Test 3: 43 neuromuscular Flashcards
why use neuromuscular blocking agents
make tracheal intubation easier
reduced skeletal muscle tone at lighter anesthetic planes
prevention of patient movement
keeps eyes in place
control respiration
does not provide analgesia, may need to ventilate if diaphragm is affected, does not affect consciousness
ACh binds to — receptor on the muscle cell
nicotinic cholinergic receptors
2 ACh binds to ion channel that lets Na, Ca in and K out
what breaksdown ACh
Acetylcholinesterase (AChE) rapidly hydrolyzes ACh
how does NMJ work
Action potential arrives at the pre-junctional motor nerve ending → nerve terminal depolarizes → adenylate cyclase converts ATP to cyclic AMP → Ca2+ enters into the nerve terminal → causes release of ACh into the synaptic cleft → ACh binds to the post-junctional receptor → Ion channels open; sodium, calcium influx, potassium effluxes → post-junctional muscle cell is depolarized → ACh is hydrolyzed by acetylcholinesterase, removed from the receptor, and
repolarization occurs
how do depolarizing agents work
mimic ACh- cause prolonged depolarization and activation of channels
Phase 1: bind and cause fasciculations
Phase II: Ach receptors become desensitized → flaccid paralysis
how do non-depolarizing agent work
bind ACh but cannot induce the conformational
change needed to open the ion channel
- No phase 1 block- no AP is made
- NMB can occur even even if only one a-subunit is blocked- decouples AP transmission and muscular contraction, causing paralysis
- Function as ACh receptor competitive antagonists, outcompete ACh based on concentration
- Success of NMB depends on the concentration of NMBA vs concentration of ACh
— is a depolarizing NMBA
succinylcholine
only small amount gets to NMJ, because it is apidly hydrolyzed by the enzyme pseudocholinesterase (plasma cholinesterase) that are made by the liver
causes transient paralysis as drug diffuses away
Greater dose administered= faster onse
pancuronium
aminosteroid non depolarizing NMBA
- Onset is about 5 mins, duration of action 40-50 mins
- Also blocks cardiac muscarinic receptors, causing ↑HR
atracurium is a — NMDA
short acting non depolarizing NMDA
(Benzylisoquinolones)
what is hofmann elimination
spontaneous degradation without enzymes; temperature and pH- dependent
Atracurium- short-acting non-depolarizing NMBA
how is atracurium broken down
Hofman elimination- spontaneous degradation without enzymes; temperature and pH-dependent
Can give to patients with hepatic or renal insufficiency without increasing duration of action
Atracurium- short-acting non-depolarizing NMBA
Cisatracurium
4x potency of atracurium and even further reduced histamine release compared to atracurium though has similar onset and duration of action, 5 mins and duration is about 30 min
Also undergoes Hofmann elimination
short-acting non-depolarizing NMBA
vecuronium
devoid of cardiovascular effects (no tachycardia, no histamine release)
More than half of the drug undergoes hepatic metabolism with the remaining portion undergoing renal excretion
Both rocuronium and vecuronium have the advantage of being reversed by suggamadex
short-acting non-depolarizing NMBA
rocuronium
derivative of vecuronium with 1/8th potency
Administered as a larger dose and thus has a faster onset though still not as fast as succinylcholine; duration of action around 40 mins
Both rocuronium and vecuronium have the advantage of being reversed by suggamadex
short-acting non-depolarizing NMBA
Guaifenesin
Disrupts nerve impulse transmission at the level of the interneurons of the
spinal cord, brainstem, and subcortical areas
- Relaxation of skeletal muscle with little effect on respiratory muscles/diaphragm at therapeutic doses
- Produces neither analgesia nor unconsciousness
- Cannot antagonize
- 10% concentration can cause hemolysis, hemoglobinuria, or venous thrombosis; 5% concentration ‘safe’
- Damaging to tissues if extravasates
- Crosses blood-placenta barrier
- Most commonly used in field anesthesia as part of a ‘triple drip’
— Interferes with excitation-contraction coupling of actin and myosin by decreasing
the amount of calcium used in the sarcoplasmic reticulum
dantrolene
— Disrupts nerve impulse transmission at the level of the interneurons of the
spinal cord, brainstem, and subcortical areas
guaifenesin
dantrolene is used to treat
Interferes with excitation-contraction coupling of actin and myosin by decreasing the amount of calcium used in the sarcoplasmic reticulum
Used in malignant hyperthermia (MH) treatment
May cause severe myocardial depression if used with calcium channel blockers
besides the NMJ NMBA can cause
- older agents may decrease BP by blocking the action of ACh at the sympathetic ganglia and decreasing vasomotor tone or via histamine release
- Pancuronium may increase HR via cardiac muscarinic receptor blockade and decreased parasympathetic activity, or via stimulating release of
norepinephrine
For modern NMBA, histamine release dose is higher than relaxant dose, and less likely with steroid relaxants than benzylisoquinolones
side effects of succinylcholine
↑ potassium- in already sick pts with i ncreased number of extrajunctional ACh receptors such as in burn patients, muscle trauma, or nerve
damage
↑ intraocular pressure
↑ intragastric pressure → worsens regurgitation and bad for GDV
post- anesthetic myalgia from phase 1 block
respiratory acidosis — intensity of muscle blockade while respiratory alkalosis — its effect
increases
decreases
Metabolic acidosis and alkalosis may both potentiate NMBA effects and make antagonism more difficult and may need to return patient to closer to physiological pH
Decreases in ECF potassium result in — of endplate
hyperpolarization
Increases in ECF potassium — the resting membrane potential (opposing relaxant effect)
lowers
Increased calcium will likely require — doses of NMBA to achieve effects
higher
— patients may be resistant to Phase I succinylcholine blockade
but extremely sensitive to non-depolarizing NMBA and Phase II blockade because of
a decreased number of ACh receptors
Myasthenia gravis
what are antibiotics that interfere with NMBA
- Polymyxin may depress post-synaptic sensitivity of ACh and enhance channel block
- Aminoglycosides depress ACh release
When an antibiotic is given to a patient receiving a NMBA, an enhanced block or residual
paralysis is possible
electrical stimulus hould be — to ensure that all nerve fibers in the nerve bundle are depolarized
supramaximal
single twitch compare with — response
pre-relaxant
- Delivered every 7-10 seconds
- Not depressed until 75-80% of receptors are blocked and abolished with 90-95% of receptors are blocked
train of four
ratio of intensity of the fourth twitch to the first (T4:T1 ratio)
Absence of block= 1.0; a ratio of 0.7 or greater is considered adequately
recovered (0.9 for some sources)
- When 70% of the receptors are occupied, the twitches will fade (4th, 3rd, 2nd, then 1st) and reappear in reverse order
— stimulation is used for detecting if there is residual blockade
Tetanic stimulation
how to reverse NMB
cholinesterase-inhibitors/anticholinesterases, such as Neostigmine,Pyridostigmine, Edrophonium
Suggamadex- a ‘selective relaxant binding agent’; selectively with antagonize rocuronium or
vecuronium
Work by enabling ACh to be in higher concentration than the NMBA at the NMJ; but as consequence ACh is also at higher concentrations than usual elsewhere (muscarinic receptor stimulation)
side effects of reversal of NMB
↑parasympathetic - bradycardia, bronchoconstrictions
what drugs go through hofmann elimination
atracurium and cisatracurium
not based on enzymes
Anticholinesterases will prevent breakdown on ACh; this will have effects (—) throughout the body, not just at the NMJ and should be paired with an anticholinergic (atropine or glycopyrrolate)
bradycardia, SLUD signs
target is the nicotinic receptors as the NMJ, but we also affect the muscarinic receptors causing these (clinically) negative effects
