THERAPEUTICS

Brands

• Zanaflex, Sirdalud

Generic?

• Yes

Class

• α2-adrenergic agonist, muscle relaxant

Commonly Prescribed for

(FDA approved in bold)

• Acute and intermittent management of increased muscle tone related to spasticity

• Migraine prophylaxis

• Neck pain/lower back pain

• Myofascial pain

• Trigeminal neuralgia

How the Drug Works

• Central α2-adrenergic agonist (mostly at α2A receptors) that also acts at imidazoline receptors. Both α2A and imidazoline receptors are involved in the supraspinal inhibitory effects on mono- or poly-synaptic reflexes, hence reducing spasticity, which can result from neurological conditions, such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, and spinal cord injury. α2A-agonist also increases presynaptic inhibition in locus coeruleus, periaqueductal gray area, and parabrachial nucleus, hence the anesthetic responses. Both receptors are involved in sympatholytic responses

How Long Until It Works

• Hours to weeks

If It Works

• Slowly titrate to most effective tolerated dose

If It Doesn't Work

• Increase to highest tolerated dose. If ineffective, gradually reduce dose and consider alternative medications

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Botulinum toxin is effective, especially as an adjunct for focal spasticity, e.g., post-stroke or head injury affecting the upper limbs. For conditions with multiple areas of spasticity, i.e., cerebral palsy, this combination can be very useful

• May be used carefully in combination with baclofen, although additive sedation can be problematic

• Use other centrally acting muscle relaxants with caution due to potential additive CNS depressant effect

Tests

• Monitor liver and renal function at baseline and at 1, 2, and 3 months. Monitor hepatic enzymes at 6 months and periodically after that

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Related to α2 and imidazoline agonist effect, causing hypotension and increased sedation

Notable AEs

• Dry mouth, weakness, and somnolence are most common. Dizziness, hypotension, and elevation of hepatic transaminases. Hallucinations (usually visual) occur in about 3% of patients

Life-Threatening or Dangerous AEs

• Bradycardia and prolongation of QTc interval with higher doses. Tizanidine withdrawal can cause rebound hypertension