DOCSLIB.ORG

Wo 2009/080693 A2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 2 July 2009 (02.07.2009) WO 2009/080693 A2 (51) International Patent Classification: AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, A61K 31/46 (2006.01) A61P 3/04 (2006.01) CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, (21) International Application Number: IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, PCT/EP2008/067856 LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, MY,MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, (22) International Filing Date: RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TJ, 18 December 2008 (18.12.2008) TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (25) Filing Language: English ZW (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, PA 2007 01834 20 December 2007 (20.12.2007) DK ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), 61/016,067 2 1 December 2007 (21.12.2007) US European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, (71) Applicant (for all designated States except US): NEU- NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, ROSEARCH A/S [DK/DK]; Pederstrupvej 93, DK-2750 CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). Ballerup (DK). (72) Inventor; and Declaration under Rule 4.17: (75) Inventor/Applicant (for US only): MEIER, Dieter, H. — as to applicant's entitlement to applyfor and be granted a [DE/DK]; NeuroSearch A/S, Pederstrupvej 93, DK-2750 patent (Rule 4.17(U)) Ballerup (DK). Published: (81) Designated States (unless otherwise indicated, for every — without international search report and to be republished kind of national protection available): AE, AG, AL, AM, upon receipt of that report (54) Title: PHARMACEUTICAL COMPOSITIONS (57) Abstract: This invention relates to novel pharmaceutical compositions comprising a therapeutically effective combination of a compound of Formula I and a beta blocker. The pharmaceutical compositions for use according to the invention are contemplated particularly useful for combating obesity or an obesity associated disease. PHARMACEUTICAL COMPOSITIONS TECHNICAL FIELD This invention relates to novel pharmaceutical compositions comprising a therapeutically effective combination of a compound of Formula I and a beta blocker. The pharmaceutical compositions for use according to the invention are contemplated particularly useful for combating obesity or an obesity associated disease. BACKGROUND ART Within the past decades the prevalence of obesity has risen in virtually all ethnic, racial and socioeconomic populations, in both genders and in all age groups. Obesity is associated with a significantly elevated risk for type 2 diabetes, coronary heart diseases, hypertension and numerous other major illnesses and overall mortality from all causes. Therefore, weight reduction is critical for the obese patient. Thus there is impetus for creating new and alternative treatments for management of obesity. Results from clinical studies with NeuroSearch proprietary compound tesofensine showed that the compound has a good safety profile and was well tolerated. However, though no clinically relevant cardiovascular adverse events or changes in either blood pressure or pulse were seen, some cardiovascular effects were measured with slight increases in heart rate and trends in blood pressure. Although such small effects have no immediate risk to the patient some medical and regulatory concerns have been raised based on observational studies that even small changes in cardiovascular parameters may have long term implications on patients' benefit/risk evaluation. SUMMARY OF THE INVENTION Investigations carried out by the inventors have lead to the conclusion that a combination of a compound of Formula I and a beta blocker constitute a particularly useful combination for use in therapy associated with obesity or an obesity associated disease. In its first aspect the invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof and a beta blocker or a pharmaceutically acceptable salt thereof, together with one or more adjuvants, excipients, carriers and/or diluents. In another aspect the invention relates to the use of a combination of a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof and a beta blocker or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment, prevention or alleviation of obesity or an obesity associated disease of a mammal, including a human. In a third aspect the invention provides a kit of parts comprising at least two separate unit dosage forms (A) and (B), wherein (A) comprises a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and (B) comprises a beta blocker or a pharmaceutically acceptable salt thereof; and optionally (C) instructions for the simultaneous, sequential or separate administration of the compound of (A) and the beta blocker of (B) to a patient in need thereof. In a fourth aspect the invention provides a method of treatment, prevention or alleviation of obesity or an obesity associated disease of a living animal body, including a human, which method comprises the step of administering to such a living animal body in need thereof, a therapeutically effective amount of a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and a beta blocker or a pharmaceutically acceptable salt thereof. Other objects of the invention will be apparent to the person skilled in the art from the following detailed description and examples. DETAILED DISCLOSURE OF THE INVENTION In its first aspect the invention provides a pharmaceutical composition comprising a therapeutically effective amount of (i) a compound of Formula I wherein Ra represents hydrogen or alkyl; Rb represents a dihalophenyl group; any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and (ii) a beta blocker; or a pharmaceutically acceptable salt thereof; together with one or more adjuvants, excipients, carriers and/or diluents. Compounds of Formula I The compounds of Formula I for use according to the invention are monoamine neurotransmitter re-uptake inhibitors, and are described in WO 97/30997 (NeuroSearch A/S). The compounds may be prepared by conventional methods for chemical synthesis, e.g. those described in WO 97/30997 and WO 2005/073228. a In one embodiment of the compound of Formula I, R represents hydrogen or methyl. In a special embodiment, Ra represents hydrogen. In a further embodiment, Ra represents methyl. In a further embodiment of the compounds of Formula I, Rb represents dichlorophenyl. In a special embodiment, Rb represents 3,4-dichlorophenyl. In a still further embodiment, the compound of Formula I is tesofensine [(-/R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl- 8-azabicyclo[3.2.1]octane]; or (7R2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8- azabicyclo[3.2.1]octane; or a pharmaceutically acceptable salt thereof. In a special embodiment, the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof. In a further special embodiment, the compound of Formula I is the citrate salt of tesofensine. Definition of Substituents In the context of this invention halo represents fluoro, chloro, bromo or iodo. In the context of this invention an alkyl group means a straight chain or branched chain of one to six carbon atoms, including but not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, and hexyl; methyl, ethyl, propyl and isopropyl are preferred groups. Steric isomers It will be appreciated by those skilled in the art that the compounds of Formula I may exist in different stereoisomer^ forms - including enantiomers, diastereomers and cis-trans-isomers. The invention includes all such isomers and any mixtures thereof including racemic mixtures. Beta blockers The present invention involves the use of a class of drugs known as beta blocking compounds or simply beta blockers. The beta blocker for use according to the invention is any conventional beta blocker known in the art. Preferably, the beta blocking drug is selected from the following groups of compounds, which groups of compounds are known in the art and may be commercially available under different brand names, or may be obtained as described in the literature: Non-selective beta blockers In one embodiment, the beta blocker for use according to the invention is a non-selective beta blocker. Examples of non-selective beta blockers include alprenolol, amosulalol, bucindolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol and timolol. In one embodiment, the beta blocker is selected from the group consisting of alprenolol, amosulalol, bucindolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol and pharmaceutically acceptable salts thereof. Beta 1-selective beta blockers In a further embodiment, the beta blocker for use according to the invention is a beta 1-selective beta blocker. Examples of beta 1-selective beta blockers include acebutolol, atenolol, betaxolol, bisoprolol, esmolol, landiolol, metoprolol and nebivolol. In one embodiment, the beta blocker is selected from the group consisting of acebutolol, atenolol, betaxolol, bisoprolol, esmolol, landiolol, metoprolol, nebivolol and pharmaceutically acceptable salts thereof.
Recommended publications
  • (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al

    (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al

    USOO9498481 B2 (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao et al. (45) Date of Patent: *Nov. 22, 2016 (54) CYCLOPROPYL MODULATORS OF P2Y12 WO WO95/26325 10, 1995 RECEPTOR WO WO99/O5142 2, 1999 WO WOOO/34283 6, 2000 WO WO O1/92262 12/2001 (71) Applicant: Apharaceuticals. Inc., La WO WO O1/922.63 12/2001 olla, CA (US) WO WO 2011/O17108 2, 2011 (72) Inventors: Tadimeti Rao, San Diego, CA (US); Chengzhi Zhang, San Diego, CA (US) OTHER PUBLICATIONS Drugs of the Future 32(10), 845-853 (2007).* (73) Assignee: Auspex Pharmaceuticals, Inc., LaJolla, Tantry et al. in Expert Opin. Invest. Drugs (2007) 16(2):225-229.* CA (US) Wallentin et al. in the New England Journal of Medicine, 361 (11), 1045-1057 (2009).* (*) Notice: Subject to any disclaimer, the term of this Husted et al. in The European Heart Journal 27, 1038-1047 (2006).* patent is extended or adjusted under 35 Auspex in www.businesswire.com/news/home/20081023005201/ U.S.C. 154(b) by Od en/Auspex-Pharmaceuticals-Announces-Positive-Results-Clinical M YW- (b) by ayS. Study (published: Oct. 23, 2008).* This patent is Subject to a terminal dis- Concert In www.concertpharma. com/news/ claimer ConcertPresentsPreclinicalResultsNAMS.htm (published: Sep. 25. 2008).* Concert2 in Expert Rev. Anti Infect. Ther. 6(6), 782 (2008).* (21) Appl. No.: 14/977,056 Springthorpe et al. in Bioorganic & Medicinal Chemistry Letters 17. 6013-6018 (2007).* (22) Filed: Dec. 21, 2015 Leis et al. in Current Organic Chemistry 2, 131-144 (1998).* Angiolillo et al., Pharmacology of emerging novel platelet inhibi (65) Prior Publication Data tors, American Heart Journal, 2008, 156(2) Supp.
  • Intraocular Pressure Rise After Phacoemulsification Prophylactic

    Intraocular Pressure Rise After Phacoemulsification Prophylactic

    British Journal of Ophthalmology 1995; 79: 809-813 809 Intraocular pressure rise after phacoemulsification Br J Ophthalmol: first published as 10.1136/bjo.79.9.809 on 1 September 1995. Downloaded from with posterior chamber lens implantation: effect of prophylactic medication, wound closure, and surgeon's experience Thomas G Bomer, Wolf-Dietrich A Lagreze, Jens Funk Abstract pressure rises usually occur between 6 and 8 Aims-A prospective clinical trial was hours after surgery.6 carried out to evaluate the effect of Various antiglaucomatous agents have been prophylactic medication, the technique of used to prevent the intraocular pressure rise wound closure, and the surgeon's experi- after cataract extraction. Oral acetazolamide15 16 ence on the intraocular pressure rise after and topical timolol'6-19 lowered the pressure cataract extraction. rise in the early period after intracapsular and Methods-In 100 eyes, the intraocular extracapsular cataract extraction. Levobunolol pressure was measured before as well as proved to be superior to timolol 4-7 hours 2-4, 5-7, and 22-24 hours after phaco- after extracapsular cataract extraction.20 Apra- emulsification and posterior chamber lens clonidine lowered the intraocular pressure rise implantation. Each of 25 patients received after uncomplicated phacoemulsification21 and either 1% topical apraclonidine, 0.5%/o extracapsular cataract extraction22 23 when topical levobunolol, 500 mg oral acetazo- given 30 minutes to 1 hour before surgery, lamide, or placebo. Forty four eyes were whereas immediate postoperative treatment operated with sclerocorneal sutureless with apraclonidine was ineffective.22 24 Miotics tunnel and 56 eyes with corneoscleral are frequently used to promote miosis and incision and suture.
  • Brimonidine Tartrate; Brinzolamide

    Brimonidine Tartrate; Brinzolamide

    Contains Nonbinding Recommendations Draft Guidance on Brimonidine Tartrate ; Brinzolamide This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the Office of Generic Drugs. Active Ingredient: Brimonidine tartrate; Brinzolamide Dosage Form; Route: Suspension/drops; ophthalmic Strength: 0.2%; 1% Recommended Studies: One study Type of study: Bioequivalence (BE) study with clinical endpoint Design: Randomized (1:1), double-masked, parallel, two-arm, in vivo Strength: 0.2%; 1% Subjects: Males and females with chronic open angle glaucoma or ocular hypertension in both eyes. Additional comments: Specific recommendations are provided below. ______________________________________________________________________________ Analytes to measure (in appropriate biological fluid): Not applicable Bioequivalence based on (95% CI): Clinical endpoint Additional comments regarding the BE study with clinical endpoint: 1. The Office of Generic Drugs (OGD) recommends conducting a BE study with a clinical endpoint in the treatment of open angle glaucoma and ocular hypertension comparing the test product to the reference listed drug (RLD), each applied as one drop in both eyes three times daily at approximately 8:00 a.m., 4:00 p.m., and 10:00 p.m. for 42 days (6 weeks). 2. Inclusion criteria (the sponsor may add additional criteria): a. Male or nonpregnant females aged at least 18 years with chronic open angle glaucoma or ocular hypertension in both eyes b.
  • The In¯Uence of Medication on Erectile Function

    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.
  • Properties and Units in Clinical Pharmacology and Toxicology

    Properties and Units in Clinical Pharmacology and Toxicology

    Pure Appl. Chem., Vol. 72, No. 3, pp. 479–552, 2000. © 2000 IUPAC INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY AND LABORATORY MEDICINE SCIENTIFIC DIVISION COMMITTEE ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)# and INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY CHEMISTRY AND HUMAN HEALTH DIVISION CLINICAL CHEMISTRY SECTION COMMISSION ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)§ PROPERTIES AND UNITS IN THE CLINICAL LABORATORY SCIENCES PART XII. PROPERTIES AND UNITS IN CLINICAL PHARMACOLOGY AND TOXICOLOGY (Technical Report) (IFCC–IUPAC 1999) Prepared for publication by HENRIK OLESEN1, DAVID COWAN2, RAFAEL DE LA TORRE3 , IVAN BRUUNSHUUS1, MORTEN ROHDE1, and DESMOND KENNY4 1Office of Laboratory Informatics, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; 2Drug Control Centre, London University, King’s College, London, UK; 3IMIM, Dr. Aiguader 80, Barcelona, Spain; 4Dept. of Clinical Biochemistry, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland #§The combined Memberships of the Committee and the Commission (C-NPU) during the preparation of this report (1994–1996) were as follows: Chairman: H. Olesen (Denmark, 1989–1995); D. Kenny (Ireland, 1996); Members: X. Fuentes-Arderiu (Spain, 1991–1997); J. G. Hill (Canada, 1987–1997); D. Kenny (Ireland, 1994–1997); H. Olesen (Denmark, 1985–1995); P. L. Storring (UK, 1989–1995); P. Soares de Araujo (Brazil, 1994–1997); R. Dybkær (Denmark, 1996–1997); C. McDonald (USA, 1996–1997). Please forward comments to: H. Olesen, Office of Laboratory Informatics 76-6-1, Copenhagen University Hospital (Rigshospitalet), 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. E-mail: [email protected] Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted without the need for formal IUPAC permission on condition that an acknowledgment, with full reference to the source, along with use of the copyright symbol ©, the name IUPAC, and the year of publication, are prominently visible.
  • Table 1. Glaucoma Medications: Mechanisms, Dosing and Precautions Brand Generic Mechanism of Action Dosage/Avg

    Table 1. Glaucoma Medications: Mechanisms, Dosing and Precautions Brand Generic Mechanism of Action Dosage/Avg

    OPTOMETRIC STUDY CENTER Table 1. Glaucoma Medications: Mechanisms, Dosing and Precautions Brand Generic Mechanism of Action Dosage/Avg. % Product Sizes Side Effects Warnings Reduction CHOLINERGIC AGENTS Direct Pilocarpine (generic) Pilocarpine 1%, 2%, 4% Increases trabecular outflow BID-QID/15-25% 15ml Headache, blurred vision, myopia, retinal detachment, bronchiole constriction, Angle closure, shortness of breath, retinal narrowing of angle detachment Indirect Phospholine Iodide (Pfizer) Echothiophate iodide 0.125% Increases trabecular outflow QD-BID/15-25% 5ml Same as above plus cataractogenic iris cysts in children, pupillary block, Same as above, plus avoid prior to any increased paralysis with succinylcholine general anesthetic procedure ALPHA-2 AGONISTS Alphagan P (Allergan) Brimonidine tartrate 0.1%, 0.15% with Purite Decreases aqueous production, increases BID-TID/up to 26% 5ml, 10ml, 15ml Dry mouth, hypotension, bradycardia, follicular conjunctivitis, ocular irritation, Monitor for shortness of breath, dizziness, preservative uveoscleral outflow pruritus, dermatitis, conjunctival blanching, eyelid retraction, mydriasis, drug ocular redness and itching, fatigue allergy Brimonidine tartrate Brimonidine tartrate 0.15%, 0.2% Same as above Same as above 5ml, 10ml Same as above Same as above (generic) Iopidine (Novartis) Apraclonidine 0.5% Decreases aqueous production BID-TID/up to 25% 5ml, 10ml Same as above but higher drug allergy (40%) Same as above BETA-BLOCKERS Non-selective Betagan (Allergan) Levobunolol 0.25%, 0.5% Decreases
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE

    )&F1y3x PHARMACEUTICAL APPENDIX to THE

    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
  • Autonomic Nervous System Final.Pdf

    Autonomic Nervous System Final.Pdf

    University of Hawai‘i Hilo Pre- Nursing Program NURS 203 – General AUTONOMIC NERVOUS SYSTEM Pharmacology Danita Narciso Pharm D 1 LEARNING OBJECTIVES Understand the basic function of the autonomic nervous system (ANS) Know the neurotransmitters and receptors of each branch of the autonomic nervous system Understand if a tissue or organ is being activated by a certain branch of the ANS what the resulting action would be Understand how these two systems work in concert for daily living and situation of fight or flight 2 AUTONOMIC NERVOUS SYSTEM – WHERE IT FITS IN Nervous System Central Peripheral Somatic Autonomic (Skeletal Muscle) Parasympathetic Sympathetic Brain (cholinergic) ACh (adrenergic) NE Spinal Cord Nicotinic Alpha Beta α1, α2 β1, β2 Muscarinic 3 AUTONOMIC NERVOUS SYSTEM Fight or Flight Adrenergic Rest & Digest Norepinephrine Cholinergic Acetylcholine 4 AUTONOMIC NERVOUS SYSTEM – WHERE IT FITS IN Nervous System Central Peripheral Somatic Autonomic (Skeletal Muscle) Parasympathetic Sympathetic Brain (cholinergic) ACh (adrenergic) NE Spinal Cord Nicotinic Alpha Beta α1, α2 β1, β2 Muscarinic 5 AUTONOMIC NERVOUS SYSTEM (ANS) Parasympathetic NS Nicotinic Muscarinic Peripheral Sympathetic NS Alpha Autonomic Beta Nerves Parasympathetic Sympathetic Carrying ACh (cholinergic) ACh (adrenergic) NE Cholinergic Carrying NE Nicotinic Beta Adrenergic Alpha α1, α2 β1, β2 Muscarinic 6 AUTONOMIC NERVOUS SYSTEM (ANS) 7 AUTONOMIC NERVOUS SYSTEM (ANS) Ganglion: Group of nerve cell bodies. Connects pre and post ganglionic nerves. 8 AUTONOMIC NERVOUS SYSTEM (ANS) 9 AUTONOMIC NERVOUS SYSTEM (ANS) 10 AUTONOMIC NERVOUS SYSTEM (ANS) Preganglionic PNS ACh Preganglionic SNS ACh Post ganglionic Post ganglionic PNS SNS ACh NE 11 ACTIONS OF THE ANS - SNS Think fight or flight Dilate pupils Let in more light to see the bear Inhibit salivation This is no time to be hungry Relax airways Increase O2 intake Increase heart rate ….
  • NEW ZEALAND DATA SHEET 1. PRODUCT NAME IOPIDINE® (Apraclonidine Hydrochloride) Eye Drops 0.5%

    NEW ZEALAND DATA SHEET 1. PRODUCT NAME IOPIDINE® (Apraclonidine Hydrochloride) Eye Drops 0.5%

    NEW ZEALAND DATA SHEET 1. PRODUCT NAME IOPIDINE® (apraclonidine hydrochloride) Eye Drops 0.5%. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each mL of Iopidine Eye Drops 0.5% contains apraclonidine hydrochloride 5.75 mg, equivalent to apraclonidine base 5 mg. Excipient with known effect Benzalkonium chloride 0.1 mg per 1 mL as a preservative. For the full list of excipients, see section 6.1. 2. PHARMACEUTICAL FORM Eye drops, solution, sterile, isotonic. 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Iopidine Eye Drops 0.5% are indicated for short-term adjunctive therapy in patients on maximally tolerated medical therapy who require additional IOP reduction. Patients on maximally tolerated medical therapy who are treated with Iopidine Eye Drops 0.5% to delay surgery should have frequent follow up examinations and treatment should be discontinued if the intraocular pressure rises significantly. The addition of Iopidine Eye Drops 0.5% to patients already using two aqueous suppressing drugs (i.e. beta-blocker plus carbonic anhydrase inhibitor) as part of their maximally tolerated medical therapy may not provide additional benefit. This is because apraclonidine is an aqueous-suppressing drug and the addition of a third aqueous suppressant may not significantly reduce IOP. The IOP-lowering efficacy of Iopidine Eye Drops 0.5% diminishes over time in some patients. This loss of effect, or tachyphylaxis, appears to be an individual occurrence with a variable time of onset and should be closely monitored. The benefit for most patients is less than one month. 4.2. Dose and method of administration Dose One drop of Iopidine Eye Drops 0.5% should be instilled into the affected eye(s) three times per day.
  • Hyperlinked Region IX SOP for MWLCEMS

    Hyperlinked Region IX SOP for MWLCEMS

    2 Region IX 2 0 0 STANDARD OPERATING PROCEDURES/ 1 1 STANDING MEDICAL ORDERS 9 9 McHenry Western Lake County EMS System Healthcare delivery requires structure (people, equipment, education) and process (policies, protocols, procedures) that, when integrated, produce a system (programs, organizations, cultures) that leads to optimal outcomes (patient survival and safety, quality, satisfaction). An effective system of care comprises all of these elements—structure, process, system, and patient outcomes—in a framework of continuous quality improvement (AHA, 2015). These protocols have been developed and approved through a collaborative process involving the Advocate Lutheran General; Greater Elgin Area, McHenry Western Lake County, Northwest Community, Amita Saint Joseph Hospital, and Southern Fox Valley EMS Systems to reduce variation in practice and establish a Region-wide System of care. They shall be used: as the written practice guidelines/pathways of care approved by the EMS Medical Directors (EMS MDs) to be initiated by System EMS personnel for off-line medical control. as the standing medical orders to be used by Emergency Communications Registered Nurses (ECRNs) when providing on-line medical control (OLMC). in medium to large scale multiple patient incidents, given that the usual and customary forms of communication are contraindicated as specified in the Region IX disaster plan. System members are authorized to implement these orders to their scope of practice. OLMC communication shall be established without endangering the patient. Under no circumstances shall emergency prehospital care be delayed while attempting to establish contact with a hospital. In the event that communications cannot be established, EMS personnel shall continue to provide care to the degree authorized by their license, these protocols, drugs/equipment available, and their scope of practice granted by the EMS MD in that System.
  • General Prescription

    General Prescription

    GENERAL PRESCRIPTION LESSON 1. INTRODUCTION. PRESCRIPTION. SOLID MEDICINAL FORMS Objective: To study the structure of the prescription, learn the rules and get practical skills in writing out solid medicinal forms in prescription. To carry out practical tasks on prescriptions it is recommended to use Appendix 1. Key questions: 1. Pharmacology as a science and the basis of therapy. Main development milestones of modern pharmacology. Sections of Pharmacology. 2. The concept of medicinal substance, medicinal agent (medicinal drug, drug), medicinal form. 3. The concept of the pharmacological action and types of the action of drugs. 4. The sources of obtaining drugs. 5. International and national pharmacopeia, its content and purpose. 6. Pharmacy. Rules of drug storage and dispensing. 7. Prescription and its structure. Prescription forms. General rules for writing out a prescription. State regulation of writing out and dispensing drugs. 8. Name of medicinal products (international non-proprietary name - INN, trade name). 9. Peculiarities of writing out narcotic, poisonous and potent substances in prescription. 10. Drugs under control. Drugs prohibited for prescribing. 11. Solid medicinal forms: tablets, dragee (pills), powders, capsules. Their characteristics, advantages and disadvantages. Rules of prescribing. Write out prescriptions for: 1. 5 powders of Codeine 0.015 g. 1 powder orally twice a day. 2. 10 powders of Didanosine 0.25 g in sachets to prepare solution for internal use. Accept inside twice a day one sachet powder after dissolution in a glass of boiled water. 3. 50 mg of Alteplase powder in the bottle. Dissolve the content of the bottle in 50 ml of saline. First 15 ml introduce intravenously streamly, then intravenous drip.
  • Sustained-Release Compositions Containing Cation Exchange Resins and Polycarboxylic Polymers

    Sustained-Release Compositions Containing Cation Exchange Resins and Polycarboxylic Polymers

    ~" ' Nil II II II II Ml Ml INI MINI II J European Patent Office *»%r\ n » © Publication number: 0 429 732 B1 Office_„. europeen des brevets © EUROPEAN PATENT SPECIFICATION © Date of publication of patent specification: 16.03.94 © Int. CI.5: A61 K 9/06, A61 K 9/1 8, A61 K 47/32 © Application number: 89312590.6 @ Date of filing: 01.12.89 © Sustained-release compositions containing cation exchange resins and polycarboxylic polymers. @ Date of publication of application: (73) Proprietor: ALCON LABORATORIES, INC. 05.06.91 Bulletin 91/23 6201 South Freeway Fort Worth Texas 76107(US) © Publication of the grant of the patent: 16.03.94 Bulletin 94/11 @ Inventor: Janl, Rajni 4621 Briarhaven Road © Designated Contracting States: Fort Worth, Texas 76109(US) AT BE CH DE FR GB IT LI LU NL SE Inventor: Harris, Robert Gregg 3224 Westcliff Road W. © References cited: Fort Worth, Texas 76109(US) EP-A- 0 254 822 J.Pharm. SCI., vol. 60, no. 9, September 1971, © Representative: Jump, Timothy John Simon et pages 1343-1345 A. HEYD:"Polymer-drug in- al teraction: stability of aqueous gels contain- Venner Shipley & Co. ing neomycin sulfate" 20 Little Britain London EC1A 7DH (GB) 00 CM CO o> CM 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. Notice of opposition CL shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee LU has been paid (Art.