Use of tizanidine (Sirdaluda) in the treatment of pain and spasm
Tizanidine (Sirdalud) for pain syndromes Monotherapy with tizanidine (Sirdalud) for pain syndromes. Muscular-tonic and myofascial pain syndromes are very often the main reason for patients visiting a doctor. In the treatment of muscular-tonic pain, the central place belongs to local influences aimed at relaxing the muscle (massage, applications of warming ointments, gels, wet compresses, etc.), and in the case of myofascial pain syndrome - at the destruction of trigger points using post-isometric relaxation, the introduction of dry needles or anesthetic into the trigger zone. The duration of therapy is significantly reduced with effective pain relief for the patient. A generally accepted method of pain relief for myofascial pain is also the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Muscle relaxants can provide great assistance in the treatment of muscular-tonic and myofascial pain syndromes by reducing pain intensity, reducing painful muscle tension, and improving motor activity. The use of muscle relaxants is justified by the recognition of the important role of muscle spasm in the pathogenesis of low back pain. Pain of various origins (due to damage to the intervertebral discs, facet joints of the spine, the muscles themselves and other reasons) increases the activity of motor neurons in the spinal cord, which leads to muscle spasm, which in turn plays a significant role in maintaining the pain itself. Pathologically increased muscle tone has various mechanisms for increasing pain: direct irritation of muscle pain receptors, deterioration of blood supply to muscles, which leads to the formation of a vicious circle leading to increased muscle spasm and accompanying pain. Muscle relaxants break the vicious circle of “pain – muscle spasm – pain” and, as a result, are able to speed up the recovery period [6]. In European recommendations for the treatment of acute pain in the lower back, tizanidine, dantrolene, diazepam, and baclofen are noted as effective muscle relaxants [19]. In our country, the most commonly used of these drugs is tizanidine (Sirdalud) [6]. The range of the effective daily dose of tizanidine (Sirdaluda) for pain syndromes is 2–12 mg (the optimal dose is 6–8 mg/day). For mild pain syndromes, the use of tizanidine (Sirdalud) can be limited to taking the drug at night at a dose of 2-4 mg until the pain stops (usually 5-7 days). In case of moderately severe pain syndrome, it is better to prescribe the first dose at night at a dose of 2–4 mg (the patient will “oversleep” the side effects), then gradually increase the dose to 6–8 mg/day. In severe cases, an additional 2–4 mg of tizanidine (Sirdaluda) may be added at night. A positive effect, as a rule, is noted already on the 3rd day of taking the drug. For chronic pain syndromes, a course of therapy is usually carried out for 2–4 weeks, adjusting the duration of treatment and dose of the drug depending on the effectiveness/tolerability. It should be noted that for mild to moderate pain associated with muscle spasm (eg, acute neck or lower back pain), tizanidine (Sirdaluda) alone may be sufficient. The effectiveness of tizanidine monotherapy (Sirdalud) has been confirmed in many studies, incl. and in a multicenter study of 2,251 patients with acute pain caused by muscle spasms in the low back, neck, or shoulder. 89% of patients rated the treatment outcome as “good” or “very good.” The study also noted very good tolerability of the drug (90% of patients rated tolerability as “good” or “very good”). These results allowed the authors to recommend tizanidine as the drug of choice among muscle relaxants for the treatment of pain associated with muscle spasm [13]. Combining tizanidine (Sirdaluda) with NSAIDs. For more severe pain, or when it is based on inflammatory changes, it is advisable to use tizanidine and NSAIDs together. Studies have shown that the use of tizanidine potentiates the effect of NSAIDs [9,16]. In addition, taking tizanidine (Sirdaluda) has a gastroprotective effect, which is associated with its adrenergic activity and antispasmodic effect. Tizanidine (Sirdalud) reduces basal and induced secretion of acid in the stomach, eliminates the imbalance of glycoproteins in the gastric mucosa and gastric secretions [11,16]. Experimental studies with the use of tizanidine have demonstrated a significant reduction in the ulcerogenic effect of acetylsalicylic acid, indomethacin, meloxicam, nimesulide and naproxen. The gastroprotective activity of tizanidine has also been proven in clinical studies. In patients receiving the combination of ibuprofen and tizanidine, the incidence of gastrointestinal side effects, including bleeding, was significantly (p=0.002) lower than in patients receiving the combination of ibuprofen and placebo [9]. Similar results were obtained when comparing the combination of diclofenac and tizanidine with the combination of diclofenac and placebo in a multicenter (12 centers), prospective, double-blind, placebo-controlled, randomized clinical trial conducted in 6 countries in the Asia-Pacific region and including 405 participants [16]. Gastropathy was reported in 12% of patients receiving the combination of diclofenac and tizanidine, versus 32% of patients receiving diclofenac in combination with placebo (p<0.001). The frequency of positive stool occult blood test results was 5% in the study group compared to 11% in the control group. The gastroprotective effect of Sirdalud is especially important for the management of patients with chronic pain syndromes who take NSAIDs for a long period of time (for rheumatological diseases), which often leads to the development of erosive gastritis and gastric and duodenal ulcers [1]. Combining tizanidine (Sirdaluda) with antidepressants and anticonvulsants. Treatment of chronic pain is more complex than treatment of acute pain and requires an integrated approach. The use of muscle relaxants here is only a component of treatment and must be justified by the presence of a therapeutic target - muscle spasm. In this regard, the patient’s expectations regarding the effect of the muscle relaxant must be correctly formed: the use of tizanidine (Sirdalud) can reduce pain, facilitate the patient’s movements, but will not stop the pain completely, because in chronic pain, the muscle component is not the leading one. Anticonvulsants and antidepressants are used in the treatment of chronic pain syndromes, so it is important to consider how tizanidine (Sirdalud) interacts with these medications. There are studies that show that tizanidine (Sirdalud) potentiates the effect of tricyclic antidepressants (amitriptyline) [10]. At the same time, it must be remembered that tizanidine (Sirdalud) cannot be combined with fluvoxamine, an SSRI antidepressant. Concomitant use of tizanidine (Sirdalud) and fluvoxamine can lead to a significant decrease in blood pressure and cause complications from the central nervous system. Thus, due to its high efficiency and minor side effects, a number of domestic and foreign experts consider tizanidine (Sirdalud) as the drug of choice for the treatment of acute and subacute myofascial pain in monotherapy and as the first-line drug of choice for the treatment of chronic myofascial syndrome in combination with other medications [2 ,13]. Tizanidine (Sirdalud) in neurological practice Disorders of muscle tone, associated pain syndromes, limitations in motor functions, secondary changes in joints and muscles form part of the clinical manifestations of many diseases of the nervous system. As a rule, the problem of increased muscle tone—hypertonicity or spasticity—acquires clinical significance [8]. However, the causes of hypertonicity and the mechanisms underlying it may be different, and therefore, differentiated treatment approaches are required to treat spasticity. The use of tizanidine (Sirdalud) has become most widespread in the treatment of spasticity in traumatic injuries of the brain and spinal cord, multiple sclerosis, and stroke. For spasticity associated with dystonic disorders, parkinsonism, it is more advisable to use other drugs (for example, clonazepam, diazepam). Spasticity leads to significant functional disorders and disruption of the patient's quality of life. However, it should be remembered that spasticity itself does not always require treatment. For example, in some patients with severe paresis, spasticity in muscles that anatomically resist gravity (antigravity muscles) may make standing and walking easier. In addition, the presence of increased muscle tone can prevent the development of muscle atrophy, soft tissue swelling and osteoporosis, and also reduce the risk of developing thrombosis of the lower extremities. Indications for the treatment of spasticity are only those cases where, due to increased tone, the patient’s “functioning, positioning or comfort” is impaired. Use of tizanidine (Sirdalud) for stroke. In case of stroke, the main goals of treatment are not only to reduce the severity of spasticity, but also to improve the functionality of paretic limbs, reduce pain and discomfort associated with high muscle tone, and facilitate care for a paralyzed patient. The most effective means in the fight against spasticity are physical therapy and physiotherapy, especially at an early stage. In cases where patients with post-stroke limb paresis have local spasticity, local administration of botulinum toxin preparations can be used. The use of antispastic drugs (muscle relaxants) for oral administration can make a significant contribution to the treatment of spasticity. The use of muscle relaxants can reduce muscle tone, improve motor functions, facilitate care for an immobilized patient, relieve painful muscle spasms, enhance the effect of physical therapy and, as a result, prevent the development of contractures. In our country, tizanidine, baclofen, tolperisone, and diazepam are used to treat post-stroke spasticity. An analysis of 20 studies comparing the use of various antispastic agents for a variety of neurological diseases accompanied by spasticity showed that tizanidine, baclofen and diazepam are approximately equally capable of reducing spasticity, but tizanidine (Sirdalud) is more effective than other antispastic agents in reducing clonus [14]. . Unlike baclofen, tizanidine (Sirdalud) does not cause a decrease in muscle strength while reducing spasticity (which is very important for improving the functionality of the limb), it is better tolerated by patients than baclofen and diazepam (with its use, patients are less likely to stop treatment due to side effects) [14,15,20]. Among the side effects identified during a study of tizanidine in patients with post-stroke spasticity conducted by Gelber (2001), the most common were drowsiness, weakness, dizziness, dry mouth, and orthostatic hypotension. These phenomena disappeared when the drug dose was discontinued or reduced. At the same time, not a single serious side effect was noted during treatment with tizanidine [Gelber, 2001], which allowed the authors to conclude that it is highly safe. Authors who have conducted studies examining the clinical effects of tizanidine (Sirdalud) and many clinicians agree that among muscle relaxants, tizanidine (Sirdalud) is the drug of first choice for the treatment of post-stroke spasticity [7,12,14,15,20]. To treat spasticity due to neurological diseases, higher doses of tizanidine (Sirdaluda) are usually used than for the treatment of pain syndromes. Typically, the optimal therapeutic effect is achieved with a daily dose of 12 to 24 mg (effective dose range is 2–36 mg). However, given the dose-dependent increase in the risk of side effects with increasing doses of the drug, treatment should begin with small (2-6 mg/day) doses, then gradually increase the dose until a therapeutic effect is achieved, observing individual tolerability (usually by 2- 4 mg every 3–7 days, dividing the daily dose into 3 doses). If side effects occur, you can temporarily stop increasing the dose (if you do not increase the dose, in many cases the side effects disappear after a few days) and continue increasing the dose after the patient gets used to the drug. This allows, firstly, to select the most effective minimum dose of the drug for a particular patient (in some patients (due to individual variability), a sufficient therapeutic effect may occur when taking lower doses than the recommended standards), and also to relieve unnecessary suffering in patients with individual poor tolerability of tizanidine (in patients with poor tolerance to tizanidine, side effects appear already when using a dose of 2–4 mg/day). Dose titration usually takes 2–4 weeks. The duration of treatment is determined individually (from several weeks to several months) [8]. The use of prolonged forms of tizanidine (Sirdalud MR). For long-term use, a convenient dosage form of tizanidine is in the form of modified-release capsules (Sirdalud MR), which is available in a dose of 6 mg. Clinical experience shows that for most patients the optimal dose is 12 mg/day. (2 capsules), in rare cases it may be necessary to increase the daily dose to 24 mg. Treatment also begins with a minimum dose of 6 mg (1 capsule), if necessary, gradually increasing the dose by 6 mg (1 capsule) at intervals of 3–7 days. Use of tizanidine (Sirdalud) for traumatic brain injury. Among the muscle relaxants, tizanidine (Sirdalud) is the drug that is most often used to treat spasticity associated with traumatic brain injury [5]. The reasons for prescribing, dose selection tactics and precautions are the same as for the treatment of post-stroke spasticity. Use of tizanidine (Sirdalud) for multiple sclerosis and spinal injury. Limitation of mobility in patients with multiple sclerosis is associated with a significant increase in muscle tone of the spastic type, mainly in the lower extremities. The basis for the treatment of muscle tone disorders are special exercises that should be performed under the supervision of a specialist in physical therapy. Drug therapy plays an additional role. Medicines used to treat spasticity include tolperisone, baclofen, tizanidine, and diazepam. Drug treatment of spastic tone should be individual, controlled by a doctor and the patient himself. This is due to the fact that most drugs that reduce tone increase the weakness of the paralyzed limbs and can lead to a deterioration in the patient's condition. In this regard, the dose of the antispastic drug must be gradually increased from the minimum to the optimal, when spasticity decreases, but there is no increase in weakness. Sirdalud in this regard is more preferable compared to baclofen and diazepam (with the use of tizanidine (Sirdalud), muscle weakness develops less frequently; due to excessive relaxation of the bladder sphincters when using baclofen, patients more often complain of an increase in pelvic disorders; the use of diazepam is associated with a higher frequency development of side effects, drug dependence) [3,17]. Sirdalud is more effective compared to other muscle relaxants against clonus [14]. The optimal daily dose of Sirdalud for the treatment of spasticity in multiple sclerosis is 6–8 mg (maximum daily dose is 36 mg). Treatment should also be started with a minimum dose, and the dose should be increased in increments of 2 mg [3]. In patients with spasticity due to spinal injury, tizanidine (Sirdalud) and baclofen are most often used, and diazepam is also used to relieve painful muscle spasms. Treatment begins with a minimum dose (4–6 mg of Sirdalud), which is gradually increased to a therapeutic dose over several days or weeks, trying to avoid unwanted side effects (muscle weakness and sedation). Baclofen is effective mainly when administered intrathecally; when taken orally, tizanidine (Sirdalud) gives a more pronounced positive effect and is better tolerated by patients than baclofen [18]. For other types of spasticity encountered in neurological practice (parkinsonism, torsion dystonia, torticollis, ALS), the use of tizanidine (Sirdaluda) is not justified. In these cases, the use of clonazepam and diazepam is more appropriate. These drugs have higher the likelihood of side effects, but also the antispathetic effect in them is more pronounced with these disorders. Optimization of treatment when using thizanine (sirdalud) is a fairly wide range of effective doses of thizanidine (sirdalud) (from 2 to 36 mg/day) allows the use of the drug for short and long -term treatment for pain and spasticity in the form of monotherapy or in combination with other drugs means. To improve clinical effectiveness, the following recommendations on the practical use of thizanine (sirdalud) may be useful. The beginning of treatment with small doses of the drug. The development of side effects when using thizanine (sirdalud) is dose -dependent (for example, the probability of developing side effects when using a dose of 12–24 mg is 2 times higher than when using a dose of 6-12 mg). At the same time, a sufficient therapeutic effect is sometimes possible to achieve at smaller doses than is recommended in treatment standards. In this regard, the treatment is recommended to start with a minimum dose (2–4 mg), then gradually increase it, observing individual tolerance. Gradual abolition of the drug. After prolonged use of Tizanidine (sirdaluda), especially in large doses, it is necessary to carry out a gradual abolition of the drug, because A sharp cancellation can cause the development of muscle weakness (this is also characteristic of other muscle relaxants). The use of Tizanidine (Sirdalud) to normalize sleep among the side effects of Tizanidine (Sirdalud) is noted increased drowsiness. Therefore, patients who have drowsiness when taking thizanidine (sirdalud) should avoid all activities requiring increased concentration of attention and speed of reaction. At the same time, many patients, especially with chronic pain syndromes, are disturbed by sleep. The indicated side effect of Tizanidine (Sirdalud) can be used for therapeutic purposes by prescribing the drug at night to improve the patient's sleep. Given the fact that the effect of Tizanidine (Sirdaluda) is short -term, some doctors in order to maintain the social activity of the patient, prescribe the drug only at night or distribute the main daily dose of the drug in the afternoon and at night. This allows the patient to maintain social activity in the first half of the day (work, drive a car), and in the evening it helps to fall asleep, as well as “sleep” other side effects. The use of thizanine (sirdalud) as an antihypertensive agent with one of the side effects when using thizanine (sirdalud) is a moderate decrease in blood pressure. Simultaneous use, together with antihypertensive agents, can enhance the antihypertensive effect. If it is necessary to prolonged use of thizanidine (sirdaluda) (for example, in the treatment of post -industry spasticity), the hypotensive effect of thizanine (siredaluda) can be used to reduce the dose or to cessation of drugs that reduce blood pressure if the patient receives antihypertensive therapy. The conclusion of Tizanidine is an effective drug both in the treatment of spasticity with a number of neurological disorders, and for the treatment of a wide range of pain syndromes associated with increasing muscle tone. 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