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PubMed1999

[Intratracheal intubation without muscle relaxant with the use of remifentanil-propofol].

OBJECTIVES: To assess tracheal intubation conditions after induction of anaesthesia with remifentanil and propofol, using itemized scoring criteria. STUDY DESIGN: Clinical, prospective, open, non comparative trial. PATIENTS: One hundred consecutive patients undergoing surgery not requiring muscle relaxation, during the study period extended over 12 months. METHODS: After premedication with lorazepam (2 mg) the day before and hydroxyzine (100 mg) one hour before surgery, anaesthesia was induced with remifentanil administered continuously with a syringe pump at a rate of 1.20 +/- 0.06 micrograms.kg-1.min-1 and propofol (3 mg.kg-1 IV bolus). The trachea was intubated two minutes later and mouth opening, glottis exposure, glottis opening, movements, additional anaesthetic agents and chest rigidity were recorded. RESULTS: Intubation conditions were excellent in 87% of patients, and the tube was inserted rapidly, within two minutes. However in 38% of patients the cuff inflation caused cough. In 13%, glottis opening was delayed and intubation required three minutes. A major decrease of arterial pressure and heart rate was recorded in 9 and 6% of patients respectively. CONCLUSION: Induction of anaesthesia using remifentanil and propofol allows satisfactory tracheal intubation without a muscle relaxant. However this technique is contraindicated: a) in patients with a full stomach, as intubation is not always successful at the first attempt; b) in patients scheduled to undergo neurosurgery or ophthalmic surgery, as tracheal intubation may elicit cough, increasing intra-cranial and intra-ocular pressure; c) in patients in poor circulatory status, as it decreases significantly arterial pressure and heart rate.

Anesthesia, Intravenous↗
PubMed1996

[Acid base changes and muscle relaxants].

Previous publications have provided conflicting results concerning the effects of respiratory and metabolic acid base changes on the neuromuscular effects of nondepolarizing muscle relaxants. The varying results can be attributed not only to experimental design or species difference, but also to the accompanying changes in the pharmacokinetics in vivo. Using the phrenic nerve-hemidiaphragm preparation of rats, in which many variables of in vivo studies can be eliminated, respiratory and metabolic acid-base changes were induced by varying carbon dioxide (PCO2) and bicarbonate (HCO3) concentrations in the Krebs' solution and their effects on the potencies of muscle relaxants were compared. Decreasing pH by increasing Pco2 or by decreasing HCO3 increased the potencies of the monoquaternary relaxants (d-tubocurarine, vecuronium and rocuronium), while pH changes did not affect the potencies of the bisquaternary relaxants (metocurine, pancuronium and pipecuronium). Above difference between mono- and bisquaternary relaxants may reflect pH-induced changes in the ionization of the tertiary ammonium and resulting in changes in the sensitivity to the anionic nicotinic receptors. Neostigmine-induced antagonism was not affected by acid-base changes. These results in vitro were compared and correlated with the previous results in vivo.

Acid-Base Equilibrium↗
PubMed1991

Effects of NA0344, a new smooth muscle relaxant, on the actin-myosin-ATP interaction and myosin light chain phosphorylation in vitro.

1. Effects of antibiotic NA0344, a smooth muscle relaxant, on phosphorylation of myosin light chain (MLC, 20 kDa) were compared with those on actin-myosin-ATP interaction using native actomyosin preparation containing MLC kinase activity. 2. MLC kinase was shown to be the site of action of NA0344. 3. NA0344 inhibited the interaction and phosphorylation with IC50 = 7.5 x 10(-6) and 1.6 x 10(-5) M, respectively. 4. The discrepancy between the inhibitory effects is explained that myosin is in an active form when myosin is fully phosphorylated. 5. However, the inhibitory effects of NA0359 and NA0362, analogs of NA0344, on the phosphorylation were similar to or more effective than those on the interaction, which cannot be explained by the active form hypothesis. 6. Plausible explanations for the discrepancies are discussed.

Actins↗
PubMed2005

Antipyretic, analgesic and muscle relaxant activities of pueraria isoflavonoids and their metabolites from Pueraria lobata Ohwi-a traditional Chinese drug.

We evaluated the antipyretic, analgesic, and muscle relaxant activities of Pueraria isoflavonoids and their metabolites in mice. The glycosides daidzin and genistin significantly reduced fever induced by lipopolysaccharide (LPS). Their metabolites, daidzein and p-ethylphenol, also significantly reduced fever induced by LPS. In addition, daidzin, daidzein, dihydrodaidzein, and p-ethylphenol showed analgesic activity as assessed by the acetic acid-induced writhing test. Furthermore, equol and p-ethylphenol showed muscle relaxant activity in the rotarod and horizontal wire test. These results suggest that these compounds play a major role in the therapeutic activity of Pueraria isoflavonoids.

Analgesics↗
PubMed1987

Influence of renal and hepatic function on pharmacodynamics and pharmacokinetics of non-depolarizing muscle relaxants.

Liver and kidney function disturbances influence the pharmacodynamic and pharmacokinetic behaviour of drugs. Because of the differences in metabolism and excretion between the various muscle relaxants, liver and kidney disturbances do influence their pharmacodynamics and pharmacokinetics to a different extent. A description of the changes is given for the most frequently used non-depolarizing muscle relaxants. It is related to the practical clinical implications of the difference in the pharmacokinetics.

Humans↗
PubMed1999

Phosphodiesterase 4 inhibitors as airways smooth muscle relaxant agents: synthesis and biological activities of triazine derivatives.

A series of triazine derivatives was synthesized. The compounds were evaluated for tracheal smooth muscle relaxant and type 4 phosphodiesterase inhibitory activities. A highly significant correlation was observed between the two effects. Two compounds exhibited potent relaxant activity (EC50: 17 and 24 nM) and might be useful for the treatment of asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Local cerebral glucose utilization in rats with decerebrate rigidity and effects of centrally acting muscle relaxants, diazepam and tizanidine.

Local cerebral glucose utilization (LCGU) was investigated in rats with decerebrate rigidity using the [14C]2-deoxyglucose (2DG) method in order to identify the site responsible for the rigidity. LCGU was increased in the medial vestibular nucleus, the fastigial nucleus, the interpositus nucleus and the dentate nucleus during decerebrate rigidity. Diazepam and tizanidine, centrally acting muscle relaxants, reduced the increase of LCGU in the vestibular and cerebellar nuclei. These results suggest that the vestibular and cerebellar nuclei are the possible sites responsible for the development of decerebrate rigidity and the action of some centrally acting muscle relaxants.

Animals↗
PubMedDate not supplied

Comparison of two muscle relaxant drugs on human sleep: diazepam and parachlorophenylgaba.

The effects of two muscle relaxant drugs of different chemical structures, parachlorophenylgaba and diazepam, were investigated in the sleep of normal young adults. Parachlorophenylgaba did not show any significant and dose-related effect. In contrast, diazepam induced clear modifications, including a decrease of stage 4 and of REM-sleep, an increase of spindles and a decrease of K potentials in stage 2, a decrease of rapid eye movements in REM-sleep, and finally a decrease of body movements. In addition, the recovery of REM-sleep upon withdrawal of the drug was much faster than the recovery of stage 4. These results add a new contribution to known differences in the pharmacological profiles of these two compounds ; for diazepam, the possible role of GABA mediated monoaminergic mechanisms is discussed.

Aminobutyrates↗
PubMed2002

Muscle relaxing activity of Hyssopus officinalis essential oil on isolated intestinal preparations.

The muscle relaxing activity of the essential oil of Hyssopus officinalis L. (Lamiaceae) and some of its main components (isopinocamphone, limonene and beta-pinene) was studied on isolated preparations of guinea-pig and rabbit intestine. The essential oil and isopinocamphone inhibited the acetylcholine- and BaCl2-induced contractions in guinea-pig ileum in a concentration-dependent manner (IC50 42.4 microg/ml and 61.9 microg/ml to acetylcholine; 48.3 microg/ml and 70.4 microg/ml to BaCl2) whereas limonene or beta-pinene left tissue contraction unchanged. In guinea-pig ileum H. officinalis essential oil also blocked the contractions induced by CaCl2. In isolated rabbit jejunum the essential oil reduced the amplitude of spontaneous movements and decreased the basal tone; neither haemoglobin, methylene blue, N(omega)-nitro-L-arginine methyl ester (L-NAME) or propranolol blocked the myorelaxant effect.

Acetylcholine↗
PubMed1955

Introduction to muscle relaxants.

The first writings of curare appeared about 1500. Two hundred and fifty years later the first real experimentation took place with the drug and an additional two hundred years elapsed before the drug found its true place in medicine. During the past decade it has become a valuable drug in anesthesia. The muscle relaxants have been divided into two groups according to their action - the curare-like or competitive inhibition blocking group, and the C-10-like or depolarizing blocking group. They act at the myoneural junction to produce relaxation with very little effect on the remainder of the body. In recent years the synthetic curare-like drugs have overshadowed purified curare.

Anesthesia↗
PubMed1981

[Prevention of myalgias caused by succinylcholine with a small dose of a non-depolarizing muscle relaxant].

Precurarisation with 1 mg/15 kg d-tubocurarine was given before 1.5 mg/kg succinylcholine to obtain muscle relaxation for tracheal intubation in 100 patients, whereas 1 mg/kg succinylcholine only was administered to 100 controls. Serious postoperative myalgia fell from 8% to 0%, and forms of average intensity from 21% to 8% in the curarised group. Muscle resolution was regarded as satisfactory in 96% (98% in the controls). The effectiveness and degree of safety of this combination are discussed, together with the indications and contraindications for the employment of the technique in the prevention of myalgia induced by succinylcholine.

Adolescent↗
PubMed1999

Potentiation of vancomycin-induced histamine release by muscle relaxants and morphine in rats.

The intravenous injection of vancomycin sometimes causes anaphylactoid reactions, in which histamine release may play a major role. These reactions are more frequently manifested when vancomycin is injected into anesthetized patients. We examined the vancomycin-induced histamine release and the interaction of vancomycin with muscle relaxants or opioid in rats. In an in vitro study with rat peritoneal mast cells, treatment with vancomycin at concentrations of greater than 1.25 mM produced significant histamine release. Tubocurarine, vecuronium, pancuronium, succinylcholine, and morphine up to concentrations of 0.25, 1, 5, 30, and 5 mM, respectively, produced no significant histamine release. However, the nonsignificant histamine release induced by 0.5 mM vancomycin was clearly enhanced by combining vancomycin with any of these agents. In the in vivo study, the intravenous injection of vancomycin significantly increased the plasma histamine levels in rats when vancomycin was injected at 200 mg/kg of body weight (63.2 +/- 34.0 ng/ml [mean +/- standard deviation]) but not when it was injected at 100 mg/kg (30.8 +/- 20.2 ng/ml) compared with that in the saline-treated rats (22.5 +/- 11.4 ng/ml). Although the subcutaneous administration of morphine (10 mg/kg) never increased the plasma histamine levels, the intravenous injection of vancomycin (100 mg/kg) 30 min after this morphine treatment markedly increased the plasma histamine levels (56.0 +/- 26.9 ng/ml). These findings provide experimental evidence that the combination of muscle relaxants or an opioid with vancomycin may increase the risk of anaphylactoid reactions by enhancing the release of histamine.

Animals↗
PubMed1995

The role of muscle relaxants in total intravenous anaesthesia.

For total intravenous anaesthesia (TIVA), all drugs that are required as part of the anaesthetic method are administered intravenously. This is usually taken to imply the use of intravenous infusions. It is normal practice to administer muscle relaxants intravenously, although other routes have been used. A muscle relaxant is required firstly to secure paralysis and secondly to maintain paralysis. The rate of onset of all the nondepolarizing neuromuscular blocking agents which are routinely available at present is similar; it takes about 3-6 min for a normal clinical dose to reach maximum effect. Maintenance of an adequate level of block is necessary, and it is usually helpful to the surgeon for the level of block to be relatively constant. The choice of drug is important. It should cause negligible side-effects. For administration by infusion, an agent with an intermediate (e.g., atracurium) or short (e.g., mivacurium) duration of action is essential to ensure a rapid recovery of effect on termination of the infusion. The routine use of neuromuscular monitoring is recommended when a continuous infusion of a relaxant is used.

Ambulatory Surgical Procedures↗
PubMed2002

Factors associated with successful tracheal intubation of children with sevoflurane and no muscle relaxant.

UNLABELLED: Better definition of end points required to achieve successful tracheal intubation after induction with sevoflurane could improve patient care. The authors therefore designed a study that could determine, with meaningful confidence intervals, the time required to successfully intubate 80% of children by using 8% inspired sevoflurane and no muscle relaxant. We hypothesized that the time required could vary by age or body mass index. One-hundred fifty-three ASA physical status I or II patients received induction with 8% sevoflurane in 60% nitrous oxide with discontinuation of nitrous oxide 1 min after the start of the induction. The time until laryngoscopy remained close to the time required to achieve 80% successful intubation by varying induction time according to the success rate in each group of five patients. A probit model of induction time and age found that both were predictive of successful intubation (P values of 0.006 and 0.02, respectively). The induction times needed to achieve 80% successful intubation were 137 s (95% confidence interval, 94.6-159 s) and 187 s (153-230 s) for ages 1-4 yr and 4-8 yr, respectively. The persistence of spontaneous ventilation at the time of laryngoscopy, despite attempts to control ventilation, was associated with poor intubation conditions (P < 0.001). IMPLICATIONS: To successfully intubate 80% of children by using sevoflurane and no muscle relaxant, induction times of 137 and 187 s were needed in children of 1-4 yr and 4-8 yr, respectively.

Age Factors↗
PubMed1981

Mechanism of smooth muscle relaxation by tiropramide.

Experiments on rabbit isolated colon show that a carbachol-induced contraction is accompanied by a decrease in cAMP content of the smooth muscle. (+/-)-alpha-(Benzoylamino)-4-[2-(diethylamino)-ethoxy]-NN-di-propylbenzen-propanamid (tiropramide, CR 605), a new tyrosine derivative with antispastic properties, increases cAMP concentrations within the same dose range that produces smooth muscle relaxation with or without carbachol (0.1 microM). These effects are potentiated by 1 mM theophylline, a phosphodiesterase inhibitor. In a purified microsomal preparation from rabbit colon smooth muscle, corresponding to sarcoplasmic reticulum, tiropramide induced a dose-dependent increase Ca2+ binding in the presence of ATP and Mg2+. Tiropramide inhibited phosphodiesterase activity in rabbit colon homogenates in a range of doses about ten times that producing relaxation, cAMP content enhancement and increase Ca2+ binding to sarcoplasmic reticulum. The effects of tiropramide on the carbachol-stimulated rabbit colon in the presence of theophylline, indomethacin of PGE1 are more in agreement with an action of tiropramide as inhibitor of cAMP catabolism than as a result of a prostaglandin-mediated effect. These observations suggest that the smooth muscle relaxant activity of tiropramide arises from drug-induced increase of cAMP concentrations possibly because of inhibition of cAMP catabolism. This effect is accompanied by the binding to the sarcoplasmic reticulum of Ca2+, preventing its interaction with the contractile proteins of the smooth muscle. A direct effect of tiropramide-enhanced cAMP content on contractile proteins in the smooth muscle cannot be excluded.

Animals↗
PubMed1983

Reserpine-induced detrusor hyperreflexia: an in vivo model for studying smooth muscle relaxants at urinary bladder level.

A new in vivo model for studying the effects of smooth muscle relaxant drugs at urinary bladder level has been developed. This involves the determination of a cystometrogram at a physiological filling rate in urethane anesthetized rats. The amount of infused saline required to elicit TTX-sensitive rhythmic contractions (micturition reflex) of urinary bladder was choosen as end point to evaluate the effect of test substances. Reserpine pretreatment significantly reduced the volume of saline required to elicit the micturition reflex. The effect of reserpine can be reproduced by intravenous prazosin, but not by propranolol or yohimbine, in control rats. Intravenous, but not topical, hexamethonium reversed the effects of reserpine pretreatment on the amount of infused saline required to elicit rhythmic contractions. The nature of rhythmic contractions produced by saline filling of the urinary bladder in these experimental conditions, as well as the potential mechanism(s) involved in the effects of reserpine, are discussed in view of the existing literature on the physiology and pharmacology of the micturition reflex. The effects of various drugs commonly used to produce a relaxation of bladder muscle suggest that this model might be useful for detecting substances of potential therapeutic usefulness in the treatment of bladder hypermotility disorders.

Animals↗