neuromuscular blocking agents Flashcards
Neuromuscular blocking agents
drugs used to immobilize patients for surgery, certain procedures and paralyze skeletal muscle and are high alert
effects of IV competitive blocking agent
motor weakness progresses to total flaccid paralysis, small moving muscels relax before larger until paralysis - recovery moves in the opposite direction
___ is the NT involved in skeletal muscle activation
ach
process of skeletal muscle action
ach released from a somatic neuron and activates Nm receptors - allowing for the influx of sodium depolarizing the t-tubule and promotes an increase in intracellular calcium contraction
Nm belongs to a family of _____
ligand-gated ion channels which also include GABA, 5HT, glycine
the general structure of Nm receptor
pentamer composed of 5 subunits, 2 ACh molecules are required to open the cahnnel and the binding site for ach is on the ALPHA (when it binds it opens), each subunit has a single peptide chain with with 4 membrane spanning units
how many configurations of neuronal nicotinic receptors
16
drugs that interact with the Nm receptor
they usually have two portions of the molecule which resemble ach. (N + ester) bc the molecule will bind to both sides to block it
succinylcholine
Nm receptor blocker depolarizing unit, resistant to AChE, rapidly metabolized by cholinesterase resulting in a short half-life
atracurium
non-depolarizing unit, more rigid in structure, Nm receptor blocker
the only depolarizing NMBA
succinylcholine - causes a muscle fasiculations because the cell membrane becomes depolarized, ion chanels on the membrane become refractory and the muscle become resistant to further stimulation (flaccid paralysis
phase 1 block
depolarizing agent immediately after admin- muscle becomes resistant to flaccid paralysis because the cell membrane becomes refractory
(depolarized to -55mV, immediate, lower dose dependent, rapid recovery, no fade, augments (inc) ach inhibition, fasiculations to paralysis)
phase 2 block
due to high doses of depolarizing NM agents, resembles non-polarizng NMBA (replarization towards -80mV, slow transition, usually higher or follows prolonged infusion, more prolonged, fade, reverse ach inhib, flaccid paralysis)
how would admin of AChE inhibitor effect the actions of succinyl choline
inch ach, turn off the receptor, one agent not reversed by cholinesterase inhibitor
amino steroids
drugs end in -uronium (rocuronium, vecuronium, pncuronium)
benzylisoquinolines
drugs end in -cruium (mivacruium, (cis)aracurium)
all _____ are competitive antagonists at the Nm receptor
non-depolarizing
would non-depolarizing cause muscle fasiculation
no, not depolarizing
would non-depolarizing be reversed by AChE inhibitor
yes, inc in Ach, compete off the drug
which non-depolarizing drugs have the shortest half life
succinylcholine, mivacurium both by BchE
what non-depolarizing drugs should be does independ
succ, atra, cis atra
where would non-depolarizing drugs primarily distribute throughout the body
total body water
mivacurium
met - renal, BuChE, short duration
cisatracurium / atracurium
met- hofman degration (except atra also has ester hydrolysis)
intermediate duration
panuronium
met- renal, some hepatic
long duration
rocuronium
met- hepatic (bile), renal
intermediate duration
succinylcholine
met- BuChE
short duration
vecuronium
met- hepatic, some renal
intermediate duration
hofmann degradation
atracurium/cisatracurim both undergo spontaneous degradation without any enzymes!
incresed fluid volume leads to
inc fluid volume bc of hepatic or renal disease will have a higher vd and will need a higher dose
t 1/2 =
0.693 x vd / Cl
hyperkalemia
concern with NMBA admin, associated with succinylcholine, prolonged depolarization of the membrane results in the efflux of potassium from within the muscle cells
depolarization =
cell trying to repolarize and k+ goes into the plasma
increased intragastric pressure
succinyl choline- abdomen contracts and stomach muscle contracts, may result in vomiting and issues with the airway
histamine release
succinylcholine and atracurium are most associated with a decrease in BP
myalgias
muscle pain caused by succinylcholine
all agents
combinded admin with inhaled anesthetic may make the pt more sensitive to the medications and reduce the dose of the NMBA
reversal of non-depolarizing block
neostigmine- Ach inhibitor- reverse paralysis
what is the rational for admin neostigmine? why not work for succinylcholine reversal
inc ach- compete with neuromuscular blocker
what is the rationale for administering neostigmine -
increase ach and compete with a NM blocker
what is the rationale for admin of a musc ADR from neostig -
getting ach - GI discomfort and bladder loss salivary increased
if the patient is bradycardia why should anti-muscurinic agent always be admin first
HR would be too low just with neostigmine, give anti muscurinic first then give the other
aged enzyme
resistant to hydrolysis- permentantly phosphorylated ser-o-p, isopropyl leaves - hardly any electrophilicity,
definition of depolarizing
Depolarizing muscle relaxants acts as ACh receptor agonists. They bind to the ACh receptors and generate an action potential. However, because they are not metabolized by acetylcholinesterase, the binding of this drug to the receptor is prolonged resulting in an extended depolarization of the muscle end-plate. As the muscle relaxant continues to bind to the ACh receptor, the end plate cannot repolarize, resulting in a phase I block. The ACh receptor can also undergo conformational and ionic changes after a period of time, resulting in a phase II block.
definition of non-depolarizing
competitive antagonists. They bind to the ACh receptors but unable to induce ion channel openings. They prevent ACh from binding and thus end plate potentials do not develop.
