Миорелаксанты: виды, действие и применение.

Drug for skeletal muscle function
skeletal muscle relaxants
A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics. Neuromuscular blockers act by interfering with transmission at the neuromuscular end plate and have no central nervous system (CNS) activity. They are often used during surgical procedures and in intensive care and emergency medicine to cause temporary paralysis. Spasmolytics, also known as "centrally acting" muscle relaxant, are used to alleviate musculoskeletal pain and spasms and to reduce spasticity in a variety of neurological conditions. While both neuromuscular blockers and spasmolytics are often grouped together as muscle relaxant, the term is commonly used to refer to spasmolytics only.

The earliest known use of muscle relaxant drugs was by natives of the Amazon Basin in South America who used poison tipped arrows that produced death by skeletal muscle paralysis. This was first documented in the 16th century, when European explorers encountered it. This poison, known today as curare, led to some of the earliest scientific studies in pharmacology. Its active ingredient, tubocurarine, as well as many synthetic derivatives, played a significant role in scientific experiments to determine the function of acetylcholine in neuromuscular transmission. By 1943, neuromuscular blocking drugs became established as muscle relaxants in the practice of anesthesia and surgery. The U. S. Food and Drug Administration (FDA) approved the use of carisoprodol in 1959, metaxalone in August 1962, and cyclobenzaprine in August 1977. 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 orphenadrine (anticholinergic), chlorzoxazone, tizanidine (clonidine relative), diazepam, tetrazepam and other benzodiazepines, mephenoxalone, methocarbamol, dantrolene, baclofen. Following depolarization, the acetylcholine molecules are then removed from the end plate region and enzymatically hydrolysed by acetylcholinesterase. The World Health Organization, in its ATC, uses the term "centrally acting agents", but adds a distinct category of "directly acting agents", for dantrolene. Use of this terminology dates back to at least 1973. The term "spasmolytic" is also considered a synonym for antispasmodic.

Spasmolytics such as carisoprodol, cyclobenzaprine, metaxalone, and methocarbamol are commonly prescribed for low back pain or neck pain, fibromyalgia, tension headaches and myofascial pain syndrome. However, they are not recommended as first line agents; in acute low back pain, they are not more effective than paracetamol or nonsteroidal anti inflammatory drugs (NSAIDs), and in fibromyalgia they are not more effective than antidepressants. In general, no high quality evidence supports their use. Muscle relaxants (according to one study) were not advised for orthopedic conditions, but rather for neurological conditions such as spasticity in cerebral palsy and multiple sclerosis. Muscle relaxants such as tizanidine are prescribed in the treatment of tension headaches. Diazepam and carisoprodol are not recommended for older adults, pregnant women, or people who have depression or for those with a history of drug or alcohol addiction.

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. 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. 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. Neurophysiologic studies show that it depresses excitatory feedback from muscles that would normally increase muscle tone, therefore minimizing spasticity. 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. The hydantoin derivative dantrolene is a spasmolytic agent with a unique mechanism of action outside of the CNS. It reduces skeletal muscle strength by inhibiting the excitation contraction coupling in 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. 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. It has powerful proconvulsant activity and should not be used in seizure prone individuals.

Patients most commonly report sedation as the main adverse effect of muscle relaxants. Usually, people become less alert when they are under the effects of these drugs. People are normally advised not to drive vehicles or operate heavy machinery while under muscle relaxants' effects. Cyclobenzaprine produces confusion and lethargy, as well as anticholinergic side effects. When taken in excess or in combination with other substances, it may also be toxic. While the body adjusts to this medication, it is possible for patients to experience dry mouth, fatigue, lightheadedness, constipation or blurred vision. Some serious but unlikely side effects may be experienced, including mental or mood changes, possible confusion and hallucinations, and difficulty urinating. In a very few cases, very serious but rare side effects may be experienced: irregular heartbeat, yellowing of eyes or skin, fainting, abdominal pain including stomach ache, nausea or vomiting, lack of appetite, seizures, dark urine or loss of coordination. 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. Common side effects eventually caused by metaxalone include dizziness, headache, drowsiness, nausea, irritability, nervousness, upset stomach and vomiting. Severe side effects may be experienced when consuming metaxalone, such as severe allergic reactions (rash, hives, 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. 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.