Tizanidine in the treatment of spasticity

• Tizanidine is a centrally acting alpha-2 receptor agonist and effectively works with spasticity caused by multiple sclerosis, an acquired brain injury, or a spinal cord injury (1)
• it is thought to work via the stimulation of pre-synaptic alpha-2 adrenoreceptors, and the enhancement of noradrenergic inhibition of polysynaptic reflexes. The overall effect of these actions is to reduce the facilitation of spinal motor neurons. Similarly, alpha-2 receptor-mediated inhibition of inter-neuronal activity appears to underlie tizanidine's additional anti-nociceptive and anti-convulsant activities.
  
• there is evidence that tizanidine reduces the frequency of muscle spasms and reduces spastic muscle tone
  
• the most common side effects of tizanidine are dry mouth, drowsiness and subjective muscle weakness - however muscle weakness (objective and subjective) is less common than with treatment with diazepam or baclofen
• tizanidine use requires caution in patients with hepatic impairment. Review articles on tizanidine report cases of severe hepatotoxicity, acute liver failure, and death. (2)
• creatinine and liver function tests require measurement at baseline, then one month after the maintenance dose is achieved. Periodically monitor liver function tests in patients managed with tizanidine chronically and in higher doses. (2)
• concomitant use of tizanidine with fluvoxamine or ciprofloxacin is contraindicated due to significant hypotension and increased psychomotor impairment. (3)

Reference

1. Kamen L, Henney HR, Runyan JD. A practical overview of tizanidine use for spasticity secondary to multiple sclerosis, stroke, and spinal cord injury. Curr Med Res Opin. 2008 Feb;24(2):425-39
2. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases; Jan 30, 2017. Tizanidine
3. Granfors MT et al. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clin Pharmacol Ther. 2004 Dec;76(6):598-606.