Neuomuscular Blocking Agents

Question 1

What are neuromuscular blockers general uses

Answer 1

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

Question 2

Why are neuromuscular blockers used only intravenously Or paraenterally?

Answer 2

They do not cross any barriers at all. Therefore if orally absorbed will not have any affected.

Question 3

D-tubocurarine

Answer 3

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

Question 4

Two classes of Neuromuscular blockers

Answer 4

Depolarization and non-depolarization

Both target nicotine cholinergic receptors

Can produce off-target adverse effects

Question 5

Muscarinic vs nicotine’s receptors

Answer 5

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.

Question 6

What isoform of acetylcholine receptor is found at the neuromuscular junction?

Answer 6

Nm

Are Ligand gated ion pentameric channels

Question 7

Depolarizing agent mechanism of action

Answer 7

Opens the ion gated cholinergic receipts and binds to the open channel pore

Causes persistent depolarization

Example: succinylcholine

Question 8

Non-depolarizing agent actions

Answer 8

Block the ion-gated channel from opening at all and prevent action potentials.

Example: everything but succinylcholine

Question 9

Specific succinylcholine action

Answer 9

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

Question 10

Pharmacokinetics of succinylcholine

Answer 10

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

Question 11

Adverse affects of succinylcholine

Answer 11

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

Question 12

Contraindications of succinylcholine

Answer 12

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

Question 13

Rare malignant hyperthermia (MH)

Answer 13

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

Question 14

Dantrolene

Answer 14

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

Question 15

non-depolarizing Tubocurarine derivatives

Answer 15

Atracurium

Cisatracurium

Question 16

Nicotinic acetylcholine receptor characteristics

Answer 16

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

Question 17

Pancuronium

Answer 17

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

Question 18

Cisatracurium

Answer 18

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.

Question 19

Atracurium

Answer 19

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

Question 20

Tubocurarine

Answer 20

Very long lasting NMB

Not clinically used

Can block the autonomic receptors.

Moderate histamine release

Eliminated renally

Question 21

Vecuronium

Answer 21

Fast acting Type of NMB agent

Relatively short onset 2-3 min

Eliminated hepatically

Question 22

Rocuronium

Answer 22

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

Question 23

Which two non-depolarizing agents have tachycardia as a adverse effect?

Answer 23

Pancuronium and rocuronium

• due to non-selective muscarinicblocking

Contraindicated in heart issue patients

Question 24

Which two non-depolarizing agents can cause unwanted histamine release as an adverse side effect?

Answer 24

Tubocurarine and atracurium

Results in hypotension and bronchospasm (can use premeditated antihistamine to reduce effect).

Question 25

NMBs and competitive inhibition

Answer 25

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

Question 26

Atropine’s part in NMBs

Answer 26

Often given in conjunction with acetylcholinesterase inhibitors to avoid overstimulation of cardiac muscarinic receptors.

Question 27

Sugammadex

Answer 27

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

Question 28

What two non-depolarizing NMBs are affected by sugammadex?

Answer 28

Rocuronium and Vecuronium