Neuomuscular Blocking Agents Flashcards
What are neuromuscular blockers general uses
Induce paralysis during surgical procedures and better control muscle spasms seen in seizures
Are peripherally acting agents and DONOT cross the blood-brain barrier. (No central nervous activity)
- act at the motor end-plate
Why are neuromuscular blockers used only intravenously Or paraenterally?
They do not cross any barriers at all. Therefore if orally absorbed will not have any affected.
D-tubocurarine
1st clinically used neuromuscular anesthetic used.
NO analgesic or sedating effects and only causes conscious paralysis.
Can still feel pain, heat and other sensations
Not used clinically anymore but is the prototype to most of the NMBs we use today
Two classes of Neuromuscular blockers
Depolarization and non-depolarization
Both target nicotine cholinergic receptors
Can produce off-target adverse effects
Muscarinic vs nicotine’s receptors
Both expressed in autonomic nervous system
Nicotinic acts on all autonomic presynaptic neurons and some postsynaptic parasympathetics.
Muscarinic acts on the parasympathetic and sympathetic only in the sweat glands.
What isoform of acetylcholine receptor is found at the neuromuscular junction?
Nm
Are Ligand gated ion pentameric channels
Depolarizing agent mechanism of action
Opens the ion gated cholinergic receipts and binds to the open channel pore
Causes persistent depolarization
Example: succinylcholine
Non-depolarizing agent actions
Block the ion-gated channel from opening at all and prevent action potentials.
Example: everything but succinylcholine
Specific succinylcholine action
Two phases
1: opens the nicotinic channels and maintains cell depolarization affectively disables voltage gated sodium channels
- causes twitching and flaccid paralysis
2: membrane finally repolarizses but nicotinic receptors become desensitized and down regulated and are now less responsive causing paralysis
Pharmacokinetics of succinylcholine
Rapid onset (1 minute) and typically only lasts for 5-10 minutes.
Is metabolized by the blood plasma by the enzyme plasma cholinesterase.
Administered via IV or IM
there is no antidote so overdose will kill
Targets cholinergic and muscarinic receptors
Adverse affects of succinylcholine
Muscle weakness
Jaw rigidity
Rhabdomyolysis
Brady cardia and heart arrest
Intraocular pressure
Hyperkalemia
Hypersensitivity and hypotension due to histamine release
need to use antihistamine w/ dosage to combat this
Contraindications of succinylcholine
Patients with burn, denervation or extreme trauma
- causes exasperated hyperkalemia due to upregulated nicotinic receptors
Duchenne muscular dystrophy (and sometimes Becker’s)
- shreds patients muscles
Renal disease or severe acidosis
- causes exasperated hyperkalemia due to upregulated nicotinic receptors
Rare malignant hyperthermia (MH)
Very rare life threatening adverse effect of succinylcholine
Autosomal dominant disorder that causes a defective ryanodine receptor causing way over release of calcium from SR
Causes elevated arterial CO2 and muscle ridgity and massive increase in muscle metabolism
Patients taking SSRIs and neuroleptics are at twice the risk of MH when given succinylcholine
Dantrolene
Antidote for MH and blockers the deficient ryanodine receptor
Does have serious ADRs including hepatotoxicity. How ever is the only antidote for MH
Only acts on skeletal muscle ryanodine receptors
non-depolarizing Tubocurarine derivatives
Atracurium
Cisatracurium
Nicotinic acetylcholine receptor characteristics
Ligand gated-ion channels that are pentameric.
5 Subunits are different based on location in the body.
Only one isoform receptor is found in the neuromuscular junction Nm
Pancuronium
Long lasting non-depolarizing NMB agent.
Is a moderate heart blocker
Acts at muscarinic receptors
Has high potency
3-4 min onset time average
Eliminated renally
Increase heart rate as adverse effect
Cisatracurium
Non-depolarizing NMB
Derivative of tubocurarine
Time to onset average-high (2-8 min)
Spontaneously degraded in blood (Hoffman elimination)
Forms low amounts of laudanosine which can cause seizures
BEST USE: renally impaired patients, or multi organ failure.
Atracurium
Fast acting Non-polarizing NMB
Derivative of tubocurarine
Slight histamine release
Onset time is average (3min)
Spontaneously degraded in blood (Hoffman elimination)
forms high amounts of laudanosine which can cause seizures
Tubocurarine
Very long lasting NMB
Not clinically used
Can block the autonomic receptors.
Moderate histamine release
Eliminated renally
Vecuronium
Fast acting Type of NMB agent
Relatively short onset 2-3 min
Eliminated hepatically
Rocuronium
Fast acting non-depolarizing agent
Fastest time to onset (30 sec-2 min)
Slight heart blocker
Blocks muscarinic receptors
Most commonly used alternative to succinylcholine if not sure that patient will have an adverse reaction to succinylcholine.
Eliminated hepatically
Increase heart rate as adverse effect
Which two non-depolarizing agents have tachycardia as a adverse effect?
Pancuronium and rocuronium
- due to non-selective muscarinicblocking
Contraindicated in heart issue patients
Which two non-depolarizing agents can cause unwanted histamine release as an adverse side effect?
Tubocurarine and atracurium
Results in hypotension and bronchospasm (can use premeditated antihistamine to reduce effect).
NMBs and competitive inhibition
Non-depolarizing agents are competitive inhibitors of one another and acetylcholine
- because of this, acetylcholinesterase inhibitors will help increase acetylcholine levels and outcompete the non-depolarizing agent.
2 main inhibitors are neostigmine and pyridostigmine
Atropine’s part in NMBs
Often given in conjunction with acetylcholinesterase inhibitors to avoid overstimulation of cardiac muscarinic receptors.
Sugammadex
Reverses rocuronium and vecuronium
Essentially does what acetylcholinesterase inhibitors do but way better and fast (3min vs 19 min for neostigmine).
Does not need to have atropine administered with it.
Only major ADR is anaphylaxis if patients are allergic
What two non-depolarizing NMBs are affected by sugammadex?
Rocuronium and Vecuronium
