Muscle Relaxants for USMLE Step One

Mechanism of Action

• Action potentials propagated down axon reach presynaptic membrane.
• Voltage-gated calcium channels open, causing calcium influx.
• This causes vesicles with neurotransmitters to exocytose and release neurotransmitters.
• Neurotransmitters act as ligands at nicotinic receptors, causing either depolarization or non-depolarization.
• Depolarizing agents (e.g., succinylcholine):
  • Cause sodium influx and potassium efflux, leading to muscle effects.
• Non-depolarizing agents: Antagonize the nicotinic receptor without causing depolarization.

Classes of Muscle Relaxants

Depolarizing Agents

• Succinylcholine:
  • Acts as a partial nicotinic receptor agonist.
  • Phase 1: Causes depolarization and muscle fasciculations (twitches).
  • Phase 2: Receptors desensitize, leading to muscle paralysis.
  • Side effects:
    • Hyperkalemia.
    • Malignant hyperthermia (caused by uncontrolled calcium release from sarcoplasmic reticulum).
    • Muscle twitches (fasciculations).
  • Antidote for Phase 2: Acetylcholinesterase inhibitors such as Pyridostigmine or Neostigmine (not Physostigmine).

Non-depolarizing Agents

• Kirari-like agents (suffix -curium):
  • Cisatracurium:
    • Safe choice with long duration.
    • Plasma clearance, no renal or hepatic dose adjustment needed.
    • No histamine release (safe for asthmatic patients).
  • Mivacurium:
    • Short duration.
    • Requires dose adjustment for renal or liver failure.
    • Histamine release (risk of bronchospasm).
  • Atracurium: Similar to Cisatracurium but less safe.
• Amino steroids (suffix -curonium):
  • Pancuronium: Muscarinic blockade leading to increased heart rate and blood pressure; renally cleared.
  • Rocuronium: Known for rapid onset.
  • Vecuronium: Standard option without much to note.

Practice Questions

Question 1

• Scenario: Patient needs mechanical ventilation, experiences muscle twitches shortly after drug administration.
• Likely drug: Succinylcholine (causes muscle fasciculations due to depolarization phase).
• Answer: C - Depolarizing agent (succinylcholine).

Question 2

• Scenario: Patient with allergies, asthma, and chronic tachycardia needs a muscle relaxant without malignant hyperthermia risk.
• Considerations:
  • Avoid succinylcholine (risk of malignant hyperthermia).
  • Avoid mivacurium (histamine release causes bronchospasm).
  • Avoid pancuronium (muscarinic block causes elevated heart rate and blood pressure).
• Safe option: Cisatracurium.
• Answer: C

Conclusion

• For depolarizing agents, focus on succinylcholine and its unique properties (phases, side effects, antidote).
• For non-depolarizing agents, distinguish between kirari-like agents and amino steroids based on suffix and side effect profile.