DOCSLIB.ORG

By Long Lasting Depolarization of the Motor End-Plates

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
By Long Lasting Depolarization of the Motor End-Plates 238 J. Physiol. (I953) I22, 238-251 MOTOR END-PLATE DIFFERENCES AS A DETERMINING FACTOR IN THE MODE OF ACTION OF NEUROMUSCULAR BLOCKING SUBSTANCES By ELEANOR J. ZAIMIS From the Department of Pharmacology, School of Pharmacy, 17 Bloomsbury Square, W.C. 1 (Received 26 February 1953) Work on cat, human, avian and frog skeletal muscle (Paton & Zaimis, 1952) led to the conclusion that true neuro-muscular block is mainly produced by two different processes: (a) by competition with acetylcholine at the motor end-plates; and (b) by long lasting depolarization of the motor end-plates. Experiments carried out upon other mammalian species reveal the possibility of a third mode of neuromuscular block which combines the two processes mentioned above. These experiments show the characteristics of such a neuro- muscular block and provide evidence that differences in the motor end-plates are a determining factor in the mode of action of a substance at the neuro- muscular junction. A preliminary account of this work has already appeared (Zaimis, 1952). METHODS The mammalian species used have been the cat, monkey, dog, rabbit and hare. Chloralose alone was used as an anaesthetic for the cats, the dose given being 80 mg/kg. To the other species between 100 and 120 mg/kg of chloralose was given, but in a few experiments it proved necessary to supplement this anaesthetic with a small dose of pentobarbitone sodium. The injections of chloralose were made into the saphenous vein. Twitches and tetani of the tibialis, soleus and flexor digitorum sublimis muscles were excited by twice-maximal shocks of 02 msec duration, applied to the tied sciatic nerve in the thigh. In some experiments records of the mechanical response of two muscles in the same leg were recorded on the same drum. Injections were made intravenously or intra-arterially. For the intra-arterial injection the external iliac of the non-operated leg was cannulated towards the bifurcation of the aorta. The aorta was ligatured below the origin of the external iliac arteries. Under such conditions the dose injected was carried to the operated leg. Respiration was recorded by the apparatus described by Paton (1949). For experiments on chicks, birds a few days old were used and injections were made into the jugular vein. NEUROMUSCULAR BLOCK AND SPECIES DIFFERENCES 239 RESULTS Decamethonium Monkeys. The investigations with which this paper deals started with the surprising observation that while a first intravenous dose of 03 mg/kg of decamethonium into a monkey produced a transitory 95 % paralysis of the tibialis muscle, a subsequent dose injected after the complete recovery of the twitch was without effect (Fig. 1 a-c). This is in contrast with the effect of 3 4 _ 1g1 k<g I 0*5 - 04 - 0-3 - 0.2 _ O Fig. 1. a-c, monkey, 3-3 kg. Contractions of tibialis excited by supramaximal shocks to the sciatic nerve, every 10 sec. At (1) and 30 min later at (2), intravenous injection of 1 mg of decamethonium iodide; 10 min later at (3) and (4) injections of 1 mg of decamethonium iodide. At (5) tetanic stimulus to motor nerve, 50/sec. d, from another experiment. Monkey, 8 kg. Chloralose. Tibialis: nerve shock every 10 sec. At (1) intravenous injection of 10 mg of decamethonium iodide (following three smaller doses of decamethonium). At (2) 2 mg neostigmine methylsulphate I.v. At (3) tetanic stimulus to motor nerve, 50/sec. decamethonium on the tibialis muscle of the cat, where a further dose produces a greater paralysis. But this is not the end of the story, for in a monkey the block is rarely preceded by potentiation of the twitch and then only to a very slight degree; the tetanus is not well maintained and antagonizes the block which is also antagonized by neostigmine (Fig. 1 d). In short, the characteristics 240 ELEANOR J. ZAIMIS of this block differ from those of a block produced by pure depolarization, which is usually preceded by a brief period of fasciculation of the muscle and potentiation of the single twitches, and in which the tension of a tetanus is well maintained during the block while neostigmine and tetanus are not antagonists. If one records simultaneously the contractions of the tibialis and soleus muscles in a cat, results show that the tibialis is much more sensitive to decamethonium than the soleus. The same muscles differ in sensitivity to 1 2 3 4 56~~~~~~~~kg7 X. ]~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. Fig. 2. Dog, 10 kg. Simultaneous records of supramaximal motor nerve twitches of tibialis (upper record) and flexor digitorum sublimiis (lower record). At (1), (2), (4) and (5) intravenous injection of 1 mg of decamethonium. At (3) 1 mg neostigmine methylsuiphate I.V. At (6) and (7) tetanic stimulus to motor nerve, 50/sec. D-tubocurarine but in the opposite way (Paton & Zaimis, 1951). If one now records the contractions of the tibialis and soleus muscles in a monkey the first dose of decamethonium causes a paralysis of tibialis, but has little effect on soleus. When the doses are progressively increased it is found that tibialis becomes less and less sensitive but soleus is increasingly affected. When the paralysis of the soleus starts spontaneous respiration stops. Briefly we start with the picture as in a cat given by decamethonium and finish with that given by D-tubocurarine. On the other hand, the block produced in the monkey by D-tubocurarine has all the well-known characteristics of that produced by competition with acetylcholine; it is not preceded by stimulation and is antagonized by a tetanus or neostigmine. During the block the muscles cannot maintain a tetanus and show an increasing sensitivity to subsequent doses of D-tubocurarine. Dogs, rabbits and hares. A number of tests were also made upon dogs and rabbits. The results show that the neuromuscular block produced by decame- thonium in these species has the same characteristics as that in the monkey. This is clearly indicated in Figs. 2 and 3. The muscles show the same decreasing sensitivity and under the influence of decamethonium they cannot maintain NEUROMUSCULAR BLOCK AND SPECIES DIFFERENCES 241 a tetanus. Moreover, the block is antagonized by tetanus and by neostigmine, and potentiated by D-tubocurarine. The only difference between the dog and rabbit is that the block produced by the first dose of decamethonium is always preceded in the rabbit (Fig. 3, 1) by potentiation of the twitch. 1 2 3 4 |E_0X1 0~~~~~~~~~~~~~~~~~0 S8 67 9 10 11~~~~~~~~~~10 Fig. 3. Rabbit, 3 kg. Contractions of tibialis excited by supramaximal shocks to the sciatic nerve, every 10 sec. At (1), (3) and (4) intravenous injection of 0-6 mg of decamethonium iodide. At (2) and (7), tetanic stimulus to motor nerve, 50/sec. At (5) 2 mg atropine sulphate i.v. At (6) 1-8 mg decamethonium iodide i.v. At (8) and (11) intravenous injection of 05 mg neostigmine methylsulphate. At (9) 1 mg decamethonium iodide and at (10) 0 5 mg D-tubocurarine chloride i.v. The following phenomenon deserves attention as it frequently occurs and is difficult to explain. It has been observed that whereas a first dose of neo- stigmine given during a neuromuscular block antagonizes the block effectively a second dose given during a subsequent dose is a far less effective antagonizer. This is clearly indicated in Fig. 3. The same phenomenon occurs when the block is produced by D-tubocurarine. Results of an experiment carried out on a single wild hare are illustrated in Fig. 4 and are sufficiently clear-cut to be worth recording. Here again the block produced by decamethonium has the same peculiar characteristics: decreasing sensitivity of the muscles to subsequent doses, the tetanus very poorly sustained, neostigmine effectively antagonizing the block and no sign of stimulation preceding it. PH. CXXII. 16 242 ELEANOR J. ZAIMIIS Other depolarizing substances An attempt was then made to study the actions of succinylcholine, a neuro- muscular blocking substance believed to produce its actions in the cat and in avian muscle by pure depolarization. The results obtained with this substance in the monkey and the dog are shown in Figs. 5 and 6. It is clear that in these species succinylcholine produces a block similar to that produced by decame- 2 3 4 6 7 8 Fig. 4. Hare, 3 kg. Simultaneous records of supramaximal motor nerve twitches of tibialis (upper record) and soleus (lower record). At (1) intravenous injection of 0 5 mg, followed at (2) by 1 mg decamethonium iodide. At (3) and (4) tetanic stimulus to motor nerve, 50/sec. 30 min later at (5) decamethonium iodide, 1 mg i.v. At (6) 1 mg neostigmine methylsulphate. At (7) 0-2 mg D-tubocurarine chloride and at (8) 1 mg neostigmine methylsulphate. NEUROMUSCULAR BLOCK AND SPECIES DIFFERENCES 243 thonium, that is to say, a block differing in many ways from one due to long- lasting depolarization only. 1 2 3 4 5 Fig. 5. Monkey 8 kg. Simultaneous records of supramaximal nerve twitches of tibialis (upper record) and soleus (lower record). At (1) and (2), 10 mg. and, 10 min later, at (3) and (4) 30 mg succinylcholine dibromide. At (5) tetanic stimulus to motor nerve, 50/sec. kg I 1.0 .-1 0-5 _05 04 03 02 01 03 _ 0.2 _ox1 I _ Fig. 6. Dog, 10 kg. Simultaneous records of supramaximal nerve twitches of tibialis (upper record) and flexor digitorum sublimis (lower record). At (1) and 20 min later at (2), intra- venous injection of 1 mg of succinylcholine dibromide. Result of interposition of a dose of D-tubocurarine between doses of decamethonium The impression resulting from the consideration of these facts is that the picture obtained from the monkey, dog and hare is similar to that obtained in the cat when an injection of D-tubocurarine is interposed between the doses of decamethonium, as all substances raising the end-plate threshold to acetyl- choline diminiish the activity of any substance producing a neuromuscular block by long-lasting depolarization.
Load more

Recommended publications
  • Use of Chemical Chelators As Reversal Agents for Drug
    (19) TZZ_ _ZZZ_T (11) EP 1 210 090 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/724 (2006.01) A61K 31/194 (2006.01) 18.06.2014 Bulletin 2014/25 A61P 39/04 (2006.01) (21) Application number: 00964006.1 (86) International application number: PCT/EP2000/007694 (22) Date of filing: 07.08.2000 (87) International publication number: WO 2001/012202 (22.02.2001 Gazette 2001/08) (54) USE OF CHEMICAL CHELATORS AS REVERSAL AGENTS FOR DRUG- INDUCED NEUROMUSCULAR BLOCK VERWENDUNG VON CHEMISCHEN CHELATOREN ZUR UMKEHRUNG VON PHARMAKOLOGISCH-INDUZIERTER NEUROMUSKULÄRER BLOCKIERUNG UTILISATION D’AGENTS CHIMIQUES CHELATANTS COMME AGENTS DE NEUTRALISATION DU BLOCAGE NEUROMUSCULAIRE PROVOQUE PAR DES MEDICAMENTS (84) Designated Contracting States: (56) References cited: AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU AU-A- 3 662 895 MC NL PT SE • B DESIRE: "Inactivaton of sarin and soman by (30) Priority: 13.08.1999 EP 99306411 cyclodextrins in vitro" EXPERIENTIA, vol. 43, no. 4, 1987, pages 395-397, XP000907287 (43) Date of publication of application: • B. DESIRE: "Interaction of soman with beta- 05.06.2002 Bulletin 2002/23 cyclodextrin" FUNDAMENTAL AND APPLIED TOXICOLOGY, vol. 7, no. 4, 1986, pages 647-657, (73) Proprietor: Merck Sharp & Dohme B.V. XP000911170 2031 BN Haarlem (NL) • C. MAY: "Development of a toxin-binding agent as a treatment for tunicamycinuracil toxicity: (72) Inventors: protection against tunicamycin poisoning of • BOM, Antonius, Helena, Adolf sheep" AUSTRALIAN VETERINARY JOURNAL, Ratho, Midlothian EH28 8NY (GB) vol. 76, no.
    [Show full text]
  • Expression of Multiple Populations of Nicotinic Acetylcholine
    EXPRESSION OF MULTIPLE POPULATIONS OF NICOTINIC ACETYLCHOLINE RECEPTORS IN BOVINE ADRENAL CHROMAFFIN CELLS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Graduate School of The Ohio State University By Bryan W. Wenger, B.A. The Ohio State University 2003 Dissertation Committee: Approved by: Professor Dennis B. McKay, Advisor Professor R. Thomas Boyd ________________________ Advisor Professor Popat N. Patil College of Pharmacy Professor Lane Wallace, Ph.D. ABSTRACT The importance of the role of nAChRs in physiological and pathological states is becoming increasingly clear. It is apparent that there are multitudes of nAChR subtypes with different expression patterns, pharmacologies and functions that may be important in various disease states. Therefore, a greater understanding of nAChR subtypes is essential for potential pharmacological intervention in nAChR systems. Bovine adrenal chromaffin cells are a primary culture of a neuronal type cell that express ganglionic types of nAChRs whose activation can be related to a functional response. While much is known about the outcome of functional activation of adrenal nAChRs, little work has been done in characterizing populations of nAChRs in adrenal chromaffin cells. These studies characterize the pharmacology and regulation of populations of nAChRs found in bovine adrenal chromaffin cells. The primary findings of this research include 1) the characterization of an irreversible antagonist of adrenal nAChRs, 2) the discovery of
    [Show full text]
  • Muscle Relaxants Physiologic and Pharmacologic Aspects
    K. Fukushima • R. Ochiai (Eds.) Muscle Relaxants Physiologic and Pharmacologic Aspects With 125 Figures Springer Contents Preface V List of Contributors XVII 1. History of Muscle Relaxants Some Early Approaches to Relaxation in the United Kingdom J.P. Payne 3 The Final Steps Leading to the Anesthetic Use of Muscle Relaxants F.F. Foldes 8 History of Muscle Relaxants in Japan K. Iwatsuki 13 2. The Neuromuscular Junctions - Update Mechanisms of Action of Reversal Agents W.C. Bowman 19 Nicotinic Receptors F.G. Standaert 31 The Neuromuscular Junction—Basic Receptor Pharmacology J.A. Jeevendra Martyn 37 Muscle Contraction and Calcium Ion M. Endo 48 3. Current Basic Experimental Works Related to Neuromuscular Blockade in Present and Future Prejunctional Actions of Neuromuscular Blocking Drugs I.G. Marshall, C. Prior, J. Dempster, and L. Tian 51 VII VIII Approaches to Short-Acting Neuromuscular Blocking Agents J.B. Stenlake 62 Effects Other than Relaxation of Non-Depolarizing Muscle Relaxants E.S. Vizi 67 Regulation of Innervation-Related Properties of Cultured Skeletal Muscle Cells by Transmitter and Co-Transmitters R.H. Henning 82 4. Current Clinical Experimental Works Related to Neuromuscular Blockade in Present and Future Where Should Experimental Works Be Conducted? R.D. Miller 93 Muscle Relaxants in the Intensive Care Unit ! J.E. Caldwell 95 New Relaxants in the Operating Room R.K. Mirakhur 105 Kinetic-Dynamic Modelling of Neuromuscular Blockade C. Shanks Ill 5. Basic Aspects of Neuromuscular Junction Physiology of the Neuromuscular Junction W.C. Bowman 117 Properties of <x7-Containing Acetylcholine Receptors and Their Expression in Both Neurons and Muscle D.K.
    [Show full text]
  • Muscle Relaxants Femoral Arteriography.,,>
    IN THIS ISSUE: , .:t.i ". Muscle Relaxants fI, \'.' \., Femoral ArteriographY.,,> University of Minnesota Medical Bulletin Editor ROBERT B. HOWARD, M.D. Associate Editors RAY M. AMBERG GILBERT S. CAMPBELL, M.D. ELLIS S. BENSON, MD. BYRON B. COCHRANE, M.D. E. B. BROWN, PhD. RICHARD T. SMITH, M.D. WESLEY W. SPINK, MD. University of Minnesota Medical School J. 1. MORRILL, President, University of Minnesota HAROLD S. DIEHL, MD., Dean, College of Medical SciencBs WILLIAM F. MALONEY, M.D., Assistant Dean N. 1. GAULT, JR., MD., Assistant Dean University Hospitals RAY M. AMBERG, Director Minnesota Medical Foundation WESLEY W. SPINK, M.D., President R. S. YLVISAKER, MD., Vice-President ROBERT B. HOWARD, M.D., Secretary-Treasurer Minnesota Medical Alumni Association BYRON B. COCHRANE, M.D., President VIRGIL J. P. LUNDQUIST, M.D., First Vice-President SHELDON M. LAGAARD, MD., Second Vice-President LEONARD A. BOROWICZ, M.D., Secretary JAMES C. MANKEY, M.D., Treasurer UNIVERSITY OF MINNESOTA Medical Bulletin OFFICIAL PUBLICATION OF THE UNIVERSITY OF MINNESOTA HOSPITALS, MINNE· SOTA MEDICAL FOUNDATION, AND MINNESOTA MEDICAL ALUMNI ASSOCIATION VOLUME XXVIII December 1, 1956 NUMBER 4 CONTENTS STAFF MEETING REPORTS Current Status of Muscle Relaxants BY J. Albert Jackson, MD., J. H. Matthews, M.D., J. J. Buckley, M.D., D.S.P. Weatherhead, M.D., AND F. H. Van Bergen, M.D. 114 Small Vessel Changes in Femoral Arteriography BY Alexander R. Margulis, M.D. AND T. O. Murphy, MD.__ 123 EDITORIALS .. - -. - ---__ __ _ 132 MEDICAL SCHOOL ACTIVITIES ----------- 133 POSTGRADUATE EDUCATION - 135 COMING EVENTS 136 PIIb1ished semi.monthly from October 15 to JUDe 15 at Minneapolis, Minnesota.
    [Show full text]
  • Pharmacological Studies on Pupillary Reflex Dilatation
    PHARMACOLOGICAL STUDIES ON PUPILLARY REFLEX DILATATION SHINJI OONO Departmentof Pharmacology,Faculty of Medicine,Kyushu University, Fukuoka Received for publication September 20, 1964 Concerning the role of sympathetic and parasympathetic mechanisms in reflex dilatation of the pupil elicited by painful stimuli, there have long been many argu ments. One group of authors, for example, Bechterew (1) and Braunstein (2) concluded that the pupillary dilatation resulting from painful stimuli was caused solely by inhibi tion of the third cranial nerve activity. Another group of investigators, for example, Lieben and Kahn (3), Bain, Irving and McSwiney (4), Ury and Gellhorn (5), Ury and Oldberg (6) and Seybold and Moore (7) were of the opinion that parasympathetic in hibition was the principal factor in the reflex dilatation while sympathetic excitation was a negligible one. On the contrary, others, for instance, Luchsinger (8), Anderson (9), and Dechaume (10) claimed that sympathetic excitation was responsible for the pupillary reaction which was absent after cervical sympathectomy. Weinstein and Bender (11) compared the pupillary reflex activity in cats and mon keys. They concluded that a species-difference exists: in both species pupillary dilata tion is accomplished by both parasympathetic inhibitory and sympathetic excitatory mechanism. In the cat, inhibition of the parasympathetic mechanism is predominant while in the monkey excitation of the sympathetic mechanism is of greater importance . Later Lowenstein and Loewenfeld (12) performed more detailed experiments in cats using their own pupillographic instrument; they observed that pupillary reflex dilata tion was mostly due to sympathetic excitation, and was reduced to less than one-fifth of the normal control dilatation after sympathectomy.
    [Show full text]
  • (12) United States Patent (10) Patent N0.: US 7,265,099 B1 Born Et A1
    US007265099B1 (12) United States Patent (10) Patent N0.: US 7,265,099 B1 Born et a1. (45) Date of Patent: *Sep. 4, 2007 (54) USE OF CHEMICAL CHELATORS AS Tarver, G. et al “2-O-Substituted cyclodextrins as reversal REVERSAL AGENTS FOR DRUG-INDUCED agents . ” Bioorg. Med. Chem. (2002) vol. 10, pp 1819-1827.* NEUROMUSCULAR BLOCK Zhang, M. “Drug-speci?c cyclodextrins . ” Drugs of the Future (2003) vol. 28, no 4, pp 347-354.* (75) Inventors: Antonius Helena Adolf Bom, Lee, C. “Structure, conformation, and action of neuromuscular Midlothian (GB); Alan William Muir, blocking drugs” Brit. J. Anesth. (2001) vol. 87, no 5, pp 755-769.* Lanark (GB); David Rees, Gothenburg B Desire: “Inactivation of sarin and soman by cyclodextrins in (SE) vitro” EXPERIENTIA, vol. 43, No. 4, 1987, pp. 395-397. B. Desire: “Interaction of soman with beta-cyclodextrin” Funda (73) Assignee: Organon N.V., Oss (NL) mental and Applied Toxicology, vol. 7, No. 4, 1986, pp. 647-657. ( * ) Notice: Subject to any disclaimer, the term of this C. May: “Development of a toxin-bindng agent as a treatment for patent is extended or adjusted under 35 tunicamycinuracil toxicity: protection against tunicamycin poison U.S.C. 154(b) by 0 days. ing of sheep” Australian Veterinary Journal, vol. 76, No. 11, 1998 pp. 752-756. This patent is subject to a terminal dis K. Uekama: “Effects of cyclodextrins on chlorpromaZine-induced claimer. haemolysis and nervous systems responses” J. Pharm. Pharmacol., vol. 33, No. 11, 1981, pp. 707-710. (21) Appl. No.: 10/049,393 T. Irie: “Protective mechanism of beta-cyclodextrin for the hemolysis induced With phenothiazine neuroleptics in vitro” J.
    [Show full text]
  • Neuronal Nicotinic Receptors
    NEURONAL NICOTINIC RECEPTORS Dr Christopher G V Sharples and preparations lend themselves to physiological and pharmacological investigations, and there followed a Professor Susan Wonnacott period of intense study of the properties of nAChR- mediating transmission at these sites. nAChRs at the Department of Biology and Biochemistry, muscle endplate and in sympathetic ganglia could be University of Bath, Bath BA2 7AY, UK distinguished by their respective preferences for C10 and C6 polymethylene bistrimethylammonium Susan Wonnacott is Professor of compounds, notably decamethonium and Neuroscience and Christopher Sharples is a hexamethonium,5 providing the first hint of diversity post-doctoral research officer within the among nAChRs. Department of Biology and Biochemistry at Biochemical approaches to elucidate the structure the University of Bath. Their research and function of the nAChR protein in the 1970’s were focuses on understanding the molecular and facilitated by the abundance of nicotinic synapses cellular events underlying the effects of akin to the muscle endplate, in electric organs of the acute and chronic nicotinic receptor electric ray,Torpedo , and eel, Electrophorus . High stimulation. This is with the goal of affinity snakea -toxins, principallyaa -bungarotoxin ( - Bgt), enabled the nAChR protein to be purified, and elucidating the structure, function and subsequently resolved into 4 different subunits regulation of neuronal nicotinic receptors. designateda ,bg , and d .6 An additional subunit, e , was subsequently identified in adult muscle. In the early 1980’s, these subunits were cloned and sequenced, The nicotinic acetylcholine receptor (nAChR) arguably and the era of the molecular analysis of the nAChR has the longest history of experimental study of any commenced.
    [Show full text]
  • Clinical Pharmacokinetics of Muscle Relaxants
    i ,I .. / ,""- Clinical Pharmacokinetics 2: 330-343 (1977) © ADIS Press 1977 Clinical Pharmacokinetics of Muscle Relaxants L.B. Wingard and DR. Cook Departments of Pharmacology and Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania SUl1lmary Muscle relaxants are commonly used as an adjunct to general anaesthesia and to facilitate ventilator care in the intensive care unit. The muscle relaxants are unique in that the degree of neurol1luscular blockade can be directly measured. Thus, for some of the muscle relaxants it is possible to correlate the degree of neuromuscular blockade with the plasma concentration of drug. This quantilalive pllGrmacokinelic approach has been applied primarily to d­ tubocurarine and to a lesser extent to suxamethonium (succinylcholine), gallamine and pan­ curoniul1l. The pharl1lacokinetic information for the other relaxants is mostly descriptive and incomplete. The variation in drug concentration over time is in.fluenced by the distribution, metabolism and excretion of drug. Metabolism by plasma cholinesterase plays a maJor role in the termina­ tion (~f action of suxamethonium. Although pancuronium is partly metabolised its major metabolites have moderate pharmacological activity. The other relaxants are excreted through the kidney. For gallamine and dimethyl-tubocurarine, renal excretion appears to be the only means qf eliinination. However, biliary excretion probably provides an alternative route of elimination for d-tubocurarine and pancuronium. In patients with impaired renal function the duration qf neuromusClilar blockade may be markedly prolonged following standard doses of gallamine or dimethyl-tubocurarine, may be slightly prolonged following standard doses of pancumnium, and is near normal following standard doses qf d-tubocurarine. Following large or repeated doses q(pancuronium or d-tubocurarine, the duration q{ neuromuscular blockade may be markedly prolonged.
    [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]
  • Nicotinic Acetylcholine Receptors
    nAChR Nicotinic acetylcholine receptors nAChRs (nicotinic acetylcholine receptors) are neuron receptor proteins that signal for muscular contraction upon a chemical stimulus. They are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the presynaptic and postsynaptic sides of theneuromuscular junction. Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. Like the other type of acetylcholine receptor-the muscarinic acetylcholine receptor (mAChR)-the nAChR is triggered by the binding of the neurotransmitter acetylcholine (ACh). Just as muscarinic receptors are named such because they are also activated by muscarine, nicotinic receptors can be opened not only by acetylcholine but also by nicotine —hence the name "nicotinic". www.MedChemExpress.com 1 nAChR Inhibitors & Modulators (+)-Sparteine (-)-(S)-B-973B Cat. No.: HY-W008350 Cat. No.: HY-114269 Bioactivity: (+)-Sparteine is a natural alkaloid acting as a ganglionic Bioactivity: (-)-(S)-B-973B is a potent allosteric agonist and positive blocking agent. (+)-Sparteine competitively blocks nicotinic allosteric modulator of α7 nAChR, with antinociceptive ACh receptor in the neurons. activity [1]. Purity: 98.0% Purity: 99.93% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in Water, Size: 10mM x 1mL in DMSO, 100 mg 5 mg, 10 mg, 50 mg, 100 mg (±)-Epibatidine A-867744 (CMI 545) Cat. No.: HY-101078 Cat. No.: HY-12149 Bioactivity: (±)-Epibatidine is a nicotinic agonist. (±)-Epibatidine is a Bioactivity: A-867744 is a positive allosteric modulator of α7 nAChRs (IC50 neuronal nAChR agonist. values are 0.98 and 1.12 μM for human and rat α7 receptor ACh-evoked currents respectively, in X.
    [Show full text]
  • Reversal of Neuromuscular Bl.Pdf
    JosephJoseph F.F. Answine,Answine, MDMD Staff Anesthesiologist Pinnacle Health Hospitals Harrisburg, PA Clinical Associate Professor of Anesthesiology Pennsylvania State University Hospital ReversalReversal ofof NeuromuscularNeuromuscular BlockadeBlockade DefiniDefinitionstions z ED95 - dose required to produce 95% suppression of the first twitch response. z 2xED95 – the ED95 multiplied by 2 / commonly used as the standard intubating dose for a NMBA. z T1 and T4 – first and fourth twitch heights (usually given as a % of the original twitch height). z Onset Time – end of injection of the NMBA to 95% T1 suppression. z Recovery Time – time from induction to 25% recovery of T1 (NMBAs are readily reversed with acetylcholinesterase inhibitors at this point). z Recovery Index – time from 25% to 75% T1. PharmacokineticsPharmacokinetics andand PharmacodynamicsPharmacodynamics z What is Pharmacokinetics? z The process by which a drug is absorbed, distributed, metabolized and eliminated by the body. z What is Pharmacodynamics? z The study of the action or effects of a drug on living organisms. Or, it is the study of the biochemical and physiological effects of drugs. For example; rocuronium reversibly binds to the post synaptic endplate, thereby, inhibiting the binding of acetylcholine. StructuralStructural ClassesClasses ofof NondepolarizingNondepolarizing RelaxantsRelaxants z Steroids: rocuronium bromide, vecuronium bromide, pancuronium bromide, pipecuronium bromide. z Benzylisoquinoliniums: atracurium besylate, mivacurium chloride, doxacurium chloride, cisatracurium besylate z Isoquinolones: curare, metocurine OnsetOnset ofof paralysisparalysis isis affectedaffected by:by: z Dose (relative to ED95) z Potency (number of molecules) z KEO (plasma equilibrium constant - chemistry/blood flow) — determined by factors that modify access to the neuromuscular junction such as cardiac output, distance of the muscle from the heart, and muscle blood flow (pharmacokinetic variables).
    [Show full text]
  • Summary of Product Characteristics
    Health Products Regulatory Authority Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT Murexal 10 mg/mL solution for injection in pre-filled syringe 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each mL of solution for injection contains 10 mg of suxamethonium chloride anhydrous (as 11 mg of suxamethonium chloride dihydrate). Each 10 ml pre-filled syringe contains 100 mg of suxamethonium chloride anhydrous (as 110 mg of suxamethonium chloride dihydrate). Excipient with known effect: Each ml of solution for injection contains 2.79 mg equivalent to 0.12 mmol of sodium. Each 10 ml pre-filled syringe contains 27.9 mg equivalent to 1.2 mmol of sodium. For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Solution for injection (injection). Clear and colourless solution. pH: 3.0 – 4.5 Osmolality: 250-350 mOsm/Kg 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Murexal is indicated as a muscle relaxant to facilitate endotracheal intubation during induction of general anaesthesia or emergency situations, in adults and paediatric population above 12 years of age. 4.2 Posology and method of administration Suxamethonium should be administered only by or under close supervision of an experienced clinician (anaesthesist, intensivist, emergency physician) familiar with its action, characteristics and hazards, who is skilled in the management of intubation and artificial respiration and only where there are adequate facilities for immediate endotracheal intubation with administration of oxygen by intermittent positive pressure ventilation. It is given intravenously after anaesthesia has been induced and should not be administered to the conscious patient. Posology Adults To achieve endotracheal intubation, suxamethonium chloride is usually administered by bolus intravenous injection in a dose of 1 mg/kg body weight.
    [Show full text]