Lecture 15: Neuromuscular Blockers

Question 1

Non-depolarizing blocking agents (competitive blockers= compete w/ Ach for binding to nicotinic receptors)

Answer 1

Mivacurium, Rocuronium, Tubocurarine, Vecuronium

Question 2

Causes flaccid paralysis

Answer 2

Mivacurium, Rocuronium, Tubocurarine, Vecuronium

Question 3

Active drug is not excreted by the kidney, so it’s useful for patients with kidney disease.

Answer 3

Mivacurium

Question 4

Mivacurium is hydrolyzed by…

Answer 4

Hydrolyzed by plasma cholinesterases (Short acting)

Question 5

Has no effect on muscarinic receptors.

Answer 5

Mivacurium

Question 6

Has only a mild and transient histamine releasing effect (transient hypotension)

Answer 6

Mivacurium

Question 7

Clinical uses of:

Mivacurium, Rocuronium, Tubocurarine, Vecuronium, Suxamethonium (succinylcholine)

Answer 7

• Clinical uses of NBDs: main use= in anesthesia and surgery:
  1) Produce complete muscle relaxation for surgical procedures.
  2) Facilitate intubation (by relaxing the trachea and vocal cords allowing easier access)
  3) Reduce the dose of general anesthetics (you need to use NBDs in combination w/ anesthetics. NMBs are not given to an awake patient bc he will get paralyzed)

Question 8

Adverse effects of:

Mivacurium, Rocuronium, Vecuronium

Answer 8

-Adverse effects:

Depression of respiration. (respiration must be supported)

Question 9

No histamine release (so no bronchoconstriction or hypotension) or ganglion block.

Answer 9

Rocuronium, Vecuronium

Question 10

Rocuronium, Vecuronium are specific to what receptors?

Answer 10

Specific to nicotinic receptors found on skeletal muscles.

Question 11

No block of muscarinic receptors, hence no tachycardia.

Answer 11

Rocuronium, Vecuronium

Question 12

Intermediate duration of action (30-40 minutes).

Answer 12

Rocuronium, Vecuronium

Question 13

_________ has rapid onset of action (1-2 minutes).

Answer 13

Rocuronium

Question 14

Depolarizing Blocker - only clinically used depolarizing NMB.

Answer 14

Suxamethonium (succinylcholine)

Question 15

The drug attaches to the nicotinic receptor and acts like Ach to depolarize the junction.

Answer 15

Suxamethonium (succinylcholine)

Question 16

Unlike Ach (which is instantly destroyed by acetylcholinesterase) the drug persists at high concentrations at the synaptic cleft, remaining attached to the receptor for a longer time = prolonged depolarization and constant stimulation for the receptors.

Answer 16

Suxamethonium (succinylcholine)

Question 17

Produces transient twitching of skeletal muscles (fasciculation) before causing block.

Answer 17

Suxamethonium (succinylcholine)

Question 18

Phases of Suxamethonium (succinylcholine):

Answer 18

• PHASE 1: membrane depolarized, resulting in an initial discharge that produces transient fasciculations followed by flaccid paralysis.
• PHASE 2: membrane repolarizes, but the receptor is desensitized to the effect of Ach (they don’t get activated again).

Question 19

Suxamethonium (succinylcholine) is used in:

Answer 19

Used in electroconvulsive therapy to reduce trauma.

Question 20

Suxamethonium (succinylcholine) is RAPIDLY hydrolyzed by ________

Answer 20

Rapid hydrolysis by plasma cholinesterases (but resistant to acetylcholinesterase)

Question 21

Very fast onset of action (1 min.), ideal for rapid endotracheal intubation during induction of anesthesia.

Answer 21

Suxamethonium (succinylcholine)

Question 22

Effect lasts for about 5 minutes but can be prolonged in plasma cholinesterase deficiency or atypical plasma cholinesterase.

Answer 22

Suxamethonium (succinylcholine)

Question 23

Adverse effects of Suxamethonium (succinylcholine):

Answer 23

• Adverse effects of depolarizing NMBs:
  1) Depression of respiration
  2) Post-operative pain (due to the twitching that initially happens)
  3) Hyperkalemia: bc the drug binds to receptor for a long period of time, an excess amount of K+ is being released. (dangerous in burn patients/those with massive tissue damage in which potassium has been rapidly lost from w/in cells).
  4) Malignant hyperthermia: Results in intense muscle spasm and dramatic rise in body temp. When certain drugs (ex: halothane) are given. Occurs in patients with rare mutation of the Calcium release channels of the sarcoplasmic reticulum.
  5) Prolonged muscle paralysis and apnea: occurs in plasma cholinesterase deficient patients due to paralysis of the diaphragm.
  6) Bradycardia
  7) Increase in intraocular pressure

Question 24

Alkaloid (active ingredient of “curare”, an arrow poison).

Answer 24

Tubocurarine: (prototype- not used but other drugs are based on it)

Question 25

Action lasts about 1-2 hours.

Answer 25

Tubocurarine: (prototype- not used but other drugs are based on it)

Question 26

Adverse effects of: Tubocurarine: (prototype- not used but other drugs are based on it)

Answer 26

Adverse effects:
Depression of respiration (respiration must be supported)
Causes histamine release, hence bronchoconstriction and hypotension.
May promote ganglionic blockade and can lower blood pressure.

Question 27

Hypotension and bronchospasm:

Answer 27

Tubocurarine: (prototype- not used but other drugs are based on it)

Question 28

Anticholinesterase that inhibits plasma cholinesterases that metabolize another NMB drug (ex: suxamethonium)

Answer 28

Neostigmine

Question 29

Gentamicin (aminoglycosides)Aminoglycosides and NMBs cause prolonged/excessive skeletal muscle paralysis.

Answer 29

Gentamicin (aminoglycosides)

Question 30

Aminoglycosides reduce the release of Ach, while non-polarizing NMBs (vecuronium) block nicotinic receptors.

Answer 30

Gentamicin (aminoglycosides)