Neuromuscular blockers

NMJ & Succinylcholine - Shock and Block

• Physiology: At the neuromuscular junction (NMJ), Acetylcholine (ACh) binds to nicotinic receptors (nAChR) on the motor end plate, causing depolarization → muscle contraction.

• Succinylcholine: A depolarizing neuromuscular blocker composed of two linked ACh molecules. Its action occurs in two phases:
  • Phase I (Depolarizing Block): Binds nAChR, causing persistent depolarization. This leads to initial muscle fasciculations (the "shock"), followed by flaccid paralysis as Na+ channels inactivate (the "block"). Cholinesterase inhibitors potentiate this phase.
  • Phase II (Desensitizing Block): With prolonged exposure, the membrane repolarizes, but nAChRs become desensitized to ACh. This block resembles that of non-depolarizing agents and can be reversed by cholinesterase inhibitors.

⭐ Succinylcholine is a major trigger for malignant hyperthermia and can cause severe hyperkalemia in patients with burns, crush injuries, or denervation (due to nAChR upregulation).

Non-Depolarizers & Reversal - The Competitive Crew

• Mechanism: Competitive antagonists at the neuromuscular junction (NMJ) nicotinic ACh receptors (nAChR), preventing ACh binding.
• Agents: Suffix -curonium or -curium (e.g., Rocuronium, Vecuronium, Atracurium, Cisatracurium).
• Effect: Induces flaccid paralysis. Effects are reversible and can be overcome by increasing synaptic ACh.
  • Order of paralysis: Eyes/face → limbs/trunk → intercostals → diaphragm. Recovery occurs in reverse order.
• Reversal:
  • AChE Inhibitors: Neostigmine or Edrophonium increase ACh to outcompete the blocker.
  • ⚠️ To prevent systemic muscarinic effects (bradycardia, salivation), co-administer with an antimuscarinic like Glycopyrrolate or Atropine.
  • Sugammadex: Directly encapsulates and inactivates Rocuronium and Vecuronium.

⭐ Atracurium and Cisatracurium are cleared by Hofmann elimination (spontaneous degradation in plasma), making them ideal for patients with renal or hepatic failure.

Adverse Effects & Monitoring - Twitches and Trouble

• All NMBs: Respiratory paralysis (requires mechanical ventilation), apnea.

• Succinylcholine (Depolarizing):

  • Hyperkalemia: ⚠️ Risk in burn, crush injury, or neuromuscular disease patients (upregulated nAChRs). Can cause cardiac arrest.
  • Malignant Hyperthermia: Especially with halothane. Treat with dantrolene.
  • Muscle pain/fasciculations, ↑ intraocular/intragastric pressure.

• Non-depolarizing Agents:

  • Histamine release: Atracurium, mivacurium → hypotension, flushing, bronchospasm.
  • Cardiovascular: Pancuronium (vagolytic) → tachycardia. Tubocurarine → hypotension.

• Monitoring (Train-of-Four Stimulation):

  • Peripheral nerve stimulator assesses twitch response.
  • Non-depolarizing: Fade response (successive twitches weaken). TOF ratio < 0.9.
  • Depolarizing: Phase I (constant but diminished response), Phase II (fade).

⭐ Succinylcholine is contraindicated >48 hours after major burns, crush injuries, or denervation due to the risk of life-threatening hyperkalemia from receptor upregulation.

High‑Yield Points - ⚡ Biggest Takeaways

• Succinylcholine is a depolarizing blocker with two phases; risks include malignant hyperthermia and hyperkalemia.
• Non-depolarizing blockers (e.g., rocuronium) are competitive ACh antagonists, reversed by neostigmine.
• Treat malignant hyperthermia (from succinylcholine + volatile anesthetics) with dantrolene.
• Dantrolene blocks ryanodine receptor Ca²⁺ release from the sarcoplasmic reticulum.
• Atracurium and cisatracurium are cleared via Hofmann elimination, safe in organ failure.
• Sugammadex provides rapid reversal for rocuronium and vecuronium.