Neuromuscular Junction and Blockade

Overview

• Neuromuscular Junction: Intersection between nerve and muscle fiber.
  • Comprises presynaptic and postsynaptic areas.
  • Connects neuron to muscle.

Key Components

• Acetylcholine (ACh): Neurotransmitter in red circles.
• Nicotinic Acetylcholine Receptor: Receptor on the postsynaptic membrane shown as red diamonds.

Normal Physiology

• Acetylcholine is released from presynaptic terminal.
• Binds to nicotinic receptor on postsynaptic membrane.
• Generates action potential, leading to muscle contraction.

Neuromuscular Blockers

• Non-Depolarizing Neuromuscular Blockers

  • Bind to nicotinic receptor and inhibit it by occupying it.
  • Result in a fade of activity, blocking impulses.
  • Mechanism involves preventing receptor depolarization.

• Depolarizing Neuromuscular Blockers

  • Bind to nicotinic receptor and constantly stimulate it.
  • Cause continuous action potential, leading to initial strong but then fading response.
  • Two phases: constant but diminished activity, then fade.

Differences Between Blockers

• Depolarizing Neuromuscular Blockers

  • Phase 1: Constant but diminished action.
  • Phase 2: Fade of activity.
  • Example: Succinylcholine
  • No antidote for Phase 1.
  • Side effects: Fasciculations, hyperkalemia, malignant hyperthermia.

• Non-Depolarizing Neuromuscular Blockers

  • Only have the fading activity phase.
  • End with '-curium'.
  • Antidote: Acetylcholinesterase inhibitors.

Mnemonic

• Depolarizing: "Sucks" (Succinylcholine)
  • Sucks: Fasciculations, hyperkalemia, rhabdomyolysis, malignant hyperthermia.
• Non-Depolarizing: "ND Curium"
  • ND: Non-depolarizing.
  • Curium: Agents ending in '-curium'.

Pathology at the Neuromuscular Junction

• Calcium Channels: Essential for vesicle release of neurotransmitters.
• Diseases:
  • Lambert Eaton Syndrome: Presynaptic calcium channel issue.
    • Associated with small cell lung cancer.
  • Botulism: Problem with acetylcholine release.
    • Associated with eating honey.
  • Myasthenia Gravis: Autoimmune attack on postsynaptic receptors.
    • Associated with thymoma.

Key Differences

• Lambert Eaton Syndrome: Presynaptic issue, calcium channel destruction.
  • Type 2 hypersensitivity reaction.
• Myasthenia Gravis: Postsynaptic nicotinic receptor issue.
  • Type 2 hypersensitivity reaction.
• Botulism: Caused by heat-labile enterotoxin.

Summary

• Understand the normal physiology and the effects of neuromuscular blockers.
• Remember the differences between depolarizing and non-depolarizing neuromuscular blockers.
• Recognize associated diseases and their underlying mechanisms.
• Use mnemonics for memorization and test preparation.