Management of spasticity and muscle spasms

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SKELETAL MUSCLE RELAXANT DRUGS

INTRODUCTION

Skeletal muscle relaxants are a heterogeneous group of drugs that relax striated muscles and are a different class of drugs used during intubation and surgery.These drugs are used to manage spasticity that occurs in neurological disorders and diseases of upper motor neuron, muscle pain or spasm in peripheral musculoskeletal disorders.

Spasticity, a component of the upper motor neuron syndrome, is a velocity dependent increased muscle tone movement disorder characterized by excessive twitching of the tendons as a result of irritable stretch reflex. It is caused by lesion in the brain and / or spinal cord and is accompanied by increased muscle tone, tendon reflexes, abnormal movements and clonus.

Muscle spasms and cramps are types of abnormal muscle activity. They are sudden, involuntary, painful muscle contractions that occur with trauma or irritation. They include: a) stiffness-rigidity at rest, b) slow relaxation of muscles, and c) fasciculation; a type of muscle spasm without pain, characterized by rapid, asynchronous contraction of many small muscle fibers at rest. The cramps can affect any muscle but are more common in the legs, feet and hands. Although painful, they are harmless in most cases and do not hide any pathology. Muscle spasms may be clonic (alternating contraction-relaxation) or tonic (sustained contraction) and may occur with musculoskeletal trauma or inflammation (eg. sprains, strains, bursitis, arthritis, acute/chronic low back pain etc.)1-4

Upper limb spasticity

MECHANISM OF ACTION

Skeletal muscle relaxants can be divided into 2 categories 5: 1) centrally acting and 2) peripherally acting. The group of centrally acting (acting on central nervous system, CNS) consists of several drugs that are chemically different. Only dantrolene has a direct action at the neuromuscular synapse. Drugs used in clinical practice are:

1)      Baclofen (Lioresal / Miorel) 6,7

Baclofen increases GABA (gammaaminobutyric acid) which is an inhibitory neurotransmitter. It works by blocking the action of excitatory neurotransmitters at the spinal cord. It is lipophilic, crosses the blood-brain barrier in a small percentage (for this reason is ideal the intrathecal administration). It is used to treat spasticity in multiple sclerosis and spinal cord injuries. Although, is contraindicated in people with hypersensitivity reactions to it and those with muscle spasm due to rheumatological diseases. Baclofen may be given when spasticity causes severe pain or inability to tolerate the program of physical therapy, to sit in a wheelchair, or to participate in self-care activities of daily living (eg, eating, dressing) orally and intrathecally through an implanted, subcutaneous pump. The action begins in an hour, the peak is at  2 hours, lasts 4 to 8 hours and is metabolized in the liver and excreted in urine; its half-life is 3 to 4 hours. Dosage must be modified in subjects with renal function problems. Drowsiness, dizziness, confusion, constipation, fatigue, headache, hypotension, insomnia, nausea, and weakness are common adverse effects. If for any reason baclofen needs to be stopped dosage should be tapered and withdrawn of the drug needs 1 to 2 weeks. Baclofen has caused fetal abnormalities in rats at doses 13 times above the human dose. Baclofen passes into breast milk, and breast feeding while taking baclofen is not recommended. Finally, the method is effective, safe, well tolerated and the dose can be easily adjusted and modified according to the degree of spasticity.
Intrathecal Baclofen Therapy (ITB) 5-8 is used for the treatment of severe spasticity of cerebral or spinal origin; considered for spasticity of the lower extremities, when oral medications are ineffective or not tolerated but also used to control upper extremity spasticity (higher catheter placement). After a successful bolus test screening (see image) the pump is implanted subcutaneously or subfascially in the abdomen, the catheter is tunneled to lumbar region, distal end inserted intrathecally. 

the screening test for baclofen pump implantation

In a procedure that lasts about an hour, the pump is placed in the abdomen while the patient is under general anesthesia. A catheter runs under the skin from the pump to the back and is inserted into the spinal fluid. Therapy delivers Lioresal intrathecal (baclofen injection), an antispasmodic drug, directly to the fluid surrounding the spinal cord in small, precisely controlled doses using a pump that is placed internally. The pump is then programmed by an external computer to release continuously a specified dose of baclofen, as determined by the physician. A programmable pump allows simple or complex programming, boluses and requires periodic refills (Lioresal® Intrathecal 500mcg/ml or 2000mcg/ml). Refills are done using a syringe and needle and take approximately 15 to 20 minutes to complete.

refill procedure

Pump will be replaced at battery end of life. The method is very effective, particularly on spasms and relatively safe, well tolerated, adjustable and potentially reversible. Possible risks in use of ITB therapy are mechanical complications with the pump and/or catheter, and chance of infection at the wound site. 

1)      Tizanidine (Zanaflex / Sirdalud)

It is an alpha 2-adrenergic agonist that inhibits motor neurons in the brain, in patients with multiple sclerosis, spinal cord and brain trauma. Given by mouth the action begins within an hour, with a peak at 2 hours and duration up to 4 hours. It should be used cautiously with renal or hepatic impairment but rarely cause liver damage. Its half life is 3 to 4 hours; it is metabolized in the liver and excreted in urine. Common adverse effects include drowsiness, dizziness, constipation, dry mouth, and hypotension. Tizanidine may cause low blood pressure so in generally the dose is increasing progressive and controlled.8

2)      Dantrolene (Dantrium)

This drug is used to manage spasticity in neurological disorders (multiple sclerosis and spinal cord injuries) and to prevent or treat malignant hyperthermia. It is the only skeletal muscle relaxant acting peripherally on the muscles by inhibiting calcium’s release in muscle cells and decreasing the strength of contraction. It is given orally and acts slowly to peak at 4-6 hours with 8-10 hours duration. Common adverse effects include drowsiness, dizziness, diarrhea, and fatigue. The most serious adverse effect is hepatotoxicity-symptomatic hepatitis, which is dose related, but may occur even with a short period of doses Liver function should be monitored periodically in all patients receiving dantrolene. In animal studies it has reduced the rate of survival of the newborn when given in doses seven times the normal human dose. Mothers should not breast feed while receiving dantrolene.10

3)      Carisoprodol (Soma) 3

Relieves acute, painful musculoskeletal disorders but is not recommended for long-term use or in high doses because it causes physical dependence. Shall be given orally, acts in 30 minutes, peaks in 1 to 2 hours, and lasts 4 to 6 hours. It is metabolized in the liver and has a half-life of 8 hours. Common adverse effects include drowsiness, dizziness, and impaired motor coordination.

4)      Orphenadrine (Norflex) 3

It has a strong anticholinergic effect and for this reason is inappropriate in a wide range of patients with glaucoma, prostatic hypertrophy and myasthenia gravis. It should also be given with caution in patients with cardiovascular diseases and disorders of renal or hepatic function. Is given orally or intramuscularly and lasts for 4 to 6 hours, is metabolized in the liver, and is excreted in urine and faces. Common adverse effects are drowsiness, dizziness, constipation, dry mouth, nausea, tachycardia, and urinary retention.

Other drugs for musculoskeletal disorders are: chlorzoxazone (Paraflex), cyclobenzaprine (Flexeril), diazepam (Valium), metaxalone (Skelaxin), methocarbamol (Robaxin) and thiocolchicoside (Muscoril). The mechanism of action of these drugs is unclear and is linked to their sedative action. Drugs used in spasticity are also benzodiazepines, clonidine, gabapentin, and botulinum toxin (BTX-A).  

Botulinum toxin BTX-A

It belongs to the chemical blocks; a neurotoxin produced by the anaerobic bacterium Clostridium botulinum. The toxin acts at the neuromuscular junction by inhibiting the release of the neurotransmitter acetylcholine. Toxin is ingested by the nerve terminal through a process of endocytosis. After administration effects of BTX-A are temporary as sprouting of new nerve terminals from the treated nerves leads to reinnervation. The functionality of the original axon is restored leading to the recovery of the affected muscles. It is used for symptomatic treatment of muscular hypertonia in upper and lower limbs, the neck, etc. under EMG / electrical stimulation for muscle localization. The maximum total dose per session is 400-600 Units. The clinical useful period is usually 3 months and after this period the injection needs to be repeated. The action starts in 24-72 hours, and peaks within 1-4 weeks.11-13

The goal of treatment is to relieve pain, muscle spasm, and muscle spasticity without impairing the ability to perform self-care activities of daily living.

References

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Yannis Dionyssiotis, MD, PhD, Director of Physical and Social Rehabilitation Center Amyntaeo, Florina, Greece, e-mail:yannis_dionyssiotis@hotmail.com
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