Inform patients about possible depressant effects such as drowsiness, lightheadedness, and fatigue. Advise them to avoid driving and other hazardous activities if significant impairment occurs. If they must be taken by older patients, it is essential to explain about the increased risk of falls. Teach patients and family members home safety measures to decrease fall risk such as ensuring adequate lighting and avoiding scatter rugs. Let patients know that CNS depressant effects are worsened by intake of other CNS depressants, including alcohol and first generations antihistamines. Warn patients against abrupt discontinuation to avoid withdrawal reactions.
Muscle spasm is defined as involuntary contraction of a muscle or muscle group. Muscle spasm is often painful and interferes with muscle function. Spasm can result from a variety of causes, including epilepsy, hypocalcemia, acute and chronic pain syndromes, and trauma (localized muscle injury). Discussion here is limited to spasm resulting from muscle injury.
Treatment of spasm involves physical measures as well as drug therapy. Physical measures include immobilization of the affected muscle, application of cold compresses, whirlpool baths, and physical therapy. For drug therapy, two groups of medicines are used: (1) analgesic antiinflammatory agents (e.g., aspirin) and (2) centrally acting muscle relaxants. The analgesic antiinflammatory agents are discussed in Chapter 55. The centrally acting muscle relaxants are discussed later in this chapter.
The family of centrally acting muscle relaxants consists of nine drugs: baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, diazepam, metaxalone, methocarbamol, orphenadrine, and tizanidine. All have similar pharmacologic properties, so we will consider these agents as a group.
Mechanism of Action
For most centrally acting muscle relaxants, the mechanism of spasm relief is unclear. In laboratory animals, high doses can depress spinal motor reflexes. However, these doses are much higher than those used in humans. Hence many investigators believe that relaxation of spasm results primarily from the sedative properties of these drugs and not from specific actions exerted on CNS pathways that control muscle tone.
Two drugs—diazepam and tizanidine—are thought to relieve spasm by enhancing presynaptic inhibition of motor neurons in the CNS. Diazepam promotes presynaptic inhibition by enhancing the effects of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. Tizanidine promotes inhibition by acting as an agonist at presynaptic alpha2 receptors.
Therapeutic Use
The centrally acting muscle relaxants are used to relieve localized spasm resulting from muscle injury. These agents can decrease local pain and tenderness and can increase range of motion. Benefits of treatment equal those of aspirin and the other analgesic antiinflammatory drugs. Because there are no studies to indicate the superiority of one centrally acting muscle relaxant over another, drug selection is based largely on risks versus benefits and patient response. With the exception of baclofen and diazepam, the central muscle relaxants are not useful for treating spasticity or other muscle disorders resulting from CNS pathology.
Adverse Effects
CNS Depression
All of the centrally acting muscle relaxants can produce generalized depression of the CNS. Drowsiness, dizziness, and lightheadedness are common. Patients should be warned not to participate in hazardous activities (e.g., driving) if CNS depression is significant. In addition, they should be advised to avoid alcohol and all other CNS depressants.
Hepatic Toxicity
Chlorzoxazone [Lorzone, Parafon Forte DSC], tizanidine [Zanaflex], and metaxalone [Skelaxin] can cause liver damage. Liver function should be assessed before starting treatment and periodically thereafter. If liver injury develops, these drugs should be discontinued. If the patient has preexisting liver disease, these drugs should be avoided.
Physical Dependence
Chronic, high-dose therapy can cause physical dependence, manifesting as a potentially life-threatening abstinence syndrome if these drugs are abruptly withdrawn. Accordingly, withdrawal should be done slowly.
Other Adverse Effects
Carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, orphenadrine, and tizanidine have significant anticholinergic properties and hence may cause dry mouth, blurred vision, photophobia, elevated heart rate, urinary retention, and constipation. Methocarbamol may turn urine brown, black, or dark green; patients should be forewarned of this harmless effect. Tizanidine can cause dry mouth, hypotension, hallucinations, and psychotic symptoms. Carisoprodol can be hazardous to patients predisposed to intermittent porphyria, so it is contraindicated for this group.
Dosage and Administration
All centrally acting skeletal muscle relaxants can be administered orally (Table 20.1). In addition, two agents—methocarbamol and diazepam—can be administered by intramuscular and intravenous injection.
TABLE 20.1
Drugs for Muscle Spasm
| Name | Preparation | Usual Adult Oral Dosage | Administration |
| Baclofen [Lioresal, Gablofen] | 10-mg, 20-mg tablets | Initial: 5 mg 3 times/day. May increase to 15-20 mg 3 or 4 times/day | May be taken with or without food |
| Carisoprodol [Soma] | 250-mg, 350 mg tablets | 250-350 mg 3 times/day and at bedtime | May be taken with or without food |
| Chlorzoxazone [Lorzone, Parafon Forte DSC] | Lorzone: 375-mg, 750-mg tablets (scored) Parafon Forte DSC: 500-mg tablets (scored) | 500-750 mg 3 or 4 times/day | May be taken with or without food |
| Cyclobenzaprine [Fexmid] | Fexmid: 7.5-mg tablets Generic: 5-mg, 7.5-mg, 10-mg tablets | 5-10 mg 3 times/day | May be taken with or without food; however, taking with food may decrease GI distress |
| Cyclobenzaprine ER [Amrix] | 15-mg, 30-mg ER capsule | 15 or 30 mg once every 24 hours | Swallow tablets whole. |
| Dantrolene [Dantrium] | 25-mg, 50-mg, 100-mg capsules | The initial adult dosage is 25 mg once, then 100 mg 3 to 4 times a day. | Capsules may be opened and sprinkled on food. |
| Diazepam [Valium] | Valium: 2-mg, 5-mg, 10-mg (scored) tablets Diazepam Intensol oral concentrated solution: 5 mg/mL Generic oral solution: 1 mg/mL | 2-10 mg 3 or 4 times/day | Taking with food is recommended. Oral concentrate should be measured by specially designed dropper (included with the medication) and then mixed with drinks or soft foods such as applesauce or pudding. |
| Metaxalone [Metaxall, Skelaxin] | Metaxall: 800-mg (scored) tablets Skelaxin: 800-mg (scored) tablets | 800 mg 3 or 4 times/day | May be taken with or without food; however, bioavailability may be increased if given with food, resulting in increased CNS depression. |
| Methocarbamol [Robaxin, Robaxin-750] | Robaxin: 500-mg (scored) tablets Robaxin-750: 750-mg tablets | 1-1.5 g 4 times/day | May be crushed and mixed with food. |
| Orphenadrine [Norflex] | 100-mg ER tablet | 100 mg twice a day | Do not crush ER tablet. |
| Tizanidine [Zanaflex] | 4-mg tablet (scored) 2-mg, 4-mg, 6-mg capsules | Initial: 2 mg every 6-8 hours May increase to 8 mg every 6-8 hours (Maximum, 36 mg/day) | Capsules may be opened and sprinkled on food; however, absorption is increased. This should be considered when selecting the strength to prescribe for those with difficulty swallowing whole capsules. |
Drugs for Spasticity
The term spasticity refers to a group of movement disorders of CNS origin. These disorders are characterized by heightened muscle tone, spasm, and loss of dexterity. The most common causes are multiple sclerosis and cerebral palsy. Other causes include traumatic spinal cord lesions and stroke. Spasticity is managed with a combination of drugs and physical therapy.
Three drugs—baclofen, diazepam, and dantrolene—can relieve spasticity. Two of these—baclofen and diazepam—act in the CNS. In contrast, dantrolene acts directly on skeletal muscle. With the exception of baclofen and diazepam, the drugs employed to treat muscle spasm (i.e., the centrally acting muscle relaxants) are not effective against spasticity.
Baclofen
Mechanism of Action
Baclofen [Lioresal, Gablofen] acts within the spinal cord to suppress hyperactive reflexes involved in regulation of muscle movement. The precise mechanism of reflex attenuation is unknown. Because baclofen is a structural analog of the inhibitory neurotransmitter GABA, it may act by mimicking the actions of GABA on spinal neurons. Baclofen has no direct effects on skeletal muscle.
Therapeutic Use
Baclofen can reduce spasticity associated with multiple sclerosis, spinal cord injury, and cerebral palsy—but not with stroke. The drug decreases flexor and extensor spasms and suppresses resistance to passive movement. These actions reduce the discomfort of spasticity and allow increased performance. Because baclofen has no direct muscle relaxant action, and hence does not decrease muscle strength, baclofen is preferred to dantrolene when spasticity is associated with significant muscle weakness. Baclofen does not relieve the spasticity of Parkinson disease or Huntington chorea.
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