effects
Respiratory paralysis
Malignant hyperthermia in genetically susceptible patients
Bradycardia from muscarinic activaiton
Hyperkalemia, from K+ outflow of nicotinic receptors and from repolarization
Myalgia from muscle twitching and fasciculations
Vomiting from muscle spasms and increased GI pressure
Order of paralysis in succinylcholine
Begins peripherally, with the arms, legs, diaphragm, and the head last.
Onset, duration, and phases of succinylcholine
onset 30-60s
Duration only 5-10 minutes. Rapidly degraded by pseudocholinesterase. Very slowly degraded by AChE
Phase 1: Depolarization.
Persistent depolarization leads to fasciculations followed by flaccid paralysis despite depolarization. No amount of AChE overcomes the paralysis, and in fact potentiates it.
Phase 2: Desensitization.
The muscle slowly repolarizes, but the receptors are inactivated and can only be stimulated by very high concentrations of ACh.
Reversal of succinylcholine effects
Can only be done during phase 2, when AChE inhibitors and increased ACh concentration begin to activate receptros in the desensitized state.
If administered during phase 1 this actually potentiates the blockade.
