The skeletal muscle relaxants are a diverse class of drugs that are used for treating painful muscle spasticity or spasms, which can substantially affect a patient’s ability to function (Table 1). About 2 million people annually report using muscle relaxants, with about 15% being elderly. The muscle relaxant class is a heterogeneous group of agents, with individual differences in drug interactions, comorbidity considerations, and ADEs. (Adverse Drug Effects)
These agents are categorized as either antispasmodics or antispasticity agents:
The antispasmodics are either benzodiazepines (eg, diazepam) or nonbenzodiazepines (eg, cyclobenzaprine) and are used for muscular pain and spasms associated with peripheral musculoskeletal conditions.
The antispasticity agents reduce hypertonicity associated with upper motor neuron disorders like multiple sclerosis and cerebral palsy.
Agents that fall into this category act at the spinal cord or supraspinal level. Well-controlled clinical studies have not conclusively demonstrated whether relief of musculoskeletal pain by cyclobenzaprine, carisoprodol, chlorzoxazone, metaxalone, or methocarbamol results from skeletal muscle relaxant effects, sedative effects, or a placebo effect of the drug
chlorzoxazone works primarily in the spinal cord and subcortical areas of the brain. As mentioned previously, there is little data supporting the effectiveness of this agent for musculoskeletal pain and spasm
Metaxalone and Methocarbamol
The mechanism of action of both metaxalone and methocarbamol are unknown but are likely due to their general CNS depressant effects. Despite this, metaxalone seems to have less sedation than other muscle relaxants, and little abuse potential.5 It has been shown to cause anemia so it is contraindicated in patients with any type of anemia, as well as any patient with liver or kidney compromise.
It is metabolized via several hepatocellular cytochrome P450 (CYP450) enzyme families; however, it has not been shown to be an inducer or an inhibitor.
Orphenadrine is similar in structure to diphenhydramine [generic Benadryl] and its effects are thought to be due to its anticholinergic properties.
This is also the mechanism of its adverse effects, including sedation, urinary retention, dry mouth, and constipation.
Carisoprodol and Soma Compound (containing carisoprodol and aspirin) have been prescribed for many years for acute back pain. Carisoprodol’s pharmacologic activity is γ-aminobutyric acid (GABA)ergic, with activity at the GABAA receptor
However, because it is metabolized to meprobamate, a sedative/hypnotic similar to barbiturates, there is concern about misuse and abuse.
The FDA recommends only short-term use (2 to 3 weeks after an acute injury). Zacny and colleagues found that at therapeutic doses, subjects noted little efficacy but had psychomotor impairment.
Due to its lack of efficacy and potential for abuse, many institutions do not have it available on their formularies
Cyclobenzaprine’s therapeutic effect is centrally mediated, and it has no direct peripheral action on the affected muscles. It functions primarily at supraspinal levels and not in the spinal cord.
Tizanidine is a centrally acting α2-agonist and is thought to act by increasing presynaptic inhibition of neuronal activity. Several studies have shown the effectiveness of tizanidine as monotherapy and in conjunction with NSAIDs in the treatment of acute low back pain with associated muscle spasm, as well as myofascial pain
Tizanidine is pharmacologically similar to clonidine, but it has less potent hypotensive effects
Postmarketing surveillance has also shown liver transaminases as high as 3 times the upper limit of normal in 5% of patients.
Other adverse effects include sedation in up to 48% of patients and hallucinations
Tizanidine clearance is significantly reduced when used in combination with oral contraceptives, ciprofloxacin, fluvoxamine, and other CYP450 1A2 inhibitors
Baclofen is an analog of GABA and is an agonist at the GABAB receptor
Baclofen is a versatile agent, and may be used intrathecally in patients with extensive spasticity, as with cerebral palsy. However, when used in high doses, baclofen can cause seizures, ataxia, and hallucinations
Abrupt withdrawal of baclofen should be avoided because it can precipitate seizures and hallucinations
Although benzodiazepines are not FDA approved for spasms or spasticity, this class of medications is effective in treating both muscle spasms and spasticity.
Benzodiazepines primarily work on the benzodiazepine receptors on the postsynaptic GABAA receptors in the spinal cord and higher motor centers in the brain
Several benzodiazepines have been utilized for the short-term relief (1 to 2 weeks) of muscular flare-ups due to chronic musculoskeletal pain. Benzodiazepines without active metabolites (lorazepam, clonazepam, temazepam, and oxazepam) may be considered for short-term use in the elderly and in patients with liver or kidney insufficiency.
The greatest risk with these agents is that of respiratory depression, particularly when used with opioids or alcohol. Withdrawal symptoms may occur after abruptly stopping benzodiazepines.
Dantrolene (Dantrium), which inhibits the release of calcium from the sarcoplasmic reticulum, does not directly affect the CNS. Though dantrolene has been found to be equally effective as the antispasticity agents, there are some significant safety concerns with this agen
The FDA has required a black-box warning for this agent due to the risk of sometimes fatal hepatic toxicity.
Muscle relaxants are a class of drugs that contain individual differences in ADEs, drug interactions, and comorbidity considerations. The antispasmodics and antispasticity agents in this drug class have the potential to cause various undesired effects, which providers need to understand in order to effectively manage the patient’s pain and minimize complications.