Neuromuscular Blocking Agents Flashcards
Explain what happens at the neuromuscular junction to cause muscle contraction.
- An action potential travels down a motor neuron to the presynaptic terminal.
- Voltage-gated calcium channels open and cause vesicles of acetylcholine to release into the synaptic cleft.
- Acetylcholine binds to acetylcholine-gated receptor channels (nicotinic receptors) at the motor end plate (post-synaptic membrane)
- Na+/K+ ion channels open causing an influx of sodium and eflux of potassium creating an action potential. The action potential depolarizes the skeletal muscle and causes it to contract.
- Acetylcholine is then degraded by acetylcholinesterase into acetate and choline. Choline can be used to make more acetylcholine.
How does succinylcholine work?
-succinylcholine (anectine) is 2 acetylcholine molecules that overwhelms the synaptic cleft & binds to nicotinic receptors on the motor end plate
-depolarizing neuromuscular blocking agent - depolarizes motor end plate until it reaches an absolute refractory period (muscles fatigue out)
Side effects of succinylcholine
-hyperkalemia - will cause a transient release of K+ to be released into circulation (0.5-1.0 mEq/L)
-myalgias - severe muscle contractions (fasiculations). patients may feel like they worked out. Can elevate ICP
normal dose of succinylcholine
1 - 2 mg/kg IV
2-4 mg/kg IM
onset & duration of succinylcholine
onset: 30 sec
duration 5 - 10 minutes (good for difficult airways because you can BVM until it wears off)
elimination of succinylcholine
enzymatically hydrolyzed by plasma cholinesterase/pseudocholinesterase/butyrocholinesterase
Acetylcholine is hydrolyzed by true cholinesterase, which is found at the neuromuscular junction as well as at tissues innervated by parasympathetic nerves.
List five conditions that may accentuate succinylcholine-induced hyperkalemia
- Unhealed third-degree burns
- denervation of skeletal muscle (paraplegia or hemiplegia)
- severe skeletal muscle trauma
- upper motor neuron injury (head injury, Parkinson’s disease, cerebrovascular accident)
5.muscular dystrophy
Why is succinylcholine contraindicated in patients with nerve damage?
When motor nerves to skeletal muscle are damaged, nicotinic receptors of the skeletal muscle cell up regulate. These extrajunctional cholinergic (nicotinic) receptors on skeletal muscle are exceptionally responsive to succinylcholine. Potassium leaves the cell in excessive quantities when succinylcholine triggers these channels to open. and hyperkalemia results
How do non-depolarizing neuromuscular blocking medications work?
Non-depolarizing NMB are competitive antagonists to acetylcholine. They prevent depolarization by binding to nicotinic receptors on the motor end plate.
What are the 2 classifications of non-depolarizing muscle relaxants?
benzylisoquinoliniums (-curium)
-cisatracurium (nimbex), atracurium (tracrium)
steroid derivatives (-curonium)
-vecuronium (norcuron), rocuronium
What is the termination of the action of non-depolarizing muscle relaxants usually due to?
Redistribution to non-muscle tissues is the major cause of the initial decrease in concentration of relaxant at the neuromuscular junction
How are benzylisoquinoliniums eliminated?
Hofmann elimination - good for kidney/liver patients
Hofmann elimination is dependent on what two factors? What body conditions are necessary for Hofmann elimination of atracurium or cisatracurium to occur?
Hofmann elimination is temperature and pH dependent. Hofmann elimination occurs in the presence of physiologic pH (7.4). The rate of Hofmann elimination is slowed by acidosis (pH<7.4) or decreases in body temperatures (<37 degrees C). Hofmann elimination is increased with an increase in pH or body temperature.
How are steroid derivative non depolarizing NMB eliminated?
biliary excretion (primary) and some renal excretion (secondary) and some metabolism (secondary).
What is the dose for vecuronium?
0.8 mcg/kg/min
What is the dose for rocuronium?
0.01 - 0.012 mg/kg/min
0.6 - 1.2 mg/kg for RSI
What is the dose for atracurium?
0.002-0.015 mg/kg/min
What is the dose for cisatracurium?
3 mcg/kg/min
Why would cisatracurium be preferred over atracurium?
atracurium can cause histamine release causing vasodilation and hypotension.
cisatracurium is cardiac stable
What is the onset & duration of rocuronium during RSI?
Onset: 45 - 120 sec
Duration: 30 - 90 minutes
Why would maximum doses of anticholinesterase drugs fail to fully reverse nondepolarizing neuromuscular blockade?
- Insufficient time has elapsed for the anticholinesterase drug to antagonize the muscle relaxant.
- The degree of neuromuscular blockade is too intense to be antagonized.
- Body temperature is abnormally low.
- There is an acid-base or electrolyte disturbance.
- The patient is receiving drugs that interfere with metabolism
- Clearance of the nondepolarizing drug is reduced by renal or hepatic disease.
At what point is the earliest possible time to reverse a nondepolarizing muscle relaxant?
Reversal should not be attempted until there is at least one detectable twitch. If one twitch in four is present and an acetylcholinesterase inhibitor is administered. 15-30 min is required for the twitch height to reach the preblock state.
Why is the ulnar nerve the preferred location for TOF monitoring?
it tells us the level of paralysis at the diaphragm
What muscle does the ulnar nerve innervate?
adductor pollicis - will see pinky move
if thumb moves, you are directly stimulating the muscle instead of the nerve (not accurate TOF)
How should leads be placed for TOF on the ulnar nerve?
on the wrist opposite of the side of the thumb
black (neg) lead should be placed distal and red (pos) should be proximal
What is supramaximal stimulation?
Max output where increasing the output no longer gives a stronger muscle contraction (20% over maximum)
Threshold - minimal output needed to achieve contraction
Submaximal - not strong enough to elicit full contraction
Maximal Stimulation - strong enough to obtain full contraction
What will be the TOF response with depolarizing NMB (succinylcholine)?
TOF stimulates all receptors at the same time. Strength of contraction will be stronger over time as the medication is metabolized.
What will be the TOF response with non depolarizing NMB?
Will see fade (the first twitch will be stronger than the rest - looks like stairs) because only some of the receptors are being blocked
What is a TOF ratio?
% of normal contraction of twitch 4 / % of normal contraction of twitch 1
if there is no 4th twitch, then TOF ratio is 0
Even if you have 4/4 twitches with non depolarizing NMB, it is important to know that up to ___ % of receptors can still be blocked.
70%
3/4: 70% blocked
2/4: 80% blocked
1/4: 90% blocked
0/4: up to 100% receptors blocked and giving more paralytic won’t increase the response
What medication is used as a non depolarizing NMB antagonist and how does it work?
Neostigmine - inhibits acetylcholinesterase (enzyme that breaks down acetylcholine in the neuromuscular junction)
Less acetylcholinesterase = more acetylcholine = more acetylcholine to outnumber the NMB for nicotinic receptor sites
Normal dose of Neostigmine and when do you give it?
0.05 - 0.07 mg/kg
Should give when the patient has 1-2 twitches (if pt has 0 twitches you have no idea how much paralytic is available)
Onset and duration of neostigmine
onset: 4 - 8 min
duration: 30 min - 2 hrs
How is neostigmine eliminated?
Renal (50%)
Plasma esterases
Important side effects of neostigmine?
increasing available acetylcholine increases the parasympathetic response: SLUDGEBM
Salivation, Lacrimation, Urination, Defecation, GI disturbances, Emesis, Bronchoconstriction, myosis (contraction of pupils)
Can also produce vagal stimulation leading to bradycardia
What medication is important to give concurrently with neostigmine?
An anticholinergic such as glycopyrulate to counteract the effects of acetylcholine (has the same onset as neostigmine)
What medication is used to reverse NMB?
Sugammadex - reversal no matter depth of block
Important to note that this only works for steroidal NMB - “uronium”
works by encapsulating and forming a tight water-soluble complex around the NMB which is then excreted through urine (80% cleared through kidneys in 24 hrs)
What is the dose for sugammadex?
2 - 16 mg/kg depending on depth of block
4/4: 2 mg/kg
0/4: 16 mg/kg
What are the adverse reactions of sugammadex?
dry mouth, N/V, chills, postural hypotension, dysgeusia (bad taste in mouth)
What percentage of nicotinic cholinergic receptors must be blocked for clinically significant paralysis? For intubation?
Paralysis permitting adequate abdominal muscle relaxation occurs when 90% of receptors are blocked (1/4 twitches). On the other hand, the patient is completely flaccid when 99% of the receptors are blocked
What is the priming principle for nondepolarizing neuromuscular relaxants?
The priming principle for nondepolarizing neuromuscular relaxants involves administering a subtherapeutic dose of a nondepolarizing agent, typically about 10% of the ED95 (the effective dose needed to achieve 95% receptor blockade). This is done prior to the administration of the full dose. The idea behind the priming principle is to hasten the onset of neuromuscular blockade by initially blocking some of the receptors
What is the law of mass action, which is also known as Le Chatelier’s principle? In relation to nondepolarizing NMB
Le Chatelier’s principle, also known as the law of mass action, explains the displacement of nondepolarizing muscle relaxant from postsynaptic receptors as acetylcholine accumulates in response to an anticholinesterase drug. This principle states that if a dynamic equilibrium is disturbed by changing the conditions, the position of equilibrium shifts to counteract the change to reestablish an equilibrium.
