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
