Neuromuscular blocking drugs

Question 1

What do NMB’s do and what are they used for?

Answer 1

Can completely paralyze skeletal muscle and are primarily used as adjuncts during surgical and orthopedic procedures

Question 2

Mechanism of action of NMB’s

Answer 2

Antagonizing the action of ACh at the nerve-muscle synapse (neuromuscular junction)

Question 3

Succinylcholine

Answer 3

The only therapeutically useful neuromuscular blocker that acts as a depolarizing agent

• short acting used in brief procedures
• stimulates autonomic ganglia; stimulates cardiac muscarinic AChR; metabolized by plasma cholinesterase

Question 4

Apnea

Answer 4

Major adverse reaction to succinylcholine; extending into the postoperative period

Question 5

Hyperkalemia

Answer 5

Results from release of K+ from the muscle via the nAChRs; and is another adverse reaction to succinylcholine
-Precludes the use of succinylcholine in children; due to undiagnosed skeletalmyopathies

Question 6

Tubocurarine

Answer 6

Long acting neuromuscular blocker

• autonomic ganglia blockade; high effect on histamine release; no effect on cardiac muscarinic AChR; metabolized in the kidney/liver
• no longer available

Question 7

Pancuronium

Answer 7

Long acting neuromuscular blocker

• no effect on autonomic ganglia; no effect on histamine release; moderate block on cardiac muscarinic AChR (incr bp or tachycardia); metabolized in the kidney
• concern for patients with heart problems and patients with kidney transplants

Question 8

Pipercuronium & Doxacurium

Answer 8

Long acting neuromuscular blocker
- no effect on autonomic ganglia; no effect on histamine release; no effect on cardiac muscarinic AChR; metabolized in the kidney

Question 9

Vercuronium

Answer 9

Intermediate acting neuromuscular blocker
- no effect on autonomic ganglia; no effect on histamine release; no effect on cardiac muscarinic AChR; metabolized in the liver

Question 10

Atracurium & Cistracurium

Answer 10

Intermediate acting neuromuscular blocker

• no effect on autonomic ganglia; low effect on histamine release; no effect on cardiac muscarinic AChR; spontaneously hydrolyzed in the liver creating laudanosine
• concern for hypotension and bronchoconstriction

Question 11

Rocuronium

Answer 11

Intermediate acting neuromuscular blocker with rapid onset

• no effect on autonomic ganglia; no effect on histamine release; slight effect on cardiac muscarinic AChR
• Alt for succinylcholine

Question 12

Mivacurium

Answer 12

Short acting neuromuscular blocker with rapid onset

• no effect on autonomic ganglia; low effect on histamine release; no effect on cardiac muscarinic AChR; metabolized by plasma cholinesterase
• alt to succinylcholine

Question 13

Response to Succinylcholine

Answer 13

Occurs in two phases. In phase I, there is initial activation followed by receptor blockade resulting from persistent depolarization (leading to Na channel inactivation). In phase II, later, nicotinic receptors will inactivate resulting in repolarization

Question 14

Succinylcholine + ChE inhibitor

Answer 14

Phase I will be enhanced while phase II will be reversed

Question 15

Reversal of NMJ blockade

Answer 15

For all blockers except succinylcholine (and mivacurium), reversal may be accelerate by using a cholinesterase inhibitor.
-idea is ACh will compete away the blocker

Question 16

Which drug would you use for brief procedures– mainly intubation?

Answer 16

Succinylcholine (depolarizing NMJ blocker)

Question 17

Alternative to Succinylcholine

Answer 17

Mivacurium or rocuronium (non-depolarizing NMJ blockers); used for brief procedures

Question 18

Which drug is widely used in surgery with no side effects

Answer 18

Vecuronium (non-depolarizing NMJ blocker); intermediate duration

Question 19

Widely used in surgery with some concern for hypotension and bronchoconstriction

Answer 19

Cisatracurium (or Atracurium; non-depolarizing NMJ blockers); intermediate duration

Question 20

Widely used in surgery with concerns in heart patients (tachycardia and increased BP)

Answer 20

Pancuronium (non-depolarizing NMJ blocker); also not for use in kidney transplants

Question 21

Which drug has a very long duration

Answer 21

Pipecuronium and doxacurium (non-depolarizing NMJ blockers)

Question 22

Which drug has a long duration but is no longer available?

Answer 22

Tubocurarine; non-depolarizing NMJ blocker

Question 23

Order of muscle susceptibility

Answer 23

Rapid orbital muscles of the eye > extremities > trunk muscles > intercostal muscles > diaphragm; with recovery in the reverse order

Question 24

Two kids of NMB’s

Answer 24

Depolarizing (succinylcholine) and non-depolarizing (competitive antagonists)

Question 25

What does significant genetic variability in ability of plasma esterase (cholinesterase for hydrolysis) lead to?

Answer 25

Leads to variable duration of action of succinylcholine or mivacurium

Question 26

Heavily muscled patients

Answer 26

When given succinylcholine, may develop myalgias, secondary to the development of fasciculations (relieved by lowering dose)

Question 27

Route of deliver of NMJ blockers

Answer 27

I.V. because they are quarternary amines and poorly absorbed orally

Question 28

Assessment of NMJ block

Answer 28

Train of four (TOF) stimulations of nerve; analyze fade

Question 29

Short acting drugs

Answer 29

• 5-15 min

- metabolized by plasma ChE

Question 30

Long acting drugs

Answer 30

1-2 hrs

-metabolized by the kidney

Question 31

Intermediate acting drugs

Answer 31

20-60 min

-metabolized by liver and spontaneous hydrolysis