Flashcards in Neuromuscular Blocking Drugs Deck (75):
Succinylcholine (only one) - mimics action of ACh
Major characteristics of succinylcholine
Long acting non-depol NMBD
Intermediate acting non-depolar NMBD
short acting non-depolar NMBD
Which non-depolar NMBD time to onset is similar to succinylcholine?
Best NMBD(s) for tracheal intubation
succinycholine (rapid onset, short duration)
rocuronium (rapid onset, much longer action)
NMBDs given when longer surgery requiring paralysis
NMBD most likely to cause an allergic reaction
succinylcholine (most likely to cause hypersensitivity of all anesthetic drugs)
Site with highest concentration of acetylcholinesterase
folds of post-synaptic end-plate region of NMJ (close proximity to site of action of ACh)
physiologically, why is there a fade in response to high frequency repetative stimulation (ie train of 4 stim)
binding and inhibition of presynatpic nAChRs (cannot uptake ACh back into nerve terminal so diminishing amount available to act)
subunits of postjunctional NMJ rectpros that ACH and NMBDs bind
two alpha subunits
How do non-depolarizing NMBDs work?
bind to 1 or both of alpha receptors = ion channel bloked/closed = no depolarization can occur
How do depolarizing NMBDs (SCh) work?
attaches to alpha site = ion channel remains open = prolonged depolarization
What is the importance of extrajunctional receptors?
Location - projectional receptors and throughout skeletal muscle
Synthesis is normaly suppressed by neural activity
Prolonged inactivity, sepsis, denervation (ALS, etc), trauma/burn = increase proliferation of extrajunctional
***Activated extrajunctional receptors = allow extra ion flow = HYPERKALEMIA IN RESPONSE TO SCh
**Proliferation = resistance/tolerance to non-depol NMBDs in burn patients/mech vent pts
Structure of NMBDs as relates to function
Quaternary ammonium compound with 1+ nitrogen charged attoms = binds with alpha subunit of postsynaptic ACh receptor
SCh = 2 ACh bound by methyl group (smaller/flexible vs non-depolar NMBDs = can activate as opposed to block)
Nondepolar NMBD most similar to ACh structurally
similarity confers high degree of NMB activity
NMBDs most likely to evoke a histamine response? Why?
atracurium, cisatracarium, mivacurium (Benzylisoquinolinium compounds)
presence of tertiary amine confers this activity
Dosing of SCh?
0.5-1.5mg/kg IV (typically 1-1.5mg/kg for tracheal intubation)
SCh time to onset? Duration?
How should doses of SCh be adjusted if you give non-depolar NMBD prior to SCh for intubation (avoid fasiculations)?
increase dose by 70%
NMBD dosing for this would be 5-10% of the effective paralytic dosing given 2-4 min before SCh
Dosing of Roccuronium (for equivalent onset time of SCh)?
Describe NM blockade by SCh
- PHASE 1
- PHASE 2
- depolarized postjunctional membrane and inactivated Na channels cannot respond to subsequent release of ACh = PHASE I BLOCK
PHASE 2 BLOCK:
postjunctional membrane repolarized by does not respond normally to ACh (desensitization block)= similar to non-depolar NMBDs
Signs of phase 2 blockade
fade to tetanic stimulation
Dose of SCH required for predominant phase 2 block
3-5 mg/kg IV
Metabolism of SCh
-hydrolysis by plasma cholinesterase (pseudocholinesterase) = rapid (only small fraction of original dose reaches site of action, controls duration of effect by nature of how much reaches NMJ)
- termination of effect = diffusion away from NMJ (no plasma cholinesterase at NMJ)
S/sx of atypical plasma cholinesterase?
otherwise healthy pt experiences prolonged skeletal muscle paralysis (> 1 hr) after conventional dose of SCh or mivacurium (cannot metabolize ester bond)
Major side effects of SCh (8)
1. Cardiac dysrhhythmias
6. increased intraocular pressure
7. increased ICP
9. increased intracastric pressure
Types of cardiac dysrrhythmias caused by SCh?
MOA of effect?
MOA- effect of action of SCh at cardiac postganglionic muscarinic receptor (mimic ACh = increased parasymp effect)
When are dyssrhtymia associated with SCH most likely to occur? tx?
2nd dose sch 5 min after first dose
tx- atropine IV 1-3min before SCh
factors predisposing to massive hyperkalemia w/ SCh?
spinal cord/neurologic damage (ALS, etc)
immobility/critical care patients
Myalgia effects which sites most often 2/2 SCh
neck/ back/ abdomen
time frame of increased intraoccular pressure with sch
2-4 min after administration, lats 5-10 min
avoid SCh in open eye injuries
consequence of increased icp from sch
minimal, does not effect decisions clinically
Drug combination with highest risk of trismus in children?
halothane + SCh
Drug combination with highest risk of trismus in children?
halothane + SCh
can make determination of trismus vs malignant hyperthermia difficult
SCH not recommended in children except for emergency airway control
best non-depol nmbd for kidney injury/failure pts
cisatricurium (no dependence on kidney for elim)
non-depol nmbd antagonized by sugammadex
intubating dose of pancuronium mg/kg
0.1mg/kg ( ED95 0.07 mg/kg)
intubating dose vecuronium mg/kg
0.08-0.1 mg/kg (ED95 0.05mg/kg)
intubating dose rocuronium mg/kg
0.6-1.2mg/kg ( ED95 0.3mg/kg)
intubating dose atracurium mg/kg
0.4-0.5 mg/kg ( ED95 0.2mg/kg)
intubating dose cisatricurium dosing
0.1 mg/kg ( ED95 0.05mg/kg)
time to onset non-dpolar nmbd
rocuronium (1-2 min) > mivacurium (2-3 min) > the rest (3-5min)
renal disease effects which non-depolar nmbds most?
pancuronium (long acting)
liver disease effects which non-depolar nmbds?
intermediate acting (rocuronium)
hoffman elimination for which non-depolar nmbds?
atricarium and cisatricarium
plasma cholinesterases effects which non-depolar nmbds?
Drugs that can decrease required NMBD (non-depolar) conc needed for effect?
drugs that diminish the effect of non-depolar nmbds?
cardiovascular effects of non-depolar nmbds?
minimal- some hypotension via histamine/muscarinic and nicotininc ACh effects
variable depending on underlying factor (autonimic, volume status, preop meds, etc)
How long maximally should NMBDs be used for?
2 days max to decrease risk of prolonged myopathy
only with concurrent use of analgesics, sedatives, and adjusted ventilator settings to decrease their use
Duration of effect of pancuronium
cardiac effects of pancuronium
modest increase in HR, MAP, and CO (block muscarinic = acts like atropine at SA node)
intermediate acting nmbd that has cardiac effects
duration of vecuronium
minimal/no cardiac effects
duration of rocuronium
20-35 min (longer ~60-90 min if using SCh onset equivalent dosing of 1.2mg/kg)
little to no cardiac effects
chemical/hofmann elimination (nonenzmatic degradation) + enzymatic ester hydrolysis
CNS stimulation occurs by metabolite laudanosine
histamine release = hypotension and tachycardia (if dose >2x ED95)
Duration of cisatricurium
hofmann elimination primary
no histamine effects = no cardiac changes
duration of mivaciurium
not available in USA
nerves typically used for peripheral nerve monitoring of nondepol nmbds
facial nerve (orbicularis oculi)
ulnar nerve (adductor pollicus) - closely reflects blockade at larynx (clinically important for reversal)
types of evoked responses used to monitor nmbds
single twitch response
train of four (TOF) ratio
double burst suppression
Questions answered by PN stim
- is block adequate for surgery
- is block excessive?
- can block be reversed?
Adequate block response per single twitch and TOF stim?
single twitch- depressed by greater than 90%
TOF - elimination of 2-3 twitches
All TOF twitches are absent? what to do next?
don't give more nmbd until some twitch is present
Some twitches are present on TOF stim...should you reverse or give more?
reversal is likely to be successful
Does tetanus stimulation fade completely or incompletely with phase 1 block of Sch?
phase 2 - similar to non-depol - completely fade
anticholinesterase typically used for nmbd reversal
all tests are normal (TOF, burst suppresion, etc), how many receptors could still be blocked by nmbd?
up to 50% - need more than this for skeletal muscle strength
tests that help determine skeletal muscle strength after nmbds
sustained head or leg lift for 5 sec
tongue depressor test
TOF > 0.9 (first twitch and 4th twitch nearly the same)
Why does neostigmine help reverse nmj blockade by non-depol nmbds?
decrease activity of acetylcholinesterase = increase ACh = increased chance ACh will bind to NMJ and not drug (increased competition) = restore NM transmission
side effects of neostigmine? how to tx it?
bradycardia (muscarinic effect)
simultaneous admin of atropine or glycopyrrolate (must be given)
Factors influencing success of antagonism of nmbds
1. intensity of blockade at time of administration
2. choice of drug
3. dose of drug
4. rate of concurrent spontaneous recovery
5. conc of inhaled anesthetic
max dose of neostigmine