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PubMed1988

Rapid pre-operative immunotherapy in a patient allergic to muscle relaxants.

Allergic reactions to muscle relaxants are not uncommon. Although, in most instances, divalent quaternary ammonium salts are involved in these reactions, some monovalent quaternary ammonium compounds can trigger IgE-mediated reactions. A woman who suffered from several episodes of anaphylaxis with divalent (suxamethonium) and monovalent quaternary ammonium salts (tiemonium) needed surgery. Regional anaesthesia was contra-indicated owing to a possible intolerance to local anaesthetics. Investigation confirmed an allergy to monovalent quaternary ammonium salts. Rapid immunotherapy was started with a monovalent quaternary ammonium salt (tiemonium) and subsequently followed by a general anaesthesia using vecuronium. The patient did not develop anaphylactic symptoms.

Adult↗
PubMed2005

Uterine muscle relaxant drugs for threatened miscarriage.

BACKGROUND: Miscarriage is the spontaneous loss of a pregnancy before the fetus is viable. Uterine muscle relaxant drugs have been used for women at risk of miscarriage in the belief they relax uterine muscle, and hence reduce the risk of miscarriage. OBJECTIVES: To assess the effects for the woman and her baby of uterine muscle relaxant drugs when used for threatened miscarriage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (4 May 2004), and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004). SELECTION CRITERIA: Randomised trials were included, and quasi-randomised trials were excluded. The participants were women with a pregnancy of less than 20 weeks' gestation having a threatened miscarriage. The interventions were any uterine muscle relaxing drugs (including tocolytic and antispasmodic agents) compared with either placebo or no drug. Primary outcomes for the review were miscarriage: defined as spontaneous pregnancy loss before fetal viability, baby death (stillbirth or neonatal death) and maternal death. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed studies for eligibility and trial quality, and extracted data. MAIN RESULTS: One poor quality trial (170 women) was included. This compared a beta-agonist with placebo. There was a lower risk of intrauterine death associated with the use of a beta-agonist (relative risk (RR) 0.25, 95% confidence interval (CI) 0.12 to 0.51). Preterm birth was the only other outcome reported (RR 1.67, 95% CI 0.63 to 4.38). AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of uterine muscle relaxant drugs for women with threatened miscarriage. Any such use should be restricted to the context of randomised trials.

Abortion, Threatened↗
PubMed1993

Quantitative grip strength assessment as a means of evaluating muscle relaxation in mice.

The effects of various centrally acting drugs and some peripherally acting agents on the forelimb grip strength of CD-1 mice were explored. Forelimb grip strength was assessed by use of a strain gauge to measure the lateral pull force, in grams, exerted by mice as an index of muscle relaxation. The muscle relaxants, diazepam, midazolam, baclofen, methocarbamol, dantrolene sodium and the neuromuscular blocking agents, succinylcholine and pancuronium bromide, dose-dependently reduced forelimb grip strength. 2-Amino-7-phosphonoheptanoic acid (AP7), which has also been shown to have muscle relaxant effects, also reduced grip strength. Pentobarbital, ethanol, phencyclidine, ketamine and chlorpromazine reduced grip strength at doses which produced behavioral impairments. Lithium chloride, a toxic compound used to induce taste aversions, and clonidine, at doses which affect blood pressure, body temperature and locomotor activity, did not affect grip strength. In addition, stimulant doses of amphetamine and caffeine, but not of morphine, increased grip strength in a dose-dependent manner. These results extend previous findings and suggest that this forelimb grip strength procedure may be a useful screening test for the identification of the potential muscle relaxant properties of drugs.

Animals↗
PubMed1989

[Prospective preoperative survey of 300 patients using prick tests with muscle relaxants].

It is now well established that the retrospective diagnosis of anaphylaxis to muscle relaxants may be based on skin prick testing. These tests, which use undiluted solutions of muscle relaxants, are as sensitive, specific and reproducible as intradermal tests for the diagnosis of IgE related adverse reactions to muscle relaxants. The rate of muscle relaxant anaphylaxis (1/1 500 to 1/5 000) justifies its prevention based on a possible latent sensitization. A prospective investigation was carried out in 300 surgical patients scheduled for general anaesthesia. Prick tests were carried out using the 6 available muscle relaxants: suxamethonium, gallamine, alcuronium, pancuronium, vecuronium and atracurium. The wheal the drug might produce was compared with that obtained with codeine phosphate (a histamine releasing drug). Thirty-seven patients (13%) were considered to be atopic; 262 (87%) had undergone a previous anaesthesia. Three percent (n = 11) of tests were positive for atracurium. The wheal produced by atracurium was in favour of non-specific histamine release. One test was found positive for suxamethonium. Confirmation of this probable latent sensitization was unfortunately not possible. There were no other positive skin tests. Muscle relaxants were subsequently used in 58 patients (80% vecuronium) without any problem. Skin prick testing should be used on a larger scale to detect latent sensitization. However, predictive skin tests with atracurium should be avoided, as wheal reactions with this drug are probably due to non-specific histamine release.

Adolescent↗
PubMed2002

Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine.

The centrally acting muscle relaxant tizanidine has an imidazoline structure and binds not only to alpha(2)-adrenoceptors but also to imidazoline receptors. The role of imidazoline receptors in the muscle-relaxant effect of tizanidine was studied using the alpha(2)-adrenoceptor/imidazoline receptor antagonist idazoxan and the alpha(2)-adrenoceptor antagonist yohimbine. Tizanidine decreased the spinal mono- and polysynaptic reflexes in intact rats, and the inhibitory effects were antagonized by idazoxan but not by yohimbine. After pretreatment with prazosin, tizanidine decreased the mono- and polysynaptic reflexes in spinalized rats. While yohimbine partly inhibited tizanidine-induced depression of the polysynaptic reflex, idazoxan completely abolished tizanidine-induced depression of spinal reflexes. Furthermore, tizanidine-induced muscle relaxation in the traction test was significantly inhibited by idazoxan but not by yohimbine. From these results, it is suggested that imidazoline receptors, but not alpha(2)-adrenoceptors, are involved in the supraspinal inhibitory effects of tizanidine on spinal reflexes, and at the spinal level, alpha(2)-adrenoceptors and imidazoline receptors are involved in the inhibitory effects of tizanidine.

Animals↗
PubMed1983

Detection of serum IgE antibodies that react with alcuronium and tubocurarine after life-threatening reactions to muscle-relaxant drugs.

Although anaphylactoid reactions to muscle-relaxant drugs are now well recognised, there has been no general agreement on the mechanism(s) underlying the responses. By covalently coupling alcuronium and tubocurarine to a solid phase carrier and using the resultant complexes in radioimmunoassay experiments with patients' sera and 125I-anti-human IgE, we have found high levels of drug-specific IgE antibodies in the sera of some subjects who reacted to these muscle relaxants. These results provide important supporting evidence that, in some patients at least, life-threatening anaphylactoid reactions to muscle-relaxant drugs are mediated by drug-specific IgE antibodies.

Adult↗
PubMed2004

Transdermal eperisone elicits more potent and longer-lasting muscle relaxation than oral eperisone.

Eperisone hydrochloride is widely used for the treatment of plasticity to relieve muscle stiffness and back pain. However, oral eperisone has a very low bioavailability and short muscle relaxant activity, because of the profound intestinal first-pass metabolism. To improve the efficacy and compliance of eperisone, we designed a new dosage form, a transdermal patch, and evaluated the efficacy of the eperisone patch with the muscle relaxant activity of rats. The muscle relaxant activity was assessed by the measurement of forelimb grip strength and hanging test in rats. The transdermal patch of eperisone showed significantly enhanced muscle relaxant activity at 0.5 1.5 and 3 cm2/200 g rat (1.39, 4.17 and 8.33 mg of eperisone hydrochloride/kg, respectively) in a dose-dependent manner and the effects lasted over 24 h. Even though oral eperisone hydrochloride showed significant muscle relaxant activity at 12.5, 25 and 50 mg/kg in a dose-dependent manner, the activity lasted only 1 or 2 h after administration. These results suggest that eperisone as transdermal patch form showed efficient absorption with more potent and longer-lasting muscle relaxant activity than oral solution. The transdermal patch form of eperisone will increase the efficacy and compliance in the clinical use of eperisone.

Administration, Cutaneous↗
PubMed1986

On-line control of atracurium induced muscle relaxation.

We described recently a microcomputer system capable of controlling muscle relaxation during surgical procedures; the system was tested and evaluated in 42 clinical trials involving the use of the muscle relaxant, d-tubocurarine. The advent of new non-depolarizing neuromuscular blocking drugs with significant clinical advantages makes it essential that any automatic control system for muscle relaxation can also be used with such drugs, and benefit from their improved properties. This paper describes a series of 22 clinical trials in which our controller was used successfully to control muscle relaxation using atracurium. We also investigated an alternative control strategy, taking advantage of the rapid elimination of atracurium from the body.

Atracurium↗
PubMed2004

The multiple mediators of neurogenic smooth muscle relaxation.

The regulation of smooth muscle relaxation is vitally important for normal functioning of respiratory airways, gastrointestinal organs and the circulatory system. Since the recognition that such relaxation is not under adrenergic or cholinergic control, there has been an active search for the nonadrenergic, noncholinergic (NANC) mediators. A recent paper highlights the complex but coordinated control of the internal anal sphincter by three neurotransmitters.

Animals↗
PubMed2005

Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation.

It has been reported that nitric oxide (NO) is involved in the relaxation mechanism of ginsenoside saponin in various smooth muscle in experimental animals. Although ginsenoside Rg(3) showed both endothelium-dependent and -independent component relaxation in vascular smooth muscle, the action mechanism of the relaxation of corporal muscle is not clear. We, thus, investigated the relaxation mechanism of ginsenoside Rg(3) using isolated canine corpus cavernosum. Ginsenoside Rg(3) concentration-dependently relaxed the canine corpus cavernosum that had been contracted by phenylephrine (PE), in which IC(50) was 1.68 x 10(-5) g/ml. Ginsenoside Rg(3) significantly (P < 0.05) potentiated acetylcholine (ACh)-induced relaxation in endothelium intact corpus cavernosum. Methylene blue (MB) but not N(omega)-nitro-L-arginine methylester (L-NAME) or ODQ (1H-[1,2,4]oxadiazol-[4,3-]quinoxsalin-1-one) modified the dose-response curve of ginsenoside Rg(3). Ginsenoside Rg(3) also significantly potentiated relaxation response to UV light in the presence of streptozotocin (STZ), which was almost completely (P < 0.01) blocked by ODQ. Ginsenoside Rg(3) concentration-dependently inhibited corporal phosphodiesterases (PDE), which resulted in increase of cyclic adenosine monophosphate (cAMP) as well as cyclic guanosine monophosphate (cGMP) contents in corporal smooth muscles. MB inhibited the accumulation of cGMP but not cAMP by ginsenoside Rg(3). These results indicate that mechanism responsible for the relaxation by ginsenoside Rg(3) is not by stimulating endothelial nitric oxide synthase (eNOS) of the canine corporal smooth muscle but by increasing cyclic nucleotide levels through PDE inhibition.

Animals↗
PubMed1978

Pharmacological profile of N-(2,6-DIMETHYLPHENYL)-N-(1-methyl-2pyrrolidinylidene)urea, xilobam, a new centrally acting skeletal muscle relaxant.

The pharmacological profile of a new centrally acting skeletal muscle relaxant, xilobam, is described and compared to that of existing skeletal muscle relaxants. The potencyof xilobam, administered intravenously, is approximately ten times that of methocarbamol in the linguomandibular assay in the cat. When evaluated in the strychnin assay in the mouse, the potency of xilobam is approximately seven times that of chlorzoxazone and eleven tomes that of methocarbamol and five times that of metaxalone. In contrast to methocarbamol, xilobam exhibits little or no sedative activity and appears devoid of antianxiety properties. When administered to non-anesthetized dogs, xilobam and other centrally acting muscle relaxants, such as chlorzoxazone and methocarbamol, increased arterial pressure and heart rate. Mydraiasis, vocalization and muscle rigidity were concomitantly observed. These effects appear to be centrally induced. It is concluded that xilobam appears to be a potent centrally acting muscle relaxant which should not be sedating or anxiolytic in man.

Animals↗
PubMed1975

The role of bronchoconstrictors in evaluating smooth muscle relaxant activity.

Several bronchoconstrictor and smooth muscle relaxant agents were studied in a dog preparation (in vivo) and on guinea pig tracheal strips (in vitro). Isoproterenol, isoetharine and N-t-butylnorepinephrine, individually, had similar dose-response curves and ED50 values when tested as antagonists of histamine and carbamylcholine-induced bronchoconstriction in dogs. Diphenhydramine, cyproheptadine, thenyldiamine, atropine and suloxifen each exhibited more selective antagonism. A ratio of anticholinergic and antihistamine ED50s was obtained in dogs and on guinea pig tracheal strips. The rank order correlation coefficient of this ratio for each drug in the two species (rs = 0.93) was highly significant. Dose-responses to smooth muscle relaxant effects of isoproterenol were obtained with several different constrictors and experimental conditions on guinea pig tracheal strips. The choice of a constrictor and experimental conditions was found to affect EC50 values. The influence of resting tension, temperature, season, dibenamine-pretreatment and manner of performing the dose-response was evaluated. Both Ba and carbamylcholine were found to be suitable constricting agents under various conditions, whereas histamine, serotonin, potassium and rubidium had more limitations and eight other inorganic ions were not suitable.

Aerosols↗
PubMed1998

The impact of price labeling of muscle relaxants on cost consciousness among anesthesiologists.

STUDY OBJECTIVE: To determine whether placing price labels on the vial caps of muscle relaxants increases cost consciousness among anesthesiologists. DESIGN: Retrospective study. SETTING: University hospital departments of anesthesia and pharmacy. MEASUREMENTS AND MAIN RESULTS: We placed price labels on the vial caps of all muscle relaxants for a study period of 1 year. At the beginning of the investigation, we informed the anesthesiologists of the study, discussed the prices for different muscle relaxants, and encouraged utilizing less expensive muscle relaxants whenever possible without compromising patient care. The price labels on the vial caps served as visual reminders of the various costs of muscle relaxants during daily practice. We compared the total amount spent on each muscle relaxant during the period from October 1993 to September 1994 with the period from October 1994 to September 1995. The total number of surgical cases from October 1993 to September 1994 and from October 1994 to September 1995 was unchanged and equaled 20,389 and 20,358 cases, respectively. Expenditures for pancuronium increased 104.1%. Total expenditure decreased by 12.5%, with a net savings of $47,111. CONCLUSION: Expenditures for the less costly pancuronium increased while expenditures for vecuronium and atracurium decreased. Price labeling of muscle relaxants in conjunction with education reduces total pharmacy expenditure on muscle relaxants.

Androstanols↗
PubMed1983

Adverse reactions to suxamethonium and other muscle relaxants under general anesthesia.

The mechanisms of anaphylactic reactions to muscle relaxants under general anesthesia are not completely understood. Extending an earlier study, we report 41 cases of anaphylactic shock investigated by intradermal skin tests with muscle relaxants (suxamethonium, pancuronium, gallamine, nortoxiferine), in vitro leukocyte histamine release, and Prausnitz-Küstner tests. Intradermal tests were significantly positive at concentrations ranging from 10 to 10(5) times less than those in controls. Reproducibility tested for suxamethonium at a 1-year interval in five patients was good. Histamine release induced by muscle relaxants in Tris-albumin-Ca++-Mg++ buffer showed positive results in 8/25 instances and was inhibited by antigen excess in seven cases. Addition of 50% deuterium oxide (D2O) caused significant increase of histamine release in positive cases and induced release in all five negative cases studied. Muscle relaxant-induced histamine release was inhibited by in vitro anti-IgE leukocyte desensitization. The mean maximal histamine release dropped from 58.2% +/- 9.7 to 5.8% +/- 2 (p less than 0.01). Similarly, leukocyte desensitization also inhibited histamine release induced by anti-IgE but not by formyl-L-methionyl-L-leucyl-L-phenylalanine or poly-L-arginine. Prausnitz-Küstner tests were positive in five out of 21 cases studied and became negative after heat inactivation. These results confirm the usefulness of intradermal skin tests in diagnosis of patients' reaction to muscle relaxants and suggest an IgE-mediated rather than an idiosyncratic mechanism.

Adult↗
PubMed1999

Subsequent general anaesthesia in patients with a history of previous anaphylactoid/anaphylactic reaction to muscle relaxant.

Of 151 patients with a possible anaphylactoid/anaphylactic reaction to a muscle relaxant investigated over a 20-year period, follow-up for any subsequent general anaesthesia was complete in 145 (96%). One hundred and twenty-two anaesthetics in 72 patients were documented. There were no anaesthetic-related deaths. No subsequent reactions were seen if muscle relaxants were not used in the subsequent anaesthetic, nor were they in patients with severe reactions if the original intradermal test had been equivocal or negative. In the patients with a severe reaction and a positive intradermal test to one or more muscle relaxants, six out of 40 later anaesthetics using muscle relaxants were associated with clinical problems, three being probable anaphylactic reactions, whilst three were minor. Intradermal testing should be performed prior to surgery in this group of patients for the muscle relaxant(s) planned, or an anaesthetic technique which avoids relaxants should be used. This review should encourage other centres to undertake similar follow-up.

Adult↗
PubMed2005

Reversed ipsilateral acoustic reflex: a study on subjects treated with muscle relaxants.

OBJECTIVES: To rule out any possible involvement of the middle ear muscles in the genesis of the reversed ipsilateral acoustic reflex (RIAR). DESIGN: Prospective study to evaluate the effects of muscle relaxants on the RIAR of otosclerotic ears as well as on the acoustic reflex of individuals with normal middle ear function. Admittance recording during ipsilateral acoustic stimulation was performed in patients undergoing pharmacological treatment for surgical procedures. Fentanyl, propofol, and a muscle relaxant were sequentially administered intravenously. Ipsilateral acoustic reflexes were recorded before and after each drug injection. Three patients were affected from otosclerosis, whereas 14 individuals had normal middle ear function. Moreover, the ipsilateral acoustic reflex obtained in normal subjects after their treatment with muscle relaxants was compared with that of 10 otosclerotic patients who were not treated pharmacologically. RESULTS: The RIAR of three otosclerotic ears was not inhibited by muscle relaxants as well as by fentanyl and propofol. Moreover, muscle relaxants, when administered in normal subjects, always induced the block of the stapedial reflex that was replaced by a reversed reflex strictly similar to the RIAR of the 10 otosclerotic patients not treated pharmacologically. Propofol could also induce, in most of the cases, the reduction and in some occasion even the reversal of the stapedial reflex, whereas fentanyl did not affect it significantly. CONCLUSION: The RIAR does not appear to be related to the contraction of the middle ear muscles.

Acoustic Stimulation↗
PubMed1984

[A comparison of the effects of baclofen and some other muscle relaxants on alpha-rigidity in rats].

Muscle relaxant effects of baclofen were compared with those of dantrolene, diazepam, chlordiazepoxide and tolperisone. When administered intraduodenally (i.d.), baclofen and dantrolene but not diazepam suppressed the sustained rigidity of forelimbs in anemically decerebrated rats, and ED50 values of the former two drugs were 2.9 and 22 mg/kg, respectively. Baclofen, dantrolene and diazepam reduced the phasic rigidity of the decerebrated animals induced by mechanical stimulation of hindlimbs, with their respective ED50 values of 6.2, 140 and 1.4 mg/kg, i.d. Both the rigidities were almost insensitive to chlordiazepoxide and tolperisone. With the exception of tolperisone, these drugs also produced a muscle relaxation in intact animals as measured by traction (rats), rotarod (mice), and grip-strength (mice) tests. ED50 or eD25 values were calculated to be in the following ranges: 5.6 approximately 12 mg/kg, p.o. for baclofen, 15 approximately 35 mg/kg, p.o. for dantrolene, 2.1 approximately 6.5 mg/kg, p.o. for diazepam and 33 approximately 64 mg/kg, p.o. for chlordiazepoxide. These results suggest that baclofen, unlike other drugs, may be effective in reducing both tonic and phasic rigidities at lower doses than those causing muscle relaxation in intact animals.

Animals↗
PubMed2004

Skeletal muscle relaxant use in the United States: data from the Third National Health and Nutrition Examination Survey (NHANES III).

STUDY DESIGN: Population-based cross-sectional prevalence survey. OBJECTIVES: To define muscle relaxant use patterns in the United States. SUMMARY OF BACKGROUND DATA: Despite a long history of use for back pain and musculoskeletal disorders, national prevalence patterns of prescription muscle relaxant use have not been defined. METHODS: NHANES III (1988-1994) is an in-person health examination survey of the U.S. civilian population, based on a complex, multistage probability sample design. RESULTS: An estimated 2 million American adults reported muscle relaxant use (1-month period prevalence 1.0%; 95% confidence interval 0.8-1.3%). While virtually all (94%) used individual muscle relaxants rather than fixed combination muscle relaxant analgesics, two thirds took an additional prescription analgesic. Men and women had similar usage. Median user age was 42 years, but 16% of users were older than 60 years. Eighty-five percent of users took muscle relaxants for back pain or muscle disorders. Two thirds of muscle relaxant users had histories of recent back pain; however, only 4% of all those with a recent history of back pain reported any muscle relaxant use. Mean length of use was 2.1 years (95% confidence interval 1.6-2.6), with 44.5% taking medication longer than a year (95% confidence interval 35.7-53.3). Muscle relaxant use in the elderly, among older persons with ambulatory impairments, and in chronic obstructive pulmonary disease appeared undiminished compared with general population use. CONCLUSIONS: Although typically recommended for short-term treatment of back pain, muscle relaxants are often used chronically and are prescribed to subpopulations potentially at risk for adverse effects.

Adolescent↗