Ex4 NMBA Flashcards
when nerve potential reaches the nerve terminal, _______ occurs
ACh is released into synaptic cleft near nAChRs
ACh is synthesized in nerve terminal from
choline + acetyl-coenzyme A
*in the presence of choline acetyltransferase
80% of ACh is stored in
synaptic vesicles
20% of ACh is stored in
nonvesicular reserve
post junctional receptor agonists
ACh
Sux
post junctional receptor antagonits
NDMRs
Subunits of post junctional receptors
2 alpha
1 beta
1 epsilon
1 delta
depolarizing muscle relaxant
Succinylcholine
nAChR agonist
nAChR antagonist
NMDRs
receptor activation occurs when
both alpha subunits are occupied by (2) agonists
- 1ACh + 1 Sux
- 2ACh
- 2Sux
1 NMDR + 1 ACh
or
1NDMR + 1 Sux
won’t open channel at receptor site
NDMRs work by
prevent depolarization of skeletal muscle by binding to 1 or both alpha units
NMDRs may also block
an open receptor pore
*especially after a large dose
After NDMRs bind to site, ____ occurs
- ACh competitively inhibited, opening of receptor pore does not occur
- muscle cell does not depolarize
- no ion influx
NDMRs are competitive inhibitors of ______ at _______
acetylcholine at alpha subunit of presynaptic Nn receptor
depolarizing muscle relaxant
succinylcholine
succinylcholine mimics the action of ____
ACh
Succinylcholine is hydrolyzed by
plasma cholinesterase
**NOT AChEase
Succinylcholine must be terminated in the _____
plasma
*plasma cholinesterase is not present in NMJ
Activity of sux must be terminated by ____ of drug
diffusion of drug away from NMJ
NM blockade from Sux occurs because
the depolarized post-junctional membrane cannot respond to additional agonist
closed channel blockade
drug reacts around mouth of channel and prevents passage of ions
*ie cocaine, antbx, quinidine
open channel blockade
drug enters an open channel but does not pass all the way thru “gets stuck” - impedes flow of ions
*ie NDMRs in large doses
extrajunctional receptors
- normally not present in large numbers (synthesis suppressed by normal neural activity)
- may proliferate if normal neural activity is decreased (sepsis, prolonged bedrest)
extrajunctional receptors differ from nAChRrs
- change in the epsilon subunit - structurally different from nAChRs
- stay open longer (allow larger amounts of K+ efflux after administration of DMR)
Risk of extrajunctional receptors after SCh administration
hyperkalemic arrest
prejunctional membranes
- nAChRs
- regulate release of ACh from presynaptic membrane
stimulation of prejunctional receptors results in
- inhibits release of ACh from presynaptic membrane
- may stimulate production of more ACh in nerve terminal
effect of NDMRs on prejunctional membranes
- antagonize pre-JRs
- inhibit ACh production
- -explains tetanic fade after NDMR (ACh depletion)
tetanic stimulation before and after administration of NDMR
post-tetanic facilitation
tetanic stimulation before and after administration of DMR
NO post-tetanic facilitation
All NMBAs contain
quaternary ammonium group (NH4+)
All NMBAs are _____ soluble
ionized, water soluble, limited lipid solubility
NMBAs characteristics
- limited Vd
- do not cross BBB
- PO not effective
- do not cross placenta
- no CNS effects
- minimal renal reabsorption
NMBA P-kinetics
- Not highly protein bound
- influenced by age, hepatic/renal dx
NMBAs have a Vd that is equivalent to
Extracellular compartment (~14L)
NMBAs + volatile anesthetics
- do not directly alter p-kinetics
- NDMRs are enhanced via pharmacodymanic actions of VAs
volatile anesthetics ______ the effects of NDMRs via _____
- potentiate
2. Ca2+ channels
______ dosage required for NDMRs in presence of VAs
decreased
ED95
dose necessary to produce 95% suppression of a single twitch in response to peripheral nerve stimulator
recommended dose to facilitate tracheal intubation (intubating dose)
2 x ED95
________ depression is adequate for surgical relaxation
90%
standard of care - degree of NM blockade is evaluated by
monitoring the evoked response to electrical stimulation using a peripheral nerve stimulator (PNS)
Residual paralysis
inadequate return of function
- difficulty focusing/diplopia
- *inability to swallow/dysphagia (unable to protect airway)
- ptosis
- weakness of mandibular muscles
- low VT (hypoxia)
- “floppy”
NMBAs lack ______ effects
CNS/analgesic
NMBAs are all structurally similar to
ACh
which portion of the NMBA binds to the alpha subunit of the AChR?
N (from quaternary ammonium group)
NMBAs cause the majority of ______ during anesthesia
anaphylactic reactions
most likely to evoke histamine release
benzylisoquinoliniums - d/t tertiary amine
atracurium
cisatracurium
mivacurium
benzylisoquinoliniums all end in
“urium”
aminosteroids all end in
“curonium”
Succinylcholine chloride ED95
0.25-0.5 mg/kg
Sux onset
rapid 30-60s
Sux DOA
Short: 5-10 minutes
Sux: general dosage for tracheal intubation
1-1.5mg/kg
Sux: dosage for RSI
1.5mg/kg
depolarization is sustained, the depolarized membrane/receptors cannot respond to additional agonist
Sux: Phase I blockade
Fasciculations occur due to
sustained depolarization
Sux - sustained depolarization is associated with
leakage of K+ from muscle cell
approximate plasma K+ plasma increase d/t Sux
0.5 mEq/L
overdose to Sux is d/t
- single large dose
- repeated doses
- infusion
- leads to postjunctional membranes responding abnormally
OD to Sux results in
characteristics change to Phase II Blockade
Phase I Blockade - Sux
- Decreased contractile force in response to single twitch
- sustained tetany w/ decreased amplitude
- TOF ratio >0.7 (~1.0)
- no post tetanic facillitation
- fasciculations
- augmentation after admin anticholinesterase
Phase II Blockade - Sux
- Decreased contractile force in response to single twitch
- decreased amplitude/tetanic fade to sustained stimulus
- TOF ratio<0.7
- no fasciculations
- can be antagonized by anticholinesterase
- abrupt onset manifests as tachyphylaxis/increased dose reqmts
Which phase of Sux resembles characteristics of NDMRs?
Phase II
Sux Phase II Characteristics
Post tetanic facilitation
Sux Phase I characteristics
NO post tetanic facilitation
Biggest offenders of anaphylactic rxn during anesthesia
Sux, Roc
NMBAs Vd
similar to ECF
NMBAs: ionized or nonionized
ionized
aminosteroids
pancuronium
vecuronium
rocuronium
benzylisoquinoliniums
atracurium
cisatracurium
mivacurium
Which Rx do not possess any hormonal activity?
Aminosteroids
pancuronium
vecuronium
rocuronium
How is Sux metabolized?
hydrolyzed via pseudocholinesterase in plasma
-slow
TOF ratio
TOF last twitch/first twitch
TOF graph - which will produce 4 twitches at equal height?
Sux
TOF graph - which will produce 4 twitches at sequentially smaller heights?
NDMR
Sux hydrolyzed into
succinylmonocholine + choline
termination of action of sux d/t
diffusion of drug away from site of action
plasma cholinesterase is sythesized by
liver
sux DOA may be prolonged d/t
-decreased synthesis of enzyme
-Rx induced dec. of enzyme
-atypical plasma cholinesterase
< 75% norm serum levels necessary to prolong plasma cholinesterase
atypical plasma cholinesterase
-dibucaine test
dibucaine # that confirms normal plasma cholinesterase
80
dibucaine # that indicates NMB lasting hours
20
Resistance to Sux in which patients
myasthenia gravis d/t decreased fxnal nAChRs
NMBA w/ greatest histamine release
Sux
Large/Rapid dose of Sux may result in
face/truncal flushing
*bronchospasm
decreased bp/anaphylaxis rxns
Cardiac AE to Sux
- cardiac dysrhythmias (sinus brady, junctional, sinus arrest)
- increased HR/BP
AEs to Sux
- HyperK
- Myalgia
- increased intragastric pressure (risk for aspiration)
MH is d/t
ryanodine receptors = defective
MH manifests
rigidity, hyperpyrexia, hypermetabolism/O2 consumption, hypercarbia, tachycardia, metabolic acidosis, rhabdomyolysis
MH Tx
dantrolene
MOA NDMRs
-competitive antagonist at nAChRs in NMJ
high doses of NDMRs can cause
channel blockade
receptor occupation required to interrupt transmission of signal
80-90%
80% receptors occupied
VT 5mL/kg
70% receptors occupied
TOF = no fade
VC at least 20 mL/kg
60% receptors occupied
Sustained tetany = no fade
DBS = no fade
50% receptors occupied
Head Lift - 180 degrees, 5s
Hand grip - sustained 5s
Characteristics of NDMR blockade
Decreased twitch to single stimulus tetanic fade TOF ratio < 0.7 post-tetanic facilitation potentiation of other NDMRs
NDMRs are antagonized by
anticholinesterase drugs
difference between required dose for NM blockade and dose for circulatory effects
autonomic margin of safety
very narrow autonomic margin of safety
pancuronium
wider autonomic margins of safety
vec, roc, cis
NDMR Rx intxn: VAs
dose dependent potentiation
biggest = Des
NDMR Rx intxn: antibiotics
aminoglycosides: enhance NDMRs+DMRs
may be via decr. prejunctional release of ACh by competing w/ Ca++
NDMR/DMR Rx intxn: enhances
local anesthetics antidysrhythmics lithium not Sux: diuretics magnesium hypothermia cyclosporin
NDMR Rx intxn: decreases
phenytoin
increased K+ effects NDMR/DMR how?
Increased K+ –> enhances DMR, resistance to NDMR
decreased K+ effects NDMR/DMR how?
decreased K+ –> enhances NDMR, resistance to DMR
Resistance to NDMRs
Thermal injury (10 days) paresis/hemiplegia (affected side)
males are _____ sensitive to NDMRs than women
less
women require _______ than men
22% less vec
