Skeletal Muscle Relaxants

Question 1

MOA of succinylcholine

Answer 1

Agonist at nicotinic acetylcholine receptors causing an initial twitch, then persistent depolarization

Question 2

Interactions of succinylcholine with other autonomic receptors

Answer 2

Stimulates ANS ganglia and muscarinic receptors.

Has slight ability to release histamine.

Question 3

How is succinylcholine inactivated?

Answer 3

Phase I depolarization cannot be inactivated.
Phase II depolarization is inactivated by acetylcholinesterase inhibitors, such as neostigmine or pyridostigmine.
*NB: the paralysis produced during phase I is actually INCREASED by acetylcholinesterase inhibitors.

Question 4

Adverse effects of succinylcholine

Answer 4

1. Muscle pain. To prevent skeletal muscle fasciculation and the resulting postoperative pain, a small non paralyzing dose of a non depolarizing drug (such as cisatracurium) is often given immediately before succinylcholine.
2. Hyperkalemia, especially in patients with burn or spinal cord injury, peripheral nerve dysfunction, or muscular dystrophy.
3. Hypercalcemia
4. Increased intragastric pressure (caused by fasciculations). Regurgitation and aspiration of gastric contents are possible complications of this.
   * NB this complication is more likely in patients with delayed gastric emptying, such as those with esophageal dysfunction or diabetes.
5. Increased intraocular pressure

Question 5

MOA of non depolarizing skeletal muscle relaxants (SMRs)

Answer 5

Competitive antagonists at skeletal muscle nicotinic acetylcholine receptors.

Question 6

Nondepolarizing SMR most often associated with hypotension caused by histamine release

Answer 6

Tubocurarine

*NB: tubocurarine also weakly blocks ANS ganglia

Question 7

Distinctive characteristic of pancuronium

Answer 7

Can block muscarinic receptors, especially those in the HEART. Has sometimes been caused tachycardia and hypertension and may cause dysrhythmias in predisposed individuals.

Question 8

How do you reverse the effects of non depolarizing SMRs?

Answer 8

1. Acetylcholinesterase inhibitors.
2. Muscarinic blocking agents, such as glycopyrrolate or atropine. (Glycopyrrolate is preferred because it lacks CNS effects)
   Rationale: Acetylcholinesterase inhibitors reverse the effects of non depolarizing SMRs by overcoming the competitive inhibition. However, administration of acetylcholinesterase inhibitors will increase the concentration of ACh in the synaptic clefts everywhere, including at muscarinic receptors, where they can cause bradycardia. Therefore you must give muscarinic blocking agents, in order that the acetylcholinesterase inhibitors have effects at nicotinic acetylcholine receptors only.

Question 9

Histamine release is an adverse effect of which 2 non depolarizing SMRs?

Answer 9

tubocurarine

mivacurium

Question 10

Which non depolarizing SMR causes laudanosine formation, which theoretically could lower the seizure threshold in a susceptible patient?

Answer 10

atracurium

Question 11

What other drugs potentiate skeletal muscle relaxation of non depolarizing blockers?

Answer 11

Inhaled anesthetics, aminoglycosides, and possibly quinidine

Question 12

Nondepolarizing blockers listed in K&T

Answer 12

tubocurarine, atracurium, cistracurium, mivacurium, rocuronium, vecuronium

Question 13

MOA of baclofen

Answer 13

Facilitates SPINAL inhibition of motor neurons via GABA(b) receptor activation: pre- and postsynaptic
*NB: GABA(b) receptors are coupled to K+ channels, unlike GABA(a) receptors, which are coupled to Cl- channels, and are modulated by BDZs

Question 14

What is baclofen used for?

Answer 14

CHRONIC spasmolytic therapy, in diseases such as cerebral palsy, MS, and stroke that are associated with hyperreflexia/painful spasms

Question 15

MOA of cyclobenzaprine

Answer 15

Unknown. Believed to act in the brain stem, possibly by interfering with polysynaptic reflexes that maintain skeletal muscle tone.

Question 16

What is cyclobenzaprine used for?

Answer 16

ACUTE spasmolytic therapy, for spasms resulting from muscle injury.

Question 17

Other drugs used for acute muscle spasm

Answer 17

cyclobenzaprine, metaxalone, methocaramol, orphenadrine

Question 18

Adverse effects of baclofen

Answer 18

sedation, muscle weakness

Question 19

Adverse effects of cyclobenzaprine

Answer 19

muscarinic blockade, sedation, confusion, and visual hallucinations

Question 20

Which drug has spasmolytic activity and could also be used in the management of seizures caused by OD of a local anesthetic?

Answer 20

Diazepam; works at GABA(a) receptors
*NB: Gabapentin and pregabalin are anti seizure drugs that have been shown to be effective spasmolytics in patients with MS.

Question 21

What is tizanidine used for?

Answer 21

Chronic spasmolytic therapy

Question 22

MOA of tizanidine

Answer 22

alpha-2 agonist in the spinal cord

Question 23

adverse effects of tizanidine

Answer 23

muscle weakness, sedation, and hypotension

Question 24

Route of administration common to all centrally acting spasmolytic drugs?

Answer 24

oral

Question 25

MOA of dantrolene

Answer 25

Blocks RyR1 Ca2+ channels in skeletal muscle, which weakens muscle contraction by reducing myosin-actin interaction.
*NB: dantrolene has NO significant effect on the release of Ca2+ from CARDIAC and/or smooth muscle.