Neuromuscular Junction and Blockade Lecture Notes

Overview of Neuromuscular Junction

• Intersection between a muscle fiber and a nerve.
• Contains presynaptic nerve terminal and postsynaptic membrane.
• Key components:
  • Acetylcholine (ACh): Neurotransmitter released from the presynaptic terminal.
  • Nicotinic Acetylcholine Receptor: Located on the postsynaptic membrane.

Normal Physiology

• ACh is released and binds to nicotinic receptors, generating an action potential.
• Action potential aids muscle contraction, essential for normal movement and muscle tone.

Neuromuscular Blockers

• Non-depolarizing blockers: Inhibit nicotinic receptors without depolarizing them, causing a quick fade in muscle activity.
• Depolarizing blockers: Stimulate nicotinic receptors continuously, causing an initial sustained action followed by a fade as the muscle tires.

Examples

• Non-depolarizing: Ends in "-curium" (e.g., rocuronium).
• Depolarizing: Example is succinylcholine.

Mechanisms of Action

Non-depolarizing Neuromuscular Blockers

• Occupy nicotinic receptors, preventing ACh from binding.
• Result in fading muscle activity.
• Antidote: Acetylcholinesterase inhibitors increase ACh levels.

Depolarizing Neuromuscular Blockers

• Constantly stimulate nicotinic receptors, leading to:
  • Phase 1: Constant but diminished activity.
  • Phase 2: Fading activity.
• No antidote for Phase 1.

Key Side Effects of Depolarizing Blockers

1. Fasciculations: Muscle twitches due to constant receptor stimulation.
2. Hyperkalemia: Risk increased in patients with tissue damage or burns.
3. Malignant Hyperthermia: Can occur with depolarizing agents.

Diseases Affecting Neuromuscular Junction

Lambert-Eaton Syndrome

• Caused by destruction of presynaptic calcium channels.
• Associated with small cell lung cancer.

Botulism

• Interferes with ACh release.
• Associated with eating honey.

Myasthenia Gravis

• Autoimmune attack against postsynaptic nicotinic receptors.
• Associated with thymoma.

Key Differences

• Lambert-Eaton: Presynaptic issue (calcium channels).
• Myasthenia Gravis: Postsynaptic issue (nicotinic receptors).
• Both are type 2 hypersensitivity reactions.
• Associations are important for diagnosis on tests.

Mnemonics

• Depolarizing: "Sucks" refers to succinylcholine, which can cause significant side effects and exhausts receptor activity.
• Non-depolarizing: "Curium" drugs are "curious" as they don't stimulate receptor action, only cause fade.

Final Notes

• Understand differences between depolarizing and non-depolarizing agents.
• Be aware of side effects and treatment strategies.
• Recognize associated diseases and their characteristics for exams.
• Review symptoms of neuromuscular disorders independently.