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PubMed1996

Intubation without muscle relaxant: an alternative technique for rapid tracheal intubation.

The quality of laryngoscopy and tracheal intubation with propofol augmented by alfentanil was investigated as an alternative technique for rapid tracheal intubation. 119 patients aged between 18 and 60 years (ASA 1 and 2) undergoing elective surgery were prospectively studied in a randomized double-blind controlled fashion. Tracheal intubation facilitated by suxamethonium 1.0 mg/kg alfentanil 15 mu g/kg alfentanil 30 mu g/kg or saline control was compared after propofol induction. The quality of laryngoscopy and intubation were graded according to jaw relaxation, ease of insertion of the endotracheal tube and coughing on intubation. Failure to intubate occurred in 4% and 17% with alfentanil 15 mu g/kg and saline control respectively Tracheal intubation was successful in all patients with alfentanil 30 mu g/kg and suxamethonium 1.0 mg/kg. Alfentanil 15 mu g/kg was not statistically significantly different from saline (P = 0.112). Alfentanil 30 mu g/kg provided similar overall intubating conditions (P = 0.5) to suxamethonium 1.0 mg/kg. Alfentanil in both dosages effectively attenuated the haemodynamic responses to laryngoscopy and tracheal intubation.

Adolescent↗
PubMed2001

[Progressive muscle relaxation (PMR) according to Jacobson in a department of psychiatry and psychotherapy - empirical results].

267 patients admitted to a psychiatric hospital, who were taking part in PMR treatment from 10/98 to 9/00, were questioned about their experiences. Analysis of the data reveals a division into three groups: 1(st) patients with positive effects 69 %, 2(nd) patients with negative effects showing a deterioration of symptoms 15 %, 3(rd) patients with nonspecific reactions 16 %. Marked difficulties are found in patients with major depressive disorder, especially those with a distinctive feeling of emptiness and disturbance of body sense. Difficulties are also found in patients with personality disorders, who respond with depersonalization and/or dissociative phenomena. Alternative therapeutic methods (body movement therapy, self-awareness training) or PMR in a modified way (single setting) should be employed for those patients.

Combined Modality Therapy↗
PubMed1987

Effect of progressive muscle relaxation on the objective symptoms and subjective responses associated with asthma.

Our findings suggest that PMR can increase an asthmatic's ability to cope with asthma, by enabling him or her to exert greater control over the symptoms associated with the disease. Findings of this study also offer insight into patient responses and give direction to the approaches needed in the individual treatment and education of asthmatics. Findings of this study also suggest that proper patient selection may be of importance when using self-management or behavior modification techniques in asthma. Maximum profit from future use of PMR in the behavioral treatment of asthma might be achieved by identifying patients who are characterized as moderate or high in panic-fear. They will receive the greatest benefit from this treatment modality.

Adult↗
PubMed2003

Kinetic study of alkaline induced hydrolysis of the skeletal muscle relaxant chlorzoxazone using ratio spectra first derivative spectrophotometry.

2-Amino-4-chlorophenol was found to be the alkaline induced degradation product and the synthetic precursor of chlorzoxazone. The aim of this work is to study different factors affecting the degradation process due to the high toxicity of 2-amino-4-chlorophenol. Chlorzoxazone was found to follow pseudofirst order kinetics. Ratio spectra first derivative spectrophotometry (DR(1)) was developed for monitoring the change in chlorzoxazone concentration during the degradation process. Kinetic parameters (rate constant (K) and half-life (t(0.5))) were calculated at different temperatures (40-120 degrees C) and different sodium hydroxide concentrations (3-10 M). Activation energy at 3 and 8 M sodium hydroxide concentration and alkaline induced catalysis constant at 60, 70 and 80 degrees C were also calculated.

Chlorophenols↗
PubMed1976

[Various risk factors in the precipitaiton of complications caused by anesthetics and muscle relaxants].

From this study an important notion emerges concerning the risk factors in accidents due to general anaesthetics and myorelaxants. Among these factors, three are clinical parameters which can be assessed by any anaesthetist: the presence of atopy, of a previous drug allergy, of previous, repeated general anaesthesia, close together in timel Two factors were the subject of an experimental study, routinely investigating an abnormal histamine reactivity of the skin, and a latent spasmophilia. No definite conclusion can be made from the results, bearing in mind certain criticisms of technical order and the small number of subjects investigated. However, these works merit being pursued. Thus, if all subjects are not equal when faced with the risks inherent to anaesthesia, a thorough study of individual risk factors will enable a preventive approach, utilising a premedication prescribed with mature consideration.

Anaphylaxis↗
PubMed1984

Tizanidine (DS103-282), a centrally acting muscle relaxant, selectively depresses excitation of feline dorsal horn neurones to noxious peripheral stimuli by an action at alpha 2-adrenoceptors.

The effects of microiontophoretic ejection of tizanidine were compared with those of adrenoceptor agonists on responses of single laminae IV and V neurones to noxious and innocuous cutaneous stimuli. Tizanidine, noradrenaline and clonidine depressed neuronal responses to noxious but not innocuous stimuli. Spontaneous activity was also depressed by these three substances. By contrast, beta- and alpha 1-adrenoceptor agonists had no consistent effect on neuronal responses to cutaneous stimuli. The selective actions of tizanidine, noradrenaline and clonidine were reversibly antagonized by the alpha 2-adrenoceptor antagonist RX781094 but not by WB4101 (alpha 1 antagonist). The binding of an alpha 2-adrenoceptor ligand to rat brain membranes was preferentially displaced by tizanidine. These results indicate an interaction of tizanidine with central alpha 2-adrenoceptors.

Animals↗
PubMed2006

Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMP-mediated inhibition of the IP3 receptor.

BACKGROUND: It has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca2+ oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca2+ oscillations. METHODS: The effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca2+ signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy. RESULTS: All three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca2+ oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca2+ oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca2+ oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca2+ stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca2+ available to stimulate contraction because an elevation of intracellular Ca2+ concentration induced by exposure to a Ca2+ ionophore (ionomycin) or by photolysis of caged-Ca2+ did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca2+-activated K+ channels, which would be expected to increase Ca2+ influx and contraction. By contrast, the photolysis of caged-IP3 in the presence of agonist, to further elevate the intracellular IP3 concentration, reversed the slowing of the frequency of the Ca2+ oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP3R to IP3 was reduced by FSK and this was supported by the reduced ability of IP3 to release Ca2+ in SMCs in the presence of FSK. CONCLUSION: These results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca2+ oscillation frequency by reducing internal Ca2+ release through IP3 receptors.

Animals↗
PubMed1995

Prejunctional actions of muscle relaxants: synaptic vesicles and transmitter mobilization as sites of action.

1. Nicotinic antagonists such as tubocurarine affect acetylcholine release from motor nerve terminals at the neuromuscular junction. 2. Electrophysiological studies comparing the prejunctional actions of tubocurarine to those of vesamicol and vecuronium have been used to provide an insight into the mechanisms involved in the prejunctional effects of tubocurarine-like compounds. 3. The observed prejunctional actions of tubocurarine can be accounted for by a model in which the compound has two separately identifiable effects on the nerve terminal. At low frequencies of nerve stimulation tubocurarine augments acetylcholine release while at high frequencies of nerve stimulation tubocurarine depresses acetylcholine release. 4. Both of the effects of tubocurarine on acetylcholine release are a consequence of a change in the number of quanta within the nerve terminal immediately available for release upon nerve stimulation. 5. On the basis of our experimental observations, we suggest that the two prejunctional effects of tubocurarine are mediated through two pharmacologically distinct prejunctional nAChRs.

Animals↗
PubMed1984

Time course of muscle relaxation with a combination of pancuronium and tubocurarine.

A combination of pancuronium and d-tubocurarine is associated with potentiation of the neuromuscular blocking effects of each drug used singly. The time to onset of maximum block and the time to 25% recovery after administration of equipotent (ED95) doses of pancuronium (0.07 mg/kg) alone, d-tubocurarine (0.51 mg/kg) alone, and pancuronium (0.024 mg/kg) in combination with d-tubocurarine (0.144 mg/kg) were studied in three groups of 10 patients each. The time to onset of maximum block was slightly but not significantly shorter with the combination (3.5 min) than with pancuronium (4.78 min) or d-tubocurarine (4.88 min). The time to 25% recovery with the pancuronium-d-tubocurarine combination (39.7 min) was significantly shorter than it was after d-tubocurarine (57.6 min) but not significantly different from pancuronium (54.4 min). The combination of pancuronium and d-tubocurarine also was associated with greater cardiovascular stability.

Adult↗
PubMed1988

Muscle relaxation in patients with Duchenne's muscular dystrophy. Use of vecuronium in two patients.

Cumulative 50% and 90% neuromuscular blocking doses of vecuronium were determined in two 4-yr-old boys with Duchenne's muscular dystrophy. Vecuronium 20 micrograms kg-1 was required for 50% twitch depression in both patients. The 90% blocking doses were 43 and 57 micrograms kg-1. Although these data do not indicate a greater than normal sensitivity to vecuronium, the recovery time (75-25% block) of twitch tension was three to almost six times as long as in normal children. The evoked compound EMG, additionally recorded in one patient, reflected almost the same dose-response relationship as twitch tension, yet the EMG recovered faster than the twitch. The present findings do not exclude an increased sensitivity to neuromuscular blocking drugs in a larger population of patients with muscular dystrophy. Thus, the titration of the individual neuromuscular blocking dose with the aid of a nerve stimulator is mandatory. During a previous anaesthetic, cardiac arrest and acute rhabdomyolysis had occurred in one patient. The substitution of suxamethonium by vecuronium, or probably any other non-depolarizing myoneural blocking drug of intermediate or short duration of action, may help to avoid this complication.

Child, Preschool↗
PubMed1975

[Comparative study of the relationship between the blood concentration of gentamicin and streptomycin and their muscle-relaxing activity].

A mathematical model of relation between the miorelaxant effect value of aminocyclitol antibiotics and their blood levels is proposed. The kinetics of the reduction of the neuromuscle transmission damaged under the action of the drugs was studied in detail in acute experiments with cats treated with gentamycin or streptomycin administered intravenously. The changes in the effect value in time were satisfactorily described by the logistic function. Parallel determination of the blood levels of the antibiotics in the animals provided construction of an adequate model of their pharmacokinetics. Tabulation of the corresponding biexponential equations and logistic functions for the same time intervals during reduction of the neuromuscle transmission provided necessary information for plotting the "effect: concentration" curves. Comparison of the drug levels at which the effect of inhibition of the neuromuscle transmission was equal to 50% of the maximum one, revealed a statistically reliable difference in the miorelaxant activity of gentamycin and streptomycin. A high miorelaxant activity of gentamycin in comparison to streptomycin was also shown on comparison of the average "effect: concentration" curves plotted on the basis of tabulation of the general equations presenting a combination of the logistic and biexponential equations.

Animals↗
PubMedDate not supplied

The safe use of anaesthetics and muscle relaxants in older surgical patients.

Age greater than or equal to 75 years is not a special risk for adverse outcomes after general anaesthesia on its own but an indicator of risk. Biological or physiological age expressed by preoperative health status is much more important than chronological age. The type of anaesthesia seems to play no, or only a minor role. It is, however, most important to reduce the dosage considerably. As a rule of thumb, the dosage should be reduced by 10 to 15% for every decade over the age of 40. In addition, patients must be monitored extensively intra- and postoperatively, ideally in an intensive care setting. The controversy concerning regional versus general anaesthesia should be studied further. Regional anaesthesia techniques like high spinal or epidural anaesthesia that are haemodynamically effective do not reduce morbidity and mortality postoperatively but have the risk of profound hypertension. Peripheral blockades and spinal or epidural anaesthesia without additional sedation may, however, be associated with a reduced incidence of complications. The reduced reserves of geriatric patients demand for experienced anaesthetists and surgeons as well as intense intra- and postoperative monitoring. To secure a short recovery period, we recommend administration of short-acting drugs like propofol, midazolam, alfentanil, vecuronium, atracurium or isoflurane in appropriately reduced dosages.

Aged↗
PubMed1992

[Muscle relaxation with no effect on oxygen uptake during isoflurane anesthesia?].

To determine the effects of vecuronium neuromuscular blockade on O2 consumption (VO2) during isoflurane anaesthesia 12 patients were studied. 12 patients (ASA-PS I-II, 37.1 +/- 12.1 yr, 173 +/- 8 cm, 70.1 +/- 8.6 kg), scheduled for urological lower abdominal surgery, received isoflurane-N2O-O2-anaesthesia under steady-state conditions (1.3 MAC). Duration of anaesthesia was 169 +/- 32 min and 0.057 +/- 0.016 mg/kg/h vecuronium were needed. The desired level of neuromuscular transmission was set to 10% of control. This level of neuromuscular blockade was kept constant for 60 min by a negative feedback controlled infusion of vecuronium. VO2 was measured by an indirect calorimetry device (MMC Horizon, STPD). During and after recovery of neuromuscular function anaesthesia was maintained and oxygen measurements were continued. Preanaesthetic values of VO2 were in the predicted range for basal metabolism. Steady-state general anaesthesia lead to an 26-28% reduction of VO2 (Range: 144-232 ml/min) compared to the preanaesthetic values (202-288 ml/min, p < 0.01). Neuromuscular blockade showed no significant effect on O2 uptake. We conclude that in patients with adequate depth of anaesthesia vecuronium-induced neuromuscular blockade does not lead to a further reduction of oxygen consumption, since muscular tone is already reduced by general anaesthesia.

Abdomen↗
PubMed1993

Effect of the centrally acting muscle relaxant tizanidine on spinal reflexes: involvement of descending noradrenergic systems.

Experiments were performed on intact and spinalized rats anesthetized with urethane and alpha-chloralose. In intact rats, administration of tizanidine (0.1 mg/kg, i.v.) decreased the mono- (MSR) and polysynaptic reflex potentials (PSR). Blood pressure was initially elevated and then lowered by tizanidine. Although pretreatments with hexamethonium and phentolamine prevented the tizanidine-induced decrease in blood pressure, the depressant effects of tizanidine on the reflexes remained. The alpha 2-antagonist idazoxan inhibited the tizanidine-induced decrease in spinal reflexes, suggesting that central alpha 2-adrenoceptors are involved in the depression of the reflexes. In spinalized rats, tizanidine transiently increased the MSR and gradually decreased the PSR. Blood pressure was elevated transiently by tizanidine. Although the hypertensive effect of tizanidine was inhibited by phentolamine, the effect of tizanidine on the PSR did not change. Prazosin blocked the stimulatory effect of tizanidine on the MSR and caused a rapid decrease of the PSR, suggesting that spinal alpha 1-adrenoceptors are involved in the enhancement of the reflexes. These results suggest that the depressant effects of tizanidine on spinal reflexes are due to the supraspinal and spinal effects of the drug, and not to changes in blood pressure.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1983

Competitive nonspecific binding does not explain the potentiating effects of muscle relaxant combinations.

Combination of pancuronium (Pm) with d-tubocurarine (dTC) or metocurine (mTC) produces potentiation of neuromuscular effects. We tested the hypothesis that this effect is due to decreased plasma protein and/or nonspecific (noncholinergic) tissue binding by one or the other drug such that a greater than expected proportion of unbound drug reaches its neuromuscular site of activity. By varying the concentration of Pm, dTC, and mTC, competitive binding by Pm and dTC or Pm and mTC to plasma constituents was tested in vitro by equilibrium dialysis. Drug interaction and displacement from nonspecific binding sites in tissues was tested in vivo with Pm-mTC combinations. During recovery of mTC-induced neuromuscular paralysis, monitored by evoked twitch tension, 1 mg of Pm was administered intravenously. The twitch height and plasma mTC concentrations before and after Pm administration were noted. The in vitro plasma dTC or mTC binding was not significantly altered by the addition of Pm. Similarly, plasma mTC concentrations in vivo did not increase following the administration of Pm. Thus, there was no displacement of mTC from nonspecific tissue binding sites by Pm. Our in vitro and in vivo experiments both demonstrate that there is no interaction between Pm--dTC and Pm--mTC relative to plasma or tissue binding and thus cannot explain the potentiating effect of the drug combination.

Binding, Competitive↗
PubMed1990

Concomitant depression of locus coeruleus neurons and of flexor reflexes by an alpha 2-adrenergic agonist in rats: a possible mechanism for an alpha 2-mediated muscle relaxation.

The alpha 2-agonist tizanidine, clinically used as an antispastic drug, also strongly reduces polysynaptic flexor reflexes. The hypothesis was tested that the noradrenergic coerulespinal system exerts a tonic facilitation on spinal reflexes and that the depressant effects of tizanidine may be explained by an alpha 2-mediated autoinhibition of the tonic activity of locus coeruleus neurons, resulting in a disfacilitation of the spinal reflexes. The following results support this working hypothesis: (1) systemic injections of tizanidine markedly decreased the spontaneous activity of locus coeruleus neurons, but not of non-locus coeruleus neurons. The alpha 2-antagonist yohimbine reversed this effect. (2) The time course of diminished locus coeruleus activity paralleled that of depressed flexor reflexes. (3) Flexor reflexes were also markedly depressed by the alpha 1-adrenergic antagonist prazosin, administered alone, which is in line with the proposition that the noradrenergic system exerts a tonic facilitation on spinal neurons by way of alpha 1-adrenergic receptor activation. (4) Flexor reflexes were facilitated by conditioning microstimulation of locus coeruleus neurons, and this effect was reversed by prazosin. (5) Flexor reflexes significantly diminished in size following placement of an irreversible lesion in the ipsilateral locus coeruleus. Although these results strongly support the above hypothesis regarding a descending modulatory function of the descending locus coeruleus system on spinal reflexes, possible additional mechanisms, perhaps also involving the ascending projection of the locus coeruleus to supraspinal motor structures, remain to be elucidated.

Adrenergic alpha-Agonists↗
PubMed2006

Highlights in muscle relaxants.

The aim of this article is to provide an overview on neuromuscular blocking agents and a rational selection of the most appropriate agents, along with pharmacological and pharmacoeconomic considerations on neuromuscular blockers and their antagonists. Neuromuscular blocking agents are used during anesthesia to facilitate endotracheal intubation and provide surgically required paralysis. There is continuing development in the field of neuromuscular blocking agents, with new products appearing at regular intervals. All new agents come at increased costs. The proportion of anesthesia-related drug costs on a per-patient basis are small and vary from country to country, but account for no more than 12% of hospital drug budgets. However, given the large number of anesthetics performed over time, the total cost is significant. Moreover, such costs should be put into the perspective of the operating theater and patient admission costs. Appropriate selection of neuromuscular blocking agents can help not only to reduce biological costs secondary to complications, but also to make operating lists proceed smoothly and without incident. The paucity of outcome studies in relation to anesthetic drugs is not surprising given that anesthesia is used to facilitate the provision of therapy rather than being therapeutic in its own right. Accordingly, the assessment of anesthetic drugs has a different priority to therapeutic drugs. As anesthetic drugs are nontherapeutic, it is also difficult to determine the best choice of agent. However, new neuromuscular blocking agents are marketed on the basis of improvements in the frequency of side effects, safety, reliability, duration, reversibility and undesirable hemodynamic effects.

Anesthesia↗
PubMed1989

Influence of alpha-chloralose on muscle relaxant effect of chlorzoxazone in rats and pharmacodynamic analysis.

The Pharmacological response intensity of chlorzoxazone (CZX) was measured by the crossed extensor reflex (CER) method in anesthetized rats. The appropriate dose of alpha-chloralose (ACH) was examined to bring about a quantitative effect of CZX. The pharmacodynamics of CZX was also characterized in the anesthetized rats at three different doses of CZX. When rats were anesthetized with ACH at three different doses (80, 110, and 150 mg/kg i.p.), the CER response caused by CZX at the doses of 25, 50, and 75 mg/kg p.o. was depressed dose-dependently. Among these three different doses of ACH, 80 and 110 mg/kg gave similar results in describing the pharmacological response induced by CZX with time, whereas a dose of 150 mg/kg of ACH elicited a stronger and longer CZX response than the other two doses. The area under the intensity-time curve also showed the same tendency. These findings suggested that the dose size ranging from 80 to 110 mg/kg of ACH for surgical anesthesia was appropriate to evaluate the quantitative pharmacological response of CZX. Pharmacodynamic analysis offered the results that the dose-normalized biophase levels of CZX were coincident with each other when CZX was given at three different doses under ACH anesthesia at the dose of 80 mg/kg. This suggested that the disposition of CZX in rats obeyed linear kinetics and the theoretical values of CZX-induced response would be predictable. This implied that pharmacological response intensity of CZX was reasonably related to the relative biophase CZX level via Hill's equation.

Animals↗