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Skeletal muscle relaxants

Last updated: November 4, 2020

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Skeletal muscle relaxants are drugs that block the neuromuscular junction (NMJ) by binding to acetylcholine (ACh) receptors located on it. This process leads to paralysis of all skeletal muscles, starting with the small muscles of the face and paralyzing the diaphragm last. Succinylcholine, the only depolarizing NMJ-blocking drug, binds to ACh receptors and causes a prolonged depolarization of the motor end plate, resulting in flaccid paralysis. Nondepolarizing NMJ-blocking drugs bind to the ACh receptors and prevent depolarization of the motor end plate (depolarization block). These drugs are subdivided into short-acting, intermediate-acting, and long-acting agents. Based on the duration of action, NMJ-blocking drugs are useful adjuncts to anesthetic agents and are, therefore, used for laryngeal intubation, artificial ventilation, or intraoperative skeletal muscle relaxation. All NMJ-blocking drugs cause respiratory arrest (apnea) by paralyzing the diaphragm and intercostal muscles, requiring patients to be artificially ventilated. Succinylcholine is a known trigger of malignant hyperthermia and can also cause hyperkalemia, postoperative muscle pain, and cardiac arrhythmias. Nondepolarizing drugs that cause histamine release (atracurium) or have sympathomimetic properties (pancuronium) can cause bronchospasms and tachycardia. Patients who have received NMJ-blocking drugs must be monitored either clinically (e.g., ability to lift head/legs or open eyes) or with a peripheral nerve stimulator to assess the degree of skeletal muscle paralysis. Antagonists to nondepolarizing drugs (neostigmine, pyridostigmine, sugammadex) are used to reverse the NMJ block. Inadequate reversal can cause respiratory complications. Succinylcholine does not have a specific antagonist.

Depolarizing NMJ blockers (depolarizing muscle relaxants)
Time until onset of effect Duration of action Elimination Characteristics

Succinylcholine

  • ∼ 60 seconds
  • 5–10 min
Nondepolarizing NMJ blockers (nondepolarizing muscle relaxants)
Short-acting

Mivacurium

  • 2–4 min
  • 15–25 min
  • 90%: enzymatic hydrolysis
  • < 10%: hepatic clearance
Intermediate-acting

Rocuronium

  • 1–3 min
  • 60–90 min
  • 70% hepatic
  • 30% renal
  • Used for rapid-sequence induction of anesthesia when succinylcholine is contraindicated (second fastest acting muscle relaxant)
  • Does not cause histamine release (see “Side effects” below)
  • Specifically antagonized by sugammadex
Atracurium
  • 2–3 min
  • 45–60 min
  • 60%: enzymatic hydrolysis
  • 30%: Hoffmann elimination
  • Ideal for patients with renal and hepatic insufficiency
  • Causes histamine release
Cisatracurium
  • 3–5 min
  • 45–60 min
  • Ideal for patients with renal and hepatic insufficiency
  • Does not cause histamine release
Vecuronium
  • 2–3 min
  • 60–90 min
  • 70% hepatic
  • 30% renal
Long-acting Pancuronium
  • 3–5 min
  • 90–120 min
  • 70% renal
  • 30% hepatic
  • Used if skeletal muscle paralysis > 1 hour is required
  • Cardiovascular side effects are common
Tubocurarine
  • ∼ 5 min
  • 60–120 min
  • ∼ 75% renal
  • ∼ 25% hepatic
  • Respiratory side effects are common

References:[1][2][3][4][5][6][7]

Depolarizing and nondepolarizing muscle relaxants only target Nm nicotinic receptors at the NMJ; they do not target autonomic Nn receptors.

Depolarizing muscle relaxants

Nondepolarizing muscle relaxants

Paralysis affects the small muscles of the face first, progresses to the extremities and trunk, and affects the intercostal muscles and diaphragm last.
References:[4][8][9][10]

Depolarizing NMJ blocker (succinylcholine)

Nondepolarizing NMJ blockers

References:[4][8][10][13][14][15][16][17][18]

We list the most important adverse effects. The selection is not exhaustive.

References:[3]

  1. Rocuronium Bromide. https://www.drugs.com/ppa/rocuronium-bromide.html. Updated: February 18, 2017. Accessed: February 18, 2017.
  2. Wright PM, Caldwell JE, Miller RD. Onset and duration of rocuronium and succinylcholine at the adductor pollicis and laryngeal adductor muscles in anesthetized humans. Anesthesiology. 1994; 81 (5): p.1110-1115.
  3. Tietze KJ. Use of Neuromuscular Blocking Medications in Critically Ill Patients. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/use-of-neuromuscular-blocking-medications-in-critically-ill-patients.Last updated: October 25, 2016. Accessed: February 18, 2017.
  4. Neuromuscular Blockers. http://www.pharmacology2000.com/Central/NMJ/NMJobj1.htm. Updated: February 18, 2017. Accessed: February 18, 2017.
  5. Succinylcholine Chloride. https://www.drugs.com/monograph/succinylcholine-chloride.html. Updated: January 1, 2018. Accessed: March 7, 2018.
  6. Singh D, Sivashanmugam T, Kumar H, Nag K, Parthasarathy S, Shetti A. Sugammadex: A revolutionary drug in neuromuscular pharmacology. Anesth Essays Res. 2013; 7 (3): p.302. doi: 10.4103/0259-1162.123211 . | Open in Read by QxMD
  7. Kunjappan VE, Brown EM, Alexander GD. Rapid sequence induction using vecuronium. Anesth Analg. 1986; 65 (5): p.503-6.
  8. Harvey RA, Champe PC, Finkel R, Clark MA, Cubeddu LX. Lippincott's Illustrated Reviews: Pharmacology. Lippincott Williams & Wilkins ; 2008
  9. Naguib M, Brull SJ. Sugammadex: a novel selective relaxant binding agent. Expert Rev Clin Pharmacol. 2009; 2 (1): p.37-53. doi: 10.1586/17512433.2.1.37 . | Open in Read by QxMD
  10. Appiah-Ankam J, Hunter JM. Pharmacology of neuromuscular blocking drugs. Contin Educ Anaesth Crit Care Pain. 2004; 4 (1): p.2-7. doi: 10.1093/bjaceaccp/mkh002 . | Open in Read by QxMD
  11. Kulkarni L, Sanikop C, Shilpa H, Vinayan A. Anaesthetic management in a patient with multiple sclerosis. Indian Journal of Anaesthesia. 2011; 55 (1): p.64. doi: 10.4103/0019-5049.76598 . | Open in Read by QxMD
  12. Chandy T, Nandhakumar A, Thampi S, David D. Anesthetic management of a patient with amyotrophic lateral sclerosis for transurethral resection of bladder tumor. Indian Journal of Anaesthesia. 2013; 57 (2): p.197. doi: 10.4103/0019-5049.111863 . | Open in Read by QxMD
  13. . Pseudocholinesterase Deficiency. Pseudocholinesterase Deficiency. New York, NY: WebMD. http://emedicine.medscape.com/article/247019-overview. Updated: September 26, 2016. Accessed: February 18, 2017.
  14. Naguib M, Magboul MM. Adverse Effects of Neuromuscular Blockers and Their Antagonists. Drug Saf. 1998; 18 (2): p.99-116.
  15. Huggins RM, Kennedy WK, Melroy MJ, Tollerton DG. Cardiac arrest from succinylcholine-induced hyperkalemia. Am J Health Syst Pharm. 2003; 60 (7): p.694-697.
  16. Meakin GH. Neuromuscular blocking drugs in infants and children. Contin Educ Anaesth Crit Care Pain. 2007; 7 (5): p.143-147. doi: 10.1093/bjaceaccp/mkm032 . | Open in Read by QxMD
  17. Moss J. Muscle relaxants and histamine release. Acta Anaesthesiol Scand Suppl. 1995; 106 : p.7-12.
  18. Pharmacology of Muscle Relaxants and their Antagonists.