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BACKGROUND: In order to facilitate rapid tracheal intubation, the development of a rapid onset, short duration, non-depolarizing muscle relaxant without cardiovascular side-effects would be a significant accomplishment in the field of anesthesiology. The aim of the present study was to test the action of a new non-depolarizing muscle relaxant (SZ1677) on neuromuscular transmission, muscarinic (M2, M3) receptors and cardiovascular reactions and to compare it with clinically used muscle relaxants. METHODS: Neuromuscular transmission was studied by recording muscle contractions elicited by indirect electrical stimulation, using (i). in vitro isolated phrenic nerve-hemidiaphragm preparation of mice, rats and guinea pigs and (ii). in vivo sciatic nerve-anterior tibial muscle preparation of anesthetized rats, guinea pigs and cats. Cardiovascular effects of muscle relaxants were evaluated on the grounds of their effects on changes of blood pressure and heart rate induced by electrical stimulation of the right vagal nerve in anesthetized cats. To study postsynaptic antimuscarinic affinity of muscle relaxants on M3 receptors, oxotremorine-induced contractions of longitudinal muscle strip of guinea pig ileum were registered in their presence and absence. RESULTS: One of more than 120 newly synthesized non-depolarizing muscle relaxants compounds, 1-3[alpha-hydroxy-17beta-acetyloxy-2beta-(1,4-dioxa-8-azaspiro[4,5]dec-8-yl)-5alpha-androstane-16beta-il] -1-(2-propenyl)pyrrolidinium bromide (SZ1677), excelled with its advantageous pharmacological properties: relatively short duration of action, no accumulation and lack of unwanted side-effects. Pharmacodynamic studies show that SZ1677 is a non-depolarizing neuromuscular blocking agent with a relatively short duration and rapid onset of action in a variety of laboratory animal species. It is without cumulative effect, does not reduce blood pressure, and fails to produce tachycardia. Significant cardiac vagal blocking effects were not observed even at concentrations or dosages of 8 times the ED90. This compound, unlike many other muscle relaxants, does not have atropine-like effects on human atrial tissue; it does not increase the release of NA from sympathetic innervation in the heart. In all practical ways, at least from the vantage point of the preclinical study, SZ1677 compares favorably with all presently available short-acting muscle relaxants, including rapacuronium. CONCLUSION: In experiments, SZ1677 proved to be a short-acting neuromuscular blocking compound having a large safety margin between the doses required to produce neuromuscular block and those likely to lead to cardiovascular side-effects.
Skeletal muscle relaxants are a heterogeneous group of medications used to treat two different types of underlying conditions: spasticity from upper motor neuron syndromes and muscular pain or spasms from peripheral musculoskeletal conditions. Although widely used for these indications, there appear to be gaps in our understanding of the comparative efficacy and safety of different skeletal muscle relaxants. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions. Randomized trials (for comparative efficacy and adverse events) and observational studies (for adverse events only) that included oral medications classified as skeletal muscle relaxants by the FDA were sought using electronic databases, reference lists, and pharmaceutical company submissions. Searches were performed through January 2003. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 101 randomized trials were included in this review. No randomized trial was rated good quality, and there was little evidence of rigorous adverse event assessment in included trials or observational studies. There is fair evidence that baclofen, tizanidine, and dantrolene are effective compared to placebo in patients with spasticity (primarily multiple sclerosis). There is fair evidence that baclofen and tizanidine are roughly equivalent for efficacy in patients with spasticity, but insufficient evidence to determine the efficacy of dantrolene compared to baclofen or tizanidine. There is fair evidence that although the overall rate of adverse effects between tizanidine and baclofen is similar, tizanidine is associated with more dry mouth and baclofen with more weakness. There is fair evidence that cyclobenzaprine, carisoprodol, orphenadrine, and tizanidine are effective compared to placebo in patients with musculoskeletal conditions (primarily acute back or neck pain). Cyclobenzaprine has been evaluated in the most clinical trials and has consistently been found to be effective. There is very limited or inconsistent data regarding the effectiveness of metaxalone, methocarbamol, chlorzoxazone, baclofen, or dantrolene compared to placebo in patients with musculoskeletal conditions. There is insufficient evidence to determine the relative efficacy or safety of cyclobenzaprine, carisoprodol, orphenadrine, tizanidine, metaxalone, methocarbamol, and chlorzoxazone. Dantrolene, and to a lesser degree chlorzoxazone, have been associated with rare serious hepatotoxicity.
The purpose of this study is to test our hypothesis that muscle relaxation is effective on the psychological well-being of juvenile delinquents. Subjects were 16 juvenile delinquents who had entered a reform school. Subjects were divided into two groups. The muscle relaxation group received muscle relaxation therapy once a week for a total of 4 times. The control group spent an ordinary daily life in the reformatory. Psychological questionnaires used were the Rosenzweig Picture Frustration Study (P-F study), the Psychological Stress Response Scale (PSRS), and the Eysenck Personality Questionnaire (EPQ). There was a significant Group Time interaction of the Group Conformity Rating (GCR) of the P-F study (F [1,14] =10.1, P=0.007). There were no significant interactions in the other psychological subscales. Thus, muscle relaxation therapy may improve frustration tolerance among juvenile delinquents.
The use of sedation, muscle relaxation, or analgesia in the management of ventilated neonates has been controversial. Many neonatologists face a difficult decision on whether or not to use a muscle relaxant on a ventilated infant. This article reviews neonatal physiology and pharmacology, drug administration, absorption, distribution, and certain selected sedatives and analgesics. The muscle relaxants, financial issues, and family issues are also discussed.
Nitric oxide (NO) mediates penile erection by inducing cavernosal smooth muscle relaxation. Superoxide anion (O2-) can influence the activity of NO by reacting with it to produce peroxynitrite (PN). This is a highly reactive species that is known to attack a variety of biological targets. It is far more reactive and damaging than its precursors. We therefore, investigated the effect of PN on rabbit cavernosal smooth muscle relaxation and compared it to NO. Cavernosal strips from nine adult New Zealand White rabbits were excised (n = 12 strips for each arm of the study) and mounted in organ baths. After pre-contraction with phenylephrine (PE) (100 microM) the strips were exposed to either NO or PN (1-100 microM) and subsequent smooth muscle relaxations monitored. Some tissues were incubated with oxadiazoloquinoxalin-1-one (ODQ; 10 microM), an inhibitor of guanylyl cyclase, before the addition of NO or PN. NO and PN induced concentration-dependent relaxations in all strips. However, PN (IC50: 26 +/- 3.6 microM) was significantly less potent than NO (IC50: 11 +/- 0.7 microM) [P < 0.01]. Relaxation induced by NO was immediate and short-lived, with the tension returning to its original level. In contrast, PN-initiated relaxations were of a slower onset and more prolonged, with the tissues unable to recover tension. However, after several washouts the tissues were fully responsive to PE. Both NO- and PN-mediated relaxations were inhibited by ODQ, suggesting the involvement of cGMP in this process. Although PN mediates cavernosal smooth muscle relaxation, it is much less potent than NO. As PN is thought to play a role in a variety of pathologies where erectile dysfunction is prominent, it may also contribute to the pathogenesis of erectile dysfunction.
There are exceptions and variations to the general clinical rule that muscle relaxants depress respiration and have no effect on circulation. Variation may be attributed to differences in animal species, in individual response, in muscle affected, in drug used and in dose employed. Conclusions about muscle relaxants derived from animal experiments cannot always be assumed to apply to man. The "respiratory sparing" action of a muscle relaxant cannot be relied upon in any individual patient. Facilities for adequate artificial respiration must always be available when any dose of any muscle relaxant drug is administered. Muscle relaxants affect circulation by inhibition of parasympathetic and sympathetic ganglia, by anticholinesterase activity and by release of histamine.
The classification of neuromuscular diseases with regard to the use of muscle relaxants is based on the localisation of the particular abnormality. Three types of syndromes can be differentiated: (1) denervation states; (2) disturbances of neuromuscular transmission; and (3) intracellular disease. Succinylcholine should be avoided in all types of denervation syndrome due to the possibility of life-threatening hyperkalaemia. The time frame during which succinylcholine must be avoided following a traumatic denervation or burn begins 24 h after the event. The exact period of risk is unknown, but a duration of 6 months can be considered the absolute minimum. Patients may display increased sensitivity to non-depolarising muscle relaxants following damage to the second motoneuron (e.g., amyotrophic lateral sclerosis), whereas in diseases of the first motoneuron (e.g., cerebral apoplexy), increased resistance to muscle relaxants may be observed in the affected parts of the body. In diseases of the neuromuscular junction (myasthenia gravis) there is increased sensitivity to non-depolarising muscle relaxants. No complications have been described following the use of succinylcholine in these patients, however, the use of reversal agents may lead to prolongation of the effect of succinylcholine. Patients with a primary myopathy may display increased sensitivity to non-depolarising muscle relaxants. The use of drugs with acetylcholine-like actions (succinylcholine, reversal agents) should be avoided due to the danger of triggering muscle spasms in patients with myotonic disease and the risk of rhabdomyolysis in patients with dystrophic muscle disease. Irrespective of the type of muscle disease present, titration of the dose of muscle relaxant should always be done using a nerve stimulator.(ABSTRACT TRUNCATED AT 250 WORDS)
Several postsynaptic nondepolarizing muscle relaxants are used today mainly for maintenance of muscular relaxation in surgical operations. They possess a highly selective effect on the cholinoceptors (CC) of the skeletal muscle postsynaptic membrane. Aminosteroid derivatives are important among them. The first to be suggested was pancuronium, and later pipecurium and the monoquaternary aminosteroid derivatives vecoronium and rocuronium. Highly selective muscle relaxants are atracurium and its isomers, cisatracurium in particular, as well as some atracurium derivatives: mivacurium and doxacurium. Tercuronium also has a highly selective effect on the CC of the skeletal muscles.
Hypnosis has been shown to be efficacious in a range of clinical conditions, including the management of chronic pain. However, not all individuals are able to enter a hypnotic state, thereby limiting the clinical utility of this technique. We sought to determine whether hypnotic susceptibility could be increased using three methods thought to facilitate relaxation, with particular interest in an EEG neurofeedback protocol which elevated the theta to alpha ratio. This was compared with progressive muscle relaxation and self-hypnosis. Ten subjects with moderate levels of susceptibility (2-7/12) were randomly assigned to each condition and assessed for hypnotic susceptibility prior to and upon completion of 10 sessions of training. Hypnotic susceptibility increased post-training in all groups, providing further evidence that operant control over the theta/alpha ratio is possible, but contrary to our predictions, elevation of the theta/alpha ratio proved no more successful than the other interventions. Nonetheless, all three techniques successfully enhanced hypnotic susceptibility in over half of the participants (17/30), a similar incidence to that reported using other methods. As previously reported, the majority who were not susceptible to modification were at the lower levels of susceptibility, and the greater increases tended to occur in the more susceptible subjects. However, here enhancement was disclosed in some at low levels, and capability was found of reaching high levels, both features not typically reported. Further research is warranted.
A previous study showed that DA-8159, a potent type 5 phosphodiesterase inhibitor, enhanced the relaxation of the smooth muscles in the normal rabbit corpus cavernosum. In this study, we investigated the in vitro effects of DA-8159 on cavernosal smooth muscle relaxation and the in vivo erectogenic potential in diabetic rabbits, since erectile dysfunction is a well-known sequela of diabetes mellitus. Diabetes mellitus was induced in male New Zealand White rabbits with alloxan monohydrate. Cavernosal strips from age-matched control and 8-week diabetic animals were mounted in organ baths. The relaxation responses to sodium nitroprusside (10(-9)--10(-5) M), a nitric oxide donor, were assessed in the presence or absence of DA-8159 (10(-9)--10(-6) M). For the penile erection test, DA-8159 was given orally (1-10 mg/kg) to diabetic rabbits and the length of the uncovered penile shaft was measured in a time-course manner in the presence or absence of intravenous sodium nitroprusside. The sodium nitroprusside-stimulated relaxations were significantly impaired in the corpus cavernosum from the diabetic group (IC(50)=1.07 x 10(-6) M following 8 weeks of diabetes mellitus; compared with 0.48 x 10(-6) M for age-matched controls). DA-8159 significantly and dose-dependently enhanced the sodium nitroprusside-stimulated relaxation in the diabetic groups. In addition, DA-8159 induced a dose-dependent penile erection in diabetic rabbits, which was potentiated by intravenous sodium nitroprusside. These results suggest that DA-8159 is an effective treatment for diabetic erectile dysfunction but further evaluation of the efficacy on human needs to be performed.
The aim of this study was to evaluate the use of muscle relaxants during induction of anesthesia in patients without risk of aspiration of stomach contents. Of the 2,996 questionnaires sent out, 2,054 (68.6%) could be analysed and the results show that succinylcholine is used regularly in 13.6% of anesthesia departments. The next most commonly used muscle relaxants are atracurium, vecuronium and mivacurium, followed by cis-atracrium, rocuronium and pancuronium. Alcuronium is the least frequently used muscle relaxant. During induction of an elective anesthesia procedure, a priming technique is used by 19% of anesthesiologists, 22% utilize precurarization, and a timing technique is performed in 7.1%. The use of muscle relaxants for on-going relaxation follows the same pattern as for induction of neuromuscular blockade and succinylcholine is used in 1.4% if further relaxation is needed. The desire for specific qualities of muscle relaxants is correlated with higher use of the specific substance: short onset time for rocuronium, good controllability with mivacurium, no side-effects with cisatracurium and economical aspects with alcuronium. Of the participants 76.6% voiced the desire for a non-depolarizing replacement for succinylcholine.Private practices use mivacurium more often than hospitals, level one hospitals use rocuronium and cisatracurium more often. This survey could not show a definite standard of use in terms of muscle relaxants for an elective case.Precurarization, priming and timing are used frequently in patients not at risk of aspiration. This should be reduced by on-going teaching.
The effect of aminophylline on the muscle relaxant action of both diazepam and phenobarbitone was studied in genetically spastic rats of the Han-Wistar strain which exhibit spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Both diazepam (0.8 and 4.0 mg/kg i.p.) and phenobarbitone (20 and 30 mg/kg i.p.) reduced the spontaneous activity measured in the electromyogram in a dose-related manner. Aminophylline (50 mg/kg i.p.), a methylxanthine with potent antagonistic activity of adenosine-mediated inhibition, partially reversed the muscle relaxant action of diazepam (4 mg/kg) but not that produced by phenobarbitone. The muscle relaxant effect of phenobarbitone (30 mg/kg) was antagonised by beta-carboline-3-carboxylic acid methylester (beta-CCM), 2 mg/kg i.p. The reversal of the muscle relaxant effect of phenobarbitone produced by beta-CCM was abolished by CGS 8216 (2-phenylpyrazolo-(4,3c)quinolin-3(5H)-one), 5 mg/kg i.p. Aminophylline altered neither the muscle relaxant effect of a low dose of diazepam (0.8 mg/kg) nor the reversal of the muscle relaxant effect of phenobarbitone produced by beta-CCM. These findings indicate that the interaction between diazepam and aminophylline does not involve competition for the benzodiazepine receptor and add further support to the suggestion that purinergic mechanisms may be engaged in the muscle relaxant action of diazepam.
Sixty-seven patients who had life-threatening reactions to muscle relaxant drugs diagnosed by intradermal testing or challenge were studied. Six patients reacted on two occasions; four reacted to different relaxants. There was a significantly greater ratio of female-to-male patients who reacted than in a nonreacting population. Patients who reacted to muscle relaxants had an incidence of allergy, atopy, asthma, and previous reactions to anesthesia that was significantly greater than nonreacting patients, but not greater than patients who had reacted to induction agents. Eighty-five percent of patients who reacted to muscle relaxants had never previously been exposed to the drug, whereas 60% of patients reacting adversely to induction agents had been previously exposed to induction agents. The reactions were not related to additives or preservatives. In spite of a lack of previous exposure, type I hypersensitivity appears the most likely mechanism responsible for life-threatening reactions to muscle relaxants.
Muscle relaxant effect of Elaeagnus angustifolia L. (Elaeagnaceae) fruit seeds was studied in mice using traction test. The aqueous and ethanolic extracts (i.p) induced a muscle relaxant effect in a dose dependent manner as effective as diazepam (1 mg/kg). The aqueous extract was partitioned with methanol-chloroform (MeCh) and n-butanol (Bu.) saturated with water. The MeCh and Bu. fractions did not show activity. Preliminary phytochemical tests showed that the extract contains flavonoid. The results suggested that E. angustifolia fruit seeds exerted muscle relaxant activity via flavonoid component(s).
OBJECTIVE: To describe the outcomes of a relaxed muscle technique for treatment of dysthyroid strabismus. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Twenty-four patients with thyroid-related orbitopathy (TRO) underwent strabismus surgery using a novel relaxed muscle technique. METHODS: Charts of all patients who underwent rectus muscle recession surgery using a relaxed muscle technique between 1997 and 2004 were reviewed. Twenty-four of 28 patients had more than 2 months of follow-up and were included. The extent of recession was determined by marking where the tendon naturally fell while the relaxed muscle rested freely on the globe with the eye in the primary position. The muscle was sutured to the globe at the mark. Linear regression was used to determine the correlation between the degree of strabismus and the amount of recession required to eliminate diplopia. MAIN OUTCOME MEASURES: Surgical outcomes were analyzed 2 months, 6 months, and 1 year after strabismus repair. Excellent success was defined as no diplopia in primary and reading gazes without prisms. Good outcome was defined as no diplopia in primary and reading positions with the use of <10 prism diopters. Poor outcome was defined as persistent diplopia in primary or reading positions despite prisms, or the inability of the patient to tolerate the necessary prisms. RESULTS: Twenty-four patients underwent 60 muscle recessions. Nine had diplopia without a history of orbital decompression, 8 had diplopia before decompression, and 7 developed diplopia only after orbital decompression. Twenty-one patients (87.5%) had an excellent final outcome. A clinically acceptable (excellent or good) final outcome was achieved in 24 of 24 patients (100%) after an average of 1.08 surgeries. All 7 patients who developed diplopia only after decompression had an excellent outcome. Linear regression did not show good correlation between the degree of strabismus and the amount of recession required to eliminate diplopia (maximum R2 = 0.7292). There were no complications. CONCLUSIONS: The relaxed muscle technique provides excellent ocular alignment and relief from diplopia in a majority of patients with TRO-associated strabismus. Patients who develop diplopia only after orbital decompression may have a higher success rate.