Pharmacology Shanbhag-4e: Centrally Acting Muscle Relaxants

Centrally Acting Skeletal Muscle Relaxants

• Most centrally acting skeletal muscle relaxants are available in combination with nonsteroidal anti-inflammatory drugs (NSAIDs).
• They cause certain degree of sedation.
• They act by depressing polysynaptic pathways in spinal and supra-spinal sites.
• They are used to reduce spasm associated with cerebral palsy, trauma, sprain, tetanus, multiple sclerosis, etc.

Characteristics of Centrally Acting Skeletal Muscle Relaxants

• Baclofen: GABAB agonist, used in spinal cord lesions, multiple sclerosis, and amyotrophic lateral sclerosis.
• Diazepam and other benzodiazepines: GABAA agonists, used in multiple sclerosis, spinal cord injury or disease.
• Tizanidine: Central a2-agonist, used in multiple sclerosis, spinal cord injury or disease.
• Chlorzoxazone and methocarbamol: Act on spinal interneurons, used in acute muscle spasm due to trauma.
• Riluzole: Inhibits glutamate release, used in amyotrophic lateral sclerosis.
• Carisoprodol: Mechanism of action not clearly known, used in muscle sprain.
• Thiocolchicoside: Block release of excitatory transmitter in the spinal cord, used in sprain, muscle spasm due to trauma.

Neuromuscular Blockers

• They interfere with neuromuscular transmission, do not affect CNS and are administered intravenously.
• Include nondepolarizing (competitive) and depolarizing blockers.

Depolarizing Blockers: Succinylcholine (Suxamethonium)

• A quaternary ammonium compound, structure resembles two molecules of ACh linked together.
• Acts as a partial agonist at NM receptors, causing initial fasciculations and later flaccid paralysis due to prolonged depolarization (phase I block).
• With continued exposure, the membrane becomes desensitized, leading to phase II block, which resembles the nondepolarizing block and is partially reversed by anti-cholinesterases.
• Adverse effects:
  • Muscle pain due to initial fasciculations.
  • Increased IOP due to contraction of external ocular muscles.
  • Aspiration of gastric contents may occur due to increased intragastric pressure.
  • Hyperkalaemia due to fasciculations releasing K+ into the blood.
  • Sinus bradycardia due to vagal stimulation.
  • SCh apnoea (prolonged apnoea).
  • Malignant hyperthermia, especially when used with halothane in genetically susceptible individuals.
• Rapidly hydrolysed by pseudocholinesterase, hence has a very short duration of action (3-8 minutes).
• Transient apnoea is usually seen at the peak of its action.
• In people with liver disease or atypical pseudocholinesterase, the metabolism of SCh becomes slow, leading to severe neuromuscular blockade and respiratory paralysis with prolonged apnoea.