Skeletal Muscle Relaxants

Overview

• Also known as spasmolytics.
• Used to relax or decrease skeletal muscle tone.
• Act in two ways:
  • Centrally on the central nervous system (CNS).
  • Peripherally on the neuromuscular junction (NMJ).

Centrally Acting Skeletal Muscle Relaxants

• Mechanism of Action:
  • Depress polysynaptic pathways in spinal and supraspinal sites.
  • Involvement of upper motor neurons, lower motor neurons, and inhibitory neurons.
  • Receptors Involved:
    • Alpha 2 receptor: Autoreceptor on upper motor neuron.
    • GABA A and GABA B receptors: Present on lower and upper motor neurons.
  • Neurotransmitters:
    • Excitatory neurotransmitters: Glutamate, norepinephrine.
    • Inhibitory neurotransmitter: GABA (leads to hyperpolarization).
• Drugs Used:
  • Tizanidine: Acts on alpha 2 receptors, decreases norepinephrine release.
  • Baclofen: Acts on GABA receptors; decreases calcium influx and increases potassium exit.
  • Benzodiazepines: Increase chloride influx by acting on GABA A receptors.
  • Gabapentin: Increases GABA within the synaptic cleft.

Peripherally Acting Skeletal Muscle Relaxants

• Categories Based on Action:
  • Depolarizing Blockers:
    • Mechanism: Two phases (depolarization and desensitization).
    • Drugs: Succinylcholine, Suxamethonium, Decamethonium.
  • Non-Depolarizing Blockers:
    • Mechanism: Block nicotinic M-type receptors to prevent acetylcholine action.
    • Short-acting: Nevacurium (10-20 mins).
    • Intermediate-acting: Atracurium, Rocuronium, Vecuronium (20-35 mins).
    • Long-acting: D-tubocurarine, Doxacurium, Pancuronium (>35 mins).
  • Botulinum toxin A: Inhibits acetylcholine release, causing flaccid paralysis.

Directly Acting on Skeletal Muscle

• Dantrolene:
  • Inhibits calcium release from sarcoplasmic reticulum.
  • Used for treating malignant hyperthermia caused by anesthetics (e.g., halothane).

Important Points

• The importance of hyperpolarization in preventing muscle contraction.
• Differences between central and peripheral mechanisms.
• Specific roles of each drug and their mechanism of action.