DOCSLIB.ORG

The Effects of Anticholinesterase Agents on the Blood Cholinesterases Levels of Normal and Glaucoma Subjects*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effects of Anticholinesterase Agents on the Blood Cholinesterases Levels of Normal and Glaucoma Subjects* THE EFFECTS OF ANTICHOLINESTERASE AGENTS ON THE BLOOD CHOLINESTERASES LEVELS OF NORMAL AND GLAUCOMA SUBJECTS* BY Irving H. Leopold, M.D. AND (BY INVITATION) JVarendra Krishna, B.SC., M.B.B.S.,** AND Robert A. Lehman, PH.D.*** ANTICHOLINESTERASE AGENTS (cholinesterase inhibitors) are used ex- tensively in the-management of the glaucomas, in the form of local application to the eyes. In primary glaucomas, these drugs are used to lower intraocular pressure because of their effects on the iris, the ciliary body, and the vascular system of the eye. In closed angle or angle closure glaucoma, they act by freeing the angle of the obstructive effect of the iris, by producing miosis. In open angle or wide angle glaucoma, it is not known whether they exert their beneficial effect primarily by their action on the ciliary body musculature or by their action on the blood vessels, but it is known that they improve the facility of aqueous outflow. Inhibition of cholinesterases (ChE) results in the %preservation of acetylcholine from hydrolysis so that it can exert its muscarinic action on the iris, the ciliary body, and the blood vessels. These tissues, like the erythrocytes of the normal human being, possess Group I cholines- terases or acetylcholinesterases (AChE) (other equivalent terms pro- posed: specific ChE, true ChE, e-ChE, aceto-ChE), which are con- cerned in the neurohumeral function of acetylcholine. The blood plasma contains Group II cholinesterases (various terms designated: non-specific ChE, unspecific ChE, pseudo-ChE, s-ChE, butyro or butyryl-ChE, propiono-ChE, X-ChE) which are not concerned with neurohumeral transmission (1, 2, 3, 4). No reliable reports are avail- able on the cholinesterase content of the iris and ciliary body of glaucomatous eyes because of the obvious difficulty of obtaining the *From the Department of Ophthalmology, Graduate School of Medicine of the University of Pennsylvania, and the Research and Clinical Departments of the Wills Eye Hospital, Philadelphia, Pa. **"Fight for Sight" Research Fellow of the National Council to Combat Blind- ness, Inc., New York, N.Y. ***Director of Research, Campbell Pharmaceuticals, Inc., New York, N.Y. TR. AM. OPHTH. Soc., vol. 57, 1959 64 Leopold, Krishna and Lehman material in the early stages of the disease. The cholinesterases levels in the whole blood of glaucoma patients have been shown to lie within the normal range (5). In clinical use, anticholinesterase drugs are instilled repeatedly and' for an indefinite period into glaucomatous eyest It is reasonable to expect that some absorption may take place from the conjunctival sac, the nasal mucosa, and even the gastrointestinal tract into the general blood stream. That this is indeed so has been shown for DFP and Humorsol, with which the blood cholinesterases levels were depressed a few hours following a single instillation into the eyes (6, 7, 8). The short- acting cholinesterase inhibitors, physostigmine and prostigmine, ap- proximately equally inhibit Group I ChE or AChE and Group II ChE; whereas among the long-acting cholinesterase inhibitors DFP inhibits mainly group II ChE, while Phospholine and Humorsol in- hibit chiefly AChE (9, 10, 11, 12). The present investigation has been undertaken to determine the effects of these anticholinesterase agents on the red blood cells and plasma cholinesterases levels of normal human subjects and glaucoma patients when administered locally into the eyes over periods from a few hours to two months. METHODS Cholinesterases determinations were carried out by the method of continuous titration at constant pH. To a reaction vessel bearing calomel and glass electrodes is added 100 c.c. of a solution having the following composition: acetylcholine bromide, recrystallized from alcohol (0.012M), 0.27 percent; NaCl, 0.9 percent; KC1, 0.03 percent; CaC12 * 2H20, 0.034 percent; q.s. with glass distilled water, 100 percent. The vessel is inserted into a water bath at 37.5° + 0.010 C. and con- nection made to apparatus for automatic titration with 0.02N sodium hydroxide solution with simultaneous plotting of volume of base added against time. After the reaction vessel has reached the bath tempera- ture, sodium hydroxide is run in until the pH is 7.4. Then, 1 to 2 c.c. of sample is added and the acetic acid, liberated by hydrolysis of the substrate, is titrated continuously at a pH of 7.4 + 0.05. After 20 min. the reaction' is stopped. The slope of the line is estimated graphically from the chart and the rate is expressed in milliequivalents of acetyl- choline hydrolyzed per hour per cubic centimeter of sample. The titration equipment has been described previously (13). This study was carried out on out-patients at Wills Eye Hospital, Philadelphia. "Normal subjects" were patients with no ocular pathology Anticholinestierase Agents 65 other than refractive error. Venous blood samples were used in all cases and clotting was prevented by adding 1 mg. of heparin per 10 c.c. All samples were refrigerated until analyses were completed. Hematocrits were determined within 24 hours and whole blood and plasma were analysed for cholinesterases within five days. Packed red cell values were obtained by calculation. Drugs used in this study were physostigmine salicylate (eserine salicylate); Prostigmine methylbromide (neostigmine methylbromide); DFP (Floropryl, Isoflurophate) Phospholine iodide (echothiophate iodide, 217-MI); Humorsol (demecarium bromide, BC-48). BASE LINE CHOLINESTERASES LEVELS OF THE BLOOD OF NORMAL HUMAN SUBJECTS AND GLAUCOMA PATIENTS Twenty-two normal subjects and 19 patients with primary glaucoma were selected. An attempt was made in all cases to exclude any other disease which would influence the blood cholinesterases levels, such as liver diseases, blood dyscrasias, etc. (14, 15). Only those patients with glaucoma were included who had been on pilocarpine therapy at WHOLE BLOOD PLASMA R.B.C. NORMAL GLAUCOMA NORMAL GLAUCOMA NORMAL GLAUCOMA .6- *0.0 0 - E .5-. I.- 0 0 ,4-. 40 000 _J 0) * 0 .3- 0 0 . wC.) -~ *00 _J - ow' .2+ 0 *4t 0 .1- 00 0 - FIGURE 1 Comuparison of base line blood, plasma, and red blood cells cholinesterases levels in normal and glaucoma patients, 66 Leopold, Krishna and Lehman TABLE 1. BASE LINE BLOOD PLASMA AND RED BLOOD CELLS CHOLINESTERASES LEVELS OF NORMAL HUMAN SUBJECTS Cholinesterase activity (mM acetylcholinc hydrolyzed,ljhr.1'c.c.) Patient Whole blood Plasma Red blood cells 1 .309 .182 .493 2 .334 .193 .521 3 .430 .220 .620 4 .269 .124 .500 5 .379 .255 .550 6 .303 .173 .505 7 .394 .309 .507 8 .295 .169 .448 9 .309 .136 .617 10 .240 .109 .483 11 .283 .164 .448 12 .415 .307 .571 13 .227 .098 .420 14 .326 .154 .518 15 .281 .136 .481 16 .352 .167 .577 17 .302 .164 .510 18 .378 .312 .476 19 .385 .260 .567 20 .19:3 .120 .314 21 .328 .169) .486 22 .224 .087 .438 the time of this study and in whom no cholinesterase inhibitor had been used for a period of at least two months prior to the collection of blood samples. One blood sample from each patient was subjected to analysis and the results are given in Tables 1 and 2. The mean and standard deviations for normals and glaucoma patients were computed from these data and compared with those of Sawitsky et al. (16), who employed a similar procedure in their determinations. These have been summarized in Table 3. Our normals are quite consistent with the normals reported by Sawitsky et al. However, significantly lower red blood cell cholinesterases levels were found in glaucoma patients. Rados (5) failed to find a change in whole blood cholinesterases in glaucoma which is not surprising since the unchanged plasma would obscure changes occurring in the erythrocytes. Studies to elucidate this point further are in progress and wvill be reported subsequently. It Anticholinesterase Agents 67 TABLE 2. BASE LINE BLOOD PLASMA.AND RED BLOOD CELLS CHOLINESTERASES LEVELS OF GLAUCOMA PATIENTS Cholinesterase activity (mM acetylcholine hydrolyzed/hr./c.c.) Paticnt Whole blood Plasma Red blood cells 23 .307 .149 .510 24 .326 .211 .485 25 .285 .206 .403 26 .366 .252 .544 27 .212 .082 .352 28 .316 .181 .485 29 .316 .195 .453 30 .292 .223 .400 31 .292 .170 .468 32 .219 .052 .440 33 .269 .161 .400 34 .172 .072 .323 35 .323 .172 .542 36 .224 .146 .293 37 .248 .145 .430 38 .238 .114 .425 39 .354 .166 .549 40 .302 .184 .487 41 .251 .143 .421 TABLE 3. MEAN AND STANDARD DEVIATIONS OF BLOOD PLASMA AND RED BLOOD CELLS CHOLINESTERASES LEVELS OF NORMAL HUMAN SUBJECTS AND GLAUCOMA PATIENTS Cholinesterase activity (mM acetylcho- line hydrolyzed/hr./c.c.) No. of pts. Plasma Red blood cells Normals (Wills Eye Hospital) 22 0.182 ±0.068 0.502 A0.068 Normals ( Sawitsky et al.)* 15 0.199 ±0.060 0.525 ±0.053 Glaucoma patients (Wills Eye Hospital) 19 0.159 ±0.052 0.443 ±0.072 *Figures obtainied by multiplyinig the values by 0.06 for activity in mM/hr./c.c. of sample (16). 68 Leopold, Krishna and Lehman 0.5 % ESERINE (0.1cc 02) 5.0% PROSTIGMINE (Olccc02) WHOLE PWLHSMA ROLEB.C | D L O C. BLOOD PLSA RBC BLOOD PLSA RBC .6- .5~~2 4 V ~ ~ ~ ~~~~V` ,,i'~~\,,A.N \/':. 3 : *..2 'NAN~~~~~~~~~~~D I.~ ~~H BEFORE 35 1 3 5 135 1 3 5 1 3 5 1 3 5 INSTILL.4) - HOURS A F T E R I NSTILLATION - FIGURE 2 Hourly influence of eserine and prostigmine on blood, plasma, and red blood cells cholinesterases levels. seems pertinent to mention here that the cholinesterases activity may vary widely from individual to individual, but tends to remain fairly constant in one individual. Age, sex, diet, physical exertion, heart rate, and blood pressure are without influence on it (16, 17).
Load more

Recommended publications
  • Supplementary Information
    Supplementary Information Network-based Drug Repurposing for Novel Coronavirus 2019-nCoV Yadi Zhou1,#, Yuan Hou1,#, Jiayu Shen1, Yin Huang1, William Martin1, Feixiong Cheng1-3,* 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA 2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA 3Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA #Equal contribution *Correspondence to: Feixiong Cheng, PhD Lerner Research Institute Cleveland Clinic Tel: +1-216-444-7654; Fax: +1-216-636-0009 Email: [email protected] Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. Supplementary Table S2. Protein sequence identities across 5 protein regions in 15 coronaviruses. Supplementary Table S3. HCoV-associated host proteins with references. Supplementary Table S4. Repurposable drugs predicted by network-based approaches. Supplementary Table S5. Network proximity results for 2,938 drugs against pan-human coronavirus (CoV) and individual CoVs. Supplementary Table S6. Network-predicted drug combinations for all the drug pairs from the top 16 high-confidence repurposable drugs. 1 Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. GenBank ID Coronavirus Identity % Host Location discovered MN908947 2019-nCoV[Wuhan-Hu-1] 100 Human China MN938384 2019-nCoV[HKU-SZ-002a] 99.99 Human China MN975262
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • Mechanism of Central Hypopnoea Induced by Organic Phosphorus
    www.nature.com/scientificreports OPEN Mechanism of central hypopnoea induced by organic phosphorus poisoning Kazuhito Nomura*, Eichi Narimatsu, Hiroyuki Inoue, Ryoko Kyan, Keigo Sawamoto, Shuji Uemura, Ryuichiro Kakizaki & Keisuke Harada Whether central apnoea or hypopnoea can be induced by organophosphorus poisoning remains unknown to date. By using the acute brainstem slice method and multi-electrode array system, we established a paraoxon (a typical acetylcholinesterase inhibitor) poisoning model to investigate the time-dependent changes in respiratory burst amplitudes of the pre-Bötzinger complex (respiratory rhythm generator). We then determined whether pralidoxime or atropine, which are antidotes of paraoxon, could counteract the efects of paraoxon. Herein, we showed that paraoxon signifcantly decreased the respiratory burst amplitude of the pre-Bötzinger complex (p < 0.05). Moreover, pralidoxime and atropine could suppress the decrease in amplitude by paraoxon (p < 0.05). Paraoxon directly impaired the pre-Bötzinger complex, and the fndings implied that this impairment caused central apnoea or hypopnoea. Pralidoxime and atropine could therapeutically attenuate the impairment. This study is the frst to prove the usefulness of the multi-electrode array method for electrophysiological and toxicological studies in the mammalian brainstem. Te pre-Bötzinger complex (preBötC) in the ventrolateral lower brainstem is essential for the formation of the unconscious breathing rhythm in mammals1,2. Tis is because the cyclic burst excitation generated from preBötC synchronizes with the respiratory rhythm through phrenic nerve fring and the diaphragmatic contractions, and destruction of preBötC causes the disappearance of the rhythm. Periodic respiratory burst excitation has also been confrmed from an island specimen derived by isolating preBötC in an island shape to block input from other neurons2.
    [Show full text]
  • 2020 Welldyne Formulary.Pdf
    LEGEND TIER DESCRIPTION 1 Preferred Generics 2 Non-Preferred Generics 3 Preferred Brands 4 Non-Preferred Brands 5 Preferred Specialty 6 Non-Preferred Specialty TYPE DESCRIPTION There is a limit on the amount of this drug that is covered per QL Quantity Limit prescription, or within a specific time frame. You (or your physician) are required to get prior authorization before PA Prior Authorization you fill your prescription for this drug. Without prior approval, we may not cover this drug. In some cases, you may be required to first try certain drugs to treat ST Step Therapy your medical condition before we will cover another drug for that condition. This prescription drug may only be covered if you meet the minimum AL1 Age Limit or maximum age limit. LA Limited Access This prescription drug is limited to certain pharmacies. Specialty drugs are high-cost drugs used to treat complex or rare S Specialty Drug conditions, such as multiple sclerosis, rheumatoid arthritis, hepatitis C, and hemophilia. PAGE 1 LAST UPDATED 01/2020 LIST OF COVERED PRESCRIPTION MEDICATIONS PRODUCT DESCRIPTION TIER LIMITS & RESTRICTIONS ADHD/ANTI-NARCOLEPSY /ANTI-OBESITY/ANOREXIANT AGENTS ADHD/ANTI-NARCOLEPSY/ANTI-OBESITY/ANOREXIANTS ADDERALL 4 AL1 Up to 25 yrs old ADDERALL XR 4 AL1 Up to 25 yrs old QL 30 / 30 day(s) ADHANSIA XR 4 AL1 Up to 25 yrs old QL 30 / 30 Days ADIPEX-P 4 PA QL 300 / 30 day(s) ADZENYS ER 4 AL1 Up to 25 yrs old QL 30 / 30 Days ADZENYS XR-ODT 4 AL1 Up to 25 yrs old QL 300 / 30 day(s) AMPHETAMINE ER 4 AL1 Up to 25 yrs old QL 180 / 30 day(s) amphetamine
    [Show full text]
  • Partial Agreement in the Social and Public Health Field
    COUNCIL OF EUROPE COMMITTEE OF MINISTERS (PARTIAL AGREEMENT IN THE SOCIAL AND PUBLIC HEALTH FIELD) RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies, and superseding Resolution AP (82) 2) AND APPENDIX I Alphabetical list of medicines adopted by the Public Health Committee (Partial Agreement) updated to 1 July 1988 APPENDIX II Pharmaco-therapeutic classification of medicines appearing in the alphabetical list in Appendix I updated to 1 July 1988 RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (superseding Resolution AP (82) 2) (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies) The Representatives on the Committee of Ministers of Belgium, France, the Federal Republic of Germany, Italy, Luxembourg, the Netherlands and the United Kingdom of Great Britain and Northern Ireland, these states being parties to the Partial Agreement in the social and public health field, and the Representatives of Austria, Denmark, Ireland, Spain and Switzerland, states which have participated in the public health activities carried out within the above-mentioned Partial Agreement since 1 October 1974, 2 April 1968, 23 September 1969, 21 April 1988 and 5 May 1964, respectively, Considering that the aim of the Council of Europe is to achieve greater unity between its members and that this
    [Show full text]
  • Drug Class Review Ophthalmic Cholinergic Agonists
    Drug Class Review Ophthalmic Cholinergic Agonists 52:40.20 Miotics Acetylcholine (Miochol-E) Carbachol (Isopto Carbachol; Miostat) Pilocarpine (Isopto Carpine; Pilopine HS) Final Report November 2015 Review prepared by: Melissa Archer, PharmD, Clinical Pharmacist Carin Steinvoort, PharmD, Clinical Pharmacist Gary Oderda, PharmD, MPH, Professor University of Utah College of Pharmacy Copyright © 2015 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved. Table of Contents Executive Summary ......................................................................................................................... 3 Introduction .................................................................................................................................... 4 Table 1. Glaucoma Therapies ................................................................................................. 5 Table 2. Summary of Agents .................................................................................................. 6 Disease Overview ........................................................................................................................ 8 Table 3. Summary of Current Glaucoma Clinical Practice Guidelines ................................... 9 Pharmacology ............................................................................................................................... 10 Methods .......................................................................................................................................
    [Show full text]
  • United States Patent (19) 11 Patent Number: 4,765,973 Heller 45 Date of Patent: Aug
    United States Patent (19) 11 Patent Number: 4,765,973 Heller 45 Date of Patent: Aug. 23, 1988 54) POLYMERS CONTAINING PEN DANT ACD Assistant Examiner-M. L. Moore FUNCTIONALITIES AND LABILE Attorney, Agent, or Firm-Manfred Polk; Michael C. BACKBONE BONDS Sudol (75) Inventor: Jorge Heller, Woodside, Calif. 57 ABSTRACT Assignee: Merck & Co., Inc., Rahway, N.J. The instant invention is directed to a polymer with at 73 least one labile backbone bond per repeat unit and at (21) Appl. No.: 915,348 least one pendant acid functionality per thousand repeat 22 Filed: Oct. 6, 1986 units. The instant invention is also directed to a controlled Related U.S. Application Data release device which comprises: (A) a polymer with at least one labile backbone bond (62) Division of Ser. No. 68,002, Jun. 6, 1984, Pat. No. per repeat unit and at least one pendant acid func 4,639,366. tionality per thousand repeat units; and 51 Int. Cl'.............................................. A61K 31/74. (B) a beneficial substance incorporated within or 52) U.S. C. ....................................... 424/486; 424/78 surrounded by the matrix of said polymer. (58) Field of Search ........................ 424/19, 20, 22, 78 Primary Examiner-John Kight 3 Claims, No Drawings 4,765,973 1. 2 Tri- and higher hydroxyl functional polyols may be POLYMERS CONTAINING PEN DANT ACID used, which will result in crosslinked polymers. FUNCTIONALTES AND LABLE BACKBONE Any polymer containing at least one acid labile back BONDS bone bond per repeat unit (preferably two per repeat 5 acid unit) may be used to react with the polyol contain This is a division of application Ser.
    [Show full text]
  • Professor Jo Klaveness School of Pharmacy University of Oslo
    SUPERVISORS Professor Jo Klaveness School of Pharmacy University of Oslo Associate professor Pål Rongved School of Pharmacy University of Oslo 1 TABLE OF CONTENTS TABLE OF CONTENTS 1 ABBREVIATIONS..........................................................................5 2 ABSTRACT.....................................................................................6 3 INTRODUCTION............................................................................7 3.1 Acetylcholine- a neurotransmitter Synthesis, release and inactivation ... 7 3.1.1 Structure of acetylcholinesterase .................................................................... 8 3.2 Anticholinesterases interfere with acetylcholine activity ........................ 9 3.3 Effects of anticholinesterases................................................................... 9 3.4 Different groups of anticholinesterases.................................................. 10 3.4.1 Short- acting anticholinesterases .................................................................. 10 3.4.2 Medium- duration anticholinesterases .......................................................... 11 3.4.3 Irreversible anticholinesterases..................................................................... 12 3.5 Nerve agents: Irreversible anticholinesterases....................................... 13 3.5.1 The dawn of a deadly weapon ...................................................................... 14 3.5.2 Biochemistry................................................................................................
    [Show full text]
  • Demecarium Bromide/Homatropine 1881
    Demecarium Bromide/Homatropine 1881 Dyflos (BAN) junctival injection of pralidoxime has been used to reverse severe ocular adverse effects. Supportive treatment, including assisted DFP; Difluorophate; Di-isopropyl Fluorophosphate; Di-isopro- ventilation, should be given as necessary. CH3 pylfluorophosphonate; Fluostigmine; Isoflurofato; Isoflurophate. Di-isopropyl phosphorofluoridate. To prevent or reduce development of iris cysts in patients receiv- N ing ecothiopate eye drops, phenylephrine eye drops may be giv- C6H14FO3P = 184.1. en simultaneously. CAS — 55-91-4. ATC — S01EB07. Precautions ATC Vet — QS01EB07. As for Neostigmine, p.632. For precautions of miotics, see also OH under Pilocarpine, p.1885. In general, as with other long-acting anticholinesterases, ecothiopate should be used only where ther- O apy with other drugs has proved ineffective. Ecothiopate iodide CH3 should not be used in patients with iodine hypersensitivity. O O H3C O Interactions P CH3 As for Neostigmine, p.632. The possibility of an interaction re- O F mains for a considerable time after stopping long-acting anti- Homatropine Hydrobromide (BANM) CH3 cholinesterases such as ecothiopate. Homatr. Hydrobrom.; Homatropiinihydrobromidi; Homatropi- Pharmacopoeias. In US. Uses and Administration na, hidrobromuro de; Homatropine, bromhydrate d’; Homatro- USP 31 (Isoflurophate). A clear, colourless, or faintly yellow liq- Ecothiopate is an irreversible inhibitor of cholinesterase; its ac- pin-hidrobromid; Homatropinhydrobromid; Homatropin-hydro- uid. Specific gravity about 1.05. Sparingly soluble in water; sol- tions are similar to those of neostigmine (p.632) but much more bromid; Homatropini hydrobromidum; Homatropinium Bro- uble in alcohol and in vegetable oils. It is decomposed by mois- prolonged. Its miotic action begins within 1 hour of its applica- mide; Homatropino hidrobromidas; Homatropinum Bromatum; ture with the evolution of hydrogen fluoride.
    [Show full text]
  • Chapter 6 PRETREATMENT for NERVE AGENT EXPOSURE
    Pretreatment for Nerve Agent Exposure Chapter 6 PRETREATMENT FOR NERVE AGENT EXPOSURE MICHAEL A. DUNN, M.D., FACP*; BRENNIE E. HACKLEY, JR., PH.D.†; AND FREDERICK R. SIDELL, M.D.‡ INTRODUCTION AGING OF NERVE AGENT–BOUND ACETYLCHOLINESTERASE PYRIDOSTIGMINE, A PERIPHERALLY ACTING CARBAMATE COMPOUND Efficacy Safety Wartime Use Improved Delivery CENTRALLY ACTING NERVE AGENT PRETREATMENTS NEW DIRECTIONS: BIOTECHNOLOGICAL PRETREATMENTS SUMMARY *Colonel, Medical Corps, U.S. Army; Director, Clinical Consultation, Office of the Assistant Secretary of Defense (Health Affairs), Washing- ton, D.C. 20301-1200; formerly, Commander, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Mary- land 21010-5425 †Scientific Advisor, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425 ‡Formerly, Chief, Chemical Casualty Care Office, and Director, Medical Management of Chemical Casualties Course, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425; currently, Chemical Casualty Consultant, 14 Brooks Road, Bel Air, Maryland 21014 181 Medical Aspects of Chemical and Biological Warfare INTRODUCTION Nerve agents are rapidly acting chemical com- cal as well and may impair physical and mental pounds that can cause respiratory arrest within performance. A pretreatment must be administered minutes of absorption. Their speed of action im- to an entire force under a nerve agent threat. Any poses a need for rapid and appropriate reaction by resulting performance decrement, even a compara- exposed soldiers, their buddies, or medics, who tively minor one, would make pretreatment use must administer antidotes quickly enough to save unacceptable in battlefield situations requiring lives. A medical defense against nerve agents that maximum alertness and performance for survival.
    [Show full text]
  • Pharmacology of Ophthalmologically Important Drugs James L
    Henry Ford Hospital Medical Journal Volume 13 | Number 2 Article 8 6-1965 Pharmacology Of Ophthalmologically Important Drugs James L. Tucker Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal Part of the Chemicals and Drugs Commons, Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Tucker, James L. (1965) "Pharmacology Of Ophthalmologically Important Drugs," Henry Ford Hospital Medical Bulletin : Vol. 13 : No. 2 , 191-222. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol13/iss2/8 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. For more information, please contact [email protected]. Henry Ford Hosp. Med. Bull. Vol. 13, June, 1965 PHARMACOLOGY OF OPHTHALMOLOGICALLY IMPORTANT DRUGS JAMES L. TUCKER, JR., M.D. DRUG THERAPY IN ophthalmology, like many specialties in medicine, encompasses the entire spectrum of pharmacology. This is true for any specialty that routinely involves the care of young and old patients, surgical and non-surgical problems, local eye disease (topical or subconjunctival drug administration), and systemic disease which must be treated in order to "cure" the "local" manifestations which frequently present in the eyes (uveitis, optic neurhis, etc.). Few authors (see bibliography) have attempted an introduction to drug therapy oriented specifically for the ophthalmologist. The new resident in ophthalmology often has a vague concept of the importance of this subject, and with that in mind this paper was prepared.
    [Show full text]