Eicosanoids & Platelet Activating Factor
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E001466.Full.Pdf
Editorial BMJ Glob Health: first published as 10.1136/bmjgh-2019-001466 on 11 April 2019. Downloaded from WHO recommendations on uterotonics for postpartum haemorrhage prevention: what works, and which one? Joshua P Vogel, 1,2 Myfanwy Williams,3 Ioannis Gallos,4 Fernando Althabe,1 Olufemi T Oladapo1 To cite: Vogel JP, THE GLOBAL BURDEN OF POSTPARTUM trials of tranexamic acid for PPH treatment Williams M, Gallos I, et al. HAEMORRHAGE and a heat-stable formulation of carbetocin WHO recommendations on 6–12 uterotonics for postpartum Obstetric haemorrhage, especially post- for PPH prevention. The increasing haemorrhage prevention: partum haemorrhage (PPH), was responsible number of PPH prevention and management what works, and which for more than a quarter of the estimated 303 options makes it challenging for providers one?BMJ Glob Health 000 maternal deaths that occurred globally in and health system stakeholders to choose 2019;4:e001466. doi:10.1136/ 2015.1 PPH—commonly defined as a blood where and how to invest limited resources in bmjgh-2019-001466 loss of 500 mL or more within 24 hours after order to optimise health outcomes. birth—affects about 6% of all women giving Multiple uterotonics have been eval- Handling editor Seye Abimbola birth.1 Uterine atony is the most common uated for PPH prevention over the past Received 4 February 2019 cause of PPH, but it can also be caused by four decades, including oxytocin receptor Revised 10 March 2019 genital tract trauma, retained placental tissue agonists (oxytocin and carbetocin), prosta- Accepted 16 March 2019 or maternal bleeding disorders. The majority glandin analogues (misoprostol, sulprostone, of women who experience PPH have no iden- carboprost), ergot alkaloids (such as ergo- tifiable risk factor, meaning that PPH preven- metrine/methylergometrine) and combina- tion programmes rely on universal use of PPH tions of these (oxytocin plus ergometrine, © Author(s) (or their prophylaxis for all women in the immediate or oxytocin plus misoprostol). -
New Zealand Data Sheet
NEW ZEALAND DATA SHEET 1. PRODUCT NAME PROSTIN 15M 250 microgram (µg)/mL Solution for Injection 2. QUALITATIVE AND QUANTITIATIVE COMPOSITION Each 1 mL contains 250 μg carboprost or 332 μg carboprost (as tromethamine). Excipient(s) with known effect Each 1 mL contains 9.45 mg/mL benzyl alcohol (added as preservative). For the full list of excipients, see section 6.1. 3. PHARMACEUTIAL FORM Solution for Injection. PROSTIN 15M is a clear colourless solution. 4. CLINCAL PARTICUALRS 4.1 Therapeutic indications PROSTIN 15M is indicated for the treatment of postpartum haemorrhage due to uterine atony which has not responded to conventional methods of management. Prior treatment should include the use of intravenously administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations. Studies have shown that in such cases, the use of PROSTIN 15M has resulted in satisfactory control of haemorrhage, although it is unclear whether or not ongoing or delayed effects of previously administered embolic agents have contributed to the outcome. In a high proportion of cases, PROSTIN 15M used in this manner has resulted in the cessation of life threatening bleeding and the avoidance of emergency surgical intervention. 4.2 Dose and method of administration Dose An initial dose of 250 µg (1 mL) is to be given by deep intramuscular injection. In clinical trials, it was found that the majority of successful cases (73%) responded to single injections. In some selected cases, however, multiple dosing at intervals of 15 to 90 minutes was carried out with successful outcome. The need for additional injections and the interval at which these should be given can be determined only by the attending physicians as dictated by the course of clinical events. -
Role of Thrombin and Thromboxane A2 in Reocclusion Following Coronary
Proc. Natl. Acad. Sci. USA Vol. 86, pp. 7585-7589, October 1989 Medical Sciences Role of thrombin and thromboxane A2 in reocclusion following coronary thrombolysis with tissue-type plasminogen activator (thrombolytic therapy/coronary thrombosis/platelet activation/reperfusion) DESMOND J. FITZGERALD*I* AND GARRET A. FITZGERALD* Divisions of *Clinical Pharmacology and tCardiology, Vanderbilt University, Nashville, TN 37232 Communicated by Philip Needleman, June 28, 1989 (receivedfor review April 12, 1989) ABSTRACT Reocclusion of the coronary artery occurs against the prothrombinase formed on the platelet surface after thrombolytic therapy of acute myocardlal infarction (13) and the neutralization ofheparin by platelet factor 4 (14) despite routine use of the anticoagulant heparin. However, and thrombospondin (15), proteins released by activated heparin is inhibited by platelet activation, which is greatly platelets. enhanced in this setting. Consequently, it is unclear whether To address the role of thrombin during coronary throm- thrombin induces acute reocclusion. To address this possibility, bolysis, we have examined the effect of a specific thrombin we examined the effect of argatroban {MCI9038, (2R,4R)- inhibitor, argatroban {MCI9038, (2R,4R)-4-methyl-1-[N-(3- 4-methyl-l-[Na-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfo- methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2- nyl)-L-arginyl]-2-piperidinecarboxylic acid}, a specific throm- piperidinecarboxylic acid} on the response to tissue plasmin- bin inhibitor, on the response to tissue-type plasminogen ogen activator (t-PA) in a closed-chest canine model of activator in a dosed-chest canine model of coronary thrombo- coronary thrombosis. MCI9038, an argimine derivative which sis. MCI9038 prolonged the thrombin time and shortened the binds to a hydrophobic pocket close to the active site of time to reperfusion (28 + 2 min vs. -
Tachykinins in the Gut. Part II. Roles in Neural Excitation, Secretion and Inflammation
Pfxnma~ol.Ther. Vol. 73, No. 3, pp. 219-263, 1997 ISSN 0163-7258197$32.00 CopyrIght0 1997 ElsevierScience Inc. PI1 SO163-7258(96)00196-9 ELSEVIER A.wciate Editor: 1. We&r Tachykinins in the Gut. Part II. Roles in Neural Excitation, Secretion and Inflammation Peter Holzer” and Ulrike Holw-er-Pets&e DEPARTMENT0FEXPERIMENTALANDCLINlCALPHARMACOLOGY,UNIVERSlTYOFGRAZ,UNlVERSITiiTSPLATZ4,A-8010GRAZ,AUSTRIA ABSTRACT. The preprotachykinin-A gene-derived peptides substance (substance P; SP) and neurokinin (NK) A are expressed in intrinsic enteric neurons, which supply all layers of the gut, and extrinsic primary afferent nerve fibers, which innervate primarily the arterial vascular system. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK,, NKr and NK, receptors. Within the enteric nervous system, SP and NKA are likely to mediate, or comediate, slow synaptic transmission and to modulate neuronal excitability via stimulation of NK, and NK, receptors. In the intestinal mucosa, tachykinins cause net secretion of fluid and electrolytes, and it appears as if SP and NKA play a messenger role in intramural secretory reflex pathways. Secretory processes in the salivary glands and pancreas are likewise influenced by tachykinins. The gastrointestinal arterial system may be dilated or constricted by tachykinins, whereas constriction and an increase in the vascular permeability are the only effects seen in the venous system. Various gastrointestinal disorders are associated with distinct changes in the tachykinin system, and there is increasing evidence that tachykinins participate in the hypersecretory, vascular and immunological disturbances associated with infection and inflammatory bowel disease. In a therapeutic perspective, it would seem conceivable that tachykinin antagonists could be exploited as antidiarrheal, anti- inflammatory and antinociceptive drugs. -
Product Monograph
PRODUCT MONOGRAPH HEMABATE® STERILE SOLUTION (carboprost tromethamine injection USP) 250 µg/mL Prostaglandin Pfizer Canada Inc. Date of Revision: 17,300 Trans-Canada Highway February 21, 2014 Kirkland, Quebec H9J 2M5 Control No. 170114 ® Pfizer Enterprises SARL Pfizer Canada Inc, Licensee © Pfizer Canada Inc. 2014 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION ..........................................................3 SUMMARY OF PRODUCT INFORMATION ..................................................................3 INDICATIONS AND CLINICAL USE ..............................................................................3 CONTRAINDICATIONS ...................................................................................................4 WARNINGS AND PRECAUTIONS ..................................................................................4 ADVERSE REACTIONS ....................................................................................................7 DRUG INTERACTIONS ..................................................................................................10 DOSAGE AND ADMINISTRATION ..............................................................................11 OVERDOSAGE ................................................................................................................11 ACTION AND CLINICAL PHARMACOLOGY ............................................................12 STORAGE AND STABILITY ..........................................................................................12 DOSAGE -
Preparation and Chiral HPLC Separation of the Enantiomeric Forms of Natural Prostaglandins
Article Preparation and Chiral HPLC Separation of the Enantiomeric Forms of Natural Prostaglandins Márton Enesei 1,2,László Takács 2, Enik˝oTormási 3, Adrienn Tóthné Rácz 3, Zita Róka 3, Mihály Kádár 3 and Zsuzsanna Kardos 2,* 1 Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, M˝uegyetemrakpart 3, 1111 Budapest, Hungary; [email protected] 2 CHINOIN, a member of Sanofi Group, PG Development, Tó utca 1-5, 1045 Budapest, Hungary; laszlo.takacs@sanofi.com 3 CHINOIN, a member of Sanofi Group, PG Analytics, Tó utca 1-5, 1045 Budapest, Hungary; robertne.tormasi@sanofi.com (E.T.); adrienn.tothneracz@sanofi.com (A.T.R.); zita.roka@sanofi.com (Z.R.); mihaly.kadar@sanofi.com (M.K.) * Correspondence: zsuzsanna.kardos@sanofi.com Received: 15 June 2020; Accepted: 10 August 2020; Published: 18 August 2020 Abstract: Four enantiomeric forms of natural prostaglandins, ent-PGF α (( )-1), ent-PGE ((+)-2) 2 − 2 ent-PGF α (( )-3), and ent-PGE ((+)-4) have been synthetized in gram scale by Corey synthesis used 1 − 1 in the prostaglandin plants of CHINOIN, Budapest. Chiral HPLC methods have been developed to separate the enantiomeric pairs. Enantiomers of natural prostaglandins can be used as analytical standards to verify the enantiopurity of synthetic prostaglandins, or as biomarkers to study oxidation processes in vivo. Keywords: preparation; ent-PGF2α; ent-PGF1α; ent-PGE2; ent-PGE1; chiral HPLC; enantiomeric separation; mirror images; enantiopurity 1. Introduction Interest in the field of prostaglandins has been steadily growing since the basic work of Bergström Samuelsson, and Vane [1–3]. Their discoveries revealed the structure, the enzyme-controlled biochemical synthesis from arachidonic acid, and the main physiological effects of prostaglandins as well as their related substances. -
Postpartum Haemorrhage
Guideline Postpartum Haemorrhage Immediate Actions Call for help and escalate as necessary Initiate fundal massage Focus on maternal resuscitation and identifying cause of bleeding Determine if placenta still in situ Tailor pharmacological management to causation and maternal condition (see orange box). Complete a SAS form when using carboprost. Pharmacological regimen (see flow sheet summary) Administer third stage medicines if not already done so. Administer ergometrine 0.25mg both IM and slow IV (contraindicated in hypertension) IF still bleeding: Administer tranexamic acid- 1g IV in 10mL via syringe driver set at 1mL/minute administered over 10 minutes OR as a slow push over 10 minutes. Administer carboprost 250micrograms (1mL) by deep intramuscular injection Administer loperamide 4mg PO to minimise the side-effect of diarrhoea Administer antiemetic ondansetron 4mg IV, if not already given Prophylaxis Once bleeding is controlled, administer misoprostol 600microg buccal and initiate an infusion of oxytocin 40IU in 1L Hartmann’s at a rate of 250mL/hr for 4 hours. Flow chart for management of PPH Carboprost Bakri Balloon Medicines Guide Ongoing postnatal management after a major PPH 1. Purpose This document outlines the guideline details for managing primary postpartum haemorrhage at the Women’s. Where processes differ between campuses, those that refer to the Sandringham campus are differentiated by pink italic text or have the heading Sandringham campus. For guidance on postnatal observations and care after a major PPH, please refer to the procedure ‘Postpartum Haemorrhage - Immediate and On-going Postnatal Care after Major PPH 2. Definitions Primary postpartum haemorrhage (PPH) is traditionally defined as blood loss greater than or equal to 500 mL, within 24 hours of the birth of a baby (1). -
Effect of Prostanoids on Human Platelet Function: an Overview
International Journal of Molecular Sciences Review Effect of Prostanoids on Human Platelet Function: An Overview Steffen Braune, Jan-Heiner Küpper and Friedrich Jung * Institute of Biotechnology, Molecular Cell Biology, Brandenburg University of Technology, 01968 Senftenberg, Germany; steff[email protected] (S.B.); [email protected] (J.-H.K.) * Correspondence: [email protected] Received: 23 October 2020; Accepted: 23 November 2020; Published: 27 November 2020 Abstract: Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D2 (PGD2), prostaglandin-E1, -E2 and E3 (PGE1, PGE2, PGE3), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane-A2 (TXA2) on platelet activation and aggregation via their respective receptors. Keywords: prostacyclin; thromboxane; prostaglandin; platelets 1. Introduction Hemostasis is a complex process that requires the interplay of multiple physiological pathways. Cellular and molecular mechanisms interact to stop bleedings of injured blood vessels or to seal denuded sub-endothelium with localized clot formation (Figure1). -
Disruption of Protein-Protein Interactions
Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2016 Supplementary data Disruption of Protein-Protein Interactions: Hot spot detection, structure-based virtual screening and in vitro testing for anti-cancer drug target – Survivin Sailu Sarvagalla,a Chun Hei Antonio Cheung,b,c Ju-Ya Tsai,b Hsing Pang Hsieh,d and Mohane Selvaraj Coumara,* aCentre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India. bDepartment of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan R.O.C. cInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan R.O.C. dInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan, ROC. * Corresponding author: M.S. Coumar; Phone, +91-413-2654950; fax, +91-413-2655211; e-mail, [email protected] S1 Contents A. Figures....................................................................................................................................S3 B. Tables…………………………………………………………………………………….... S6 S2 a Borealin hot spots per-residue energy decomposition 1 0 -1 l -2 o m -3 / l a c -4 k -5 G Δ -6 -7 -8 -9 Residues b INCENP hot spots per-residue energy decomposition 0 l -0.5 o m -1 / l a c -1.5 k -2 G Δ -2.5 -3 Residues Figure S1. Hot spot residue-wise energy contribution for the complex (a) Borealin hot spot residues energy contribution and (b) INCENP protein hot spot residues energy contribution. S3 Figure S2. Mapping of the energetically important residues in CPC interface region. Hot spots, warm hot spots and null spots are represented in red, gold and light green color, respectively. -
PPH 2Nd Edn #23.Vp
43 Standard Medical Therapy for Postpartum Hemorrhage J. Unterscheider, F. Breathnach and M. Geary INTRODUCTION firm contraction of the organ. If severe haemorrhage has already set in, it is highly recommended that the drug should Failure of the uterus to contract and retract following be given by the intravenous route. For this purpose one-third childbirth has for centuries been recognized as the of the standard size ampoule may be injected or, for those most striking cause of postpartum hemorrhage (PPH) who wish accurate dosage, a special ampoule containing and complicates up to 10% of pregnancies globally. In 0.125 mg is manufactured. An effect may be looked for in less the developing world, PPH is responsible for one than one minute.’ maternal death every 7 minutes1. Another uterotonic agent, oxytocin, the hypothalamic In the 19th century, uterine atony was treated by polypeptide hormone released by the posterior pitu- intrauterine placement of various agents with the aim itary, was discovered in 1909 by Sir Henry Dale8 and of achieving a tamponade effect. ‘A lemon imperfectly synthesized in 1954 by du Vigneaud9. The develop- quartered’ or ‘a large bull’s bladder distended with ment of oxytocin constituted the first synthesis of water’ were employed for this purpose, with apparent a polypeptide hormone and gained du Vigneaud a success. Douching with vinegar or iron perchloride Nobel Prize for his work. was also reported2,3. Historically, the first uterotonic The third group of uterotonics comprises the ever- drugs were ergot alkaloids, -
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). -
The Value of Urotensin II in Patients with Left-Sided Rheumatic Valvular Regurgitation
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector The Egyptian Heart Journal (2016) xxx, xxx–xxx HOSTED BY Egyptian Society of Cardiology The Egyptian Heart Journal www.elsevier.com/locate/ehj www.sciencedirect.com The value of urotensin II in patients with left-sided rheumatic valvular regurgitation Ibrahim Elmadbouh a,*, Mahmoud Ali Soliman b, Ahmed Abdallah Mostafa c, Haitham Ahmed Heneish d a Biochemistry Department, Faculty of Medicine, Menoufia University, Egypt b Cardiology Department, Faculty of Medicine, Menoufia University, Egypt c Cardiology Department, Police Academy Hospital, Egypt d Cardiology Department, Nasser Institute Hospital, Egypt Received 20 May 2016; accepted 24 September 2016 KEYWORDS Abstract Aims: Rheumatic valve diseases are most common etiological valve diseases in develop- Urotensin II; ing countries. Urotensin II is cardiovascular autacoid/hormone and may be associated with patients Mitral regurgitation; of heart valve diseases. The present study was to measure plasma urotensin II concentrations in Cardiovascular autacoid patients with left-sided rheumatic valve diseases such as mitral regurgitation (MR) and aortic regur- hormone gitation (AR), and to examine its correlation with severity of valve impairment, function (New York Heart association, NYHA) class and pulmonary artery pressure (PAP). Methods and results: Sixty patients with moderate to severe rheumatic left-sided valve regurgitation and 20 healthy controls were selected after performing the echocardiography. Plasma urotensin II level was measured in all subjects. The patients with MR and AR were significantly increased of left ventricular end diastolic dimension (LVEDD), left ventricular end systolic dimension (LVESD), left atrial diameter, PAP, but decreased of EF% versus the controls.