DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 7,863,296 B2 Weiner Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 7,863,296 B2 Weiner Et Al USOO7863296B2 (12) United States Patent (10) Patent No.: US 7,863,296 B2 Weiner et al. (45) Date of Patent: *Jan. 4, 2011 (54) SELECTIVE SEROTONIN RECEPTOR 5,795,894. A 8, 1998 Shue et al. NVERSEAGONSTS AS THERAPEUTICS 5,869,488 A 2f1999 Shue et al. FOR DISEASE 5,874.445 A * 2/1999 Carr et al. ................... 514,317 5,877,173 A 3/1999 Olney et al. 5,912,132 A 6/1999 Brann (75) Inventors: David M. Weiner, San Diego, CA (US); 5,952.324 A 9/1999 Barbachyn et al. Robert E. Davis, San Diego, CA (US); 5,955,281 A 9, 1999 Brann Mark R. Brann, Del Mar, CA (US); 6,107,324 A 8, 2000 Behan et al. Anna-Maria Frost-Jensen, legal 6,140,509 A 10/2000 Behan et al. representative, Rye, NH (US); Norman 6,150,393 A 11/2000 Behan et al. Nash, Carlsbad, CA (US) 6,358,698 B1 3/2002 Weiner et al. 6.479,480 B1 1 1/2002 Moyes et al. (73) Assignee: ACADIA Pharmaceuticals, Inc., San 6,486,153 B1 1 1/2002 Castro Pineiro et al. Diego, CA (US) 6,617.339 B1 9, 2003 Gravestock 6,756,393 B2 6/2004 Andersson et al. (*) Notice: Subject to any disclaimer, the term of this 6,815,458 B2 11/2004 Andersson et al. 6,911,452 B2 6/2005 Schlienger patent is extended or adjusted under 35 7,022,698 B2 4/2006 Hamied et al. U.S.C. 154(b) by 1393 days. 7,041,667 B1 5/2006 Armour et al. 7,115,634 B2 10/2006 Thurieau et al. This patent is Subject to a terminal dis 7,253,186 B2 8/2007 Andersson et al. claimer. 7,601,740 B2 10/2009 Weiner et al. 2002, 0004513 A1 1/2002 Andersson et al. (21) Appl. No.: 11/134,769 2002.0035145 A1 3/2002 Tsai et al. 2002fO156068 A1 10/2002 Behan et al. (22) Filed: May 20, 2005 2002fO165225 A1 11/2002 Hamied et al. (Under 37 CFR 1.47) 2003/0092700 A1 5/2003 CZollner et al. 2003, O22031.6 A1 11/2003 Andersson et al. (65) Prior Publication Data US 2005/0288328A1 Dec. 29, 2005 (Continued) FOREIGN PATENT DOCUMENTS Related U.S. Application Data CA 984843 3, 1976 (63) Continuation of application No. 10/854,035, filed on May 24, 2004, now abandoned, which is a continua tion-in-part of application No. 10/850.819, filed on (Continued) May 21, 2004. OTHER PUBLICATIONS (51) Int. Cl. Avemaria, F. et al., “Synthesis of aryl azides via post-cleavage modi A6 IK 3/445 (2006.01) fication of polymer-bound triazenes.” Synlett 7:1163-1166 (2004). A6IP 25/00 (2006.01) Barnes and Sharp, "A review of central 5-HT receptors and their function.” Neuropharmacology 38: 1083-1152 (1999) (Abstract). (52) U.S. Cl. ....................................... 514/317; 514/277 Barr and Manning, "Agonist-independent Activation of G by the (58) Field of Classification Search ................. 514/277, 5-Hydroxytryptamine Receptor Co-expressed in Spodoptera 514/317 frugiperda Cells,” J. Biol. Chem. 272:32979-32987 (1997). See application file for complete search history. Brane, “Identification of ligands by selective amplification of cells transfected with receptors and marker enzymes.” Chem Abstr. (56) References Cited 128: 111548 (1998). U.S. PATENT DOCUMENTS Cerione, R. A. et al., “The mammalian beta 2-adrenergic receptor: reconstitution of functional interactions between pure receptor and 3,983,234 A 9/1976 Sayers pure stimulatory nucleotide binding protein of the adenylate cyclase 4,138.492. A 2f1979 Noverola et al. system.” Biochemistry 23:4519-4525 (1984) (Abstract). 4.255.432 A 3/1981 Kluge et al. 4,332,804 A 6, 1982 Clark (Continued) 4,353,900 A 10, 1982 Clark 4,353,901 A 10, 1982 Clark Primary Examiner Sreeni Padmanabhan 4,367,232 A 1/1983 Boix-Igleasias et al. Assistant Examiner Sahar Javanmard 4,401,665 A 8, 1983 Sheinaus et al. ............ 514,162 (74) Attorney, Agent, or Firm Jones Day 4,853,394 A 8/1989 King et al. 4,908,369 A * 3/1990 Schechter et al. ........... 514,277 (57) ABSTRACT 5,025,013 A 6, 1991 Barreau et al. 5,214,044 A 5/1993 Cooper et al. Disclosed herein are pharmaceutical compositions compris 5,214,055 A 5/1993 Peglion et al. ing an inverse serotonin receptoragonist or a serotonin recep 5,216,165 A 6, 1993 Mobilio et al. 5,461,066 A 10, 1995 Gericke et al. tor antagonist and an anti-insomnia agent. Disclosed herein 5,595,872 A 1/1997 Wetterau, II et al. are also methods of treating insomnia using the disclosed 5,621,010 A 4/1997 Sueda et al. pharmaceutical compositions. 5,689,488 A 1 1/1997 Yamaguchi 5,707,798 A 1/1998 Brann 18 Claims, No Drawings US 7,863,296 B2 Page 2 U.S. PATENT DOCUMENTS WO WO 2005/112927 12/2005 WO WO-2005-115361 A 12/2005 2004.0006081 A1 1/2004 Burrows et al. WO WO 2006/036874 4/2006 2004/0106600 A1 6/2004 Andersson et al. WO WO 2006/037043 4/2006 2004/021381.6 A1 10, 2004 Weiner et al. WO WO 2006,104.826 10, 2006 2005, OO14757 A1 1/2005 Andersson et al. 2005, 0148018 A1 7/2005 Weiner et al. OTHER PUBLICATIONS 2005/0244862 A1 11, 2005 Brann 2005/0256108 A1 1 1/2005 Schlienger Gershon et al., “5-Hydroxytryptamine and enteric neurones.” Chap 2006/0094758 A1 5/2006 Andersson et al. ter 11, pp. 247-272 from The Peripheral Actions of 2006/0106063 A1 5/2006 Thygesen et al. 5-Hydroxytryptamine (1989). 2006/011 1399 A1 5/2006 Thygesen et al. Glennon, R.A., 'Serotonin receptors: clinical implications.” 2006/O194778 A1 8/2006 Andersson et al. Neurosci. Biobehavioral Rev. 14:35-47 (1990). 2006, O194834 A1 8/2006 Andersson et al. Julius, D. et al., “The 5HT2 receptor defines a family of structurally 2006/O1997.94 A1 9/2006 Schlienger distinct but functionally conserved serotonin receptors.” PNAS USA 2006/0199818 A1 9, 2006 Andersson et al. 87-928-932 (1990). 2006, O199842 A1 9, 2006 Weiner et al. Meltzer, H.Y., “The Role of Serotonin in Antipsychotic Drug 2006/0205710 A1 9/2006 Schlienger et al. Action.” Neuropsychopharmacology 21:106S-115S (1999). 2006/0205722 A1 9/2006 Andersson et al. Moulignier, A. "Central serotonin receptors. Principal fundamental 2006/0205780 A1 9/2006 Thygesen et al. and functional aspects. Therapeutic applications. Rev. Neurol. 2006/0205781 A1 9/2006 Thygesen et al. 150:3-15 (1994) (Abstract). 2006/0264465 A1 11/2006 Weiner et al. Nagabina, N. et al., “Applied Technique of 1,3-Dipolar Cycloaddi 2006/0264466 A1 11/2006 Weiner et al. tion to Synthesis of New Fluoroquinolones.” Russian J. Organic 2006/028661.0 A1 12, 2006 Brann Chem. Consultants Bureau, US, pp. 1548-1555 (1997). 2006,029.2606 A1 12, 2006 Brann Saltzman, A.G. et al., “Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes.” Biochem. Biophys. Res. Comm. FOREIGN PATENT DOCUMENTS 181: 1469-1478 (1991) (Abstract). Saxena et al., "Cardiovascular Effects of Serotonin Agonists and EP 0 005 3.18 11, 1979 Antagonists,” J. Cardiovascular Pharmacol. 15(Supp. 7):S17-S34 EP O056144 A1 7, 1982 (1990). EP O 061333 9, 1982 PCT/US06/076317 WO Search Report dated Jul. 20, 2006. EP O 379 441 7, 1990 International Search Report and Written Opinion for PCT/US2005/ EP O 548 O15 6, 1993 0.17808 filed May 20, 2005, mailed Sep. 29, 2005, 13 pgs. EP O 260 070 8, 1993 R. A. Bond et al., “Physiological effects of inverse agonists in EP O 625 507 11, 1994 transgenic mice with myocardlal overexpression of the EP 1656938 A1 5, 2006 B—adrenoceptor', Nature vol. 374, pp. 272-276, 1995. FR 28O2206 6, 2001 D. M. Weiner, “5-Hydroxytryptamine Receptor Inverse Agonists HU 1573.25 3, 1998 as Antipsychotics”. J. Pharmacol Exp. Ther. vol. 299, No. 1. pp. JP 51052176 5, 1976 268-276, 2001. JP 52O8517 5, 1977 Acadia Pharmaceuticals Announces Results from Phase III Trial of WO WO 94,27967 12/1994 Pimavanserin in Parkinson's Disease Psychosis, Press Release (Busi WO WO97,081.66 3, 1997 ness Wire, San Diego), Sep. 1, 2009. WO WO97,11940 4f1997 Acadia Pharmaceuticals Provide Update on Pimavanserin Collabo WO WO97/38665 10, 1997 rative Development Program, Press Release (Business Wire, San WO WO97,38984 10, 1997 Diego), Oct. 6, 2009. WO WO98, 11128 3, 1998 Notice of Allowance dated Jun. 17, 2009 in U.S. Appl. No. WO WO98, 17646 4f1998 10/759,561. WO WO98/44921 10, 1998 ACADIA Pharmaceuticals Announces Results from Phase III Trial of WO WO98,50534 11, 1998 Pimavanserin in Parkinson's Disease Psychosis ACADIA Pharma WO WO99, 52927 10, 1999 ceuticals Announces Results from Phase III Trial of Pimavanserin in WO WOOO, 23076 4/2000 Parkinson's Disease Psychosis, Press Release (Business Wire, San WO WOOO,56335 9, 2000 Diego), Sep. 1, 2009. WO WOOO. 59497 10, 2000 ACADIA Pharmaceuticals Provide Update on Pimavanserin Col WO WOOOf 69810 11, 2000 laborative Development Program, Press Release (BusinessWire, San WO WOO1/44.191 6, 2001 Diego), Oct. 6, 2009. WO WOO1? 66521 9, 2001 Adam, et al. “Effects of repeated ritanserin on middle-aged poor WO WOO1f87839 11, 2001 sleepers.” Psychopharmacology, 99:219-221 (1989). WO WOO2,24649 3, 2002 Adell, et al., “Strategies for producing faster acting antidepressants.” WO WO O2/O79 186 10, 2002 Drug Discovery Today, 10(8):578-585 (2005).
Load more

Recommended publications
  • Guidelines for the Forensic Analysis of Drugs Facilitating Sexual Assault and Other Criminal Acts
    Vienna International Centre, PO Box 500, 1400 Vienna, Austria Tel.: (+43-1) 26060-0, Fax: (+43-1) 26060-5866, www.unodc.org Guidelines for the Forensic analysis of drugs facilitating sexual assault and other criminal acts United Nations publication Printed in Austria ST/NAR/45 *1186331*V.11-86331—December 2011 —300 Photo credits: UNODC Photo Library, iStock.com/Abel Mitja Varela Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Guidelines for the forensic analysis of drugs facilitating sexual assault and other criminal acts UNITED NATIONS New York, 2011 ST/NAR/45 © United Nations, December 2011. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. List of abbreviations . v Acknowledgements .......................................... vii 1. Introduction............................................. 1 1.1. Background ........................................ 1 1.2. Purpose and scope of the manual ...................... 2 2. Investigative and analytical challenges ....................... 5 3 Evidence collection ...................................... 9 3.1. Evidence collection kits .............................. 9 3.2. Sample transfer and storage........................... 10 3.3. Biological samples and sampling ...................... 11 3.4. Other samples ...................................... 12 4. Analytical considerations .................................. 13 4.1. Substances encountered in DFSA and other DFC cases .... 13 4.2. Procedures and analytical strategy...................... 14 4.3. Analytical methodology .............................. 15 4.4.
    [Show full text]
  • The In¯Uence of Medication on Erectile Function
    International Journal of Impotence Research (1997) 9, 17±26 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 The in¯uence of medication on erectile function W Meinhardt1, RF Kropman2, P Vermeij3, AAB Lycklama aÁ Nijeholt4 and J Zwartendijk4 1Department of Urology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; 2Department of Urology, Leyenburg Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands; 3Pharmacy; and 4Department of Urology, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands Keywords: impotence; side-effect; antipsychotic; antihypertensive; physiology; erectile function Introduction stopped their antihypertensive treatment over a ®ve year period, because of side-effects on sexual function.5 In the drug registration procedures sexual Several physiological mechanisms are involved in function is not a major issue. This means that erectile function. A negative in¯uence of prescrip- knowledge of the problem is mainly dependent on tion-drugs on these mechanisms will not always case reports and the lists from side effect registries.6±8 come to the attention of the clinician, whereas a Another way of looking at the problem is drug causing priapism will rarely escape the atten- combining available data on mechanisms of action tion. of drugs with the knowledge of the physiological When erectile function is in¯uenced in a negative mechanisms involved in erectile function. The way compensation may occur. For example, age- advantage of this approach is that remedies may related penile sensory disorders may be compen- evolve from it. sated for by extra stimulation.1 Diminished in¯ux of In this paper we will discuss the subject in the blood will lead to a slower onset of the erection, but following order: may be accepted.
    [Show full text]
  • Pregnancy-Safe-Medications
    PEACHTREE WOMEN’S SPECIALISTS, P.C. Obstetrics and Gynecology Melissa Counihan, M.D Bonita Dozier, M.D. James P. Ingvoldstad, MD James Knoer, M.D. Helen McSwain, M.D. Archie Roberts, M.D. Lillian Schapiro, MD PREGNANCY SAFE MEDICATIONS Antihistamines o Actifed o Benadryl o Claritin o Claritin-D o Chlor-Trimeton-D o Chlor-Trimeton-DM o Sudafed* o Zyrtec and Zyrtec-D * Georgia law now requires that Sudafed be requested from the pharmacist, even though it is not a prescription medication. Cough o Robitussin o Robitussin DM o Robitussin PE* o You may take any cough drop *DO NOT use if taking Sudafed or Brethine/Terbutaline. Calcium Supplement o Tums EX- two tablets twice daily o Viactiv Constipation o Colace o Fibercon o Konsyl o Metamucil o Milk of Magnesia o Perdiem Increase dietary roughage, bran, dark green leafy vegetables and fruits. Drink eight to ten glasses of water daily. Decongestants* o Sudafed o Sudafed Sinus o Sudafed Non-drying o Actifed o Tylenol Sinus o Benadryl o Doxylamine Succinate *After the first trimester PREGNANCY SAFE MEDICATIONS (Continued) Dry Skin o Cocoa Butter o Eucerin Lotion o Vitamin E Lotion Fever o Tylenol* o Tylenol Extra Strength* *DO NOT take more than 12 tablets of Regular Strength Tylenol in 24 hours and no more than 6 tablets of Extra Strength Tylenol in 24 hours. Gas o Mylicon o Mylanta GAS o Phazyme o Mylanta Antacid/Anti-gas Hemorrhoids o Preparation H o Colace o Annusol Suppository/Ointment (With or without Cortisone) Increase dietary roughage, bran, dark green leafy vegetables and fruits.
    [Show full text]
  • Doxylamine Succinate and Pyridoxine Hydrochloride (Diclegis®, Bonjesta®) Duration Limit
    Cigna National Formulary Coverage Policy Drug Quantity Management – Per Days Doxylamine succinate and pyridoxine hydrochloride (Diclegis®, Bonjesta®) Duration Limit Table of Contents Product Identifer(s) National Formulary Medical Necessity ................ 1 60889 Conditions Not Covered....................................... 2 Background .......................................................... 2 References .......................................................... 2 Revision History ................................................... 2 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation.
    [Show full text]
  • Doxylamine Succinate-Pyridoxine Hydrochloride
    Doxylamine succinate-pyridoxine hydrochloride This sheet is about exposure to doxylamine succinate-pyridoxine hydrochloride in pregnancy and while breastfeeding. This information should not take the place of medical care and advice from your healthcare providers. What is doxylamine succinate-pyridoxine hydrochloride? The combination of 10mg of doxylamine succinate and 10mg of pyridoxine hydrochloride is a medication used to treat nausea and vomiting of pregnancy (NVP), also called “morning sickness.” For more information on NVP, please see the MotherToBaby fact sheet Nausea and Vomiting of Pregnancy (https://mothertobaby.org/fact-sheets/nausea-vomiting-pregnancy-nvp/pdf/). Doxylamine succinate is an antihistamine. Antihistamines lessen the symptoms of allergic reactions and colds and help to treat insomnia (hard time sleeping). Pyridoxine hydrochloride is a form of vitamin B6. In the United States, the combination of doxylamine and pyridoxine has been sold under the name Diclegis® since 2013. In Canada, it has been sold under the brand name Diclectin®. Diclegis® and Diclectin® are delayed-release tablets available by prescription. Delayed-release means that the tablet coating prevents the ingredients from being absorbed too quickly by the body. Doxylamine succinate and/or pyridoxine hydrochloride may also be available as over-the- counter medicines. I take doxylamine succinate-pyridoxine hydrochloride. Can it make it harder for me to get pregnant? Based on the data available, it is not known if doxylamine succinate-pyridoxine hydrochloride can make it harder to become pregnant. I just found out I am pregnant. Should I stop taking doxylamine succinate-pyridoxine hydrochloride? Talk with your healthcare providers before making any changes to how you take your medication(s).
    [Show full text]
  • Restavit-PI.Pdf
    AUSTRALIAN PRODUCT INFORMATION-RESTAVIT (DOXYLAMINE SUCCINATE) 1.NAME OF THE MEDICINE Doxylamine succinate 2.QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 25mg doxylamine succinate. For the full list of excipients, see Section 6.1 List of excipients 3. PHARMACEUTICAL FORM White uncoated biconvex tablets with a break bar on one side. 4.CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS Temporary relief of insomnia 4.2 DOSE AND METHOD OF ADMINISTRATION Adults: One or two tablets twenty minutes before bed. Swallow tablets with a glass of water. Restavit should not be used for more than a few days at a time as insomnia may be symptomatic of a serious underlying medical condition. Children: Do not give to children under 12 years of age Impaired hepatic and renal function: Dosage reduction may be necessary. 4.3 CONTRAINDICATIONS Patients with hypersensitivity to doxylamine, other antihistamines in the ethanolamine class, lactose or any other component should not use this product. Doxylamine should not be given to premature or new born infants due to their heightened susceptibility to antimuscarinic effects. 1 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE Avoid concurrent use with alcohol and medications which suppress the CNS as the effects of both may be enhanced1. A risk-benefit approach should be adopted for patients with glaucoma. Increased ocular pressure could precipitate an attack of angle closure glaucoma2. Use with caution in patients with asthma, bladder neck obstruction, urinary retention, chronic bronchitis, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy and epilepsy1,6. Use in hepatic impairment: Use with caution. Use in renal impairment Use with caution.
    [Show full text]
  • Medicines Classification Committee
    Medicines Classification Committee Meeting date 1 May 2017 58th Meeting Title Reclassification of Sedating Antihistamines Medsafe Pharmacovigilance Submitted by Paper type For decision Team Proposal for The Medicines Adverse Reactions Committee (MARC) recommended that the reclassification to committee consider reclassifying sedating antihistamines to prescription prescription medicines when used in children under 6 years of age for the treatment of medicine for some nausea and vomiting and travel sickness [exact wording to be determined by indications the committee]. Reason for The purpose of this document is to provide the committee with an overview submission of the information provided to the MARC about safety concerns associated with sedating antihistamines and reasons for recommendations. Associated March 2013 Children and Sedating Antihistamines Prescriber Update articles February 2010 Cough and cold medicines clarification – antihistamines Medsafe website Safety information: Use of cough and cold medicines in children – new advice Medicines for Alimemazine Diphenhydramine consideration Brompheniramine Doxylamine Chlorpheniramine Meclozine Cyclizine Promethazine Dexchlorpheniramine New Zealand Some oral sedating antihistamines available without exposure to a prescription (pharmacist-only and pharmacy only), sedating therefore usage data is not easily available. antihistamines Table of Contents 1.0 PURPOSE ......................................................................................................................................
    [Show full text]
  • Histamine and Antihistamines Sites of Action Conditions Which Cause Release Aron H
    Learning Objectives I Histamine Pharmacological effects Histamine and Antihistamines Sites of action Conditions which cause release Aron H. Lichtman, Ph.D. Diagnostic uses Associate Professor II Antihistamines acting at the H1 and H2 receptor Pharmacology and Toxicology Pharmacological effects Mechanisms of action Therapeutic uses Side effects and drug interactions Be familiar with the existence of the H3 receptor III Be able to describe the main mechanism of action of cromolyn sodium and its clinical uses Histamine Pharmacology First autacoid to be discovered. (Greek: autos=self; Histamine Formation akos=cure) Synthesized in 1907 Synthesized in mammalian tissues by Demonstrated to be a natural constituent of decarboxylation of the amino acid l-histidine mammalian tissues (1927) Involved in inflammatory and anaphylactic reactions. Local application causes swelling redness, and edema, mimicking a mild inflammatory reaction. Large systemic doses leads to profound vascular changes similar to those seen after shock or anaphylactic origin Histamine Stored in complex with: Heparin Chondroitin Sulfate Eosinophilic Chemotactic Factor Neutrophilic Chemotactic Factor Proteases 1 Conditions That Release Histamine 1. Tissue injury: Any physical or chemical agent that injures tissue, skin or mucosa are particularly sensitive to injury and will cause the immediate release of histamine from mast cells. 2. Allergic reactions: exposure of an antigen to a previously sensitized (exposed) subject can immediately trigger allergic reactions. If sensitized by IgE antibodies attached to their surface membranes will degranulate when exposed to the appropriate antigen and release histamine, ATP and other mediators. 3. Drugs and other foreign compounds: morphine, dextran, antimalarial drugs, dyes, antibiotic bases, alkaloids, amides, quaternary ammonium compounds, enzymes (phospholipase C).
    [Show full text]
  • The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum
    The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum Green-top Guideline No. 69 June 2016 The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum This is the first edition of this guideline. Executive summary of recommendations Diagnosis of nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum (HG) How is NVP diagnosed? NVP should only be diagnosed when onset is in the first trimester of pregnancy and other causes of D nausea and vomiting have been excluded. How is HG diagnosed? HG can be diagnosed when there is protracted NVP with the triad of more than 5% prepregnancy D weight loss, dehydration and electrolyte imbalance. How can the severity of NVP be classified? An objective and validated index of nausea and vomiting such as the Pregnancy-Unique C Quantification of Emesis (PUQE) score can be used to classify the severity of NVP. What initial clinical assessment and baseline investigations should be done before deciding on treatment? Clinicians should be aware of the features in history, examination and investigation that allow NVP and HG to be assessed and diagnosed and for their severity to be monitored. P What are the differential diagnoses? Other pathological causes should be excluded by clinical history, focused examination and investigations. P What is the initial management of NVP and HG? How should the woman be managed? Women with mild NVP should be managed in the community with antiemetics. D Ambulatory daycare management should be used for suitable patients when community/primary C care measures have failed and where the PUQE score is less than 13.
    [Show full text]
  • Preparation for Your First Visit and Allergy Testing
    PREPARATION FOR YOUR FIRST VISIT AND ALLERGY TESTING Please allow up to 2 hours for your skin test appointment. In order to obtain valid and useful skin testing results, you need to discontinue the use of certain medications for a specific time before the skin test and your appointment. 1. All sleep aids and over the counter medications must be withheld for 2 to 5 days before your appointment. 2. Because most cough preparations contain antihistamines, these must be withheld for 2 days. 3. Prescription nose sprays like Nasonex, Nasacort AQ, Rhinocort AQ, Flonase, Nasarel, Beconase and Singulair Tablets DO NOT interfere with testing. You do not need to stop them before your appointment. 4. Asthma inhalers (inhaled corticosteroids) do not need to be discontinued. 5. Asthma medications such as theophylline and Singulair (montelukast) do not need to be discontinued. 6. If you are pregnant or suspect you may be pregnant please notify our staff immediately. You are not eligible for allergy skin testing at anytime during pregnancy. Blood testing for allergens is recommended during pregnancy. 7. Please allow a minimum of 2 hours for allergy testing. Feel free to bring reading materials, an iPod, handheld games or some other type of activity to entertain you during the test. 8. We respectfully request that our patients refrain from wearing perfumes and/or colognes which may harm those individuals with respiratory problems. 9. If you are taking medication with antihistamine effects which cannot be stopped because of the severity of your condition or any other reason, continue taking the medication and let the clinic know at your initial visit.
    [Show full text]
  • 021876Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 021876Orig1s000 PHARMACOLOGY REVIEW(S) MEMO FOOD AND DRUG ADMINISTRATION Division of Reproductive and Urologic Products Center for Drug Evaluation and Research Date: April 5, 2013 From: Kimberly Hatfield, Ph.D. Toxicologist To: NDA 21876 Subject: Changes to nonclinical scientific bridge and labeling for NDA 21876 (Diclegis) Scientific bridge: NDA 21876 has been submitted as a 505(b)(2) application for the drug product Diclegis (combination of doxylamine succinate and pyridoxine hydrochloride), with nonclinical evidence supporting the safety of Diclegis being based on the Agency’s determination of safety for the Reference Listed Drug (RLD), Bendectin® (NDA 10-598). The nonclinical scientific bridge between Diclegis and the RLD Bendectin® has been revised since submission of the initial nonclinical NDA review. It now states: The bridge for reliance on the nonclinical data generated with Bendectin (10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride) to support the NDA for Diclegis (10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride) is based on: 1) in vivo delayed release, 2) similar pharmacodynamic characteristics, and 3) in vitro dissolution based on Diclectin (a Canadian approved drug product containing 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride) manufactured at (b) (4) and 4) chemical criteria for doxylamine succinate and pyridoxine hydrochloride defined in the US Pharmacopeia e.g., composition, structure, molecular weight and chemical characteristics. Refer also to the clinical pharmacology memo further elaborating on the scientific bridge submitted by CAPT E. Dennis Bashaw, PharmD. Labeling changes: During label negotiations, a change in Section 13 Carcinogenesis, Mutagenesis and Impairment of Fertility was made.
    [Show full text]
  • Sleep Medications in Primary Care Disclosure • No Real Or Potential
    Sleep Medications in Primary Care Disclosure Sleep Medications in Primary Care • No real or potential conflict of Margaret A. Fitzgerald, interest to disclose. DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC, FNAP President, • No off-label, experimental or Fitzgerald Health Education Associates, North Andover, MA investigational use of drugs or Family Nurse Practitioner, Greater Lawrence (MA) Family Health Center devices will be presented. Editorial Board Member The Nurse Practitioner Journal, The Prescriber’s Letter, American Nurse Today Member, Pharmacy and Therapeutics Committee Neighborhood Health Plan, Boston, MA Fitzgerald Health Education Associates 2 Objectives Objectives (continued) • Upon completion of the learning • Upon completion of the learning activity the participant will be able to: activity the participant will be able – Describe the process of naturally- to: (cont.) occurring sleep. – Recognize the anticipated sleep – Identify the pharmacokinetics and outcomes with select medications pharmacodynamics of medications and commonly prescribed or used to herbal products to enhance sleep. enhance sleep as well as the risks associated with these products. Fitzgerald Health Education Associates 3 Fitzgerald Health Education Associates 4 Sleep Defined Insomnia: The Cost of the Problem (Or Best Defined in its Absence?) • Difficult to define and characterized • Costs the average American worker by observable changes in behavior – 11.3 days per year, $2,280 in lost and responsiveness productivity each year – Decreased activity • Presenteeism vs. absenteeism – Recognizable posture •Entire USA – Brain is less attentive to external stimuli – $63.2 billion in lost productivity – Source: http://healthland.time.com/2011/09/01/the-high-cost- – Altered consciousness yet easily aroused of-bad-sleep-63-billion-per-year/ –Source: http://healthysleep.med.harvard.edu/healthy/science/what/characteristics Fitzgerald Health Education Associates 5 Fitzgerald Health Education Associates 6 Fitzgerald Health Education Associates.
    [Show full text]