Blocking Drugs Research Articles

P 248. Cortical inhibition by Retigabine in epilepsy patients: Assessment by transcranial magnetic stimulation

Introduction Transcranial magnetic stimulation (TMS) has been used to investigate the mechanism of action of several drugs. Sodium-channel blocking drugs elevate the threshold, while drugs that act on GABAergic transmission improve intracortical inhibition or prolong the silent period. While these basic studies are designed to investigate physiology and pharmacology, TMS can be suitable as biomarker in individual patients. A prospective study in newly diagnosed epilepsy demonstrated that TMS responses measured shortly after the application of an antiepileptic drug can predict long-term seizure control. ∗ Retigabine is a first-in-class antiepileptic drug that acts on potassium channels. Indirectly, changes in GABAergic synaptic transmission may contribute to its efficacy. In-vivo studies of the physiological effect of Retigabine on motor cortex excitability in patients with epilepsy could deepen our understanding of the involved mechanisms. The results of such a study may be compared with the literature on TMS-effects of classical anti-epileptic and other drugs acting on the central nervous system. Objectives The study aims to investigate the effect of Retigabine on cortical excitability measured by TMS in patients with partial onset epilepsy. If there is a change in the TMS variables after starting Retigabine, we would like to see whether this correlates with the therapeutic effect. Materials and methods This is an observational neurophysiological/neuropharmacological study. Fifteen patients with uncontrolled partial onset epilepsy, with or without secondary generalization that have an indication to initiate adjuvant treatment with Retigabine will participate. Doses of conconcurrent medication are kept constant during the study. TMS is performed before starting Retigabine, on 600 mg/day (post1), on 900/dag (post2) or after any other different maintenance dose is reached (post3). In each session resting motor threshold, short interval (2 and 5 ms) intracortical inhibition, intracortical facilitation (10 and 15 ms), long interval intracortical inhibition (250 and 300 ms) en silent period are measured. Results and conclusion At the conference preliminary results and conclusions will be presented.

Comparison of heart rate variability response in children undergoing elective endotracheal intubation with and without neuromuscular blockade: a randomized controlled trial

The routine use of neuromuscular blocking drugs (NMBD) for endotracheal intubation in children is the subject of much controversy. The analysis of heart rate variability (HRV) can reveal information about the functional state of the autonomic nervous system (ANS). The purpose of this study was to determine if HRV elucidates differences in the sympathovagal balance of children undergoing elective endo-tracheal intubation with and without neuromuscular blockade (NMB). In this prospective study, 38 children (2-6 years) scheduled for adenotonsillectomy were randomized into two groups to receive fentanyl 2 μg·kg(-1) and propofol 4 mg·kg(-1) , with either mivacurium 0.25 mg·kg(-1) (NMB group) or saline solution (NoNMB group) for anesthesia induction. The same experienced, blinded anesthesiologist performed endotracheal intubation. Heart rate variability, RR intervals, ECG as well as an electroencephalogram were recorded with HRV and BIS XP monitors, respectively. Heart rate variability was analyzed in the frequency domain. There was no significant difference in HRV changes immediately after mivacurium administration compared with an administration of saline. The groups were comparable for the bispectral index value (NMB 35 [33-41] vs NoNMB 34 [32-42]) during endotracheal intubation. Changes in both the low-frequency power and the low-/high-frequency ratio immediately after endotracheal intubation compared with the unstimulated state before laryngoscopy were significantly higher without NMB (P = 0.015 and P = 0.006, respectively), whereas there was no significant difference with respect to the high-frequency power. The stress response during endotracheal intubation in pediatric patients represented by the frequency domain analysis of HRV was found to be higher without NMB. When mivacurium was added to a propofol-fentanyl induction regimen, the ANS alterations during endotracheal intubation decreased significantly.

Neuromuscular disease and anesthesia

Patients with neuromuscular disease pose many anesthetic challenges and are at greater risk for perioperative complications, including respiratory or cardiovascular dysfunction and pulmonary aspiration. Therefore, these patients require special precautions, including interdisciplinary communication between primary care physicians, neurologists, physiatrists, surgeons, and anesthesiologists. Preoperative evaluation and optimization of comorbid conditions is critical. These patients may have adverse response to neuromuscular blocking drugs and the reversal drugs (e.g., neostigmine). They should be used with caution and titrated based on objective neuromuscular monitoring. Drugs that potentiate neuromuscular blocking drugs should also be avoided or their doses limited if possible. The risk of malignant hyperthermia in certain neuromuscular diseases mandates avoidance of triggering agents such as succinylcholine and inhaled anesthetics. Patients with neuromuscular disease may also be sensitive to sedative-hypnotics and opioids, which should be used judiciously. Finally, the postoperative period requires close monitoring due to increased risk of postoperative cardiorespiratory dysfunction.

The Impact of Drug Discontinuation in Patients Treated with Temporary Pacemaker Due to Atrioventricular Block

Patients treated with a temporary pacemaker (TPM) due to atrioventricular (AV) block are often monitored after discontinuation of AV node blocking drugs to evaluate the indication for permanent pacing. However, the impact of drug discontinuation is sparsely documented. We investigated to what extent drug discontinuation abolished the need for permanent pacemaker (PPM) implantation. All hospital records of patients who received a TPM at Aalborg Hospital, Denmark, between January 2000 and March 2011 (n = 575) were retrospectively reviewed. Patients with AV block who were treated with a TPM and concomitant cessation of drug therapy were included if there was no other underlying mechanism causing the AV block. AV blocking drugs included antiarrhythmic agents classes II-IV and digoxin. Fifty-five patients fulfilled our inclusion criteria. Forty-seven patients had an indication for a PPM at the initial hospital admission, despite drug discontinuation. Of the remaining 8 patients who were discharged without a PPM, 3 subsequently experienced events: 2 had recurrence of AV block requiring a PPM, and 1 experienced syncope. Thus, in total, 49 (89%) patients had a final indication for a permanent pacemaker (PPM). Of patients receiving beta-blocker monotherapy, 26 (96%) had an indication for a PPM. TPM implantation was complicated by infection or displacement in 11% of cases. The vast majority of patients treated with a TPM due to AV block and who receive beta-blockers alone or in combination with digoxin have a final indication for a PPM despite cessation of drug treatment. TPM are frequently associated with complications.

Sugammadex to rescue a ‘can't ventilate’ scenario in an anticipated difficult intubation: is it the answer?

Sugammadex to rescue a ‘can't ventilate’ scenario in an anticipated difficult intubation: is it the answer?

An Ipsilateral Comparison of Acceleromyography and Electromyography During Recovery from Nondepolarizing Neuromuscular Block Under General Anesthesia in Humans

Residual neuromuscular block is defined as a mechanomyography (MMG) or electromyography (EMG) train-of-four (TOF) ratio <0.90, and is common in patients receiving neuromuscular blocking drugs. Objective neuromuscular monitoring is the only reliable way to detect and exclude residual neuromuscular block. Acceleromyography (AMG) is commercially available and easy to use in the clinical setting. However, AMG is not interchangeable with MMG or EMG. Currently, it is unclear what value must be reached by AMG TOF ratio to reliably exclude residual neuromuscular block. During spontaneous recovery from neuromuscular block, we monitored TOF ratio on the same arm using AMG at the adductor pollicis and EMG at the first dorsal interosseus. AMG and EMG TOF ratios were compared by the Bland-Altman analysis for repeated measurements. The precision of each device was assessed by the repeatability coefficient. A small repeatability coefficient indicates high precision of the device. The agreement between the devices was assessed by the bias and the 95% limits of agreement. Small bias and narrow limits of agreement indicate strong agreement. We defined clinically acceptable agreement between AMG and EMG as a bias <0.025 and limits of agreement within -0.050 to 0.050, provided that the control comparison between EMG and itself can fulfill these criteria. In 26 patients, 261 comparisons between AMG and EMG were made. The repeatability coefficient of AMG and EMG were 0.094 (95% confidence interval [CI], 0.088-0.100) and 0.051 (95% CI, 0.048-0.055), respectively. The bias between AMG and EMG TOF ratio was 0.176 (95% CI, 0.162-0.190), with limits of agreement -0.045 to 0.396 (95% CI, -0.067 to 0.419). AMG is less precise than EMG and overestimates EMG TOF ratio by at least 0.15. The lack of agreement cannot be attributed to instrumental imprecision or the baseline difference between successive measurements during spontaneous recovery of neuromuscular function. Residual neuromuscular block cannot be excluded on reaching an AMG TOF ratio of 1.00.

Anaesthetic management of a child with PEHO syndrome

SummaryProgressive encephalopathy with oedema, hypsarrhythmia and optic atrophy (PEHO) syndrome is a rare neurodegenerative disorder of probable autosomal recessive inheritance. Specific challenges faced by the anaesthetist include difficult venous access, aspiration risk, and muscular hypotonia contraindicating the use of suxamethonium.A 3‐yr‐old boy with PEHO syndrome underwent tonsillectomy for the management of obstructive sleep apnoea. Our anaesthetic technique consisted of a gaseous induction followed by total intravenous anaesthesia, following which the patient was awoken and admitted electively to the intensive care unit for monitoring. We approached the case adopting techniques used when anaesthetising patients with more common neuromuscular diseases. Although we considered the option of using rocuronium followed by reversal with sugammadex, total avoidance of neuromuscular blocking drugs was felt to be the safest choice. The availability of intensive care in the postoperative period played an important role in our overall management.

Reversal with Sugammadex in the Absence of Monitoring Did Not Preclude Residual Neuromuscular Block

In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-induced neuromuscular blockade, this advantage has not been confirmed in clinical settings when no neuromuscular monitoring is used. In this multicenter observational study, we sought to determine whether sugammadex reduces the incidence of postoperative residual weakness compared with neostigmine when the administration of rocuronium and its antagonists is not guided by neuromuscular monitoring. This study was conducted in two 5-month periods that preceded and followed the introduction of sugammadex into clinical practice in Japan. Five university-affiliated teaching hospitals participated in this study. Neostigmine was used to antagonize rocuronium-induced neuromuscular blockade in the first phase, and sugammadex was used in the second phase. The timing and doses of rocuronium, neostigmine, and sugammadex were determined by the attending anesthesiologists without the use of neuromuscular function monitoring devices. To ascertain the incidence of postoperative residual neuromuscular weakness, the train-of-four ratio (TOFR) was determined acceleromyographically after tracheal extubation. Since our practice also does not usually involve calibration and normalization of accelerographic responses, both TOFR <0.9 and TOFR <1.0 were used as the criteria for defining postoperative residual weakness. In the first phase, 109 patients received neostigmine (average dose 33 µg/kg) and 23 patients were considered (by clinical criteria) to have adequate recovery and did not receive neostigmine (spontaneous recovery group). In the second phase, 117 patients received sugammadex (average dose 2.7 mg/kg) for antagonism of rocuronium-induced blockade. The incidence (95% confidence interval) of TOFR <0.9 under spontaneous recovery, after neostigmine, and after sugammadex, was 13.0% (2.8%-33.6%), 23.9% (16.2%-33.0%), and 4.3% (1.7%-9.4%), respectively. The incidence (95% confidence interval) of TOFR <1.0 in these groups was 69.6% (47.1%-86.6%), 67.0% (57.3%-75.7%), and 46.2% (36.9%-55.6%), respectively. The use of sevoflurane in the neostigmine group and the short interval between the administration of the last doses of rocuronium and sugammadex were associated with a higher incidence of postoperative residual weakness. This study demonstrated that the risk of TOFR <0.9 after tracheal extubation after sugammadex remains as high as 9.4% in a clinical setting in which neuromuscular monitoring (objective or subjective) was not used. Our finding underscores the importance of neuromuscular monitoring even when sugammadex is used for antagonism of rocuronium-induced neuromuscular block.

Rationally Designed Transmembrane Peptide Mimics of the Multidrug Transporter Protein Cdr1 Act as Antagonists to Selectively Block Drug Efflux and Chemosensitize Azole-resistant Clinical Isolates of Candida albicans

Drug-resistant pathogenic fungi use several families of membrane-embedded transporters to efflux antifungal drugs from the cells. The efflux pump Cdr1 (Candida drug resistance 1) belongs to the ATP-binding cassette (ABC) superfamily of transporters. Cdr1 is one of the most predominant mechanisms of multidrug resistance in azole-resistant (AR) clinical isolates of Candida albicans. Blocking drug efflux represents an attractive approach to combat the multidrug resistance of this opportunistic human pathogen. In this study, we rationally designed and synthesized transmembrane peptide mimics (TMPMs) of Cdr1 protein (Cdr1p) that correspond to each of the 12 transmembrane helices (TMHs) of the two transmembrane domains of the protein to target the primary structure of the Cdr1p. Several FITC-tagged TMPMs specifically bound to Cdr1p and blocked the efflux of entrapped fluorescent dyes from the AR (Gu5) isolate. These TMPMs did not affect the efflux of entrapped fluorescent dye from cells expressing the Cdr1p homologue Cdr2p or from cells expressing a non-ABC transporter Mdr1p. Notably, the time correlation of single photon counting fluorescence measurements confirmed the specific interaction of FITC-tagged TMPMs with their respective TMH. By using mutant variants of Cdr1p, we show that these TMPM antagonists contain the structural information necessary to target their respective TMHs of Cdr1p and specific binding sites that mediate the interactions between the mimics and its respective helix. Additionally, TMPMs that were devoid of any demonstrable hemolytic, cytotoxic, and antifungal activities chemosensitize AR clinical isolates and demonstrate synergy with drugs that further improved the therapeutic potential of fluconazole in vivo.

Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011

Neuromuscular blocking drugs (NMBDs) are the most common cause of intraoperative anaphylaxis in Western Australia. Differences in the rates of anaphylaxis between individual agents have been surmised in the past, but not proven, and are an important consideration if agents are otherwise equivalent. We estimated a rate of anaphylaxis to NMBDs by analysing cases of NMBD anaphylaxis referred to the only specialized diagnostic centre in Western Australia over a 10 yr period. Exposure was approximated by analysing a 5 yr period of NMBD ampoule sales data. Agents were also ranked according to the prevalence of cross-reactivity in patients with previous NMBD anaphylaxis. Rocuronium was responsible for 56% of cases of NMBD anaphylaxis, succinylcholine 21%, and vecuronium 11%. There was no difference in the severity of reactions for different NMBDs. Rocuronium had a higher rate of IgE-mediated anaphylaxis compared with vecuronium (8.0 vs 2.8 per 100,000 exposures; P=0.0013). The prevalence of cross-reactivity after NMBD anaphylaxis suggested that succinylcholine also has a high risk of triggering anaphylaxis. Cisatracurium had the lowest prevalence of cross-reactivity in patients with known anaphylaxis to rocuronium or vecuronium. Rocuronium has a higher rate of IgE-mediated anaphylaxis compared with vecuronium, a result that is statistically significant and clinically important. Cisatracurium had the lowest rate of cross-reactivity in patients who had previously suffered anaphylaxis to rocuronium or vecuronium.

Intraoperative Neuromuscular Monitoring Site and Residual Paralysis

Thilen, Stephan R.; Hansen, Bradley E.; Ramaiah, Ramesh; Kent, Christopher D.; Treggiari, Miriam M.; Bhananker, Sanjay M. Author Information

Residual anaesthesia drugs in intravenous lines – a silent threat?

Residual anaesthesia drugs in intravenous lines – a silent threat?

Neuromuscular monitoring, residual blockade, and reversal: Time for re-evaluation of our clinical practice

Even with the advent of shorter-acting muscle relaxants, the risk of residual blockade continues to persist. Consequently, in daily practice, we are confronted with the following contradiction, namely, how best to combine muscular relaxation throughout the operative procedure without exposing patients to the risk of residual blockade at the end of the case. A Continuing Professional Development (CPD) module concerning residual blockade is published in this issue of the Journal. Why was it necessary to publish a CPD module on this topic when a number of related studies and surveys reports are already available? While many clinicians are convinced about the benefits of both neuromuscular monitoring and reversal in current practice, nevertheless, reality seems to differ. Anesthesiologists are well trained in the use of neuromuscular blocking agents. In fact, anesthesiology is the only specialty where these drugs are routinely used. And yet, many clinicians tend not to follow the basic recommendations for using both neuromuscular monitoring and reversal agents. The circumstances leading to this state of affairs are likely more complex. The last updated version of the American Society of Anesthesiologists’ (ASA) Practice Guidelines for Postanesthetic Care states that: ‘‘Assessment of neuromuscular function primarily includes physical examination and, on occasion, may include neuromuscular blockade monitoring’’. With such an assertion regarding the potential for occasional use of neuromuscular monitoring, it would, in all likelihood, be difficult to convince our colleagues regarding the benefits of neuromuscular monitoring and modify existing behaviour. Clinical methods for determining signs of residual blockade may not have the degree of sensitivity to detect partial paralysis. For example, residual paralysis is likely in patients who are able to maintain a sustained head lift. It is only with objective neuromuscular monitoring that one can exclude residual blockade. Clearly, the ASA Task Force on Postanesthetic Care developed their recommendation based on data lacking in sufficient evidence. This is also the basis for SpO2 monitoring. Pedersen et al. from the Cochrane Collaboration updated the systematic review on the use of pulse oximetry during the perioperative period. The authors’ conclusions are comparable with two previous reviews published by the same group. Even if the use of pulse oximetry helped decrease the frequency of hypoxemic episodes, it does not influence patient outcome on major end points (e.g., death and cardiovascular, respiratory, or neurological complications). Even when we consider these evidence-based data on pulse oximetry, can any one of us imagine starting a case without its use? This depiction reveals the limits of evidence-based medicine. This topic has previously been addressed with humour in a study on whether or not there are benefits to using a parachute to prevent death during free fall. Residual blockade remains a specific concern in daily anesthesia practice. The use of neuromuscular blocking drugs has facilitated major progress in performing additional and more complex surgical procedures. This view was first addressed by Dr. Harrold Griffith et al. 70 years ago when Benoit Plaud is consultant for MSD France and MSD International and has participated in the clinical development of sugammadex (Bridion ).

Beta blockers and angiotensin-converting enzyme inhibitors’ purported benefit on breast cancer survival may be explained by aspirin use

Preclinical and epidemiologic evidence supports a possible role for beta-adrenergic blocking drugs (beta-blockers), and angiotensin-converting enzyme inhibitors (ACEIs) in promoting survival after breast cancer. However, these drugs are often used concurrently with aspirin, and there is a growing body of evidence indicating a survival benefit for aspirin. Therefore, we analyzed the use of beta-blockers and ACEIs after a breast cancer diagnosis and their association with breast cancer mortality, both individually, combined with each other, and in combination with aspirin use in the Nurses' Health Study, using updated measures of medication use and Cox proportional hazards models. There were 4,661 women with stages I-III breast cancer included; 292 breast cancer deaths occurred during median follow-up time of 10.5 years. Modeled individually, the multivariable relative risk and 95 % confidence intervals (RR, 95 % CI) for breast cancer death were (0.76, 0.54-1.05) for beta blockers, (0.89, 0.60-1.32) for ACEIs, and (0.46, 0.35-0.60) for aspirin. Modeled simultaneously, the multivariable (RR, 95 % CI) for breast cancer death were (0.83, 0.60-1.16) for beta blockers, (1.00, 0.68-1.46) for ACEIs, and (0.46, 0.35-0.61) for aspirin. We did not see a significant association with beta blockers and survival, but there was a suggestion. Our study was limited in that we could not assess type of beta blocker and the number of events among users was still quite low. We found no evidence of a protective effect for ACEIs. The strong protective association with aspirin use confounds the associations with these other drugs and underscores the importance of considering aspirin use in analyses of breast cancer survival.

Cardiologists are more willing to prescribe β‐blockers than respiratory physicians: an Australasian clinical scenario survey

Recent data show great benefit from beta adrenergic blocking drug (β-blocker) use in heart failure and has resulted in increased use of these established agents. Older data caution against their use in patients with reversible airways disease because of risks of bronchoconstriction. Anecdotally, we noted a difference in willingness to prescribe β-blockers by cardiologists and respiratory physicians, especially for patients with coexisting airways disease. We sought to test this difference. Nine clinical scenarios were created, tested and emailed to all members of the Cardiac and Thoracic societies of Australasia. Scenarios combined varying degrees of benefit and risk (bronchoconstriction). An inducement to return questionnaires was applied. Cardiologists and respiratory physicians were similarly willing to prescribe β-blockers for patients at little risk of bronchoconstriction, irrespective of potential benefit. Cardiologists were more willing to prescribe β-blockers than respiratory physicians for patients at greater risk of bronchoconstriction, particularly when the potential therapeutic benefit was greater. Our perception that cardiologists were more willing to prescribe β-blockers than respiratory physicians was confirmed. This probably results from a difference in focus (namely focus on benefit by cardiologists vs focus on risk by respiratory physicians), although other factors including awareness of limitations of pulmonary function testing by respiratory physicians may have been involved. Until better tests are available (that discriminate between patients who are likely to suffer bronchoconstriction from those who are not), it is likely that this difference between the specialties will remain.

Reply to

Editor, We appreciate the interest and comments of Errando and Perez-Caballero1 concerning our paper on the anaesthetic management of patients with Duchenne muscular dystrophy2 and are grateful for the opportunity to reply. We agree with Errando and Perez-Caballero that the use of neuromuscular blocking agents in patients with Duchenne muscular dystrophy is of major concern. In our review, we considered many important points arising during anaesthesia and the perioperative period when treating patients with Duchenne muscular dystrophy. It is correct that we have not addressed in detail the use of neuromuscular blocking drugs and reversal agents. However, in the past, we have published several investigations regarding the use of neuromuscular blocking agents in patients with Duchenne muscular dystrophy.3–6 In addition, in one investigation, we reported on the efficacy of pyridostigmine to reverse rocuronium-induced neuromuscular block in patients with Duchenne muscular dystrophy after spinal surgery.7 In group A of our review (patients with minor surgery of the lower extremity), there was no case documented requiring postoperative ventilatory support whether or not neuromuscular blocking drugs had been used. In contrast, following major orthopaedic surgery, many factors influence weaning from the ventilator in patients with Duchenne muscular dystrophy. Apart from the strength of respiratory muscles mentioned by Errando and Perez-Caballero, parameters like perioperative blood loss, cardiac performance, need for sympathomimetic drugs, body temperature and others must be considered when deciding on the time of extubation. On average after spinal surgery, patients reported in our review were ventilated postoperatively for a duration of 19 h. Therefore, we do not routinely use reversal agents before removing the tracheal tube after spinal surgery. We have no experience with the use of sugammadex in patients with Duchenne muscular dystrophy. Acknowledgements Assistance with the letter: none declared. Financial support and sponsorship: none declared. Conflicts of interests: none declared.

An introduction to anaesthesia

British Journal of Hospital MedicineVol. 74, No. Sup5 What You Need to Know AboutAn introduction to anaesthesiaCiara Donohue, Ben Hobson, Robert CM StephensCiara DonohueSearch for more papers by this author, Ben HobsonSearch for more papers by this author, Robert CM StephensSearch for more papers by this authorCiara Donohue; Ben Hobson; Robert CM StephensPublished Online:14 Nov 2014https://doi.org/10.12968/hmed.2013.74.Sup5.C71AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Al-Shaikh B, Stacey S (2007) Non invasive monitoring. In: Al-Shaikh B, Stacey S, eds. Essentials of Anaesthetic Equipment. 3rd edn. Churchill Livingstone, London: 151–3 Google ScholarAppiah-Ankam J, Hunter J (2004) Pharmacology of neuromuscular blocking drugs. Contin Educ Anaesth Crit Care Pain 4(1): 2–7 Crossref, Google ScholarCranshaw J, Cook T (2011) Airway assessment and management. In: Allman K, Wilson I, eds. Oxford Handbook of Anaesthesia. 3rd edn. Oxford University Press, Oxford: 970–6 Google ScholarDavis P, Kenny G (2007) Biological Electrical Potentials: Their display and recording. In: Davis P, Kenny G, eds. Basic Physics and Measurement in Anaesthesia. 5th edn. Butterworth-Heinemann, London: 171 Google ScholarDoherty M, Buggy D (2012) Intraoperative fluids: how much is too much? Br J Anaesth 109(1): 69–79 Crossref, Medline, Google ScholarHarper CM, Andrzejowski JC, Alexander R (2008) NICE and warm. Br J Anaesth 101(3): 293–5 Crossref, Medline, Google ScholarKing JM, Hunter J (2002) Physiology of the neuromuscular junction. Br J Anaesth CEPD Reviews 2(Sup5): 129–33 Google ScholarKnight DJW, Mahajan RP (2004) Patient positioning in anaesthesia. Contin Educ Anaesth Crit Care Pain 4(Sup5): 160–3 Crossref, Google ScholarPeck TE, Hill S, Williams M (2008) Core drugs in anaesthetic practice. In: Peck TE, Hill S, Williams M, eds. Pharmacology for Anaesthesia and Intensive Care. 3rd edn. Cambridge University Press, Cambridge: 99–102 Crossref, Google ScholarSasada M, Smith S (2008) Drugs in Anaesthesia and Intensive Care. 3rd edn. Oxford University Press, Oxford Google ScholarSinclair RCF, Luxton MC (2005) Rapid sequence induction. Contin Educ Anaesth Crit Care Pain 5(2): 45–8 Crossref, Google ScholarWalker A, Reshamwalla S, Wilson I (2012) Surgical safety checklists: do they improve outcomes? Br J Anaesth 109(1): 47–54 Crossref, Medline, Google ScholarYentis S, Hirsch N, Smith G (2009) Anaesthesia and Intensive Care A-Z. 4th edn. Churchill Livingstone, London: 354 Google ScholarYuill G, Simpson M (2002) An introduction to total intravenous anaesthesia. Br J Anaesth CEPD Reviews 2(1): 24–6 Google Scholar FiguresReferencesRelatedDetailsCited ByA comparative analysis of the anaesthetic effect of sodium bicarbonate (NaHCO 3 ) on male and female three spotted tilapia ( Oreochromis andersonii )20 April 2022 | Journal of Applied Animal Research, Vol. 50, No. 1CFD investigation of CO2 separation from anesthesia gaseous stream applying novel cholinium lysinate amino acid-based ionic liquid inside the gas–liquid membrane contactor14 September 2022 | The European Physical Journal Plus, Vol. 137, No. 9A Co-Induction Technique Utilizing 4% Sevoflurane Followed by 0.75 mg/kg Propofol in Elderly Patients Undergoing Minimally Invasive Procedures: A Prospective Randomized Control Study10 December 2020 | Medicina, Vol. 56, No. 12Preoperative Evaluation Before Noncardiac SurgeryMayo Clinic Proceedings, Vol. 95, No. 4Sense and Insensibility – An Appraisal of the Effects of Clinical Anesthetics on Gastropod and Cephalopod Molluscs as a Step to Improved Welfare of Cephalopods24 August 2018 | Frontiers in Physiology, Vol. 9The principles of surgical care: intraoperative care2 December 2015 | British Journal of Healthcare Assistants, Vol. 9, No. 11 1 May 2013Volume 74Issue Sup5ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 14 November 2014 Published in print 1 May 2013 Information© MA Healthcare LimitedPDF download

β-Adrenergic Blockade in Cardiovascular Disease

The development and subsequent clinical application of the β-adrenergic receptor blocking drugs represent one of the major advances in human pharmacotherapeutics. No other class of synthetic drugs has demonstrated such widespread therapeutic utility for the treatment and prevention of so many cardiovascular diseases. In addition, these drugs have proven to be molecular probes that have contributed to our understanding of the disease, and on the molecular level, both the structure and function of the 7 transmembrane G protein receptors that mediate the actions of many different hormones, neurotransmitters, and drugs. The evolution of β-blocker drug development has led to refinements in their pharmacodynamic actions that include agents with relative β1-selectivity, partial agonist activity, concomitant α-adrenergic blockers activity, and direct vasodilator activity. In addition, long-acting and ultra-short-acting formulations of β-blockers have also demonstrated a remarkable record of clinical safety in patients of all ages.

Latent inhibition of a conditioned taste aversion in fetal rats

The etiology of schizophrenia's cognitive symptoms may have its basis in prenatal alterations of glutamate N-methyl-D-aspartate (NMDA) receptor functioning. Therefore, the current study investigated the effects of ketamine (an NMDA receptor blocking drug) on both a conditioned taste aversion (CTA) and latent inhibition (LI; a model of attentional capacity) in rat fetuses. We first sought to determine if a CTA could be diminished by nonreinforced preexposure to a CS in fetal rats (i.e., LI). We injected E18 pregnant Sprague-Dawley rats with 100% allicin (garlic taste) or an equal volume of saline. Some of the pregnant dams also received ketamine (100 mg/kg, i.p.). One day later (E19), the dams received a second injection of the CS, followed by either lithium chloride (the US) or saline. Finally, on E21 pups received oral lavage with allicin and observations of ingestive orofacial motor responses were recorded. When allicin had been paired with LiCl in utero, E21 fetuses exhibited a conditioned suppression of orofacial movements, indicative of an aversion to this taste. Preexposure to the garlic taste on E18 produced a LI of this CTA. Ketamine significantly disrupted the formation of the CTA and had some impact on LI. However, the direct effect of ketamine on LI is less certain since the drug also blocked the original CTA.

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