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PubMed2001

Smooth muscle relaxation and local hydraulic impedance properties of the aorta.

Smooth muscle relaxation is expected to yield beneficial effects on hydraulic impedance properties of large vessels. We investigated the effects of intravenous diltiazem infusion on aortic wall stiffness and local hydraulic impedance properties. In seven anesthetized, closed-chest dogs, instantaneous cross-sectional area and pressure of the descending thoracic aorta were measured using transesophageal echocardiography combined with acoustic quantification and a micromanometer, respectively. Data were acquired during a vena caval balloon inflation, both at the control condition and with diltiazem infusion. At the operating point, diltiazem reduced blood pressure in all dogs but did not alter aortic dimensions or wall stiffness. Over the observed pressure range, aortic area-pressure relationships were linear. Whereas diltiazem affected the slope of this relationship variably (no change in 3 dogs, increase in 1 dog, decrease in 3 dogs), the zero-pressure area intercept was significantly increased in every case such that higher area was observed at any given pressure. When comparisons were made at a common level of wall stress, wall stiffness was either increased or unchanged during diltiazem infusion. In contrast, diltiazem decreased wall stiffness in every case when comparisons were made at a common level of aortic midwall radius. Aortic characteristic impedance and pulse wave velocity, components of left ventricular hydraulic load that are determined by aortic elastic and geometric properties, were affected variably. A comparison of wall stiffness at matched wall stress appears inappropriate for assessing changes in smooth muscle tone. Because of the competing effects of changes in vessel diameter and wall stiffness, smooth muscle relaxation is not necessarily accompanied by the expected beneficial changes in local aortic hydraulic impedance. These results can be reconciled by recognizing that components other than vascular smooth muscle (e.g., elastin, collagen) contribute to aortic wall stiffness.

Algorithms↗

PubMed2000

[Centrally acting muscle relaxants and traffic hazards].

BACKGROUND: An increasing number of the centrally acting muscle relaxants were withdrawn from the Norwegian market during the 1988-98 period. The only drug in this group now marketed in Norway is carisoprodol. The National Institute of Forensic Toxicology in Norway analyses all blood samples from suspected drugged drivers. In later years there has been a marked increase in the number of blood samples testing positive for carisoprodol or meprobamate (the major metabolite). MATERIAL AND METHODS: 480 cases testing positive for central muscle relaxants in the years 1984-1998 were further studied. RESULTS: Compared with blood samples positive primarily for benzodiazepines, there were more women in the group (39% vs. 15%), and fewer drugs and less alcohol were detected. INTERPRETATION: The positive samples may indicate misuse or abuse due to the fact that high drug concentrations and concomitant use of benzodiazepines were frequent. This knowledge should have implications for doctors prescribing centrally acting muscle relaxants.

Accidents, Traffic↗

PubMedDate not supplied

Antagonism of anthracene-9-carboxylic acid as screening test for muscle relaxants.

Veratrinic response produced by anthracene-9-carboxylic acid in mice has been used as a model for studying effect of variety of drugs which induce muscle relaxation. None of the drugs listed as general depressants, central muscle relaxants, neuromuscular blocking agents and anti-convulsants were effective even at doses causing 100% loss of righting reflex. Local anaesthetics/direct acting muscle relaxants were effective. This simple model employed in conjunction with Straub's tail test can differentiate various categories of muscle relaxants and their mechanism of action.

Anesthetics, Local↗

PubMed1995

Is systematic preoperative screening for muscle relaxant and latex allergy advisable?

We investigated a female population prior to general anaesthesia, using skin prick tests with latex and muscle relaxants to appraise the validity and feasibility of a systematic preoperative screening for these substances. Anaesthetists performed skin tests, and positive and doubtful tests were checked in our allergy department. Of 114 patients, 42 had uninterpretable tests because of dermographism (28 patients) or suppression of skin reactivity (14 patients). Among the other 72, nine had a positive or doubtful test to latex, and seven a positive or doubtful test to one or more muscle relaxants. After checking, only four sensitizations to latex and one to muscle relaxant were confirmed. In conclusion, a systematic screening for latex and muscle relaxant allergy is not advisable. In contrast, screening for latex allergy in selected high-risk groups (spina bifida, health-care workers) is necessary.

Adult↗

PubMed2000

Remifentanil and propofol without muscle relaxants or with different doses of rocuronium for tracheal intubation in outpatient anaesthesia.

BACKGROUND: The use of muscle relaxants in outpatient anaesthesia is controversial; some authors recommend an induction regimen including propofol and opioids without muscle relaxants. This study evaluated the requirements for rocuronium after remifentanil/propofol. METHODS: We examined in four groups of ASA I-II patients (n= 30 for each) the intubating conditions three minutes after induction of anaesthesia with remifentanil 0.5 microg kg(-1) min(-1), propofol 2 mg kg(-1) without muscle relaxants or with different doses of rocuronium (0.6 mg kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1)) applying the criteria proposed by the Copenhagen Consensus Conference. In the second part of the study the time course of neuromuscular block was determined by electromyography using train-of-four (TOF) stimulation. To this end, another 60 ASA I-II patients were randomly assigned to receive remifentanil 0.5 microg kg(-1) min(-1), propofol 2 mg kg(-1) and either rocuronium 0.6 mg kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1), or 0.3 mg kg(-1) followed by neostigmine 40 microg kg(-1) and atropine 20 microg kg(-1) at a T1 recovery of 10% (n=15 for each). RESULTS: Intubating conditions were good or excellent in 30 patients after rocuronium 0.6 mg kg(-1) and in 18 patients when rocuronium was omitted (P<0.01). After 0.45 mg kg(-1) and 0.3 mg kg(-1) rocuronium the numbers were 29 and 30 patients, respectively. Reducing rocuronium from 0.6 mg kg(-1) to 0.45 mg kg(-1) or 0.3 mg kg(-1) increased the onset time from 136 (35) s to 199 (34) s and 249 (52) s (mean (SD)), (P<0.01); the clinical duration decreased from 38 (10) min to 24 (8) min and 16 (5) min, respectively (P<0.01); and the duration to a TOF-ratio of 0.8 decreased from 60 (11) min to 45 (9) min and 34 (7) min (P<0.01). After rocuronium 0.3 mg kg(-1) this time interval further decreased to 22 (3) min when neostigmine was given at a T1 of 10% (P<0.01 compared with spontaneous recovery after rocuronium 0.3 mg kg(-1)). CONCLUSION: After remifentanil/propofol intubation conditions were poor in 40% of patients without muscle relaxants; adding reduced doses of rocuronium to this regimen improved the intubation conditions significantly. In addition, reducing the initial dose of rocuronium markedly shortened its time course of action.

Adult↗

PubMed1984

Eserine-induced hypertone of guinea pig distal colon in vivo: a new pharmacological procedure for testing smooth muscle relaxants.

A new in vivo procedure suitable for testing the smooth muscle relaxant properties of a test substance is described. Topical eserine produced a long-lasting steady increase in tone of guinea pig distal colon and enhanced the atropine-sensitive phasic activity. Intravenously administered atropine, pirenzepine, and dicyclomine (which possess competitive antimuscarinic properties) produced a dose-related inhibition of eserine-induced muscle tone and suppressed phasic contractions. On the other hand, verapamil and octylonium bromide (which produce smooth muscle relaxation by interfering with Ca++ availability for contraction) did not suppress phasic contraction although they were fully effective in inhibiting eserine-induced tone. The eserine-induced contraction of guinea pig distal colon appears to be a suitable, quick, and inexpensive test for evaluating the effects of potential smooth muscle relaxants against background hypermotility produced by amplifying the neurogenic drive to the target organ.

Animals↗

PubMed1981

A new skeletal muscle relaxant (DS 103-282) compared to diazepam in the treatment of muscle spasm of local origin.

The myotonolytic activity of a new muscle-relaxant, DS 103-282, was compared with that of diazepam in a randomized double-blind study on thirty patients suffering from acute muscular spasm due to disorders of the cervical and lumbar segments of the spine. Fifteen patients received 5 mg DS 103-282 and fifteen received 5 mg diazepam on a three times daily regime for 7 days. DS 103-282 was found to alleviate symptoms and improve mobility to a significant degree (p less than or equal to 0.05) in all parameters evaluated and was also significantly superior to diazepam in 5 of these. Onset of action was particularly rapid for DS 103-282. Both medications were well tolerated and there was no significant difference between them. On the basis of these data DS 103-282 may be considered a more powerful and faster-acting myotonolytic agent than diazepam with which it was compared in similar clinical indications.

Adult↗

PubMed1981

Smooth muscle relaxing drugs and guinea pig ileum.

The effects of various smooth muscle relaxing drugs on contractile responses to acetylcholine (ACh), Ba2+ and Ca2+, and on the tissue cyclic AMP levels were examined in the guinea pig ileum. Papaverine and theophylline caused a decrease both in the maximum height and the slope of dose-response curves induced by the three stimulants, and an increase in the cyclic AMP levels. Diltiazem and D-600 produced a decrease in the maximum and the slope of ACh and Ba2+ dose-response curves, shifted the Ca2+ dose-response curves to higher concentrations, in a parallel manner, but failed to change the cyclic AMP levels. Etomidoline and benactyzine shifted the curves for the three stimulants in parallel to the right, but at higher concentrations depressed the maximum of ACh and Ba2+ responses with a further parallel shift. These drugs exerted little influence on the basal level of tissue cyclic AMP, but etomidoline significantly depressed the Ba2+ -induced increase in cyclic AMP level. The smooth muscle relaxing drugs used could be classified in three types, thereby suggesting that there are at least three different mechanisms involved in smooth muscle relaxing action.

Acetylcholine↗

PubMed1983

[Use of muscle relaxants under electrostimulation anesthesia (ESA)].

A comparative study was made of the consumption of muscle relaxants during electrostimulation anaesthesia (ESA) in comparison to halothane anaesthesia and neurolept anaesthesia. 441 operations (struma surgery, saphenous vein bypass grafts, varicotomies) showed a significantly raised consumption of muscle relaxants when performed under ESA. For struma surgery and varicotomies the consumption was 17.2% respectively 13.9% higher than during halothane anaesthesia and for vein bypass grafting 14.3% higher than during neurolept anaesthesia. The potentiating effect of inhalation anaesthetics on muscle relaxants and the possibility of an activation of the reticular formation via electrical stimulation of muscular and nervous tissues under ESA are discussed.

Anesthesia↗

PubMed1983

Anaphylaxis to muscle relaxant drugs: cross-reactivity and molecular basis of binding of IgE antibodies detected by radioimmunoassay.

IgE antibodies that bind the muscle relaxant alcuronium were found in sera from six patients who experienced anaphylactic-like reactions following administration of the drug during induction of anaesthesia. Drug-specific antibodies were detected by radioimmunoassay employing a covalently coupled alcuronium-Sepharose complex and 125I-labelled anti-human IgE. Quantitative inhibition studies undertaken with the sera revealed specificity differences between IgE antibodies from different patients. One serum reacted with alcuronium but not with five other muscle relaxants, decamethonium, gallamine, pancuronium, succinylcholine and tubocurarine. IgE antibodies in the other sera cross-reacted with the muscle relaxants, other quaternary ammonium compounds and some pharmacologically unrelated drugs including promethazine, morphine, neostigmine and pentolineum. The inhibition experiments revealed that the alcuronium-IgE reaction could be prevented or diminished by structures containing a substituted ammonium ion. As these ions occur widely in man's environment in drugs, cosmetics, disinfectants, foods and industrial materials, it seems possible that sensitization of patients may occur without previous exposure to muscle relaxants.

Adult↗

PubMed1979

Anaphylactic reactions to muscle relaxants under general anesthesia.

Eleven patients who suffered a reaction to the administration of muscle relaxants during induction of general anesthesia were explored using skin tests, leukocyte histamine release, lymphocyte transformation test, and the Prausnitz-Küstner test (P-K). Fifteen normal subjects served as controls. Patients who suffered a reaction showed considerable cutaneous hypersensitivity to muscle relaxants. Leukocyte histamine release was positive in three cases and the P-K test was positive in one case. These findings suggest possible specific serum IgE antibodies to muscle relaxants. However, reliable discrimination between immunological and idiosyncratic pharmacological mechanism is difficult to obtain.

Anaphylaxis↗

PubMed1982

Clinical experience with ORG NC45 (norcuron) as the sole muscle relaxant.

The neuromuscular effects of ORG NC45, used as the sole muscle relaxant, were compared with a succinylcholine-pancuronium sequence in patients during nitrous oxide-fentanyl anaesthesia. The subjects were divided into four groups with ten in each group. After induction of anaesthesia they received either succinylcholine, 1 mg . kg-1 or ORG NC45 in doses of 50, 70 or 90 micrograms . kg-1 and tracheal intubation was done 90 seconds later. Neuromuscular transmission was monitored using train-of-four stimulation. Succinylcholine produced 100 per cent block with uniformly excellent intubating conditions whereas the three doses of ORG NC45 were associated with blocks of 7.5, 18.7 and 30.7 per cent and acceptable conditions in only 30 per cent of subjects. Muscle relaxation was maintained in the NC45 groups with increments of 10 micrograms . kg-1 and in the succinylcholine group with pancuronium, initially as a bolus of 40 micrograms . kg-1, followed by increments of 5 mg . kg-1. All increments were given at 10 per cent recovery of twitch height. The overall requirement to maintain 90 per cent block with pancuronium was 1.1 microgram/kg-1 . min-1 compared with 1.28 microgram . kg-1 . min-1 with ORG NC45. No cumulative effects were seen with either drug during the first hour of neuromuscular blockade. At the end of the operation the neuromuscular block was antagonized with atropine 18 micrograms . kg-1, and neostigmine 36 micrograms . kg-1 and recovery was significantly more rapid with NC45 than pancuronium. We conclude that the lack of cumulation, easy reversibility and lack of cardiovascular effects suggest that NC45 has advantages over currently available non-depolarizing muscle relaxants but that its onset of action is too slow for rapid intubation.

Adult↗

PubMed1992

Clinical evaluation of in vitro leukocyte histamine release in allergy to muscle relaxant drugs.

We have evaluated the in vitro leukocyte histamine release tests for the diagnosis of allergy to muscle relaxant drugs in 40 patients (Group A) and a control group of 44 subjects with negative leukocyte histamine release (Group B). Non-IgE dependent histamine release, expressed as a percentage of the total blood histamine, was 3.94% +/- 0.49 in Group B. The upper limit of positivity was estimated to be 5% (mean + 2 SD). Leukocyte histamine release tests were positive in 65% of the patients from Group A. The concordance between LHR and QAS-RIA was 64%. The maximal histamine release was observed at dilutions of 10(-2)-10(-4) in 20 of the 26 positive cases. The maximal histamine release was 43.8% +/- 23.3. The spontaneous histamine release was as low as 1.7% +/- 1.1. Cross-reactivity among the 5 different muscle relaxant drugs has been investigated and compared by intradermal testing. The muscle relaxant drugs which gave the lower skin reaction (M2) and the drug responsible for shock (M1) were selected for the study of in vitro leukocyte histamine release. Of 20 M2. All of the 10 cases had negative ID tests with M2. Three of these patients subsequently underwent general anesthesia with the muscle relaxant chosen as harmless (M2) without any clinical reaction.

Adult↗

PubMed1993

Characterization of calcium channel blocker induced smooth muscle relaxation using a model of isolated corpus cavernosum.

Several classes of smooth muscle relaxing agents have proven effective in relaxing cavernosal smooth muscle and useful in the pharmacotherapy of erectile dysfunction. The purpose of this investigation was to determine whether the calcium channel blockers (CCB) relax cavernosal smooth muscle. Thirty-two rabbit cavernosal strips were contracted by electrical field stimulation, and contraction inhibition was tested in response to cumulative doses (10(-8) M. to 10(-4) M.) of verapamil (V), diltiazem (D), isradipine (I), nicardipine (Nc) and nifedipine (Nf). All of the calcium channel blockers were effective at inhibiting electrically induced contractions (p < 0.0001 when CCB was compared with control; p < 0.05 when V or D was compared with I, Nc or Nf). Sixteen cavernosal strips were precontracted with 10(-5) M. norepinephrine. Relaxation in response to cumulative doses of each CCB was determined. Verapamil and the dihydropyridines (isradipine, nicardipine and nifedipine), but not diltiazem, were effective at relaxing norepinephrine induced contractions at 10(-5) and 10(-4) M. with verapamil most effective at 10(-4) M. concentration (p < 0.0001 by ANOVA at both concentrations when V, I, Nc, or Nf was compared with control). Sixteen cavernosal strips were incubated in solutions of 10(-5) and 10(-4) M. of each CCB followed by cumulative addition of norepinephrine (concentration range 10(-8) to 10(-4) M.). Preincubation with CCB did not affect the concentration of norepinephrine at which 50% of maximal cavernosal contractile response occurred (ED50). Maximum active tension of norepinephrine induced contractions was moderately decreased after CCB preincubation with 10(-4) M. of each dihydropyridine. It is concluded that the calcium channel blockers are effective in relaxing cavernosal smooth muscle and therefore possess potential as intracavernous pharmacotherapeutic agents for the treatment of erectile dysfunction. Verapamil appears to be the best candidate for further testing and clinical trial.

Animals↗

PubMed1999

Tracheal intubation of healthy pediatric patients without muscle relaxant: a survey of technique utilization and perceptions of safety.

UNLABELLED: We conducted a survey of Society for Pediatric Anesthesia anesthesiologists practicing within the United States to determine the frequency of tracheal intubation of healthy infants and children using an inhaled anesthetic without muscle relaxation (IAWMR). We also examined reasons for the use of this technique. Of all responders who listed their most often used technique for tracheal intubation of healthy infants and children, IAWMR was chosen over intubation with a muscle relaxant by 38.1% and 43.6%, respectively. Anesthesiologists who most often used IAWMR for tracheal intubation of healthy infants and children had over twice the odds (odds ratio [OR] 2.30 for infants, 95% confidence interval [CI] 1.18-4.50; P = 0.015) of classifying their own practice as nonacademic, and one-third the odds (OR 0.34 for infants, 95% CI 0.17-0.68; P = 0.002) of conducting more than half of their cases in a supervisory role. Anesthesiologists who use IAWMR to tracheally intubate healthy pediatric patients most commonly selected as their reasons the lack of need for a muscle relaxant and the desire to avoid both succinylcholine and the excessive duration of nondepolarizing muscle relaxants. IMPLICATIONS: Inhaled anesthetic without muscle relaxation is the most often used method of intubation for more than one third of Society for Pediatric Anesthesia anesthesiologists when tracheally intubating healthy, fasted pediatric patients undergoing elective procedures. The frequency of this practice seems to be highest in nonacademic practices.

Analysis of Variance↗

PubMed1984

Effects of zoxazolamine and related centrally acting muscle relaxants on nigrostriatal dopaminergic neurons.

The effects of zoxazolamine (ZOX) and related centrally acting muscle relaxants on striatal dopamine (DA) metabolism and turnover, and substantia nigra zona compacta DA neuronal impulse flow were studied in rats. ZOX, chlorzoxazone and mephenesin, but not meprobamate, chloral hydrate, diazepam, pentobarbital, ethanol or dantrolene, decreased striatal DA metabolism without affecting striatal DA concentrations. More specifically, ZOX, as a representative muscle relaxant, was shown to decrease striatal DA turnover without directly affecting DA synthesis, catabolism, reuptake, or release. ZOX decreased nigral DA neuronal firing rates and dramatically decreased firing rate variability (normally many of the cells fire with bursting firing patterns but after ZOX the cells often fired with a very regular pacemaker-like firing pattern). ZOX and related centrally acting muscle relaxants appear to decrease striatal DA turnover by decreasing both neuronal firing rate and firing rate variability. The possible relationships between DA neuronal activity and muscle tone are discussed.

Animals↗

PubMed1991

Wheal and flare responses to muscle relaxants in humans.

Chemically and pharmacologically unrelated molecules release histamine in humans to produce both cutaneous and systemic responses. It has been suggested that molecular changes in the new benzylisoquinoline-derived muscle relaxant, atracurium, make it less likely to cause histamine release. We therefore injected volunteers intradermally with equimolar concentrations of various muscle relaxants, morphine, papaverine (a benzylisoquinoline), and histamine, to evaluate the relative ability of these drugs to cause wheal and flare responses, and mast-cell degranulation. There were no significant differences in wheal and flare responses among the three benzylisoquinoline-derived muscle relaxants, D-tubocurarine, metocurine, and atracurium. The cutaneous effects of morphine were significantly greater than those of the benzylisoquinoline muscle relaxants, suggesting both direct vascular changes and histamine release. Papaverine injection was followed by a significant wheal but no flare. Skin biopsies from vecuronium- and papaverine-induced wheals revealed normal intact mast-cell granules, suggesting a direct cutaneous vascular response rather than histamine release. Skin biopsies after morphine and atracurium injections revealed mast-cell degranulation. All evaluated benzylisoquinoline muscle relaxants are equipotent histamine releasers at equimolar concentrations. A hydrogenated, benzylisoquinoline-nitrogen-containing ring, present in atracurium but not in papaverine, appears to be the molecular conformation responsible for mast-cell degranulation by atracurium.

Atracurium↗

PubMed1987

1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]-2,4- imidazolidinediones, a new class of skeletal muscle relaxants.

A series of 1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]- 2,4-imidazolidinediones (6a-t) was synthesized, and the compounds were evaluated for direct skeletal muscle inhibition in the pithed rat gastrocnemius muscle preparation. The correctness of structural assignment of the new series was verified by alternate, unequivocal synthesis of one representative structure (6f). The phenyloxazoles 6d, 6g, 6j, 6k, and 6l exhibited significant skeletal muscle relaxant activity when administered intravenously and orally. The skeletal muscle relaxant effect of these five compounds is similar to that of other direct-acting skeletal muscle relaxants. The oxazole moiety proved to be an acceptable isosteric replacement for furan, as the biological activity in the oxazole series was retained. The synthesis of this new class of compounds is described, and pharmacologic evaluation data are presented. A discussion of structure-activity relationships is also presented.

Animals↗