Betamethasone and Salicylic Acid
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Synthesis of Aspirin
SYNTHESIS OF ASPIRIN I. OBJECTIVES AND BACKGROUND You will: synthesize acetylsalicylic acid (aspirin) by carrying out a simple organic reaction, separate your product from the reaction mixture by vacuum filtration, purify your product by recrystallization, perform a chemical test to identify the change in functional group from reactant to product, and determine the success of your synthesis by calculating the percentage yield of your product. INTRODUCTION Aspirin is one of the most widely used medications in the world. It is employed as an analgesic (pain relief), an anti-pyretic (fever control) and an anti-inflammatory. More recently, studies have indicated that daily intake of small doses of aspirin can lower the risk of heart attack and stroke in high-risk patients. The history of aspirin and its precursor dates back to ancient times. Documents attributed to Hippocrates, the father of modern medicine, from the 4th century B.C. refer to the alleviation of pain by chewing on the bark of a willow tree or ingesting a powder made from the bark and leaves of the willow. This remedy was passed on from generation to generation. Fast forward now to the 19th century, where the field of organic chemistry began to experience tremendous growth. By 1838, chemists had managed to isolate, purify and identify the component of willow bark that provided the analgesic benefit. The compound was named salicylic acid, which was based on the genus name of the willow. Efforts to market salicylic acid met with failure, due to an unfortunate side effect-- prolonged ingestion of salicylic acid led to stomach pain, and in some cases, ulcers. -
Pharmacokinetics of Salicylic Acid Following Intravenous and Oral Administration of Sodium Salicylate in Sheep
animals Article Pharmacokinetics of Salicylic Acid Following Intravenous and Oral Administration of Sodium Salicylate in Sheep Shashwati Mathurkar 1,*, Preet Singh 2 ID , Kavitha Kongara 2 and Paul Chambers 2 1 1B, He Awa Crescent, Waikanae 5036, New Zealand 2 School of Veterinary Sciences, College of Sciences, Massey University, Palmerston North 4474, New Zealand; [email protected] (P.S.); [email protected] (K.K.); [email protected] (P.C.) * Correspondence: [email protected]; Tel.: +64-221-678-035 Received: 13 June 2018; Accepted: 16 July 2018; Published: 18 July 2018 Simple Summary: Scarcity of non-steroidal anti-inflammatory drugs (NSAID) to minimise the pain in sheep instigated the current study. The aim of this study was to know the pharmacokinetic parameters of salicylic acid in New Zealand sheep after administration of multiple intravenous and oral doses of sodium salicylate (sodium salt of salicylic acid). Results of the study suggest that the half-life of the drug was shorter and clearance was faster after intravenous administration as compared to that of the oral administration. The minimum effective concentration required to produce analgesia in humans (16.8 µL) was achieved in sheep for about 0.17 h in the current study after intravenous administration of 100 and 200 mg/kg body weight of sodium salicylate. However, oral administration of these doses failed to achieve the minimum effective concentration as mentioned above. This study is of significance as it adds valuable information on pharmacokinetics and its variation due to breed, species, age, gender and environmental conditions. -
Salsalate Tablets, USP 500 Mg and 750 Mg Rx Only
SALSALATE RX- salsalate tablet, film coated ANDAPharm LLC Disclaimer: This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA. For further information about unapproved drugs, click here. ---------- Salsalate Tablets, USP 500 mg and 750 mg Rx Only Cardiovascular Risk NSAIDs may cause an increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. (See WARNINGS and CLINICAL TRIALS). Salsalate tablets, USP is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (See WARNINGS). Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. (See WARNINGS). DESCRIPTION Salsalate, is a nonsteroidal anti-inflammatory agent for oral administration. Chemically, salsalate (salicylsalicylic acid or 2-hydroxybenzoic acid, 2-carboxyphenyl ester) is a dimer of salicylic acid; its structural formula is shown below. Chemical Structure: Inactive Ingredients: Colloidal Silicon Dioxide, D&C Yellow #10 Aluminum Lake, Hypromellose, Microcrystalline Cellulose, Sodium Starch Glycolate, Stearic Acid, Talc, Titanium Dioxide, Triacetin. CLINICAL PHARMACOLOGY Salsalate is insoluble in acid gastric fluids (<0.1 mg/mL at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. -
Salicylate, Diflunisal and Their Metabolites Inhibit CBP/P300 and Exhibit Anticancer Activity
RESEARCH ARTICLE Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity Kotaro Shirakawa1,2,3,4, Lan Wang5,6, Na Man5,6, Jasna Maksimoska7,8, Alexander W Sorum9, Hyung W Lim1,2, Intelly S Lee1,2, Tadahiro Shimazu1,2, John C Newman1,2, Sebastian Schro¨ der1,2, Melanie Ott1,2, Ronen Marmorstein7,8, Jordan Meier9, Stephen Nimer5,6, Eric Verdin1,2* 1Gladstone Institutes, University of California, San Francisco, United States; 2Department of Medicine, University of California, San Francisco, United States; 3Department of Hematology and Oncology, Kyoto University, Kyoto, Japan; 4Graduate School of Medicine, Kyoto University, Kyoto, Japan; 5University of Miami, Gables, United States; 6Sylvester Comprehensive Cancer Center, Miami, United States; 7Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; 8Department of Biochemistry and Biophysics, Abramson Family Cancer Research Institute, Philadelphia, United States; 9Chemical Biology Laboratory, National Cancer Institute, Frederick, United States Abstract Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation of NF-kB activity, and direct activation of AMPK. However, the full spectrum of their activities is incompletely understood. Here we show that salicylate specifically inhibits CBP and p300 lysine acetyltransferase activity in vitro by direct *For correspondence: everdin@ competition with acetyl-Coenzyme A at the catalytic site. We used a chemical structure-similarity gladstone.ucsf.edu search to identify another anti-inflammatory drug, diflunisal, that inhibits p300 more potently than salicylate. At concentrations attainable in human plasma after oral administration, both salicylate Competing interests: The and diflunisal blocked the acetylation of lysine residues on histone and non-histone proteins in cells. -
Opinion on Salicylic Acid (CAS 69-72-7) - Submission I - Corrigendum of 20-21 June 2019
SCCS/1601/18 Final Opinion Corrigendum of 20-21 June 2019 Scientific Committee on Consumer Safety SCCS OPINION ON salicylic acid (CAS 69-72-7) Submission I The SCCS adopted the final Opinion by written procedure on 21 December 2018 Corrigendum of 20-21 June 2019 SCCS/1601/18 Final Opinion Opinion on salicylic acid (CAS 69-72-7) - Submission I - Corrigendum of 20-21 June 2019 ___________________________________________________________________________________________ ACKNOWLEDGMENTS Members of the Working Group are acknowledged for their valuable contribution to this Opinion. The members of the Working Group are: For the preliminary and the final Opinion The SCCS members: Dr U. Bernauer Dr L. Bodin Prof. Q. Chaudhry (SCCS Chair) Prof. P.J. Coenraads (SCCS Vice-Chair and Chairperson of the WG) Prof. M. Dusinska Dr J. Ezendam Dr E. Gaffet Prof. C. L. Galli Dr B. Granum Prof. E. Panteri (Rapporteur) Prof. V. Rogiers (SCCS Vice-Chair) Dr Ch. Rousselle Dr M. Stepnik Prof. T. Vanhaecke Dr S. Wijnhoven External experts: Dr A. Simonnard Dr A. Koutsodimou Prof. W. Uter The additional contribution of the following external expert is gratefully acknowledged: Dr. N. von Goetz All Declarations of Working Group members are available on the following webpage: http://ec.europa.eu/health/scientific_committees/experts/declarations/sccs_en.htm This Opinion has been subject to a commenting period of a minimum eight weeks after its initial publication (from 10 September until 14 November 2018). Comments received during this time were considered by the SCCS. For this Opinion, comments received resulted in the following main changes: sections 3.3.1.1. -
Non Steroidal Anti-Inflammatory Drugs
Non Steroidal Anti‐inflammatory Drugs (NSAIDs) 4 signs of inflammation • Redness ‐ due to local vessel dilatation • Heat ‐ due to local vessel dilatation • Swelling – due to influx of plasma proteins and phagocytic cells into the tissue spaces • Pain – due to local release of enzymes and increased tissue pressure NSAIDs • Cause relief of pain ‐. analgesic • Suppress the signs and symptoms of inflammation. • Exert antipyretic action. • Useful in pain related to inflammation. Esp for superficial/integumental pain . Classification of NSAIDs • Salicylates: aspirin, Sodium salicylate & diflunisal. • Propionic acid derivatives: ibuprofen, ketoprofen, naproxen. • Aryl acetic acid derivatives: diclofenac, ketorolac • Indole derivatives: indomethacin, sulindac • Alkanones: Nabumetone. • Oxicams: piroxicam, tenoxicam Classification of NSAIDs ….. • Anthranilic acid derivatives (fenamates): mefenamic acid and flufenamic acid. • Pyrazolone derivatives: phenylbutazone, oxyphenbutazone, azapropazone (apazone) & dipyrone (novalgine). • Aniline derivatives (analgesic only): paracetamol. Clinical Classif. • Non selective Irreversible COX inhibitors • Non slective Reversible COX inhibitors • Preferential COX 2 inhibitors • 10‐20 fold cox 2 selective • meloxicam, etodolac, nabumetone • Selective COX 2 inhibitors • > 50 fold COX ‐2 selective • Celecoxib, Etoricoxib, Rofecoxib, Valdecoxib • COX 3 Inhibitor? PCM Cyclooxygenase‐1 (COX‐1): -constitutively expressed in wide variety of cells all over the body. -"housekeeping enzyme" -ex. gastric cytoprotection, hemostasis Cyclooxygenase‐2 (COX‐2): -inducible enzyme -dramatically up-regulated during inflammation (10-18X) -constitutive : maintains renal blood flow and renal electrolyte homeostasis Salicylates Acetyl salicylic acid (aspirin). Kinetics: • Well absorbed from the stomach, more from upper small intestine. • Distributed all over the body, 50‐80% bound to plasma protein (albumin). • Metabolized to acetic acid and salicylates (active metabolite). • Salicylate is conjugated with glucuronic acid and glycine. • Excreted by the kidney. -
Synthesis of Some Aiæides of Gentisio Aoid Dissertation
SYNTHESIS OF SOME AIÆIDES OF GENTISIO AOID DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By ALLEN I. DHŒS, B. S., M. Sc, ****** The Ohio State Uhiversity 1958 Approved by: Department of Pharmaoy ACKNOV/LEDaMTS I wish to acknowledge the generous advice and assistance rendered by Dr. Frank V/. Bope, Associate Professor of Pharmacy, in the development of this dissertation. To the American Foundation for Pharmaceutical Education, I wish to express my gratitude for extending to me financial assistance in the form of a Fellowship— without this assistance it would not have been possible for me to complete my graduate studies. To the members of the faculty of the College of Pharmacy of The Ohio State University, I wish to express my sincere appreciation for their guidance throughout my graduate studies, I also wish to eatress my sincere thanks and grate ful appreciation to all others who have assisted me in any way. As a final note, I would like to thank my wife, Charlotte, for her wonderful moral support during the com pletion of my graduate studies; for behind every man there is his wife. ii TABLE OF CONTENTS Page INTRODUCTION .......... 1 DISCUSSION OF LITERATURE General ........................ 3 Some New Gentisio Aoid Derivatives 15 Preparation of Amides .......... 16 GENERAL PROCEDURES 21 EXPERIMENTAL 23 Preparation of 2,5- Dimethoiybenzoio Acid . , 23 Preparation of 2,5- Dimethoxybenzoyl Chloride 26 Classification of N- Substituted Amides Prepared 27 Monosubstituted Amides of 2,5- Dimethoxybenzoio A o i d ........................................ 29 Alkyl ..................................... -
Aspirin and Other Anti-Inflammatory Drugs
Thorax 2000;55 (Suppl 2):S3–S9 S3 Aspirin and other anti-inflammatory drugs Thorax: first published as 10.1136/thorax.55.suppl_2.S3 on 1 October 2000. Downloaded from Sir John Vane Historical introduction inhibiting COX, thereby reducing prosta- Salicylic acid, the active substance in plants glandin formation, providing a unifying expla- used for thousands of years as medicaments, nation for their therapeutic actions and their was synthesised by Kolbe in Germany in 1874. side eVects. This also firmly established certain MacLagan1 and Stricker2 showed that it was prostaglandins as important mediators of eVective in rheumatic fever. A few years later inflammatory disease (see reviews by Vane and sodium salicylate was also in use as a treatment Botting7 and Vane et al8). COX first cyclises for chronic rheumatoid arthritis and gout as arachidonic acid to form prostaglandin (PG) well as an antiseptic compound. G2 and the peroxidase part of the enzyme then Felix HoVman was a young chemist working reduces PGG2 to PGH2. at Bayer. Legend has it that his father, who was taking salicylic acid to treat his arthritis, Discovery of COX-2 complained to his son about its bitter taste. Over the next 20 years several groups postu- Felix responded by adding an acetyl group to lated the existence of isoforms of COX. Then salicylic acid to make acetylsalicylic acid. Rosen et al,9 studying COX in epithelial cells Heinrich Dreser, the Company’s head of phar- from the trachea, found an increase in activity macology, showed it to be analgesic, anti- of COX during prolonged cell culture. -
Nsaids: Friend Or Foe in the Battle Against Pain?
NSAIDs: Friend or Foe in the Battle against Pain? Presented by June E. Oliver, MSN, CCNS, AP-PMN, APRN/CNS NO Conflicts of Interest to Declare Old & Natural! 1763 fever Rx- bark/leaves of willow/myrtle (salicylic acid) 1859-chemical structure discovered & synthesized in Germany 1914- Bayer Co. started manufacturing ASA Current sales 11 billion ( 2014) Early 20 th Century- NSAIDs discovered 1971- discovered mechanism of action of NSAIDs by John R. Vane 1990s-COX-2 isoenzyme successfully identified & cloned Current- script & OTC use = > 30 billion doses/yr of NSAIDs In US Numbers increase every year Prostaglandin (PG) Mechanism of Action Prostaglandins( PG) - lipids derived from acids: i.e. arachidonic (AA), lineolic, others PGs have Variety of functions Constitutive GI mucosal protection Kidney function Trauma response Cell membrane trauma- releases AA & COX enzyme converts to PGs inflammation Peripheral & central sensitization of nociceptors to mechanical & chemical stimuli Pyretic response PGs rise in CSF w/ pyrogen introduction Although not an NSAID, acetaminophen blocks brain PG synthetase (COX3 inhibition ) Cyclo-oxygenase (COX): “The Convertors” Cyclo-oxygenase 1&2 = isoenzymes that convert AA to PGs (i.e. prostacyclin, & thromboxanes) COX-1 Expressed regularly- provides gastric & duodenal mucosal protection Stimulates production mucin/bicarbonate/phospholipid that covers surface of stomach Enhances GI mucosal blood flow w/ local vasodilation Enhanced epithelial cell reproduction & migration towards lumen Can be induced -
The Drug Salicylamide Is an Antagonist of the Aryl Hydrocarbon Receptor That Inhibits Signal Transduction Induced by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin
[CANCER RESEARCH 64, 429–434, January 1, 2004] The Drug Salicylamide Is an Antagonist of the Aryl Hydrocarbon Receptor That Inhibits Signal Transduction Induced by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Christopher J. MacDonald, Henry P. Ciolino, and Grace Chao Yeh Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, Maryland ABSTRACT (a)pyrene, and heterocyclic amines such as 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine. These classes of xenobiotics are all 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environ- suspected human carcinogens. For example, TCDD, a widespread mental contaminant, that has been linked with a variety of deleterious environmental contaminant generated by a variety of industrial pro- effects on human health, including increased cancer rates and reproduc- tive anomalies. The detrimental effects of TCDD are mediated via the aryl cesses, has been linked to an increase in many types of human hydrocarbon receptor (AhR), a transcription factor that regulates the cancers, including hepatocellular cancer (3, 4). In animal models, expression of the carcinogen-activating enzymes cytochromes P-450 TCDD has been shown to cause acute toxicity (5), increased oxidative (CYP) 1A1, 1A2, and 1B1. In the present study, we examined the ability stress (6), impaired ovulation (7), and immunotoxicity (8). These of synthetic derivatives of salicylic acid to affect TCDD-stimulated AhR- effects in animal models are believed to closely reflect the deleterious mediated signal transduction in human hepatoma HepG2 cells. Salicyl- effects of TCDD in humans (9). TCDD has the highest affinity for the amide (SAL), an analgesic drug, caused a potent and long-lasting inhibi- AhR of any known compound, and is considered the prototypical AhR tion of TCDD-induced CYP enzyme activity. -
Seborrheic Dermatitis
Seborrheic Dermatitis Seborrheic dermatitis shows up as redness and greasy scale in the “seborrheic areas”—which include the eyebrows and the space between them, the grooves beside the nose, around the ears, in the scalp and sometimes on the central chest or central upper back. Dandruff may be noticed in the scalp or eyebrows. While some of the areas mentioned are usually involved in anyone with seborrheic dermatitis, any facial area is likely to be involved, and just about any area of the skin can be involved in unusual cases. The condition is likely to last a very long time, with unpredictable remission and relapse, and there is no “cure.” It is EXTREMELY common. Cause: The cause of seborrheic dermatitis is not known, although several explanations have been proposed. These include a reaction to a yeast that lives on sebum (this is the most widely accepted explanation), a reaction to sebum itself, a reaction to bacteria, or nerve abnormalities. Although the cause is not understood, there are many things that are widely felt to make seborrheic dermatitis worse: stress, wintertime, strokes, immunodeficiency (like AIDS), Parkinson’s disease, and some medications. Treatment of the face: • Mild steroid creams—including OTC 1% hydrocortisone cream. These work quickly and are preferred by many patients and doctors. For truly mild steroid creams the risk of use is very, very slight, but steroids CAN cause problems if the skin becomes “addicted” to them, and can result in a red, pimply rash. This is a real problem when stronger steroid creams are used on the face. -
Dolobid® (Diflunisal)
9676203 TABLETS DOLOBID® (DIFLUNISAL) Cardiovascular Risk • NSAIDS may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. (See WARNINGS.) • DOLOBID is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS). Gastrointestinal Risk • NSAIDS cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. (See WARNINGS.) DESCRIPTION Diflunisal is 2', 4'-difluoro-4-hydroxy-3-biphenylcarboxylic acid. Its empirical formula is C13H8F2O3 and its structural formula is: Diflunisal has a molecular weight of 250.20. It is a stable, white, crystalline compound with a melting point of 211-213°C. It is practically insoluble in water at neutral or acidic pH. Because it is an organic acid, it dissolves readily in dilute alkali to give a moderately stable solution at room temperature. It is soluble in most organic solvents including ethanol, methanol, and acetone. DOLOBID* (Diflunisal) is available in 250 and 500 mg tablets for oral administration. Tablets DOLOBID contain the following inactive ingredients: cellulose, FD&C Yellow 6, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, starch, talc, and titanium dioxide. CLINICAL PHARMACOLOGY Action DOLOBID is a non-steroidal drug with analgesic, anti-inflammatory and antipyretic properties.