Anti-spasticity Drugs
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Direct answer
Spasticity differs from a simple muscle spasm — it is velocity-dependent hypertonia from upper motor neuron disinhibition — so its drugs must be matched to the site of the lesion: baclofen (GABA-B agonist, 5 mg titrated up to about 80 mg daily) works best for spinal-origin spasticity, tizanidine (central alpha-2 agonist) suits both spinal and cerebral tone with sedating hypotension, dantrolene acts directly on skeletal muscle (ryanodine receptor) making it lesion-agnostic but globally weakening, and botulinum toxin A delivers focal chemistry to the overactive muscle. The safety rim around this class is what exams love: abrupt baclofen withdrawal causes seizures and hallucinations, tizanidine is hepatotoxic and metabolised by CYP1A2 (fluvoxamine and ciprofloxacin interactions), and dantrolene carries chronic hepatotoxicity requiring enzyme monitoring.
What you must remember
- Baclofen: GABA-B receptor agonist reducing excitatory transmitter release in the cord; start 5 mg three times daily, usual ceiling 80 mg/day (intrathecal pump for refractory cases, test-dose first); adverse effects — sedation, and withdrawal seizures with hallucinations if stopped abruptly (the pump patient is the high-risk one).
- Tizanidine: alpha-2 agonist reducing spinal interneuron excitability; 2-4 mg at night titrated to 36 mg/day max; dry mouth, sedation, hypotension (advantageous in hypertensives), rebound hypertension on abrupt stop; hepatotoxic — LFTs at baseline and monthly for three months; CYP1A2 metabolism means ciprofloxacin and fluvoxamine multiply levels several-fold.
- Dantrolene: direct ryanodine receptor (RyR1) blocker in skeletal muscle — the only peripherally acting oral agent, hence useful across lesions but causing generalised weakness; hepatotoxicity with chronic use; the same molecule treats malignant hyperthermia at 2.5 mg/kg IV.
- Botulinum toxin A: focal chemodenervation (SNARE cleavage at the neuromuscular junction) for adductor spasticity, equinus foot, post-stroke upper limb; effect peaks about two weeks, wears off about three months; antibody-mediated failure follows high-frequency high-dose use.
- Adjuncts: diazepam (GABA-A, night spasms in spinal injury; dependence limits use), gabapentin/pregabalin, clonidine; cannabinoid oromucosal spray (nabiximols) for multiple sclerosis spasticity in some countries.
- Physiotherapy is the base layer: stretching, casting and positioning; drugs that sedate or weaken can defeat functional spasticity that the patient is using as a crutch — the examinable "treat the disability, not the tone" principle.
A worked ward round
A 34-year-old with a C6 spinal cord injury has painful nocturnal flexor spasms and adductor tone interfering with catheterisation. The ladder: positioning and stretching first; baclofen 5 mg three times daily titrated every few days to 10 mg three times daily, spasms settle and sleep improves. When later tone escalates despite 80 mg, the discussion is intrathecal baclofen — a 50-microgram test dose via lumbar puncture predicting pump response. Contrast the stroke patient with a spastic hemiplegic arm: systemic drugs would sedate without helping gait, so botulinum toxin into biceps, flexor carpi radialis and finger flexors targets the problem, with therapy to stretch the newly relaxed muscles — and the cerebral palsy child mixes both worlds (focal botulinum plus night baclofen or diazepam).
The third comparator is the multiple sclerosis patient on tizanidine who returns confused and hypotensive after a course of ciprofloxacin for a urinary infection — CYP1A2 inhibition raising tizanidine levels several-fold; the answer is dose reduction during the antibiotic, not discontinuation.
Where the exam frames it
Site-of-action matching is the core stem: spinal spasticity (baclofen first), cerebral origin spasticity (often tizanidine or diazepam; baclofen less effective), focal pattern (botulinum), malignant hyperthermia or heat-stroke-like rigidity (dantrolene by ryanodine blockade). Adverse-effect matching supplies the second family: withdrawal seizures (baclofen), hepatotoxicity (tizanidine, dantrolene), sedation-hypotension-dry mouth (tizanidine), generalised weakness (dantrolene), and the CYP1A2 interactions of tizanidine — a pharmacokinetics favourite. Mechanism one-liners: baclofen GABA-B, diazepam GABA-A, dantrolene ryanodine, botulinum SNARE cleavage; examiners routinely scramble these pairings across options. Indian practice notes: baclofen and tizanidine are inexpensive and ubiquitous, botulinum toxin access concentrates in urban neurology and PMR units with cost as the rate-limiter, and intrathecal pumps are limited to a handful of centres — so titration discipline and physiotherapy integration matter even more.
Frequently asked questions
Which anti-spasticity drug is preferred for spinal-origin spasticity?
Baclofen, a GABA-B agonist acting on spinal cord inhibitory systems — titrated to effect with intrathecal delivery for refractory cases, never stopped abruptly because withdrawal seizures and hallucinations follow.
Why does dantrolene work regardless of the lesion site?
It blocks ryanodine receptors on skeletal muscle sarcoplasmic reticulum directly, uncoupling excitation-contraction peripherally — lesion-agnostic, at the price of generalised muscle weakness.
Which interaction can dangerously raise tizanidine levels?
CYP1A2 inhibitors — ciprofloxacin and fluvoxamine — can multiply tizanidine exposure severalfold, causing hypotension and sedation; dose reduction is required during the antibiotic course.
How does botulinum toxin reduce focal spasticity?
The heavy chain binds cholinergic terminals and the light chain cleaves SNARE proteins, blocking acetylcholine release and chemically denervating the injected muscle for roughly three months.
What happens if baclofen is abruptly withdrawn?
Rebound hyperexcitability — seizures, hallucinations, and marked spasticity rebound, classically after intrathecal pump failure — so tapering is mandatory and pump patients need urgent refill management.