Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hyperthermia is a main cause of death during general anesthesia, particularly in children. However, research has been hampered by the lack of a convenient animal model, the only one available being a special strain of pig. In this study, we describe spontaneous myopathy and a fatal syndrome of generalized muscle rigidity triggered by halothane in an outbred strain of rat. Histological examination of skeletal muscle reveals severe abnormalities indicating chronic underlying myopathy. The association of histological abnormalities with an acute, fatal syndrome clinically resembling malignant hyperthermia provides a strong basis for a new and extremely useful animal model to study this fatal disorder.
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PMID:A rat model of spontaneous myopathy and malignant hyperthermia. 954 71

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.
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PMID:Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. 974 65

The pharmacokinetic parameters of buprenorphine (BN) after a single bolus dose of 10 microg/kg i.v. was investigated in 6 male patients whose age averaged 59+/-9.8 years and body weight of 65.8+/-5.7 kg undergoing coronary artery bypass graft surgery (CABG). The unbound BN plasma concentrations were detected using ultrafiltration and high performance liquid chromatography/electro-chemical detection (HPLC/ECD) method. During cardiopulmonary bypass (CPB) there was a fall in BN plasma concentrations, observations similar to reports on fentanyl, sufentanil and alfentanil. This is probably due to haemodilution, hypothermia and hydrophobic sequestration of drug on to the CPB tubing. After CPB the concentrations rose to values higher than during CPB, though it did not attain pre CPB concentrations. These variations were not statistically significant indicating that plasma levels were adequately stable during CPB. The plasma concentration time curves were biexponential and the pharmacokinetic parameters obtained were : distribution half-life 37.24+/-6.57 min, elimination half-life 482.69+/-79 min, clearance 1221.97+/-209.42 ml/min, and volume of distribution 736.46+/-71.25 L. BN in the dose used follows the pharmacokinetic pattern of other commonly used narcotics during CABG. The mean +/- SEM plasma BN concentration during CPB was 0.51+/-0.03 ng/ml which was adequate for the maintenance of analgesia and anaesthesia, as none of our patients expressed the signs and symptoms of awareness during surgery. Further, unlike the other narcotics muscle rigidity was absent. Thus BN is a safe and good alternative to other narcotics for patients undergoing CABG.
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PMID:Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery. 1023 58

The clinical pharmacology of neuromuscular blocking agents is described. During neuromuscular blockade, succinylcholine attaches to receptors in the motor end plate and depolarizes the neuromuscular junction, making the end plate refractory to acetylcholine. The nondepolarizing relaxants have a structure similar to that of succinylcholine and bind to the same receptors. Instead of depolarizing the junction, they block acetylcholine from binding to the receptor and cause channel blockade. As the concentration of nondepolarizing relaxant increases relative to acetylcholine, neuromuscular transmission is compromised. This relationship is used clinically to facilitate recovery from nondepolarizing agents. Succinylcholine is popular because its onset is faster than that of the nondepolarizing relaxants and metabolism by pseudocholinesterase clears it quickly. It is commonly given as an i.v. bolus to facilitate tracheal intubation. The onset of these agents varies widely and is dose dependent. Large doses are usually given to hasten the onset of paralysis; subsequent doses are adjusted according to response. The nondepolarizing agents interact with inhaled anesthetics, magnesium, and many antimicrobials. Drugs like neostigmine, edrophonium, and pyridostigmine antagonize neuromuscular blockade; an anticholinergic drug is typically administered to counteract the cardiovascular effects. The most serious adverse effects of succinylcholine are malignant hyperthermia syndrome, masseter muscle rigidity, and bradycardia. Some nondepolarizing relaxants (atracurium, mivacurium, and pancuronium) are associated with histamine release, occasionally causing serious hypotension and tachycardia. Neuromuscular blocking agents are essential to anesthesia. Older compounds produce greater toxicity than newer compounds, and several of these older compounds therefore are no longer in clinical use.
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PMID:Clinical pharmacology of neuromuscular blocking agents. 1043 10

Dexmedetomidine is a relatively new, highly selective, short-acting central alpha 2 agonist. Although not yet officially introduced for clinical use in Israel, it has become increasingly popular among anesthesiologists and intensive care physicians abroad when used as an adjuvant to the classical regimen of anesthesia techniques. Its administration potentiates the effect of other sedative and hypnotic agents while causing minimal respiratory depression. It also blunts the sympathetic response--thus minimizing changes in blood pressure and heart rate--during critical moments such as laryngoscopy and intubation. However, bradycardia and hypotension may ensue. DXM minimizes opioid-induced muscle rigidity and attenuates postoperative shivering. These pro-anesthesia effects are attributed to the capability of DXM to reduce central adrenergic outflow. Although its precise mechanism(s) of action are still debatable, DXM will undoubtedly find an increasing role in clinical peri-operative anesthesia.
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PMID:Dexmedetomidine: a promising agent for anesthesia and perioperative care. 1134 41

We examined the effects of propofol on a paramyotonia congenita mutant skeletal muscle sodium channel in vitro, because life-threatening complications resulting from severe muscle rigidity during induction of anesthesia have been observed using other anesthetics in patients with hereditary sodium channel myopathies. Our hypothesis was that propofol might interact directly with mutant channels, causing enhanced muscle excitability in affected patients. Whole-cell voltage-clamp experiments were performed on HEK 293 cells expressing R1448H mutant sodium channels. Propofol blocked sodium inward current at clinical concentrations (5 micromol/L) when depolarizing pulses were started from holding potentials close to the physiological resting potential (-70 mV). Higher propofol concentrations (>/=25 micromol/L) accelerated pathologically delayed inactivation kinetics and delayed pathologically enhanced recovery from inactivation. Our in vitro results show that inactivation-deficient sodium channels are specifically targeted and blocked by propofol. This might reduce enhanced muscle excitability experienced by affected patients in vivo.
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PMID:The anesthetic propofol modulates gating in paramyotonia congenita mutant muscle sodium channels. 1136 Feb 54

A case of droperidol-induced neuroleptic malignant syndrome during anaesthesia is presented. An 86-year-old man underwent spinal anaesthesia for open reduction and internal fixation of a trochanteric hip fracture. He received droperidol 5 mg intravenously for sedation towards the end of surgery. He subsequently became very drowsy and experienced marked muscle rigidity and autonomic instability. He became febrile postoperatively. The clinical syndrome resolved after 12 hours. When using droperidol in anaesthesia or intensive care--especially when large doses are given--the development of neuroleptic malignant syndrome should be suspected if the patient becomes febrile and has muscle rigidity and autonomic instability.
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PMID:Neuroleptic malignant syndrome induced by droperidol. 1140 84

Tetanus continues to be a cause of high mortality in developing countries, where resources for muscle relaxation and respiratory support are not readily available. Baclofen, a GABAB receptor agonist, directly restores physiologic inhibition of alpha motoneuron, that is blocked by tetanus toxin. Its use has been suggested at high dosage by intrathecal (i.t.) route, as part of the treatment of tetanus-induced contractures, and to limit the need for general anesthesia and for tracheal intubation in afflicted patients. This review reports personal experience and focuses on published data about i.t. baclofen for severe tetanus. Although statistical analysis are difficult to perform, i.t. baclofen appears to be effective in resolving muscle rigidity and in avoiding the need for deep sedation and for tracheal intubation, thus achieving lower mortality. Nevertheless, i.t. baclofen has a narrow therapeutic range, and a large interindividual pharmacodynamic variability. Thus, its use should be reserved for patients who would have been intubated without it. I.t. baclofen is a fairly simple and cost-effective modality, with significant advantages for management of severe tetanus, especially in tropical environment.
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PMID:[Value of intrathecal baclofen in the treatment of severe tetanus in the tropical milieu]. 1143 97

We experienced two cases of malignant hyperthermia (MH) triggered by sevoflurane. Case 1 was a six-year-old girl, 15.8 kg, undergoing strabismus repair. She had flat back, elevated diaphragm and high arched palate. Anesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Her trachea was intubated without the use of muscle relaxant. Thirty minutes after the induction of anesthesia, ETco2 was over 60 mmHg despite hyperventilation. Muscle rigidity of legs and the rise in temperature were noted. MH was diagnosed and dantrolene i.v. was administered. Her maximum esophageal temperature was 40.2 degrees C. ETco2 and temperature returned to baseline values after dantrolene administration. Creatine phosphokinase (CK) level was 252 U.l-1 preoperatively, and 1690 U.l-1 next day. Case 2 was a year-and-9-month-old boy undergoing accessory ear resection. Anesthesia was induced with sevoflurane and nitrous oxide in oxygen. His trachea was intubated with an aid of vecuronium. Forty minutes after administration of sevoflurane his temperature rose to 38.6 degrees C with heart rate 191 bpm and Spo2 93%, and muscle rigidity of legs. MH was diagnosed and dantrolene was administered. His highest temperature was 39.3 degrees C and was reduced promptly after dantrolene. Postoperatively he was noted to have downslanting palpebral fissures, micrognathia, low set ears, and a single crease of the fifth finger and diagnosed as King syndrome which is reported to have association with MH. Both patients had no history of anesthesia nor abnormal family history. Both of them were rescued with dantrolene and recovered without sequelae.
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PMID:[Two pediatric cases of malignant hyperthermia caused by sevoflurane]. 1175 32

The neuromuscular disorders described are divided into four groups: motoneuron diseases, peripheral neuropathies, disturbances of neuromuscular transmission and myopathies. In motoneuron diseases problems mainly result from respiratory insufficiency and the predisposition for aspiration caused by progressive muscular weakness. Depolarising muscle relaxants may elicit myotonic reaction and massive hyperkalemia. In contrast to non-depolarising muscle relaxants there may be an extreme hypersensitivity. In peripheral neuropathies the cardiac function is often limited whereby dysautonomia may enhance cardiovascular instability. The negative inotropic effect of anaesthetic agents must be observed with care and patients with higher degree of AV blocks may need a cardiac pacemaker during general anaesthesia. The Charcot-Marie-Tooth-Syndrome is characterized with a high sensitivity to thiopental. Disturbances of neuromuscular transmission frequently cause respiratory problems The fluctuating weakness of bulbar and respiratory muscles may impair swallowing and can lead to recurrent aspirations. Due to the reduced number of acetylcholine receptors the sensitivity to non-depolarizing muscle relaxants is elevated and the response to succinylcholine is reduced. Drugs reducing neuromuscular transmission such as antibiotics and beta-blockers may enhance these symptoms and should be avoided. In progressive muscular dystrophies the anaesthetic risk is mainly dependent on cardiac and respiratory impairment. Administration of succinylcholine leads to the risk of hyperkalmic cardiac arrest. Patients with metabolic myopathies are also at risk due to the involvement of cardiac muscle but respiratory problems are less frequent. Muscle metabolism should be supported by administration of substrates depending on the underlying disorder. In membrane disorders muscle rigidity (myotonic reactions) or weakness may lead to respiratory insufficiency. In addition to the depolarising muscle relaxants also anticholinesterase drugs, hypothermia and dyskalaemia can evoke myotonic reactions.
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PMID:[Anesthesia in neuromuscular disorders. Part 2: specific disorders]. 1188 13


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