Skeletal muscle relaxants

Question 1

Succinylcholine

Answer 1

• MOA
• depolarizing neuromuscular blocking agent
• agonist at at nicotinic ACh receptors, esp at NMJ
• may stimulate ganglionic nicotinic ACh and cardiac M ACh receptors
• Effects
• initial depol. - transient contractions, followed by prolonged flaccid paralysis
• depol. then followed by repol. that is also accompanied by paralysis
• Clinical
• placement of ET tube at induction of anesthesia
• rarely for control of contractions in status epilepticus
• Kinetics, tox, int.
• rapid metabolism by plasma cholinesterase, normal duration approx 5 min
• tox: arrythmias, hyperkalemia, transient increased intraabdominal & intraocular pressure, post-op muscle pain

Question 2

Tubocurarine

Answer 2

• MOA
• nondepolarizing neuromuscular blocker
• competitive antagonist at nACh receptors, esp at NMJ
• Effects
• prevents depol by ACh, causes flaccid paralysis
• can cause histamine release with hypotension
• weak block of cardiac muscarinic ACh receptors
• Clinical
• prolonged relaxation for surgical procedures, superseded by newer agents
• Kinetics, tox, int.
• renal excretion, duration approx 40-60min
• tox: histamine release, hypotension, prolonged apnea

Question 3

Diazepam

Answer 3

• MOA
• centrally acting spasmolytic
• facilitates GABAergic transmission in CNS
• Effects
• increases interneuron inhibition of primary motor afferents in spinal cord, central sedation
• Clinical
• chronic spasm due to CP, stroke, spinal cord injury
• acute spasm due to muscle injury
• Kinetics, tox, int.
• hepatic metabolism, duration 12-24h
• tox: see ch22

Question 4

Dantrolene

Answer 4

• MOA
• direct-acting muscle relaxant
• blocks RyR1 Ca²⁺ release channels in SR of skeletal muscle
• Effects
• reduces actin-myosin interaction, weakens skeletal muscle contraction
• Clinical
• IV: malignant hyperthermia
• oral: spasm due to CP, spinal cord injury, MS
• Kinetics, tox, int.
• IV, oral
• duration 4-6h
• tox: muscle weakness

Question 5

Botulinum toxin

Answer 5

• MOA
• direct acting muscle relaxant
• cleaves fusion proteins in nerve endings
• Effects
• flaccid paralysis
• Clinical
• spasm due to CP, MS, over-active bladder, migraine
• Kinetics, tox, int.
• direct IM injection, duration 2-3 months
• tox: muscle weakness, falls