A large number of less well-studied, centrally active drugs (eg, carisoprodol, chlorphenesin, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine) are promoted for the relief of acute muscle spasm caused by local tissue trauma or muscle strains. It has been suggested that these drugs act primarily at the level of the brainstem. Cyclobenzaprine may be regarded as the prototype of the group. Cyclobenzaprine is structurally related to the tricyclic antidepressants and produces antimuscarinic side effects. It is ineffective in treating muscle spasm due to cerebral palsy or spinal cord injury. As a result of its strong antimuscarinic actions, cyclobenzaprine may cause significant sedation, as well as confusion and transient visual hallucinations. The dosage of cyclobenzaprine for acute injury-related muscle spasm is 20–40 mg/d orally in divided doses. This drug class carries risks of significant adverse events and abuse potential.
• d-Tubocurarine Competitive antagonist at nACh receptors, especially at neuromuscular junctions Prevents depolarization by ACh, causes flaccid paralysis •cancausehistaminereleasewith hypotension •weakblockofcardiacmuscarinic ACh receptors Prolonged relaxation for surgicalprocedures•supersededby newer nondepolarizing agents Renalexcretion•duration,~40–60min•Toxicities: Histamine release•hypotension•prolongedapnea • CisatracuriumSimilar to tubocurarine Like tubocurarine but lacks histamine release and antimuscarinic effects Prolonged relaxation for surgical procedures•relaxationofrespiratory muscles to facilitate mechanical ventilation in intensive care unit Not dependent on renal or hepaticfunction•duration~25–45min•Toxicities: Prolonged apnea but less toxic than atracurium • RocuroniumSimilar to cisatracurium Like cisatracurium but slight antimuscarinic effect Likecisatracurium•usefulinpatients with renal impairment Hepaticmetabolism•duration~20–35min•Toxicities: Like cisatracurium • Vecuronium: Intermediate duration; metabolized in liver • Cyclobenzaprine Poorly understood inhibition of muscle stretch reflex in spinal cord
Acute spasm due to muscle injury
Hepatic metabolism • duration, ~4–6 h • Toxicities: Strong antimuscarinic effects • Chlorphenesin, methocarbamol, orphenadrine, others: Like cyclobenzaprine with varying degrees of antimuscarinic effect. Class side effect: strong central nervous system depression; note carisoprodol is a schedule IV drug.
• DantroleneBlocks RyR1 Ca2+-release channels in the sarcoplasmic reticulum of skeletal muscle Reduces actin-myosin interaction •weakensskeletalmusclecontraction IV: Malignant hyperthermia •Oral:Spasmduetocerebralpalsy, spinal cord injury, multiple sclerosis IV,oral•duration4–6h•Toxicities: Muscleweakness•Blackboxwarning: hepatotoxicity • BotulinumtoxinInhibits synaptic exocytosis through clipping of vesicle fusion proteins in presynaptic nerve terminal Flaccid paralysis Upper and lower limb spasm due to cerebral palsy, multiple sclerosis; cervical dystonia, overactive bladder, migraine, hyperhidrosis Direct injection into muscle •duration2–3months•Toxicities: muscle weakness, falls DIRECT-ACTING MUSCLE RELAXANTS
Cisatracurium Generic, Nimbex
Rocuronium Generic, Zemuron