piperidines and Myasthenia-Gravis

Acetylcholinesterase (AChE) inhibitors are an important class of medicinal agents useful for the treatment of Alzheimer s disease, glaucoma, myasthenia gravis and for the recovery of neuromuscular block in surgery. To rationalize the structural requirements of AChE inhibitors we attempt to derive a coherent AChE-inhibitor recognition pattern based on literature data of molecular modelling and quantitative structure-activity relationship (QSAR) analyses. These data are summarised from nearly all therapeutically important chemical classes of reversible AChE inhibitors, e.g., derivatives of physostigmine, tacrine, donepezil and huperzine A. Interactions observed from X-ray crystallography between these inhibitors and AChE have also been incorporated and compared with modelling and QSAR results. It is concluded that hydrophobicity and the presence of an ionizable nitrogen are the pre-requisites for the inhibitors to interact with AChE. However the mode of interaction i.e., the 3-dimensional (3D) positioning of the inhibitor in the active site of the enzyme varies among different chemical classes. It is also recognised that water molecules play crucial roles in defining these different 3D positioning. The information on AChE-inhibitor interactions provided should be useful for future discovery of new chemical classes of AChE inhibitors, especially from De Novo design and hybrid construction.

Topics: Alkaloids; Alzheimer Disease; Cholinesterase Inhibitors; Crystallography, X-Ray; Donepezil; Drug Design; Glaucoma; Humans; Indans; Models, Molecular; Myasthenia Gravis; Neostigmine; Physostigmine; Piperidines; Sesquiterpenes; Structure-Activity Relationship; Surface Properties; Tacrine

Although several studies of the use of desflurane in anesthesia have revealed many desirable qualities, there are no data on the use and effects especially on the neuromuscular function of desflurane on myasthenia gravis (MG) patients. The purpose of this study was to evaluate the use of either desflurane or propofol, both combined with remifentanil, in patients with MG undergoing a video-assisted thoracoscopic-extended thymectomy (VATET).. Thirty-six MG patients who underwent VATET were enrolled. Nineteen patients were anesthetized with remifentanil and propofol infused with a target-controlled infusion plasma model, and 17 patients with desflurane and remifentanil. No muscle relaxant was used. The intubating conditions, hemodynamic and respiratory changes, neuromuscular transmission and post-operative complications were evaluated.. Neuromuscular transmission was significantly decreased in the desflurane group (6.7%, from 3% to 9% during anesthesia P=or<0.05). The intubating conditions were good in all 36 patients and 35 patients were successfully extubated in the operating room. The time-to-awakening, post-operatory pH and base excess were significantly different in the two groups, with a decreasing mean arterial pressure in the group administered with desflurane. No patients required reintubation due to myasthenic or cholinergic crisis, or respiratory failure. No other significant differences between the two groups studied were observed.. Our experience indicates that anesthesia with desflurane plus remifentanil in patients with MG could determine a reversible muscle relaxation effect, but with no clinical implication, allowing a faster recovery with no difference in extubation time and post-operative complications in the two groups.

Topics: Adolescent; Adult; Anesthesia; Desflurane; Drug Combinations; Female; Humans; Isoflurane; Male; Middle Aged; Myasthenia Gravis; Piperidines; Propofol; Remifentanil; Thoracic Surgery, Video-Assisted; Thymectomy

To evaluate the role of bispectral index monitoring as an adjunct to balanced anesthesia in patients with myasthenia gravis undergoing transsternal thymectomy without the use of neuromuscular blocking agents, 10 patients were enrolled into this prospective observational study. After oral midazolam premedication, general anesthesia was induced with fentanyl, propofol, and sevoflurane. Tracheal intubation was performed without neuromuscular blocking agents. During maintenance, continuous monitoring of physiological and bispectral index parameters was used to titrate the doses of remifentanil, propofol, and sevoflurane. Sevoflurane concentration and propofol doses were adjusted to achieve bispectral index values in the high 30s to low 40s. Propofol was discontinued when the sternum was approximated. Remifentanil infusion was stopped on subcutaneous tissue closure, and sevoflurane was switched off when nearing completion of skin closure. Tracheal extubation was performed when extubation criteria were met. On extubation, bispectral index levels were above 90. The median time from extubation to discontinuation of propofol was 28 +/- 4 min, that of remifentanil was 21 +/- 4 min, and it was 9 +/- 5 min for sevoflurane. Bispectral index monitoring provided excellent hemodynamic control during surgery, and allowed early problem-free tracheal extubation.

Topics: Adolescent; Adult; Anesthetics, Combined; Anesthetics, Inhalation; Anesthetics, Intravenous; Electroencephalography; Female; Hemodynamics; Humans; Intubation, Intratracheal; Male; Methyl Ethers; Monitoring, Intraoperative; Myasthenia Gravis; Pilot Projects; Piperidines; Propofol; Prospective Studies; Remifentanil; Sevoflurane; Sternum; Thymectomy; Time Factors; Young Adult

Myasthenia gravis (MG) is an autoimmune disease characterized by the production of antibodies against the acetylcholine receptor, muscle-specific kinase (MuSK), or other proteins at the neuromuscular junction. MG with antibodies against MuSK (MuSK-MG) has been described recently. Here, we report the first case of anesthetic management of a patient with MuSK-MG undergoing an open cholecystectomy. In our case, propofol and remifentanil-based anesthesia were used for successful management without using muscle relaxants. Patients with MuSK-MG have predominantly ocular, bulbar, and respiratory symptoms that may increase the risk of aspiration. Anesthesiologists need to pay attention to perioperative respiratory failure and respiratory crisis.

Topics: Analgesia, Epidural; Anesthesia, General; Anesthetics, Intravenous; Autoantibodies; Cholecystectomy; Cholecystitis; Female; Humans; Middle Aged; Myasthenia Gravis; Pain, Postoperative; Piperidines; Propofol; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Remifentanil

Myasthenia gravis (MG) is an autoimmune disease affecting neuromuscular junction, which is characterized by fluctuating muscle weakness and abnormal fatigability. The use of muscle relaxants is major concern in anesthetic management for patients with MG. Muscle relaxant is a practical tool to assure immobilization during surgery under general anesthesia Anesthetic management without muscle relaxants for patients with MG is challenging, because it is difficult to assure immobilization. However, pharmacological effects of muscle relaxants can be prolonged in patients with MG, resulting in the increased incidence of postoperative respiratory support. We, here, describe an anesthetic management of an 82-year-old man with MG undergoing laparoscopic surgery. Anesthesia was induced with propofol and remifentanil Desflurane was administered via a face mask, and the patient was manually ventilated for 10 min, and the trachea was intubated safely without muscle relaxants. Anesthesia was maintained with desflurane and remifentanil. We did not administer muscle relaxants to the patient during surgery. Throughout laparoscopic procedures, no movements of the patient were observed, and there were no problems concerning the laparoscopic view of the operation filed. The surgery was uneventful. The patient emerged from anesthesia smoothly, and was extubated safely. The postoperative course of the patient was also uneventful.

Topics: Aged, 80 and over; Anesthesia, General; Contraindications; Desflurane; Digestive System Surgical Procedures; Humans; Isoflurane; Laparoscopy; Male; Myasthenia Gravis; Neuromuscular Nondepolarizing Agents; Piperidines; Rectal Neoplasms; Remifentanil

Two patients with myasthenia gravis were scheduled for surgery. Anesthesia was managed with remifentanil and propofol target-controlled infusion without the use of muscle relaxants. In both cases, we gradually raised the effect-site concentration of remifentanil and performed tracheal intubation at 10 ng x ml(-1). For both patients, the conditions for tracheal intubation were good, and hemodynamics also stabilized during tracheal intubation. Throughout the surgery, muscle relaxants were not required. Thus, the use of these drugs for inducing anesthesia provided good conditions for tracheal intubation and surgery, and it precluded the need for muscle relaxants.

Topics: Adult; Anesthesia, Intravenous; Anesthetics, Intravenous; Female; Hemodynamics; Humans; Infusions, Intravenous; Intubation, Intratracheal; Male; Myasthenia Gravis; Neuromuscular Agents; Piperidines; Pleural Neoplasms; Propofol; Remifentanil; Thymectomy

Topics: Female; Humans; Intubation, Intratracheal; Myasthenia Gravis; Piperidines; Propofol; Remifentanil

Topics: Adult; Anesthesia, General; Anesthetics, Intravenous; Bradycardia; Bronchial Spasm; Cholinesterase Inhibitors; Drug Interactions; Drug Therapy, Combination; Humans; Hypotension; Male; Myasthenia Gravis; Piperidines; Preanesthetic Medication; Propofol; Pyridostigmine Bromide; Remifentanil; Thymectomy

Topics: Age Factors; Anesthesia, Intravenous; Anesthetics, Intravenous; Bradycardia; Child; Clinical Trials as Topic; Contraindications; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Intraoperative Complications; Multicenter Studies as Topic; Myasthenia Gravis; Perfusion; Piperidines; Remifentanil; Thoracoscopy; Thymectomy

Myasthenia gravis is a chronic autoimmune disease characterized by a reduction of postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction. Most myasthenia gravis patients require thymectomy. Intravenous (IV) anesthetics may be superior to inhalation agents in these patients. The Laryngeal Mask Airway (LMA), when compared with the endotracheal tube, causes less airway resistance, which in turn may lead to a decreased bronchoconstrictive reflex, less atelectasis, and fewer pulmonary infections. We report 5 patients with myasthenia gravis, who underwent transsternal thymectomy with total IV anesthesia and LMA.

Topics: Adult; Aged; Airway Resistance; Anesthesia, Intravenous; Anesthetics, Intravenous; Blood Pressure; Carbon Dioxide; Female; Humans; Laryngeal Masks; Male; Middle Aged; Myasthenia Gravis; Perioperative Care; Piperidines; Propofol; Remifentanil; Sternum; Thymectomy

Topics: Anesthesia, Inhalation; Anesthesia, Intravenous; Anesthetics, Inhalation; Anesthetics, Intravenous; Child; Contraindications; Drug Interactions; Female; Humans; Intubation, Intratracheal; Methyl Ethers; Myasthenia Gravis; Neuromuscular Agents; Piperidines; Pyridostigmine Bromide; Remifentanil; Sevoflurane; Thoracoscopy; Thymectomy; Thymoma; Thymus Neoplasms

Juvenile myasthenia gravis is the acquired form of the disease in children and presents with ocular signs, fatigability, weakness and bulbar problems. The majority of patients demonstrate thymic hyperplasia and have been shown to benefit from thymectomy. The main considerations for the anesthesiologist are the degree of muscle weakness, the muscle groups involved and sensitivity to neuromuscular blocking drugs and volatile agents. Total intravenous anesthesia (TIVA) with epidural analgesia is probably the anesthetic technique of choice, although the latter is often avoided, because of the risk of a very high block. Two cases of thymectomy are presented where anesthesia was provided using a combination of TIVA and thoracic epidural analgesia. Both patients tolerated the technique well and had an uncomplicated perioperative course.

Topics: Adolescent; Amides; Anesthesia, Epidural; Anesthesia, Intravenous; Anesthetics, Combined; Anesthetics, Intravenous; Anesthetics, Local; Child; Fentanyl; Humans; Intubation, Intratracheal; Male; Midazolam; Myasthenia Gravis; Piperidines; Propofol; Remifentanil; Ropivacaine; Thymectomy; Thymus Hyperplasia; Treatment Outcome

Topics: Adult; Anesthesia, General; Anesthesia, Intravenous; Anesthetics, Intravenous; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Piperidines; Propofol; Remifentanil; Thoracic Surgery, Video-Assisted; Thymectomy

Topics: Adult; Analgesics, Opioid; Anesthesia, Epidural; Anesthetics, Combined; Anesthetics, Intravenous; Anesthetics, Local; Atracurium; Blood Gas Analysis; Bupivacaine; Female; Fentanyl; Humans; Intubation, Intratracheal; Monitoring, Intraoperative; Myasthenia Gravis; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Respiration; Respiratory Function Tests; Thymectomy; Time Factors

Topics: Adult; Anesthesia Recovery Period; Anesthetics, Intravenous; Female; Humans; Myasthenia Gravis; Piperidines; Remifentanil; Thymectomy

Topics: Anesthesia, Intravenous; Anesthetics, Intravenous; Contraindications; Humans; Male; Middle Aged; Myasthenia Gravis; Neuromuscular Blocking Agents; Piperidines; Remifentanil

Topics: Adolescent; Analgesics, Opioid; Anesthesia Recovery Period; Anesthetics, Intravenous; Female; Fentanyl; Humans; Intubation, Intratracheal; Monitoring, Intraoperative; Myasthenia Gravis; Piperidines; Plasmapheresis; Propofol; Remifentanil; Thymectomy

Topics: Aged; Aged, 80 and over; Anesthetics, Combined; Anesthetics, Intravenous; Cholecystitis; Humans; Male; Myasthenia Gravis; Piperidines; Propofol; Remifentanil

A 46-year-old myasthenic man diagnosed two months earlier and experiencing nocturnal dyspnea was scheduled for transsternal thymectomy. The patient was premedicated with midazolam in the operating room. Anesthetic induction and maintenance were with inhaled sevoflurane and an intravenous infusion of remifentanil, with no need for neuromuscular relaxants. Airway management was achieved by inserting a Fastrach laryngeal mask (LM-Fastrach), through which an endotracheal tube could be inserted easily. The tube was withdrawn through the mask at the end of surgery and the mask was removed in the operating room 6 minutes later. Anesthesia in patients with myasthenia gravis is one of the greatest challenges in clinical anesthesiology. The interest of this case lies mainly in that the anesthetic technique chosen allows neuromuscular relaxants to be avoided. Moreover, airway access through the Fastrach laryngeal mask is highly useful for transsternal thymectomy of the patient with myasthenia gravis, providing immobility and adequate hemodynamic stability during sternotomy as well as facilitating safe and rapid postanesthetic recovery.

Topics: Anesthetics, Inhalation; Anesthetics, Intravenous; Humans; Laryngeal Masks; Male; Methyl Ethers; Middle Aged; Myasthenia Gravis; Piperidines; Remifentanil; Sevoflurane; Thymectomy

Infants born to mothers with myasthenia gravis may exhibit a transient form of the disease, with similar sensitivity to non-depolarizing neuromuscular blocking drugs. We report the case of an infant at risk who required major surgery when 48 h old for closure of bladder exstrophy. A combined epidural-general anaesthetic technique, with remifentanil supplementation, enabled us to avoid unnecessary neuromuscular blocking drugs and prolonged intensive care, which had been anticipated. The potential benefits of remifentanil and epidural analgesia in neonates are discussed.

Topics: Analgesia, Epidural; Analgesics, Opioid; Bladder Exstrophy; Contraindications; Humans; Infant, Newborn; Male; Myasthenia Gravis; Neuromuscular Nondepolarizing Agents; Piperidines; Remifentanil

We report a case of trans-sternal thymectomy for myasthenia gravis using a non relaxant, total intravenous technique with propofol and remifentanil. This afforded excellent control of heart rate and pressor responses during surgery while allowing early return of spontaneous ventilation and extubation within nine minutes of termination of anaesthesia. Advantages and disadvantages of this approach versus relaxant and volatile techniques are discussed with particular reference to preservation of neuromuscular function.

Topics: Adolescent; Anesthetics, Combined; Anesthetics, Intravenous; Female; Humans; Myasthenia Gravis; Piperidines; Propofol; Remifentanil; Thymectomy

Topics: Aged; Analgesics, Opioid; Humans; Male; Myasthenia Gravis; Piperidines; Remifentanil; Tongue Neoplasms

An effective and selective procedure for the extraction of ambenonium chloride (AMBC) from serum using a weak cation-exchange extraction cartridge has been developed. The solid-phase extraction procedure permitted the extraction of AMBC from serum without adhesion to materials such as the containers. A 200-microliter volume of the eluate could be directly injected on to a reversed-phase ion-pair high-performance liquid chromatographic column. The recovery was in the range 97-100%. The limit of detection for AMBC was 0.5 ng/ml in serum (signal-to-noise ratio = 3). The method was used to determine the serum concentration of AMBC in patients with myasthenia gravis. The method would be useful for monitoring AMBC in serum in order to study its pharmacokinetic behaviour in patients under oral administration therapy.

Topics: Adult; Ambenonium Chloride; Chemical Phenomena; Chemistry; Chromatography, Ion Exchange; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Piperidines; Spectrophotometry, Ultraviolet

Topics: Adolescent; Adult; Aged; Dexetimide; Humans; Middle Aged; Muscular Diseases; Myasthenia Gravis; Parasympathomimetics; Piperidines; Respiratory Insufficiency

Topics: Autoantibodies; Benzilates; Humans; Immunoglobulin G; Kinetics; Myasthenia Gravis; Parasympatholytics; Piperidines; Quinuclidinyl Benzilate; Receptors, Cholinergic; Receptors, Muscarinic

Topics: Alkaloids; Azepines; Glaucoma; Heterocyclic Compounds, Bridged-Ring; Humans; Lactones; Myasthenia Gravis; Ophthalmology; Optic Atrophy; Piperidines; Retina; Vision Tests; Visual Fields