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Author: Admin | 2025-04-28
Liver metabolism, tizanidine is relatively contraindicated in patients taking medications that require CYP1A2 metabolism. There are numerous medications that require CYP1A2 metabolism including amiodarone, mexiletine, cimetidine, famotidine, oral contraceptive medications, and fluoroquinolones.13 Of note, a small study in 1988 speculated potential protective effects of tizanidine when given in combination with nonsteroidal anti-inflammatories (NSAIDs) for acute lower back pain. The patients who received a combination of the ibuprofen and tizanidine exhibited fewer gastrointestinal side-effects than the patients who received ibuprofen and placebo. Thus, the authors speculated that tizanidine could mediate gastric mucosal protection against NSAIDs.14 Dosing of tizanidine is based on adult dosing regimens that start at 2 mg, initiated at bedtime. The dose can be repeated up to three times a day and titrated based on response and tolerance to side-effects.13Baclofen Baclofen has a similar structure as GABA and acts as a specific antagonist to GABA-B receptors. The theoretical mechanism of action of baclofen stems from inhibiting the monosynaptic and polysynaptic reflexes at the level of the spinal cord, thereby inhibiting the release of excitatory neurotransmitters.5 There is FDA approval for the use of baclofen in reversible spasticity and associated pain of spinal cord or cerebral origin. Thus, baclofen has been used for pediatric spasticity due to cerebral palsy and spinal cord injuries. Baclofen can be administered enterally or intrathecally. One of the main benefits to baclofen is that tolerance does not develop with chronic use. However, baclofen does have numerous side-effects. Baclofen can cause drowsiness, insomnia, dizziness, headaches, weakness, syncope, gastrointestinal upset, constipation, urinary retention, incontinence, paresthesia, respiratory depression, and cardiovascular depression. Baclofen can potentiate the effects of opioids, alcohol, and other central nervous system depressants. Since the bulk of baclofen is excreted unchanged in the urine, baclofen is relatively contraindicated in severe renal impairment. Baclofen can also increase blood sugars and should be used with caution in diabetics. Baclofen is considered unsafe for patients with porphyria. Since baclofen can precipitate bronchospasm, baclofen should be used with caution in asthmatics. Baclofen can cause alterations in liver function, so liver function tests should be monitored with chronic use.15While tolerance to baclofen does not develop, withdrawal from baclofen can be life threatening. There is a black box warning against abrupt discontinuation of baclofen. Withdrawal symptoms include hyperthermia, tachycardia, seizures, hallucinations, psychosis, and rebound spasticity.15 In rare circumstances, withdrawal from baclofen can cause rhabdomyolysis, multiple organ system failure, and death. To prevent withdrawal, patients on long-term baclofen therapy should be gradually weaned over several weeks before stopping the medication. Interestingly, while baclofen is widely used to treat pediatric spasticity due to cerebral palsy (CP), there remains insufficient evidence to support or refute the use of oral baclofen for CP spasticity.16,17 Thus, when
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