Harvey's Garden

Skeletal muscle relaxants

4 min read

Spasmolytics (Used for CNS-mediated spasticity or acute muscle spasm)

  • Baclofen
    • MOA: Agonist at GABA-B receptors in the spinal cord, leading to hyperpolarization and ↓ synaptic transmission.
    • Use: Spasticity in multiple sclerosis (MS), spinal cord injuries.
    • AE: Sedation, weakness. Abrupt withdrawal can cause seizures and hallucinations.
  • Cyclobenzaprine
    • MOA: Centrally acting; structurally related to tricyclic antidepressants (TCAs). Thought to act at the brainstem.
    • Use: Short-term treatment of acute muscle spasms from musculoskeletal conditions.
    • AE: Strong anticholinergic side effects (dry mouth, urinary retention, confusion), sedation.
  • Tizanidine
    • MOA: Centrally acting alpha-2 adrenergic agonist. Reduces spasticity by ↑ presynaptic inhibition of motor neurons.
    • Use: Spasticity from MS, stroke, or spinal cord injury.
    • AE: Hypotension, sedation, dry mouth, hepatotoxicity.
  • Dantrolene
    • MOA: Acts directly on skeletal muscle. Prevents the release of Ca2+ from the sarcoplasmic reticulum by binding to the ryanodine receptor (RyR1).
    • Use: Malignant hyperthermia (first-line Tx), Neuroleptic Malignant Syndrome (NMS), spasticity from stroke, MS, spinal cord injury.
    • AE: Hepatotoxicity (black box warning), muscle weakness.
  • Benzodiazepines (e.g., Diazepam)
    • MOA: Potentiate the effect of GABA at the GABA-A receptor, ↑ frequency of Cl- channel opening.
    • Use: Muscle spasms, anxiety, seizures, alcohol withdrawal.
    • AE: Sedation, risk of tolerance/dependence.

Depolarizing NMJ blockers (depolarizing muscle relaxants)

Fast onset, short duration

Agents

  • Succinylcholine (suxamethonium)

Indications

  • Anesthesia induction (esp. rapid sequence induction)

Phases of Block:

  • Phase I (Depolarizing): Initial muscle fasciculations followed by paralysis. Potentiated by cholinesterase inhibitors.
    • Typical Duration: The clinically effective neuromuscular block from a single standard IV dose of succinylcholine is very brief, lasting 5 to 10 minutes.
    • Pathophysiology: This short duration is due to its rapid hydrolysis by pseudocholinesterase (butyrylcholinesterase) in the plasma.
  • Phase II (Desensitizing): Receptor becomes desensitized to ACh. Resembles non-depolarizing block; can be reversed by cholinesterase inhibitors.
    • Typical Duration: The duration of a Phase II block is much more variable and prolonged. Spontaneous recovery is significantly longer, often taking 30 to 60 minutes or more to resolve after the drug is stopped.
    • Pathophysiology: A Phase II block is an abnormal response that occurs when the postsynaptic receptors become desensitized. This is typically seen with:
      • Large, repeated doses or a prolonged infusion of succinylcholine.
      • It can also occur in patients with pseudocholinesterase deficiency, where a standard dose is not metabolized effectively, leading to a prolonged Phase I that eventually transitions into a Phase II block lasting for hours.

Monitoring

  • Train-of-four stimulation shows an equal decrease in the amplitude of all 4 muscle twitches.
    • The muscle fiber becomes unresponsive to any further stimulation

Adverse effects

  • Hyperkalemia
    • Mechanism: depolarization of large muscle groups → efflux of potassium ions into the extracellular space
    • Succinylcholine is contraindicated in case of hyperkalemia or in conditions associated with a high-risk of hyperkalemia, including:
  • Prolonged muscle paralysis, respiratory depression and/or apnea in patients with a congenital deficiency of plasma cholinesterase
    • AChE (“True Cholinesterase”):
      • Function: Rapidly hydrolyzes acetylcholine (ACh) in synaptic clefts & neuromuscular junctions (NMJs) to terminate neurotransmission. Essential for precise control of nerve impulses.
      • Location: Primarily at postsynaptic NMJs, cholinergic synapses in CNS, red blood cells.
    • PChE (Butyrylcholinesterase, “Plasma/Serum Cholinesterase”):
      • Function: Hydrolyzes exogenous choline esters (e.g., succinylcholine, mivacurium) and some local anesthetics (e.g., procaine, cocaine). Physiological role not fully understood, but may be involved in nerve signal transmission.
      • Location: Synthesized in the liver; found in plasma, liver, pancreas, heart, brain (white matter).
      • Atypical pseudocholinesterase
        • Pseudocholinesterase is responsible for the breakdown of succinylcholine through ester hydrolysis.
        • Atypical pseudocholinesterase breaks down succinylcholine slowly and thus prolongs the duration of muscle relaxation during anesthesia from a few minutes to a few hours; this may cause respiratory depression.
  • Malignant hyperthermia

Nondepolarizing NMJ blockers (nondepolarizing muscle relaxants)

Slow onset, long duration

Mechanism of action

  • Compete with ACh to bind with the (nicotinic) ACh receptors at the motor end plate (competitive antagonists) → prevention of motor end plate depolarization (nondepolarization block)

Agents

  • Rocuronium
  • Vecuronium
  • Atracurium

Indications

  • Rapid-sequence induction of anesthesia when succinylcholine is contraindicated

Monitoring

  • Train-of-four stimulation shows a fade-off in the amplitude of the muscle twitch
    • NDMRs block nicotinic acetylcholine receptors (nAChRs) not only at the postsynaptic membrane but also at presynaptic nerve terminals
    • These presynaptic receptors normally provide positive feedback for additional ACh release
    • When blocked, there’s reduced mobilization of ACh vesicles for subsequent stimuli

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