Muscle relaxant

Source: Wikipedia, the free encyclopedia.

A muscle relaxant is a drug that affects

neurological conditions. While both neuromuscular blockers and spasmolytics are often grouped together as muscle relaxant,[1][2] the term is commonly used to refer to spasmolytics only.[3][4]

History

The earliest known use of muscle relaxant drugs was by natives of the

neuromuscular transmission.[5] By 1943, neuromuscular blocking drugs became established as muscle relaxants in the practice of anesthesia and surgery.[6]

The U.S. Food and Drug Administration (FDA) approved the use of carisoprodol in 1959, metaxalone in August 1962, and cyclobenzaprine in August 1977.[7]

Other skeletal muscle relaxants of that type used around the world come from a number of drug categories and other drugs used primarily for this indication include

Equagesic
.

Neuromuscular blockers

Muscle relaxation and paralysis can theoretically occur by interrupting function at several sites, including the

conformational change in the receptor that opens the sodium-potassium channel of the nicotinic receptor. This allows Na+
and Ca2+
ions to enter the cell and K+
ions to leave the cell, causing a depolarization of the end plate, resulting in muscle contraction.[8] Following depolarization, the acetylcholine molecules are then removed from the end plate region and enzymatically hydrolysed by acetylcholinesterase.[5]

Normal

pancuronium (a nondepolarizing agent).[5]

pancuronium
, with red lines indicating the two acetylcholine "molecules" in the structure

Spasmolytics

A view of the spinal cord and skeletal muscle showing the action of various muscle relaxants – black lines ending in arrowheads represent chemicals or actions that enhance the target of the lines, blue lines ending in squares represent chemicals or actions that inhibit the target of the line

The generation of the

GABA
.

Terminology

Because they may act at the level of the cortex, brain stem, or spinal cord, or all three areas, they have traditionally been referred to as "centrally acting" muscle relaxants. However, it is now known not every agent in this class has CNS activity (e.g., dantrolene), so this name is inaccurate.[5]

Most sources still use the term "centrally acting muscle relaxant". According to MeSH, dantrolene is usually classified as a centrally acting muscle relaxant.[9] The World Health Organization, in its ATC, uses the term "centrally acting agents",[10] but adds a distinct category of "directly acting agents", for dantrolene.[11] Use of this terminology dates back to at least 1973.[12]

The term "spasmolytic" is also considered a synonym for antispasmodic.[13]

Clinical use

Spasmolytics such as

drowsiness.[14][16] Concerns about possible abuse and interaction with other drugs, especially if increased sedation is a risk, further limit their use.[14] A muscle relaxant is chosen based on its adverse-effect profile, tolerability, and cost.[18]

Muscle relaxants (according to one study) were not advised for

neurological conditions such as spasticity in cerebral palsy and multiple sclerosis.[14]
Dantrolene, although thought of primarily as a peripherally acting agent, is associated with CNS effects, whereas baclofen activity is strictly associated with the CNS.

Muscle relaxants are thought to be useful in painful disorders based on the theory that pain induces spasm and spasm causes pain. However, considerable evidence contradicts this theory.[17]

In general, muscle relaxants are not approved by

rheumatologists often prescribe cyclobenzaprine nightly on a daily basis to increase stage 4 sleep. By increasing this sleep stage, patients feel more refreshed in the morning. Improving sleep is also beneficial for patients who have fibromyalgia.[19]

Muscle relaxants such as

pregnant women, or people who have depression or for those with a history of drug or alcohol addiction.[21]

Mechanism

Because of the enhancement of inhibition in the CNS, most spasmolytic agents have the side effects of sedation and drowsiness and may cause dependence with long-term use. Several of these agents also have abuse potential, and their prescription is strictly controlled.[22][23][24]

The benzodiazepines, such as diazepam, interact with the GABAA receptor in the central nervous system. While it can be used in patients with muscle spasm of almost any origin, it produces sedation in most individuals at the doses required to reduce muscle tone.[5]

Baclofen is considered to be at least as effective as diazepam in reducing spasticity, and causes much less sedation. It acts as a GABA agonist at GABAB receptors in the brain and spinal cord, resulting in hyperpolarization of neurons expressing this receptor, most likely due to increased potassium ion conductance. Baclofen also inhibits neural function presynaptically, by reducing calcium ion influx, and thereby reducing the release of excitatory neurotransmitters in both the brain and spinal cord. It may also reduce pain in patients by inhibiting the release of substance P in the spinal cord, as well.[5][25]

Clonidine and other imidazoline compounds have also been shown to reduce muscle spasms by their central nervous system activity. Tizanidine is perhaps the most thoroughly studied clonidine analog, and is an agonist at α2-adrenergic receptors, but reduces spasticity at doses that result in significantly less hypotension than clonidine.[26] Neurophysiologic studies show that it depresses excitatory feedback from muscles that would normally increase muscle tone, therefore minimizing spasticity.[27][28] Furthermore, several clinical trials indicate that tizanidine has a similar efficacy to other spasmolytic agents, such as diazepam and baclofen, with a different spectrum of adverse effects.[29]

The

muscle fiber. In normal muscle contraction, calcium is released from the sarcoplasmic reticulum through the ryanodine receptor channel, which causes the tension-generating interaction of actin and myosin. Dantrolene interferes with the release of calcium by binding to the ryanodine receptor and blocking the endogenous ligand ryanodine by competitive inhibition. Muscle that contracts more rapidly is more sensitive to dantrolene than muscle that contracts slowly, although cardiac muscle and smooth muscle are depressed only slightly, most likely because the release of calcium by their sarcoplasmic reticulum involves a slightly different process. Major adverse effects of dantrolene include general muscle weakness, sedation, and occasionally hepatitis.[5]

Other common spasmolytic agents include: methocarbamol, carisoprodol, chlorzoxazone, cyclobenzaprine, gabapentin, metaxalone, and orphenadrine.

Thiocolchicoside is a muscle relaxant with anti-inflammatory and analgesic effects and an unknown mechanism of action.[30][31][32][33] It acts as a competitive antagonist at GABAA and glycine receptors with similar potencies, as well as at nicotinic acetylcholine receptors, albeit to a much lesser extent.[34][35] It has powerful proconvulsant activity and should not be used in seizure-prone individuals.[36][37][38]

Side effects

Patients most commonly report

heavy machinery
while under muscle relaxants' effects.

Cyclobenzaprine produces confusion and

lack of appetite, seizures, dark urine or loss of coordination.[39]

Patients taking carisoprodol for a prolonged time have reported dependence, withdrawal and abuse, although most of these cases were reported by patients with addiction history. These effects were also reported by patients who took it in combination with other drugs with abuse potential, and in fewer cases, reports of carisoprodol-associated abuse appeared when used without other drugs with abuse potential.[40]

Common side effects eventually caused by metaxalone include dizziness,

itching, difficulty breathing, tightness in the chest, swelling of the mouth, face, lips, or tongue), chills, fever, and sore throat, may require medical attention. Other severe side effects include unusual or severe tiredness or weakness, as well as yellowing of the skin or the eyes.[41] When baclofen is administered intrathecally, it may cause CNS depression accompanied with cardiovascular collapse and respiratory failure. Tizanidine may lower blood pressure. This effect can be controlled by administering a low dose at the beginning and increasing it gradually.[42]

See also

References

  1. ^ "Definition of Muscle relaxant." MedicineNet.com. (c) 1996–2007. Retrieved on September 19, 2007.
  2. ^ "muscle relaxant Archived 2013-10-06 at the Wayback Machine." mediLexicon Archived 2013-10-06 at the Wayback Machine. (c) 2007. Retrieved on September 19, 2007.
  3. ^ "Muscle relaxants." WebMD. Last Updated: February 15, 2006. Retrieved on September 19, 2007.
  4. ^ "Skeletal Muscle Relaxant (Oral Route, Parenteral Route)." Mayo Clinic. Last Updated: April 1, 2007. Retrieved on September 19, 2007.
  5. ^ .
  6. .
  7. ^ a b "Brief History". Retrieved 2010-07-09.
  8. .
  9. ^ Dantrolene at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  10. ^ "M03B Muscle Relaxants, Centrally acting agents". ATC/DDD Index. WHO Collaborating Centre for Drug Statistics Methodology.
  11. ^ "M03CA01 Dantrolene". ATC/DDD Index. WHO Collaborating Centre for Drug Statistics Methodology.
  12. PMID 4712630
    .
  13. ^ "Dorlands Medical Dictionary:antispasmodic". Archived from the original on 2009-10-01.
  14. ^
    PMID 18711953
    .
  15. .
  16. ^ .
  17. ^ .
  18. .
  19. ^ "When Are Muscle Relaxers Prescribed For Arthritis Patients?". Retrieved 2010-07-09.
  20. ^ MedlinePlus Encyclopedia: Tension Headache
  21. ^ "Muscle Relaxants". Retrieved 2010-07-09.
  22. .
  23. .
  24. ^ Charney, D.S.; Mihic, J.; Harris, R.A. (2001). "Hypnotics and Sedatives". Goodman & Gilman's. pp. 399–427.
  25. S2CID 33042651
    .
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  28. .
  29. .
  30. .
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  38. .
  39. ^ "Cyclobenzaprine-Oral". Retrieved 2010-07-09.
  40. ^ "Carisoprodolx". Retrieved 2010-07-09.
  41. ^ "Side Effects of Metaxalone – for the Consumer". Retrieved 2010-07-09.
  42. ^ "Precautions". Encyclopedia of Surgery. Retrieved 2010-07-09.

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