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Molecular Mechanisms Underlying Ketamine-Mediated Inhibition Of
Anesthesiology 2005; 102:93–101 © 2004 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Molecular Mechanisms Underlying Ketamine-mediated Inhibition of Sarcolemmal Adenosine Triphosphate- sensitive Potassium Channels Takashi Kawano, M.D.,* Shuzo Oshita, M.D.,† Akira Takahashi, M.D.,‡ Yasuo Tsutsumi, M.D.,* Katsuya Tanaka, M.D.,§ Yoshinobu Tomiyama, M.D., Hiroshi Kitahata, M.D.,# Yutaka Nakaya, M.D.** Background: Ketamine inhibits adenosine triphosphate-sen- sensitive channel pore.3 These channels, as metabolic sitive potassium (KATP) channels, which results in the blocking sensors, are associated with such cellular functions as of ischemic preconditioning in the heart and inhibition of va- insulin secretion, cardiac preconditioning, vasodilata- sorelaxation induced by KATP channel openers. In the current 4–7 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/102/1/93/357819/0000542-200501000-00017.pdf by guest on 27 September 2021 study, the authors investigated the molecular mechanisms of tion, and neuroprotection. ketamine’s actions on sarcolemmal KATP channels that are re- In cardiac myocytes, intravenous general anesthetics, associated by expressed subunits, inwardly rectifying potas- such as ketamine racemate, propofol, and thiamylal, di- sium channels (Kir6.1 or Kir6.2) and sulfonylurea receptors 8–10 rectly inhibit native sarcolemmal KATP channels. Al- (SUR1, SUR2A, or SUR2B). though these observations suggest that intravenous an- Methods: The authors used inside-out patch clamp configura- tions to investigate the effects of ketamine on the activities of esthetics may impair the endogenous organ protective reassociated Kir6.0/SUR channels containing wild-type, mutant, mechanisms mediated by KATP channels, the possibility or chimeric SURs expressed in COS-7 cells. -
Chapter Four – TRPA1 Channels: Chemical and Temperature Sensitivity
CHAPTER FOUR TRPA1 Channels: Chemical and Temperature Sensitivity Willem J. Laursen1,2, Sviatoslav N. Bagriantsev1,* and Elena O. Gracheva1,2,* 1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA 2Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA *Corresponding author: E-mail: [email protected], [email protected] Contents 1. Introduction 90 2. Activation and Regulation of TRPA1 by Chemical Compounds 91 2.1 Chemical activation of TRPA1 by covalent modification 91 2.2 Noncovalent activation of TRPA1 97 2.3 Receptor-operated activation of TRPA1 99 3. Temperature Sensitivity of TRPA1 101 3.1 TRPA1 in mammals 101 3.2 TRPA1 in insects and worms 103 3.3 TRPA1 in fish, birds, reptiles, and amphibians 103 3.4 TRPA1: Molecular mechanism of temperature sensitivity 104 Acknowledgments 107 References 107 Abstract Transient receptor potential ankyrin 1 (TRPA1) is a polymodal excitatory ion channel found in sensory neurons of different organisms, ranging from worms to humans. Since its discovery as an uncharacterized transmembrane protein in human fibroblasts, TRPA1 has become one of the most intensively studied ion channels. Its function has been linked to regulation of heat and cold perception, mechanosensitivity, hearing, inflam- mation, pain, circadian rhythms, chemoreception, and other processes. Some of these proposed functions remain controversial, while others have gathered considerable experimental support. A truly polymodal ion channel, TRPA1 is activated by various stimuli, including electrophilic chemicals, oxygen, temperature, and mechanical force, yet the molecular mechanism of TRPA1 gating remains obscure. In this review, we discuss recent advances in the understanding of TRPA1 physiology, pharmacology, and molecular function. -
Cannabinoid Receptor and Inflammation
Cannabinoid Receptor and Inflammation Newman Osafo1, Oduro Yeboah1, Aaron Antwi1, and George Ainooson1 1Kwame Nkrumah University of Science and Technology September 11, 2020 Abstract The eventual discovery of endogenous cannabinoid receptors CB1 and CB2 and their endogenous ligands has generated interest with regards to finally understanding the endocannabinoid system. Its role in the normal physiology of the body and its implication in pathological states such as cardiovascular diseases, neoplasm, depression and pain have been subjects of scientific interest. In this review the authors focus on the endogenous cannabinoid pathway, the critical role of cannabinoid receptors in signaling and mediation of neurodegeneration and other inflammatory responses as well as its potential as a drug target in the amelioration of some inflammatory conditions. Though the exact role of the endocannabinoid system is not fully understood, the evidence found leans heavily towards a great potential in exploiting both its central and peripheral pathways in disease management. Cannabinoid therapy has already shown great promise in several preclinical and clinical trials. 1.0 Introduction Ethnopharmacological studies have shown the use of Cannabis sativa in traditional medicine for over a thousand years, with its widespread use promoted by its psychotropic effects (McCoy, 2016; Turcotte et al., 2016). The discovery of a receptor within human body, that is selectively activated by cannabinoids suggested the presence of at least one endogenous ligand for this receptor. This is confirmed by the discovery of two endogenously synthesized lipid mediators, 2-arachidonoyl-glycerol and arachidonoylethanolamide, which function as high-affinity ligands for a subfamily of cannabinoid receptors ubiquitously distributed in the central nervous system, known as the CB1 receptors (Turcotte et al., 2016). -
N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation Via Nonhematopoietic TRPV1
N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1 This information is current as Samira K. Lawton, Fengyun Xu, Alphonso Tran, Erika of October 1, 2021. Wong, Arun Prakash, Mark Schumacher, Judith Hellman and Kevin Wilhelmsen J Immunol 2017; 199:1465-1475; Prepublished online 12 July 2017; doi: 10.4049/jimmunol.1602151 http://www.jimmunol.org/content/199/4/1465 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2017/07/12/jimmunol.160215 Material 1.DCSupplemental http://www.jimmunol.org/ References This article cites 69 articles, 11 of which you can access for free at: http://www.jimmunol.org/content/199/4/1465.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on October 1, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Author Choice Freely available online through The Journal of Immunology Author Choice option Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1 Samira K. -
Iatrogenic Misadventure
BRITISH MEDICAL JOURNAL 18 MARcH 1972 733 Scientific Basis of Clinical Practice Br Med J: first published as 10.1136/bmj.1.5802.733 on 18 March 1972. Downloaded from Iatrogenic Misadventure A. G. W. WHITFIELD British Medical journal, 1972, 1, 733-734 effects. No one would pretend that our knowledge of drugs interacting with oral anticoagulants is complete. Even so, A striking feature of the history of therapeutics is the extent to sufficient is already known to indicate that anticoagulant drugs which fashion, rather than clinical science, governs the treat- have potent dangers and should be used only within the limited ment we mete out to our patients. Some ten years ago I attended sphere in which they are of proven worth. Moreover, when they a symposium on anticoagulant therapy and returned home are given, if possible, no other drug should be given at the firmly convinced that in all but a very few conditions such same time as many are known to inhibit or enhance their effect treatment was absolutely essential and indeed it was little short and many others may have similar interactions, even though of criminal negligence to withhold it. At that time the patient these are as yet unrecognized and unreported. queue for "prothrombin times" was usually the longest in our hospitals and phenindione was among the most frequently prescribed drugs, but our constant use of it stemmed from enthusiasm and ignorance of its dangers and not from scientific Hypotensive Drugs proof of its therapeutic advantages. Indeed it is only as know- Hypotensive drugs are being used increasingly and undoubtedly ledge has accumulated that we have learned of the toxic effects, their development has provided an enormous advance both in of the drug we gave so freely, on the kidney, the liver, the bone the treatment and in the prognosis of the severe forms of marrow, and the skin and that except in thromboembolic disease and in patients with hypertension-particularly in the younger age groups. -
Pharmacology – Inhalant Anesthetics
Pharmacology- Inhalant Anesthetics Lyon Lee DVM PhD DACVA Introduction • Maintenance of general anesthesia is primarily carried out using inhalation anesthetics, although intravenous anesthetics may be used for short procedures. • Inhalation anesthetics provide quicker changes of anesthetic depth than injectable anesthetics, and reversal of central nervous depression is more readily achieved, explaining for its popularity in prolonged anesthesia (less risk of overdosing, less accumulation and quicker recovery) (see table 1) Table 1. Comparison of inhalant and injectable anesthetics Inhalant Technique Injectable Technique Expensive Equipment Cheap (needles, syringes) Patent Airway and high O2 Not necessarily Better control of anesthetic depth Once given, suffer the consequences Ease of elimination (ventilation) Only through metabolism & Excretion Pollution No • Commonly administered inhalant anesthetics include volatile liquids such as isoflurane, halothane, sevoflurane and desflurane, and inorganic gas, nitrous oxide (N2O). Except N2O, these volatile anesthetics are chemically ‘halogenated hydrocarbons’ and all are closely related. • Physical characteristics of volatile anesthetics govern their clinical effects and practicality associated with their use. Table 2. Physical characteristics of some volatile anesthetic agents. (MAC is for man) Name partition coefficient. boiling point MAC % blood /gas oil/gas (deg=C) Nitrous oxide 0.47 1.4 -89 105 Cyclopropane 0.55 11.5 -34 9.2 Halothane 2.4 220 50.2 0.75 Methoxyflurane 11.0 950 104.7 0.2 Enflurane 1.9 98 56.5 1.68 Isoflurane 1.4 97 48.5 1.15 Sevoflurane 0.6 53 58.5 2.5 Desflurane 0.42 18.7 25 5.72 Diethyl ether 12 65 34.6 1.92 Chloroform 8 400 61.2 0.77 Trichloroethylene 9 714 86.7 0.23 • The volatile anesthetics are administered as vapors after their evaporization in devices known as vaporizers. -
Pharmacology for PAIN: Prescribing Controlled Substances
The Impact of Pain Pharmacology for PAIN: The National Center for Health Prescribing Controlled Statistics estimates that 32.8% of the U.S. population has persistent pain ~94 million U.S. residents have episodic or Substances persistent pain (1 in every 5 adults) Judith A. Kaufmann, Dr PH, FNP-BC Treatment for chronic pain rarely Robert Morris University results in complete relief and full functional recovery Of patients diagnosed with chronic pain and treated by a PCP, 64 percent report persistent pain two years after treatment initiation US Statistics: The Alarming Impact of Pain Facts Pain ranks low on medical tx priority Americans constitute 4.6% of world’s only 15% of primary care physicians report that they "enjoy" treating patients with chronic pain population-but consume ~ 80% of world’s Dahl et al., and Redford (2002) found that patients opioid supply said they fear dying in pain more than they fear death Americans consume 99% of world supply of hydrocodone Pain over the past 10 years has been designated the 5th vital sign Between 1999 and 2006, the number of people >age 12 using illicit prescription Pain is 3rd leading cause of absence pain relievers doubled from 2.6 to 5.2 from work million 2006 National Survey on Drug Use and Health (NSDUH) Are we the Pushers? Can we be found guilty? Since 1999, opioid analgesic poisonings on 55.7% of users obtained drugs from a death certificates increased 91% friend or relative who had been prescribed the drugs from 1 provider During same period, fatal heroin and cocaine poisonings increased 12.4% and 22.8% 19.1% of users obtained their drug directly respectively from 1 provider In 2008, 36,450 opioid deaths were 1.6% reported doctor shopping reported 3.9% reported purchasing drugs from a CDC, 2011 dealer Male:female ratio = 1.5:1 but death rate for females ia 20x higher than males 1 Is opioid abuse a recent Classifications of Pain phenomenon? Acute V. -
Drug-Induced Sexual Dysfunction in Men and Women
VOLUME 36 : NUMBER 2 : APRIL 2013 ARTICLE Drug-induced sexual dysfunction in men and women Helen M Conaglen whether the clinician is willing to ask about sexual Clinical psychologist and SUMMARY issues and does so in a sensitive way.7,8 Senior research fellow Many medical conditions and their treatments Patients on long-term medications may not be John V Conaglen aware that their sexual problems have developed Endocrinologist and contribute to sexual dysfunction. as a result of their treatment. Conversely some may Associate professor in Commonly implicated drugs include Medicine blame their drugs for sexual problems which are due Sexual Health Research Unit antihypertensives, antidepressants, to relationship difficulties or other stressors. Some Waikato Clinical School antipsychotics and antiandrogens. doctors consider that asking patients if they had Faculty of Medical and Understanding the potential for drug-induced noticed any sexual adverse effects from their drugs Health Sciences University of Auckland sexual problems and their negative impact may ‘suggest’ them to the patient, and possibly result on adherence to treatment will enable the in non-adherence. Patients attributing their sexual clinician to tailor treatments for the patient problems to their drugs are less likely to continue the Key words treatment even when necessary for their health.9 The antidepressants, and his or her partner. consultation should include discussion of the patient’s antihypertensives, Encouraging a discussion with the patient sexual issues so these can be considered in treatment antipsychotics, arousal, about sexual function and providing erectile dysfunction, decisions. hypoactive sexual desire strategies to manage the problem are critical disorder, male impotence, to good clinical care. -
Dative Metabolism of Cortisol in Humans Kunihi
臨 床 薬 理JPn J Clin Pharmacol Ther 18 (3) Sept 1987 509 Comparison of the Inhibitory Effects of Famotidine and Cimetidine on Hepatic Oxi- dative Metabolism of Cortisol in Humans Kunihiko MORITA* Hiroki KONISHI* Takeshi ONO* and Harumi SHIMAKAWA* (Receivedon Dec.19, 1986) * Hospital Pharmacy, Shiga Universityof Medical Science, Tsukinowa-cho,Seta, Ohtsu520-21, Japan The inhibitory effect of famotidine, a new H2-receptor antagonist, on hepatic oxidative metabolism of cortisol in six healthy volunteers was compared with that of cimetidine by monitoring the change in urinary 6ƒÀ-hydroxycortisol (6ƒÀ-OHF), an oxidative metabolite of cortisol. The ratio of 6ƒÀ-OHF to 17-hydroxycorticosteroids (17-OHCS) in urine was measured before, during, and after treatment with famotidine and cimetidine for 3 days in a cross-over study. The ratio was decreased by 25% -35% of the original level after 1-3 days of oral treatment with cimetidine (800 mg, b. i. d.). The reduction vanished within 2 days after the last dose of cimetidine. The ratio was not significantly changed during oral treatment with famotidine (40 mg, b. i. d.). These findings indicate that famotidine, in contrast to cimetidine, does not affect the hepatic oxidative metabolism of cortisol in man, and it is suggested that famotidine does not affect the hepatic drug-metabolizing capacity in humans. Key words: famotidine, cimetidine, H2-receptor antangonist, 6ƒÀ-hydroxycortisol, enzyme inhibition been shown to inhibit the hepatic elimination of a Introduction number of drugs coadministred.1-4) A number of Cimetidine, a histamine H2-receptor antagonist studies have demonstrated that this inhibitory widely used for the treatment of peptic ulcer, has action of cimetidine is based on its high affinity for cytochrome P-450 in hepatic microsomes *滋 賀医科大学医学部附属病院薬剤部 arising from imidazole and cyano groups.5-7) 〓520-21滋 賀県大津市瀬田月輪町 Ranitidine, an H2-receptor antagonist developed 510 hospital pharmacists, aged 24 to 35 years old (mean 28), participated in the study. -
Label-Free Cell Phenotypic Profiling Decodes the Composition And
OPEN Label-free cell phenotypic profiling SUBJECT AREAS: decodes the composition and signaling POTASSIUM CHANNELS SENSORS AND PROBES of an endogenous ATP-sensitive Received potassium channel 28 January 2014 Haiyan Sun1*, Ying Wei1, Huayun Deng1, Qiaojie Xiong2{, Min Li2, Joydeep Lahiri1 & Ye Fang1 Accepted 24 April 2014 1Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, NY 14831, United States of Published America, 2The Solomon H. Snyder Department of Neuroscience and High Throughput Biology Center, Johns Hopkins University 12 May 2014 School of Medicine, Baltimore, Maryland 21205, United States of America. Current technologies for studying ion channels are fundamentally limited because of their inability to Correspondence and functionally link ion channel activity to cellular pathways. Herein, we report the use of label-free cell requests for materials phenotypic profiling to decode the composition and signaling of an endogenous ATP-sensitive potassium should be addressed to ion channel (KATP) in HepG2C3A, a hepatocellular carcinoma cell line. Label-free cell phenotypic agonist Y.F. (fangy2@corning. profiling showed that pinacidil triggered characteristically similar dynamic mass redistribution (DMR) com) signals in A431, A549, HT29 and HepG2C3A, but not in HepG2 cells. Reverse transcriptase PCR, RNAi knockdown, and KATP blocker profiling showed that the pinacidil DMR is due to the activation of SUR2/ Kir6.2 KATP channels in HepG2C3A cells. Kinase inhibition and RNAi knockdown showed that the pinacidil * Current address: activated KATP channels trigger signaling through Rho kinase and Janus kinase-3, and cause actin remodeling. The results are the first demonstration of a label-free methodology to characterize the Biodesign Institute, composition and signaling of an endogenous ATP-sensitive potassium ion channel. -
Auspar Attachment 1. Product Information for Mifepristone
Attachment 1: Product information for AusPAR MS-2 Step mifepristone/misoprostol MS Health Pty Ltd PM-2013-01037-1-5 Final 13 October 2014. This Product Information was approved at the time this AusPAR was published. PRODUCT INFORMATION - MS-2 StepÔ It is very important that all patients receiving these medications are followed up by a medical practitioner, preferably the prescriber, to ensure that the medication has been effective. Even if no adverse events have occurred all patients must receive follow-up 14 to 21 days after taking mifepristone. Read the SPECIAL WARNINGS AND PRECAUTIONS FOR USE carefully. This document refers to the use of MS-2 StepÔ, which consists of Mifepristone Linepharma 200 mg tablet and GyMiso® misoprostol 200 microgram tablets in combination. These medicines are indicated in females of childbearing age for the medical termination of a developing intrauterine pregnancy, up to 63 days of gestation. The Mifepristone Linepharma 200 mg tablet component of this therapy is also used to treat another condition. For information about the treatment of the other condition, refer to the full Product Information for Mifepristone Linepharma 200 mg tablet individual product (AUST R 175671). NAME OF THE MEDICINE MS-2 StepÔ is a composite pack containing Mifepristone Linepharma 200 mg tablet and GyMiso® misoprostol 200 microgram tablets. Mifepristone Australian Approved Name (AAN): Mifepristone Chemical Structure: CH3 N CH 3 OH CH H CH3 3 H H O Molecular formula: C29H35NO2 Molecular weight: 429.6 Version:22May2014 [63days] Page 1 of 23 Attachment 1: Product information for AusPAR MS-2 Step mifepristone/misoprostol MS Health Pty Ltd PM-2013-01037-1-5 Final 13 October 2014. -
Pharmacokinetics and Pharmacology of Drugs Used in Children
Drug and Fluid Th erapy SECTION II Pharmacokinetics and Pharmacology of Drugs Used CHAPTER 6 in Children Charles J. Coté, Jerrold Lerman, Robert M. Ward, Ralph A. Lugo, and Nishan Goudsouzian Drug Distribution Propofol Protein Binding Ketamine Body Composition Etomidate Metabolism and Excretion Muscle Relaxants Hepatic Blood Flow Succinylcholine Renal Excretion Intermediate-Acting Nondepolarizing Relaxants Pharmacokinetic Principles and Calculations Atracurium First-Order Kinetics Cisatracurium Half-Life Vecuronium First-Order Single-Compartment Kinetics Rocuronium First-Order Multiple-Compartment Kinetics Clinical Implications When Using Short- and Zero-Order Kinetics Intermediate-Acting Relaxants Apparent Volume of Distribution Long-Acting Nondepolarizing Relaxants Repetitive Dosing and Drug Accumulation Pancuronium Steady State Antagonism of Muscle Relaxants Loading Dose General Principles Central Nervous System Effects Suggamadex The Drug Approval Process, the Package Insert, and Relaxants in Special Situations Drug Labeling Opioids Inhalation Anesthetic Agents Morphine Physicochemical Properties Meperidine Pharmacokinetics of Inhaled Anesthetics Hydromorphone Pharmacodynamics of Inhaled Anesthetics Oxycodone Clinical Effects Methadone Nitrous Oxide Fentanyl Environmental Impact Alfentanil Oxygen Sufentanil Intravenous Anesthetic Agents Remifentanil Barbiturates Butorphanol and Nalbuphine 89 A Practice of Anesthesia for Infants and Children Codeine Antiemetics Tramadol Metoclopramide Nonsteroidal Anti-infl ammatory Agents 5-Hydroxytryptamine