Skeletal Muscle Relaxants Overview

Skeletal Muscle Relaxants

  • Definition: Drugs that cause skeletal muscle paralysis.

    • Types:

    • Non-depolarizing agents

    • Depolarizing agents

  • Uses:

    • Facilitate emergency and elective intubation

    • Surgical relaxation

    • Treat tetanus

    • Adjunct to ventilator patients

History and Development

  • Curare:

    • Type: Non-depolarizing agent

    • Mechanism: Competition with acetylcholine (ACh) for receptor site.

    • Origin: Used by South American indigenous people; plant-derived.

    • Identified: 1935, first surgical use in 1942.

  • Succinylcholine:

    • Type: Depolarizing agent

    • Mechanism: Block ACh receptor site.

Uses of Neuromuscular Blockers (NM blockers)

  • Applications:

    • Endotracheal intubation

    • Muscle relaxation during surgery, particularly in abdominal and thoracic procedures

    • Enhance carbon dioxide (CO2) removal in challenging ventilation cases

    • Reduce intracranial pressure (ICP) in intubated patients with uncontrolled ICP

Physiology of Neuromuscular Junction

  • Peripheral Nervous System:

    • Composed of:

    • Autonomic nervous system: Controls smooth muscle (non-striated)

      • Affects bronchioles, heart, arterioles, venules

    • Somatic motor system: Controls striated muscle

      • Includes quadriceps, biceps, diaphragm

    • Neurotransmitter: ACh is the neurotransmitter in all somatic motor nerves and some autonomic ganglia.

  • Muscle Control:

    • Movement and breathing are under voluntary control.

Normal Action of Acetylcholine (ACh) and Receptors

  • Mechanism:

    • Nerve impulses travel to the end of the motor neuron.

    • ACh released into the synapse:

    • Binds to receptors on muscle fiber membrane.

    • End plate potential generated if enough receptors are activated:

      • Depolarization:

      • Muscle membrane becomes permeable to Na,

      • Reversal of interior/exterior potential leading to rise in membrane potential,

      • Muscle action potential propagates in both directions,

      • Triggers release of intracellular calcium, leading to actin and myosin interaction and muscle contraction.

      • Refractory Phase – Repolarization:

      • Membrane potential returns,

      • Na conductance is blocked,

      • K exchanged for Na,

      • Calcium returns to the sarcoplasmic reticulum; muscle is ready for another depolarization.

      • ACh diffuses out of synaptic gutter.

      • Inactivated by ACh esterase.

Action of Neuromuscular Blockers

  • Mechanism:

    • Competitive inhibition:

    • Non-depolarizing agents bind to and block ACh receptors without depolarizing.

    • Prolonged occupation and persistent activation leads to a depolarizing effect in depolarizing agents.

Non-Depolarizing Agents

  • Characteristics:

    • Similar action to curare.

    • Mechanism: Competitive inhibition of ACh at muscle receptor

    • Note: Depolarization does not occur.

    • Dosage Considerations:

    • Dose-dependent effects; larger doses lead to quicker blockage and longer effect.

    • Requires reversal by increasing ACh availability using Neostigmine (ACh esterase inhibitor).

    • Side Effects:

    • Blockage of autonomic ganglia can lead to vagolytic effects:

      • Tachycardia,

      • Increase in mean arterial pressure (MAP) due to unopposed sympathetic activity.

    • Histamine release from mast cells:

      • All non-depolarizing agents provoke histamine release; Vecuronium is noted to have the least side effects.

Depolarizing Agents

  • Mechanism:

    • Different action: Initial depolarization occurs, remaining refractory.

    • Effects:

    • Muscle contraction (fasciculation) followed by flaccid paralysis (phase 1 block).

    • ACh receptor sites are occupied and activated.

    • Continued occupancy activates prevents repolarization.

    • Example: Succinylcholine – 1-1.5 mg/kg leads to:

      • Total paralysis in 60-90 seconds,

      • Duration of 10-15 minutes.

    • Reversal: Not possible via ACh esterase inhibitors; instead, they prolong depolarization.

    • Side Effects:

    • Muscle pain/soreness; treatment with a small dose of non-depolarizing agents (defasciculation) may be necessary along with higher doses of succinylcholine.

    • Efflux of potassium (K) can cause hyperkalemia.

    • Increased intraocular pressure.

    • Sensitivity issues due to variations in acetylcholinesterase affecting the hydrolysis of succinylcholine.