Pharmacology for Optometry
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DE H 2281 001 PAR.Pdf
Bundesinstitut für Arzneimittel und Medizinprodukte Decentralised Procedure RMS Public Assessment Report Latanoprost Malcosa 0,005% Xalaprost 0,005% Laxatan 0,005% Pharmecol 0.005% DE/H/1999/001/DC DE/H/2281/001/DC DE/H/2282/001/DC DE/H/2382/001/DC Applicant: Malcosa Ltd. Reference Member State DE Date of this report: 06.12.2010 The BfArM is a Federal Institute within the portfolio of the Federal Ministry of Health. 1/30 CONTENTS ADMINISTRATIVE INFORMATION .............................................................................................. 3 I. RECOMMENDATION ................................................................................................................ 4 II. EXECUTIVE SUMMARY....................................................................................................... 4 II.1 Problem statement..................................................................................................................... 4 II.2 About the product ..................................................................................................................... 4 II.3 General comments on the submitted dossier .......................................................................... 5 II.4 General comments on compliance with GMP, GLP, GCP and agreed ethical principles..6 III. SCIENTIFIC OVERVIEW AND DISCUSSION ................................................................... 6 III.1 Quality aspects...................................................................................................................... -
Mechanisms of Pharmacogenomic Effects of Genetic Variation Within the Cardiac Adrenergic Network in Heart Failure
0026-895X/09/7603-466–480$20.00 MOLECULAR PHARMACOLOGY Vol. 76, No. 3 Copyright © 2009 The American Society for Pharmacology and Experimental Therapeutics 56572/3501253 Mol Pharmacol 76:466–480, 2009 Printed in U.S.A. MINIREVIEW Mechanisms of Pharmacogenomic Effects of Genetic Variation within the Cardiac Adrenergic Network in Heart Failure Gerald W. Dorn II and Stephen B. Liggett Center for Pharmacogenomics, Department of Internal Medicine, Washington University, St. Louis, Missouri (G.W.D.); and Downloaded from Cardiopulmonary Genomics Program, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland (S.B.L.) Received March 26, 2009; accepted June 2, 2009 ABSTRACT molpharm.aspetjournals.org One of the goals of pharmacogenomics is the use of genetic ology of the disease. Here we discuss polymorphisms within variants to predict an individual’s response to treatment. Al- the adrenergic receptor network in the context of heart failure though numerous candidate and genome-wide associations and -adrenergic receptor blocker therapy, where multiple ap- have been made for cardiovascular response-outcomes, little is proaches to understand the mechanism have been undertaken. known about how a given polymorphism imposes the pheno- We propose a comprehensive series of studies, ranging from type. Such mechanisms are important, because they tie the transfected cells, transgenic mice, and ex vivo and in vitro observed human response to specific signaling alterations and human studies as a model approach to explore mechanisms of thus provide cause-and-effect relationships, aid in the design action of pharmacogenomic effects and extend the field be- of hypothesis-based clinical studies, can help to devise work- yond observational associations. -
Drugs for Glaucoma
Australian Prescriber Vol. 25 No. 6 2002 Drugs for glaucoma Ivan Goldberg, Eye Associates and Glaucoma Service, Sydney Eye Hospital and the Save Sight Institute, University of Sydney, Sydney SYNOPSIS is not uncommon and the pressure slowly rises. Withdrawing Older drugs for glaucoma reduce intra-ocular pressure, the drug for a few months often re-establishes its efficacy. but often have unpleasant adverse effects. They still The main problem with timolol or levobunolol is their potential have a role in therapy, but there are now newer for systemic adverse effects. These are the same as the adverse drugs which overcome some of the problems. The topical effects of oral beta blockers, the most important of which are carbonic anhydrase inhibitors decrease the secretion of bronchoconstriction, bradyarrhythmias, and an increase in aqueous humour, while lipid-receptor agonists increase falls in the elderly. uveoscleral outflow. Alpha agonists use both mechanisms 2 As betaxolol is relatively selective for beta1 receptors it should to reduce intra-ocular pressure. If a patient needs more pose less respiratory risk. Its pharmacokinetic properties than one drug to control their glaucoma, the new drugs (higher plasma binding and larger volume of distribution) also generally have an additive effect when used in combination make it less likely to provoke other systemic effects. regimens. Miotics Index words: beta blockers, carbonic anhydrase inhibitors, Miotics (pilocarpine and carbachol) are rapidly falling out of lipid-receptor agonists. favour. While their ocular hypotensive efficacy is undisputed, (Aust Prescr 2002;25:142–6) and their systemic safety margin wide (abdominal cramping or diarrhoea are rarely reported), their use is declining because Introduction of their local effects and the need to instill them up to four Glaucoma is the second commonest cause of visual disability times daily. -
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 -
Systematic Review in Drug's Safety and Clinical
Ana Sofia Martins Penedones SYSTEMATIC REVIEW: METHODOLOGICAL ASPECTS OF ITS ROLE IN DRUG SAFETY ASSESSMENT Tese no âmbito do Doutoramento em Ciências Farmacêuticas, ramo de Farmácia Clínica orientada pelo Professor Doutor Francisco Jorge Batel Marques e apresentada à Faculdade de Farmácia da Universidade de Coimbra. Março de 2020 Faculdade de Farmácia da Universidade de Coimbra Systematic review: methodological aspects of its role in drug safety assessment Ana Sofia Martins Penedones Tese no âmbito do Doutoramento em Ciências Farmacêuticas, ramo de Farmácia Clínica orientada pelo Professor Doutor Francisco Jorge Batel Marques e apresentada à Faculdade de Farmácia da Universidade de Coimbra. Março de 2020 2 All the research work presented in this thesis was performed in strict collaboration of the Laboratory of Social Pharmacy and Public Health, Faculty of Pharmacy, University of Coimbra and the Centre for Health Technology Assessment and Drug Research, Association for Innovation and Biomedical Research on Light and Image, under the supervision of Professor Francisco Jorge Batel Marques. Todos os trabalhos apresentados nesta tese foram realizados em estreita colaboração entre o Laboratório de Sociofarmácia e Saúde Pública da Faculdade de Farmácia da Universidade de Coimbra e o Centro de Avaliação de Tecnologias em Saúde e Investigação do Medicamento da Associação para Investigação Biomédica e Inovação em Luz e Imagem, sob a supervisão do Professor Doutor Francisco Jorge Batel Marques. 3 4 Agradecimentos Ao meu orientador, Professor Doutor Francisco Batel Marques, pela oportunidade em integrar o seu grupo de trabalho no CHAD – Centre for Health Technology Assessment and Drug Research na AIBILI – Innovation and Biomedical Research on Light and Image. -
Central Nervous System 5 Objectives
B978-0-7234-3630-0.00005-4, 00005 Central nervous system 5 Objectives After reading this chapter, you will: ● Understand the functions of the central nervous system and the diseases that can occur ● Know the drug classes used to treat these conditions, their mechanisms of action and adverse effects. Parkinson’s disease is progressive, with continued BASIC CONCEPTS loss of dopaminergic neurons in the substantia nigra correlating with worsening of clinical symptoms. The The central nervous system consists of the brain and the possibility of a neurotoxic cause has been strengthe- spinal cord, which are continuous with one another. ned by the finding that 1-methyl-4-phenyl-1,2,3, The brain is composed of the cerebrum (which consists 6-tetrahydropyridine (MPTP), a chemical contaminant of the frontal, temporal, parietal and occipital lobes), of heroin, causes irreversible damage to the nigrostriatal the diencephalon (which includes the thalamus and dopaminergic pathway. Thus, this damage can lead hypothalamus), the brainstem (which consists of the mid- to the development of symptoms similar to those of brain, pons and medulla oblongata) and the cerebellum. idiopathic Parkinson’s disease. Drugs that block The brain functions to interpret sensory information dopamine receptors can also induce parkinsonism. obtained about the internal and external environments Neuroleptic drugs (p. 000) used in the treatment of TS1 and send messages to effector organs in response to a schizophrenia can produce parkinsonian symptoms as situation. Different parts of the brain are associated an adverse effect. Rare causes of parkinsonism are cere- with specific functions (Fig. 5.1). However, the brain is a bral ischaemia (progressive atherosclerosis or stroke), complex organ and is not yet completely understood. -
2.1 Organ-Bath Pharmacological Studies
PURINERGIC SIGNALLING IN THE GENITO-URINARY TRACT A thesis presentedfor the degree o f Doctor o f Medicine to the Faculty o f Medicine of the University of London By Frederick Caspar Lund Banks BSc, MBBS, FRCS The Autonomic Neuroscience Centre and Departments of Urology and Clinical Biochemistry, Royal Free and University College Medical School, (Royal Free Campus), University College London. 1 UMI Number: U591700 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U591700 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract The main objective of this thesis was to examine the role of purinergic signalling in the contraction of the smooth muscle of the genito-urinary tract of laboratory animals and compare it to that of man. It also examined purinergic signalling in the maturation of sperm within the epididymis. The main methodology involved organ bath studies on the functional physiology of smooth muscle contraction, in conjunction with immunohistochemical examination of smooth muscle P2X receptor expression. In Chapter 3, a comparative study of the smooth muscle cells of the testicular capsule or tunica albuginea of the testis from man, mouse, rat and rabbit was made. -
Skeletal Muscle Relaxant Effect of Skeletal Muscle Relaxant Effect Of
Research Paper Skeletal muscle relaxant effect of Chonemorpha macrophylla in experimental animals R.K. Roy*, N.M. Ray**, A.K. Das*** * Department of ABSTRACT Pharmacology, N.R.S. Medical College, Objective: To study the skeletal muscle relaxant property of Chonemorpha macrophylla (CM). Kolkata – 700 014 Materials and Method: The skeletal muscle relaxant effect of the alcoholic extract of CM was ** Department of studied on isolated frog rectus abdominis muscle, isolated rat phrenic nerve diaphragm muscle Pharmacology, U.C.M., preparation and in intact young chicks. The parameter studied in the isolated muscle or isolated Kolkata – 700 004 nerve muscle preparations was the extent of inhibition of acetylcholine or electrically-induced *** Department of contraction of skeletal muscles. In intact chicks, the drug was administered i.v. in wing veins Pharmacology, R.G. Kar and the onset, duration and nature of paralysis were recorded. In all the experiments, the effect Medical College, of the drug was compared with that of gallamine and succinylcholine. Kolkata – 700 004. India Results: The alcoholic extract of CM reduced the acetylcholine-induced contraction of isolated frog rectus abdominis and electrically stimulated contractions of rat phrenic nerve diaphragm in Received: 20.11.2003 a dose-dependent manner. In unanaesthetized chicks, it produced spastic type of paralysis with Revised: 14.9.2004 extension of the neck and limbs. The effects were similar to the effects of succinylcholine but Accepted: 20.9.2004 different from those of gallamine. Conclusion: The alcoholic extract of CM possesses skeletal muscle relaxant property. It produces Correspondence to: depolarizing type of muscle paralysis similar to that produced by succinylcholine. -
Organ Bath Systems "%*/4536.&/54
Organ Bath Systems "%*/4536.&/54 Introduction: The organ bath is a traditional experimental set-up that is commonly used to investigate the physiology and pharmacology of in vitro tissue preparations. Perfused tissues can be maintained for several hours in a temperature controlled organ bath. After a suitable equilibration period, the researcher can begin experiments. Typical experiments involve the addition of drugs to the organ bath or direct/field stimulation of the tissue. The tissue reacts by contracting/relaxing and an isometric or isotonic transducer is used to measure force or displacement, respectively. From the experimental results dose-response curves are generated (tissue response against drug dosage or stimulus potency). ADInstruments supply a range of organ baths and transducers for pharmacological research. LabChart software records, displays and analyzes the data which may then be analyzed or exported to graphing programs, such as GraphPad Prism®. Some of the tissues that may be studied with an organ bath system include: Smooth Muscle: Skeletal Muscle: Cardiac Muscle: Vascular, e.g. arterial/aortic rings Toad Abdominus Rectus Atrium Guinea-pig ileum Chick Biventer Cervis Ventricle Vas Deferens (secretory duct of the testicle) Mammalian Diaphragm Uterine Colon Tissues are usually prepared in a petri-dish containing physiological solution (i.e. Kreb’s solution). The ends of the tissue are then attached to the mounting hook and transducer using silk. It is important to use non-compliant material such as silk or fine wire to mount the tissue. For tissue ring preparations (i.e. arterial rings), a custom tissue-holder is required (can be sourced by ADInstruments). -
Inverse Agonism at P»Radrenergic Receptors Martin J
International Congress Series 1249 (2003) 55-61 Inverse agonism at p»radrenergic receptors Martin J. Lohse*, Carsten Hoffmann, Stefan Engelhardt Institut fur Pharmakologie, Universitat Wfirzburg, Versbacher Strafie 9, 97078 Wiirzburg, Germany Received 16 April 2003; accepted 17 April 2003 Abstract Constitutive activity and inverse agonism have been described for numerous G-protein-coupled receptors, including the p2-adrenergic receptor. We have investigated whether these properties also exist for the p^-adrenergic receptor. One line of experiments was done with cell lines transiently or stably expressing the human p>radrenergic receptor measuring intracellular cAMP or adenylyl cyclase activity. In a second set of experiments, we used transgenic mice with cardiac overexpression of the human f^-adrenergic receptor and measured spontaneous beating frequency of isolated atria as a physiological read-out. Both sets of experiments revealed that the human pradrenergic receptor displays constitutive activity, but this constitutive activity is considerably lower than that of the (32- subtype. We then tested various p-adrenergic antagonists for their ability to modulate this constitutive activity. In the p.rreceptor-transgenic atria, the p.]-selective antagonists metoprolol and bisoprolol showed significant inverse agonistic activity, whereas carvedilol behaved as a neutral antagonist. In contrast, in cellular cAMP-assays, metoprolol, bisoprolol, propranolol and carvedilol all displayed similar inverse agonist activities. We conclude that also the human pradrenergic receptor displays constitutive activity and that—depending on the read-out—p-adrenergic "antagonists" currently in clinical use may differ in their inverse agonistic activity at this receptor. © 2003 Published by Elsevier Science B.V. Keywords: prAdrenergic receptor; Adenylyl cyclase; Constitutive activity; Inverse agonism; Cardiac frequency 1. -
Development and Testing of a Microfluidic Device for Studying Resistance Artery Function
DEVELOPMENT AND TESTING OF A MICROFLUIDIC DEVICE FOR STUDYING RESISTANCE ARTERY FUNCTION by Andrei Vagaon A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Physiology University of Toronto © Copyright by Andrei Vagaon (2010) DEVELOPMENT AND TESTING OF A MICROFLUIDIC DEVICE FOR STUDYING RESISTANCE ARTERY FUNCTION MSc thesis, 2010, Andrei Vagaon, Department of Physiology at the University of Toronto ABSTRACT Introduction: Hypertension is the number one risk factor for cardiovascular diseases. Total peripheral resistance (TPR) is strongly involved in blood pressure homeostasis. TPR is primarily determined by resistance arteries (RAs). Pathogenic factors which change RA structure are associated with cardiovascular disease. Despite this, methods employed in the study of RAs lack efficiency. Methods: A polymer microfluidic device (Artery‐on‐a‐Chip Device, AoC) made from polydimethylsiloxane (PDMS) was developed. RAs from CD1 mice were measured on the device. Their responses to phenylephrine (PE), acetylcholine (Ach), FURA‐2 imaging, and 24‐h culture were assessed. Results: Following several modifications, vessel function on the AoC device was successfully measured. Robust PE constriction and Ach‐induced vasodilation were observed. AoC arteries were viable after 24‐hour culture, and FURA‐2 was successfully imaged. Conclusions: The AoC device is a viable alternative to cannulation myography. The AoC can greatly increase the efficiency of RA studies, while also decreasing training -
Drug Delivery System Utilizing Thermosetting Gels
Europaisches Patentamt European Patent Office 5) Publication number: 3 126 684 Bl Dffice europeen des brevets © EUROPEAN PATENT SPECIFICATION S Date of publication of patent specification: 28.08.91 (£) Int. CI.5: A61 K 47/00, A61K9/06 © Application number: 84400982.9 g) Date of filing: 15.05.84 © Drug delivery system utilizing thermosetting gels. (is) Priority: 16.05.83 US 495238 @ Proprietor: MERCK & CO. INC. 16.05.83 US 495239 126, East Lincoln Avenue P.O. Box 2000 16.05.83 US 495240 Rahway New Jersey 07065-0900(US) 16.05.83 US 495321 @ Inventor: Haslam, John L. @ Date of publication of application: RFD 2, Box 259-B 28.11.84 Bulletin 84/48 Lawrence Kansas 66044(US) Inventor: Higuchi, Takeru © Publication of the grant of the patent: 2811 Schwarz Road 28.08.91 Bulletin 91/35 Lawrence, Kansas 66044(US) Inventor: Mlodozeniec, Arthur R. @ Designated Contracting States: 1704 St. Andrews Drive AT BE CH DE FR GB IT LI LU NL SE Lawrence Kansas 66044(US) @ References cited: AU-A- 482 821 0 Representative: Ahner, Francis et al CA-A- 1 072 413 CABINET REGIMBEAU, 26, avenue Kleber FR-A- 1 598 998 F-75116 Paris(FR) N.F.ESTRIN et al.: "CTFA COSMETIC INGRE- DIENT DICTIONARY", Third Edition, The Cos- metic, Toiletry and Fragrance Association, Inc., Washington, D.C., US; CD 00 CO CO O Note: Within nine months from the publication of the mention of the grant of the European patent, any person - may give notice to the European Patent Office of opposition to the European patent granted.