DOCSLIB.ORG

Transcript for the July 26, 2018 Meeting of the Antimicrobial Drugs

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Transcript for the July 26, 2018 Meeting of the Antimicrobial Drugs 1 1 FOOD AND DRUG ADMINISTRATION 2 CENTER FOR DRUG EVALUATION AND RESEARCH 3 4 5 6 ANTIMICROBIAL DRUGS ADVISORY COMMITTEE (AMDAC) 7 8 9 Thursday, July 26, 2018 10 8:30 a.m. to 3:52 p.m. 11 12 13 14 15 16 17 FDA White Oak Campus 18 Building 31, the Great Room 19 10903 New Hampshire Avenue 20 Silver Spring, Maryland 21 22 A Matter of Record (301) 890-4188 2 1 Meeting Roster 2 ACTING DESIGNATED FEDERAL OFFICER (Non-Voting) 3 Kalyani Bhatt, BS, MS 4 Division of Advisory Committee and Consultant 5 Management 6 Office of Executive Programs, CDER, FDA 7 8 ANTIMICROBIAL DRUGS ADVISORY COMMITTEE MEMBERS 9 (Voting) 10 Lindsey R. Baden, MD 11 (Chairperson) 12 Director of Clinical Research 13 Division of Infectious Diseases 14 Brigham and Women’s Hospital 15 Director, Infectious Disease Service 16 Dana-Farber Cancer Institute 17 Associate Professor, Harvard Medical School 18 Boston, Massachusetts 19 20 21 22 A Matter of Record (301) 890-4188 3 1 Dean A. Follmann, PhD 2 Assistant Director for Biostatistics 3 Chief Biostatistics Research Branch 4 National Institute of Allergy and Infectious 5 Diseases 6 National Institutes of Health 7 Bethesda, Maryland 8 9 Michael Green, MD, MPH 10 Professor of Pediatrics, Surgery and Clinical & 11 Translational Science 12 University of Pittsburgh School of Medicine 13 Division of Infectious Diseases 14 Director, Antimicrobial Stewardship & Infection 15 Prevention 16 Co-Director, Transplant Infectious Diseases 17 Children’s Hospital of Pittsburgh 18 Pittsburgh, Pennsylvania 19 20 21 22 A Matter of Record (301) 890-4188 4 1 Barbara M. Gripshover, MD (via phone) 2 Associate Professor of Medicine 3 University Hospitals Cleveland Medical Center 4 Case Western Reserve University 5 Division of Infectious Diseases and HIV Medicine 6 Cleveland, Ohio 7 8 Vincent Lo Re, MD, MSCE 9 Associate Professor of Medicine and Epidemiology 10 Division of Infectious Diseases 11 Department of Medicine 12 Center for Clinical Epidemiology and Biostatistics 13 Perelman School of Medicine 14 University of Pennsylvania 15 Philadelphia, Pennsylvania 16 17 Ighovwerha Ofotokun, MD, MSC 18 Professor of Medicine 19 Division of Infectious Diseases 20 Department of Medicine 21 Emory University School of Medicine 22 Atlanta, Georgia A Matter of Record (301) 890-4188 5 1 Peter Weina, MD, PhD, FACP, FIDSA 2 Colonel, Medical Corps, USA 3 Chief, Department of Research Programs 4 Walter Reed National Military Medical Center 5 Division of Education, Training and Research 6 Bethesda, Maryland 7 8 TEMPORARY MEMBERS (Voting) 9 Warren B. Bilker, PhD 10 Professor of Biostatistics 11 Department of Biostatistics and Epidemiology 12 Perelman School of Medicine 13 University of Pennsylvania 14 Philadelphia, Pennsylvania 15 16 Josh A. Mailman, MBA 17 (Patient Representative) 18 Oakland, California 19 20 Thomas A. Moore, MD, FACP, FIDSA 21 ID Consultants, PA 22 Wichita, Kansas A Matter of Record (301) 890-4188 6 1 Michele J. Orza, ScD 2 (Acting Consumer Representative) 3 Chief of Staff 4 Patient-Centered Outcomes 5 Research Institute (PCORI) 6 Washington, District of Columbia 7 8 9 Kathrine R. Tan, MD MPH 10 Division of Parasitic Diseases and Malaria/ 11 Malaria Branch 12 Centers for Disease Control and Prevention 13 Atlanta, Georgia 14 15 Julie M. Zito, PhD 16 Professor of Pharmacy and Psychiatry 17 University of Maryland, Baltimore 18 Pharmaceutical Health Services Department 19 Baltimore, Maryland 20 21 22 A Matter of Record (301) 890-4188 7 1 ACTING INDUSTRY REPRESENTATIVE TO THE ANTIMICROBIAL 2 DRUGS ADVISORY COMMITTEE (Non-voting) 3 Ercem S. Atillasoy, MD 4 (Acting Industry Representative) 5 Vice President, Global Regulatory Affairs and 6 Clinical Safety 7 Merck & Company, Inc. 8 North Wales, Pennsylvania 9 10 11 FDA PARTICIPANTS (Non-Voting) 12 Edward Cox, MD, MPH 13 Director 14 Office of Antimicrobial Products (OAP) 15 Office of New Drugs (OND), CDER, FDA 16 17 Sumathi Nambiar, MD, MPH 18 Director 19 Division of Anti-Infective Products (DAIP) 20 Office of Antimicrobial Products (OAP) 21 OND, CDER, FDA 22 A Matter of Record (301) 890-4188 8 1 Yuliya Yasinskaya, MD 2 Clinical Team Leader 3 DAIP, OAP, OND, CDER, FDA 4 5 6 Sheral Patel, MD 7 Medical Officer 8 DAIP, OAP, OND, CDER, FDA 9 10 Xianbin Li, PhD 11 Statistical Reviewer 12 Division of Biometrics IV (DBIV) 13 Office of Biostatistics (OB) 14 Office of Translational Sciences (OTS), CDER, FDA 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 9 1 C O N T E N T S 2 AGENDA ITEM PAGE 3 4 Call to Order and Introduction of Committee 5 Lindsey Baden, MD 11 6 Conflict of Interest Statement 7 Kalyani Bhatt, BS, MS 16 8 FDA Opening Remarks 9 Yuliya Yasinskaya, MD 19 10 Applicant Presentations – 60 Degrees 11 Overview and Background 12 Development of ARAKODA 13 Geoffrey Dow, PhD 26 14 Unmet Medical Need for ARAKODA 15 Military and Civilian Travelers 16 Stephen Toovey, MD, PhD 41 17 Mark Reid, MBA 50 18 Efficacy 19 Jonathan Berman, MD, PhD 55 20 Safety 21 Bryan Smith, MD 72 22 A Matter of Record (301) 890-4188 10 1 Neuropsychiatric Safety 2 Geoffrey Dow, PhD 84 3 Future ARAKODA Use 4 Stephen Toovey, MD, PhD 99 5 Clarifying Questions 106 6 FDA Presentations 7 Presentation of Clinical Efficacy 8 Xianbin Li, PhD 114 9 Presentation of Nonclinical 10 Pharmacology and Toxicology 11 Owen McMaster, PhD 130 12 Presentation of Clinical Safety 139 13 Sheral Patel, MD 162 14 Clarifying Questions 199 15 Open Public Hearing 217 16 Clarifying Questions (continued) 269 17 Questions to the Ccommitee and Discussion 307 18 Adjournment 19 20 21 22 A Matter of Record (301) 890-4188 11 1 P R O C E E D I N G S 2 (8:30 a.m.) 3 Call to Order 4 Introduction of Committee 5 DR. BADEN: It is now 8:30. Good morning. 6 I would first like to remind everyone to please 7 silence your cell phones, smartphones, and any 8 other devices that go bleep, if you've not already 9 done so. I would also like to identify the FDA 10 press contact, Theresa Eisenman. She's waving in 11 the back. 12 I'm Dr. Lindsey Baden. I'm chairperson of 13 the Antimicrobial Drugs Advisory Committee, and 14 I'll be chairing this meeting. I'll now call this 15 meeting to order. We'll start by going around the 16 table and introducing ourselves. We'll start with 17 the FDA to my far left. 18 DR. COX: Good morning. Ed Cox, director of 19 the Office of Antimicrobial Products, CDER, FDA. 20 DR. NAMBIAR: Good morning. Sumathi 21 Nambiar, director of the Division of Anti-Infective 22 Products, CDER, FDA. A Matter of Record (301) 890-4188 12 1 DR. YASINSKAYA: Good morning. Yuliya 2 Yaskinskaya, clinical team leader, Division of 3 Anti-Infective Products, CDER, FDA. 4 DR. PATEL: Good morning. Sheral Patel, 5 clinical reviewer, Division of Anti-Infective 6 Products. 7 DR. LI: Good morning. Xianbin Li, 8 statistical reviewer from FDA. 9 DR. FOLLMANN: Dean Follmann, head of 10 biostatistics at the National Institute of Allergy 11 and Infectious Diseases. 12 DR. OFOTOKUN: Ighor Ofotokun, a member of 13 the committee from Emory University, infectious 14 diseases. 15 DR. LO RE: Vincent Lo Re from the Division 16 of Infectious Diseases in the Center for Clinical 17 Epidemiology and Biostatistics at the University of 18 Pennsylvania. 19 MS. BHATT: Dr. Gripshover, could you please 20 introduce yourself? 21 DR. GRIPSHOVER: [Inaudible - audio 22 gap] -- infectious disease, Case Western Reserve A Matter of Record (301) 890-4188 13 1 University. And unfortunately, my flight was 2 canceled, so I'm on the phone. 3 MS. BHATT: Thank you. 4 Kalyani Bhatt. I am the designated federal 5 officer for this advisory committee. 6 DR. BADEN: Lindsey Baden, infectious 7 diseases at Brigham and Women's Hospital, 8 Dana-Farber Cancer Institute, and Harvard Medical 9 School in Boston. 10 DR. WEINA: Peter Weina, infectious disease, 11 Walter Reed National Military and Medical Center. 12 DR. GREEN: Michael Green, pediatric 13 infectious diseases, The Children's Hospital, 14 Pittsburgh and the University of Pittsburgh School 15 of Medicine. 16 DR. ORZA: Michele Orza, the 17 Patient-Centered Outcomes Research Institute in 18 Washington, D.C. 19 MR. MAILMAN: Josh Mailman, FDA patient 20 representative. 21 DR. MOORE: Dr. Tom Moore, infectious 22 disease physician in Wichita, Kansas, University of A Matter of Record (301) 890-4188 14 1 Kansas. 2 DR. TAN: Kathrine Tan, chief of the 3 domestic response unit, malaria branch, CDC. 4 DR. BILKER: Warren Bilker, biostatistician, 5 Department of Biostatistics, Epidemiology, and 6 Informatics, University of Pennsylvania. 7 DR. ZITO: Julie Zito, University of 8 Maryland, pharmacoepidemiology. 9 DR. ATTILASOY: Good morning. Ercem 10 Atillasoy. I'm vice president at Merck research 11 labs for vaccines and infectious disease, 12 regulatory affairs. 13 DR. BADEN: I would like to thank the 14 committee and all presenting for being able to make 15 it here despite the weather. And, Dr. Gripshover, 16 we feel your pain, as the weather in Washington 17 yesterday made travel for all extremely difficult. 18 But I appreciate everyone's effort to be here to be 19 able to have this meeting. 20 For topics such as those being discussed at 21 today's meeting, there are often a variety of 22 opinions, some of which are quite strongly held. A Matter of Record (301) 890-4188 15 1 Our goal is that today's meeting will be a fair and 2 open forum for discussion of these issues and that 3 individuals can express their views without 4 interruption.
Load more

Recommended publications
  • Stevelinkbjpauthors Reply
    King’s Research Portal Link to publication record in King's Research Portal Citation for published version (APA): Stevelink, S., Jones, M. M., Greenberg, N., Rona, R. J., & Fear, N. T. (2019). Mental health outcomes at the end of the British involvement in the Iraq and Afghanistan conflicts: a cohort study - Authors' reply. British Journal of Psychiatry. Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • A Novel Disease Affecting US Veterans
    Identifying and Evaluating Sources of Evidence of Quinism: A Novel Disease Affecting U.S. Veterans Remington Nevin, MD, MPH, DrPH Executive Director Neuropsychiatric Quinism • Significant empirical evidence of a common set of symptoms and signs developing after exposure to quinoline drugs – Quinine, quinacrine, clioquinol, primaquine, chloroquine, mefloquine, tafenoquine, and others – 100+ years of case reports, pharmacovigilance reports, and accumulated clinical observations • Significant in vitro and in vivo evidence of a common pathophysiology – Chronic encephalopathy from focal brainstem and limbic neurotoxicity – Idiosyncratic effects at prophylactic doses Nevin RL. Neuropsychiatric Quinism: Chronic Encephalopathy Caused by Poisoning by Mefloquine and Related Quinoline Drugs. In: Ritchie EC, Llorente M, eds. Veteran Psychiatry in the US. Cham, Switzerland: Springer Nature; 2019. doi:10.1007/978-3-030-05384-0. In press. “Psychiatric symptoms such as insomnia, abnormal dreams/nightmares, acute anxiety, depression, restlessness or confusion have to be regarded as prodromal for a more serious event.” Roche UK. Lariam product documentation, June 2018. Emphasis added. Confounding Insomnia Exposure assumed causation Nightmares to Traumas Depression independent causation Anxiety correlation Confounder Confounding Insomnia Exposure assumed causation Nightmares to Traumas Depression actual causation Anxiety correlation Disequilibrium Mefloquine Vertigo Nevin RL. Mefloquine Exposure May Confound Associations and Limit Inference in Military Studies of Posttraumatic Stress Disorder. Military Medicine. 2017;182(11/12):1757. WRMI-2 • “Have you ever taken the weekly drug mefloquine (also known as Lariam®) to prevent malaria?" • If yes, “At any time while taking the drug, did you experience abnormal dreams or nightmares, insomnia, anxiety, depression, restlessness, or confusion?” © 2018 Remington Nevin. Under license to The Quinism Foundation.
    [Show full text]
  • Pharmaceutical Compositions Comprising Hydroxychloroquine (HCQ), Curcumin, Piperine/ Bioperine and Uses Thereof in the Medical Field
    (19) TZZ 56_8A_T (11) EP 2 561 868 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 27.02.2013 Bulletin 2013/09 A61K 31/12 (2006.01) A61K 31/4706 (2006.01) A61K 45/06 (2006.01) A61P 35/00 (2006.01) (21) Application number: 11178638.0 (22) Date of filing: 24.08.2011 (84) Designated Contracting States: (72) Inventor: Van Oosten, Anton Bernhard AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 3920 Lommel (BE) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (74) Representative: DeltaPatents B.V. Designated Extension States: Fellenoord 370 BA ME 5611 ZL Eindhoven (NL) (71) Applicant: Van Oosten, Anton Bernhard 3920 Lommel (BE) (54) Pharmaceutical compositions comprising hydroxychloroquine (HCQ), Curcumin, Piperine/ BioPerine and uses thereof in the medical field (57) The present invention concerns a pharmaceuti- of a premalignant plasma cell proliferative disorder like cal composition containing HCQ, curcumin and BioPer- a monoclonal gammopathy of undetermined significance ine/piperine and its application in the medical field. In (MGUS) and/or smoldering (asymptomatic) multiple my- particular, the composition according to the invention can eloma (SMM) and/or Indolent multiple myeloma (IMM) be advantageously employed in the prevention or treat- and/or to cause remission of a cancer arising from a pre- ment of a subject presenting with a proliferative disorder, malignant plasma cell proliferative disorder like multiple to slow the progression of and/or or to cause regression myeloma (MM).
    [Show full text]
  • 1 Antimalarial Activity of the 8 - Aminoquinolines Edward A
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln US Army Research U.S. Department of Defense 1991 1 Antimalarial Activity of the 8 - Aminoquinolines Edward A. Nodiff Franklin Research Center, Arvin Calspan Corporation, Valley Forge Corporate Center, Norristown, PA Sankar Chatterjee Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC Hikmat A. Musallam Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC Follow this and additional works at: http://digitalcommons.unl.edu/usarmyresearch Nodiff, Edward A.; Chatterjee, Sankar; and Musallam, Hikmat A., "1 Antimalarial Activity of the 8 - Aminoquinolines" (1991). US Army Research. 337. http://digitalcommons.unl.edu/usarmyresearch/337 This Article is brought to you for free and open access by the U.S. Department of Defense at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in US Army Research by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Progress in Medicinal Chemistry - Vol. 28, edited by G.P. Ellis and G.B. West 0 1991, Elsevier Science Publishers, B.V. 1 Antimalarial Activity of the 8- Aminoquinoline s EDWARD A. NODIFF, B.A. SANKAR CHATTERJEE, Ph.D. and HIKMAT A. MUSALLAM, Ph.D.2 Franklin Research Center, Arvin Calspan Corporation, Valley Forge Corporate Center, 2600 Monroe Boulevard, Norristown, PA 19403 and 'Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC 20307-5100, U.S.A. INTRODUCTION 2 THE PARASITE Exoerythrocytic phase Erythrocytic phase Sporogony THE DISEASE 4 CLASSIFICATION OF ANTIMALARIAL DRUGS 4 HISTORY 5 METHODS FOR ANTIMALARIAL DRUG EVALUATION 8 Rane blood schizontocidal screen (P.
    [Show full text]
  • Mefloquine Poisoning and VA Service Connection
    Mefloquine Poisoning and VA Service Connection Presentation to the State Bar of Texas Military and Veterans Law Section March 29, 2019 Salado, Texas Remington Nevin, MD, MPH, DrPH Executive Director Photo credit: Dr. Remington Nevin Photo credits: Dr. Remington Nevin Background • Mefloquine was developed by the U.S. military as an antimalarial drug – Origins in the late 1960s during a Vietnam War-era program • Widespread use in the U.S. military beginning in the early 1990s (e.g. Somalia, SOCOM, OIF/OEF, AFRICOM) – Tens (hundreds?) of thousands of veterans have been exposed • Recently deprioritized for use by DoD – Followed U.S. and international “black box” warnings and recognition of chronic psychiatric and neurologic effects 2013 “Drug of Last Resort” Policy Memorandum “Mefloquine is the drug of last resort for malaria chemoprophylaxis and should only be used in persons with contraindications to chloroquine, doxycycline and atovaquone- proguanil.” Declining Use of Mefloquine within DoD Woodson J. Memorandum. Subject: Notification for Healthcare Providers of Mefloquine Box Warning. August 12, 2013. Emphasis added. “[Mefloquine] may cause long lasting serious mental problems… Some people who have taken [mefloquine] developed serious neuropsychiatric reactions…” Roche UK. Lariam product documentation, June 2018. Emphasis added. “Psychiatric symptoms such as insomnia, abnormal dreams/nightmares, acute anxiety, depression, restlessness or confusion have to be regarded as prodromal for a more serious event.” Roche UK. Lariam product documentation, June 2018. Emphasis added. “In a small number of patients, it has been reported that neuropsychiatric reactions (e.g. depression, dizziness, or vertigo and loss of balance) may persist for months or longer, even after discontinuation of the drug.” Roche UK.
    [Show full text]
  • Quinism Foundation
    THE QUINISM FOUNDATION P.O. Box 145 White River Junction, Vermont 05001 USA July 31, 2018 Foreign Affairs, Defence and Trade Committee Department of the Senate PO Box 6100 Parliament House Canberra, Australian Capital Territory 2600 Sent electronically Re: Use of the Quinoline Anti-Malarial Drugs Mefloquine and Tafenoquine in the Australian Defence Force Dear Committee Members, The Quinism Foundation is pleased to submit the enclosed report for consideration by the Foreign Affairs, Defence and Trade References Committee in their inquiry on the use of the quinoline anti-malarial drugs mefloquine and tafenoquine in the Australian Defence Force (ADF). This report focuses on the following three terms of reference: • a comparison of international evidence/literature available on the impact of quinoline anti-malarials; • the current and past policies and practices for prescribing quinoline anti-malarial drugs to ADF personnel, and identifying and reporting adverse drug reactions from quinoline anti-malarial drugs among ADF personnel; and • how other governments [the United States] have responded to claims regarding quinoline anti-malarials Our foundation, on careful consideration, believes that a Royal Commission is needed to fully investigate several issues related to these terms of reference, particularly past policies and practices for prescribing quinoline anti-malarial drugs to ADF personnel. We thank you in advance for your careful attention to the issues in this report, the text of which, in part, has been modified from several of my publications submitted for publication elsewhere. I would be pleased to address any questions the committee may have in a further written report, and, on suitable arrangement, to appear as a witness at a future public hearing, as the committee may deem appropriate.
    [Show full text]
  • Current Antimalarial Therapies and Advances in the Development of Semi-Synthetic Artemisinin Derivatives
    Anais da Academia Brasileira de Ciências (2018) 90(1 Suppl. 2): 1251-1271 (Annals of the Brazilian Academy of Sciences) Printed version ISSN 0001-3765 / Online version ISSN 1678-2690 http://dx.doi.org/10.1590/0001-3765201820170830 www.scielo.br/aabc | www.fb.com/aabcjournal Current Antimalarial Therapies and Advances in the Development of Semi-Synthetic Artemisinin Derivatives LUIZ C.S. PINHEIRO1, LÍVIA M. FEITOSA1,2, FLÁVIA F. DA SILVEIRA1,2 and NUBIA BOECHAT1 1Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos Farmanguinhos, Fiocruz, Departamento de Síntese de Fármacos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil 2Universidade Federal do Rio de Janeiro, Programa de Pós-Graduação em Química, Avenida Athos da Silveira Ramos, 149, Cidade Universitária, 21941-909 Rio de Janeiro, RJ, Brazil Manuscript received on October 17, 2017; accepted for publication on December 18, 2017 ABSTRACT According to the World Health Organization, malaria remains one of the biggest public health problems in the world. The development of resistance is a current concern, mainly because the number of safe drugs for this disease is limited. Artemisinin-based combination therapy is recommended by the World Health Organization to prevent or delay the onset of resistance. Thus, the need to obtain new drugs makes artemisinin the most widely used scaffold to obtain synthetic compounds. This review describes the drugs based on artemisinin and its derivatives, including hybrid derivatives and dimers, trimers and tetramers that contain an endoperoxide bridge. This class of compounds is of extreme importance for the discovery of new drugs to treat malaria. Key words: malaria, Plasmodium falciparum, artemisinin, hybrid.
    [Show full text]
  • Quantification of Chloroquine by LC-MS and the Macular Degeneration Disease
    Universidade de Lisboa Faculdade de Farmácia Quantification of Chloroquine by LC-MS and the Macular Degeneration Disease David Miguel Cunha Pereira Mestrado Integrado em Ciências Farmacêuticas 2017 1 Universidade de Lisboa Faculdade de Farmácia Quantification of Chloroquine by LC-MS and the Macular Degeneration Disease David Miguel Cunha Pereira Monografia de Mestrado Integrado em Ciências Farmacêuticas apresentada à Universidade de Lisboa através da Faculdade de Farmácia Orientadora: Professora Doutora Isabel Ribeiro 2017 2 The work accomplished on this monograph was possible thanks to University of Eastern Finland (UEF), under Eramus+ Programme. Advisor: Professor Seppo Auriola 3 4 Abstract Age-related macular degeneration is a visual disease that involves a progressive loss of central vision which its consequences are dramatic for the patient’s quality of life. Age is a major risk factor for macular degeneration. Other risk factors include, ethnicity, genetics, smoking and drugs. Chloroquine appears to be the most toxic drug to the retina, which might be explained by the extensive accumulation and very long retention of chloroquine bound to melanin. Chloroquine is used for malarial prevention and treatment, as well to various inflammatory diseases such as rheumatoid arthritis and lupus erythematosus. Chloroquine toxicity in age-related macular degeneration is of serious ophthalmologic concern because it is not treatable. Nonetheless, it has been demonstrated that central vision can be preserved if damage is recognized before there
    [Show full text]
  • Synthesis, in Vitro Characterization and Applications of Novel 8-Aminoquinoline Fluorescent Probes Adonis Mcqueen University of South Florida, [email protected]
    University of South Florida Scholar Commons Graduate Theses and Dissertations Graduate School October 2017 Synthesis, in vitro Characterization and Applications of Novel 8-Aminoquinoline Fluorescent Probes Adonis McQueen University of South Florida, [email protected] Follow this and additional works at: http://scholarcommons.usf.edu/etd Part of the Medicine and Health Sciences Commons, Organic Chemistry Commons, and the Parasitology Commons Scholar Commons Citation McQueen, Adonis, "Synthesis, in vitro Characterization and Applications of Novel 8-Aminoquinoline Fluorescent Probes" (2017). Graduate Theses and Dissertations. http://scholarcommons.usf.edu/etd/7062 This Dissertation is brought to you for free and open access by the Graduate School at Scholar Commons. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. Synthesis, in vitro Characterization and Applications of Novel 8-Aminoquinoline Fluorescent Probes by Adonis McQueen A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Molecular Medicine Department of Molecular Medicine College of Medicine University of South Florida Major Professor: Dennis E. Kyle, Ph.D. Burt Anderson, Ph.D. Yu Chen, Ph.D. Lynn Wecker, Ph.D. Date of Approval: October 13, 2017 Keywords: Malaria, Primaquine, Drug Discovery, Mechanism of Action, Parasitology, Medicinal Chemistry Copyright © 2017, Adonis McQueen ACKNOWLEDGMENTS This research is a culmination of everyone I’ve interacted with, everyone who’s taught me and everyone I’ve ever taught. I thank my Creator for allowing me to make it this far. As far as people go, I owe my first thanks to Dr.
    [Show full text]
  • BP601T Medicinal Chemistry III (Theory) UNIT II Prepared By- Mrs. Sneha Kushwaha Assistant Professor Rama University Kanpur Anti
    BP601T Medicinal Chemistry III (Theory) UNIT II Prepared by- Mrs. Sneha Kushwaha Assistant Professor Rama University Kanpur Unit II 10 Hours Antibiotics Historical background, Nomenclature, Stereochemistry, Structure activity relationship Chemical degradation classification and important products of the following classes Macrolide: Erythromycin, Clarithromycin, Azithromycin. Miscellaneous: Chloramphenicol*, Clindamycin. Prodrugs: Basic concepts and application of prodrug design. Antimalarials: Etiology of malaria. Quinolines: SAR, Quinine sulphate, Chloroquine*, Amodiaquine, Primaquine phosphate, Pamaquine*, Quinacrine hydrochloride, Mefloquine. Biguanides and dihydro triazines: Cycloguanil pamoate, Proguanil. Miscellaneous: Pyrimethamine, Artesunete, Artemether, Atovoquone. Antibiotics B.Pharma – 3rd Year VI Sem. UNIT II – Antibiotics By - Sneha Kushwaha (Asst. Professor) Subject – Medicinal Chemistry (BP601 T) Macrolide Antibiotics Introduction The macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the polyketide class of natural products History The first macrolide discovered was erythromycin, which was first used in 1952. Erythromycin was widely used as a substitute to penicillin in cases where patients were allergic to penicillin or had penicillin-resistant illnesses. Later macrolides developed, including azithromycin and clarithromycin,
    [Show full text]
  • Elspeth Cameron Ritchie, MD, MPH COL (Ret) US Army
    C U R R I C U L U M V I T A E Elspeth Cameron Ritchie, MD, MPH COL (Ret) US Army Work Address: Chair, Department of Psychiatry Medstar Washington Hospital Center 110 Irving Street East Building 3105 Wash DC Work phone: 202-877-9424 Work e-mail: [email protected] [email protected] Personal e-mail: [email protected] Work Experience MAY 2018 to present Chief, Department of Psychiatry Medstar Washington Hospital Center Vice Chair, Department of Psychiatry Medstar Georgetown University Hospital NOV 2015 to March 2018 Chief Mental Health Community Based Outpatient Clinics (CBOCs) Washington DC VA 50 Irving Street Wash DC 24022 June 2017 to Oct 2017 Acting Associate Chief of Staff for Mental Health 50 Irving Street Washington DC VA April 2016—July 2017 Supervising Psychiatrist Community Resources and Referral Center (CRRC) 1500 Franklin Street Washington DC VA 1 JAN 2015—present Forensic Psychiatry Consultant Silver Spring, MD OCT 2010—DEC 2014 Chief Medical Officer Department of Behavioral Health District of Columbia DEC 2013—SEP 2014 Acting Medical Director Comprehensive Psychiatric Emergency Program Department of Behavioral Health District of Columbia MAR 2007-JUL 2010 Director, Proponency of Behavioral Health Office of the Army Surgeon General Falls Church, Virginia JUL 2004-APR 2008 Psychiatry Consultant to the Army Surgeon General Office of the Army Surgeon General JUN 1999-JUN 2003 Program Director, Mental Health Policy and Women’s Health Issues Office of the Secretary of Defense/Health Affairs
    [Show full text]
  • 214 4 Correspondence 237..238
    The British Journal of Psychiatry (2019) 214, 237–238. Correspondence Declaration of interest: R.N has been retained as consultant and expert witness in legal cases involving claims of adverse effects from antimalarial drugs, including Edited by Kiriakos Xenitidis and Colin Campbell mefloquine. References Contents ▪ Threats to the validity of studies of post-traumatic 1 Stevelink SAM, Jones M, Hull L, Pernet D, MacCrimmon S, Goodwin L, et al. stress disorder from unmeasured symptomatic Mental health outcomes at the end of the British involvement in the Iraq and Afghanistan conflicts: a cohort study. Br J Psychiatry 2018; 213: 690–7. exposure to mefloquine 2 Nevin RL. Re: ‘A decade of war: prospective trajectories of posttraumatic stress ▪ Author’s reply disorder symptoms among deployed US military personnel and the influence of combat exposure’. Am J Epidemiol 2018; 187: 1573–4. 3 Magill A, Cersovsky S, DeFraites R. Special considerations for US military deployments. In CDC Health Information for International Travel: The Yellow Book 2012 (ed GW Brunette): 561–5. Oxford University Press, 2012. 4 Livezey J, Oliver T, Cantilena L. Prolonged neuropsychiatric symptoms in a Threats to the validity of studies of post-traumatic military service member exposed to mefloquine. Drug Saf - Case Rep 2016; 3:7. stress disorder from unmeasured symptomatic 5 Nevin RL. Mefloquine and posttraumatic stress disorder. In Textbook of Military exposure to mefloquine Medicine. Forensic and Ethical Issues in Military Behavioral Health (ed EC Ritchie): 277–96. Borden Institute, 2015. 1 I read with interest the recent study by Stevelink and colleagues 6 The Quinism Foundation. The Quinism Foundation Partners with the National that studied the prevalence of various mental health outcomes, Centre for Trauma to Screen U.K.
    [Show full text]