Clomifene Citrate(BANM, Rinnm) ⊗
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Chemical Compounds As Carcinogenic Agents Second Supplementary Report: Literature of 1938 and 1939 Biological Considerations
CHEMICAL COMPOUNDS AS CARCINOGENIC AGENTS SECONDSUPPLEMENTARY REPORT: LITERATURE OF 1938 AND 1939 J. W. COOK AND E. L. KENNAWAY (From the Royal Cancer Hospital (Free), London, and the University of Glasgow) BIOLOGICALCONSIDERATIONS (Continued from page 428, Jitly 1940) II. Action of Carcinogenic Compounds in Difierent Species and Tissues A number of reports of the action of carcinogenic compounds on human tis- sues have appeared. Klar (601) developed a nodule on the forearm after completion of a series of experiments with 3:4-benzpyrene. He applied a solution of the hydrocarbon (0.25 per cent in benzol) to the skin of mice with a paint brush and for at least part of the period wore rubber gloves. He also conducted experiments, of which no description is given, with the powdered hydrocarbon contained in a glass vessel. Three months after the completion of the experiments a small nodule appeared on the dorsum of the left forearm, This was excised in May 1938 and described by Professor Huckel as a “ so- called benign calcifying epithelioma.” The growth extended into the subcu- taneous fatty tissue; the connection with the superficial epithelium is not described nor is it evident in the two photomicrographs which illustrate the report. The author does not state his age. Gordonoff and Walthard (562) record the occurrence of a tumor in a labo- ratory assistant, aged forty-two, engaged in applying methylcholanthrene (0.3 per cent in benzol) to the skin of mice. The site was in the nasolabial fold, at a spot often touched by the patient when smoking. The microscopic ap- pearance was that of a “ still well delimited stage of an incipient squamous- cell sarcoma.” Cottini and Mazzone (479) deliberately applied 3 :4-benzpyrene ( 1 per cent in benzene) to the skin, generally of the arm or thigh, of 26 patients with various cutaneous diseases, usually daily for periods up to 120 days. -
Clomid (Clomiphene Citrate USP)
PRODUCT MONOGRAPH PrCLOMID® (clomiphene citrate USP) 50 mg Tablets Ovulatory Agent sanofi-aventis Canada Inc. Date of Revision: 2905 Place Louis-R.-Renaud August 9, 2013 Laval, Quebec H7V 0A3 Submission Control No.: 165671 s-a Version 5.0 dated August 9, 2013 Page 1 of 23 PRODUCT MONOGRAPH PrCLOMID® (clomiphene citrate USP) 50 mg Tablets Ovulatory agent. ACTION AND CLINICAL PHARMACOLOGY CLOMID (clomiphene citrate) is an orally-administered, non-steroidal agent which may induce ovulation in anovulatory women in appropriately selected cases.1-16 The ovulatory response to cyclic CLOMID therapy appears to be mediated through increased output of pituitary gonadotropins, which in turn stimulate the maturation and endocrine activity of the ovarian follicle and the subsequent development and function of the corpus luteum. The role of the pituitary is indicated by increased plasma levels of gonadotropins and by the response of the ovary, as manifested by increased plasma level of estradiol. Antagonism of competitive inhibition of endogenous estrogen may play a role in the action of CLOMID on the hypothalamus. CLOMID is a drug of considerable pharmacologic potency. Its administration should be preceded by careful evaluation and selection of the patient, and must be accompanied by close attention to the timing of the dose. With conservative selection and management of the patient, CLOMID has been demonstrated to be a useful therapy for the anovulatory patient. Based on studies with 14C-labeled clomiphene, the drug is readily absorbed orally in humans, and is excreted principally in the feces. Cumulative excretion of the 14C-label averaged 51% of the oral dose after 5 days in 6 subjects, with mean urinary excretion of 8% and mean fecal excretion of 42%; less than 1% per day was excreted in fecal and urine samples collected from 31 to 53 days after 14C-labelled clomiphene administration. -
The Reactivity of Human and Equine Estrogen Quinones Towards Purine Nucleosides
S S symmetry Article The Reactivity of Human and Equine Estrogen Quinones towards Purine Nucleosides Zsolt Benedek †, Peter Girnt † and Julianna Olah * Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szent Gellért tér 4, H-1111 Budapest, Hungary; [email protected] (Z.B.); [email protected] (P.G.) * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Conjugated estrogen medicines, which are produced from the urine of pregnant mares for the purpose of menopausal hormone replacement therapy (HRT), contain the sulfate conjugates of estrone, equilin, and equilenin in varying proportions. The latter three steroid sex hormones are highly similar in molecular structure as they only differ in the degree of unsaturation of the sterane ring “B”: the cyclohexene ring in estrone (which is naturally present in both humans and horses) is replaced by more symmetrical cyclohexadiene and benzene rings in the horse-specific (“equine”) hormones equilin and equilenin, respectively. Though the structure of ring “B” has only moderate influence on the estrogenic activity desired in HRT, it might still significantly affect the reactivity in potential carcinogenic pathways. In the present theoretical study, we focus on the interaction of estrogen orthoquinones, formed upon metabolic oxidation of estrogens in breast cells with purine nucleosides. This multistep process results in a purine base loss in the DNA chain (depurination) and the formation of a “depurinating adduct” from the quinone and the base. The point mutations induced in this manner are suggested to manifest in breast cancer development in the long run. -
Management of Women with Clomifene Citrate Resistant Polycystic Ovary Syndrome – an Evidence Based Approach
1 Management of Women with Clomifene Citrate Resistant Polycystic Ovary Syndrome – An Evidence Based Approach Hatem Abu Hashim Department of Obstetrics & Gynecology, Faculty of Medicine, Mansoura University, Mansoura, Egypt 1. Introduction World Health Organisation (WHO) type II anovulation is defined as normogonadotrophic normoestrogenic anovulation and occurs in approximately 85% of anovulatory patients. Polycystic ovary syndrome (PCOS) is the most common form of WHO type II anovulatory infertility and is associated with hyperandrogenemia (1,2). Moreover, PCOS is the most common endocrine abnormality in reproductive age women. The prevalence of PCOS is traditionally estimated at 4% to 8% from studies performed in Greece, Spain and the USA (3-6). The prevalence of PCOS has increased with the use of different diagnostic criteria and has recently been shown to be 11.9 ± 2.4% -17.8 ± 2.8 in the first community-based prevalence study based on the current Rotterdam diagnostic criteria compared with 10.2 ± 2.2% -12.0 ± 2.4% and 8.7 ± 2.0% using National Institutes of Health criteria and Androgen Excess Society recommendations respectively (7). Importantly, 70% of women in this recent study were undiagnosed (7). Clomiphene citrate (CC) is still holding its place as the first-line therapy for ovulation induction in these patients (2,8,9). CC contains an unequal mixture of two isomers as their citrate salts, enclomiphene and zuclomiphene. Zuclomiphene is much the more potent of the two for induction of ovulation, accounts for 38% of the total drug content of one tablet and has a much longer half-life than enclomiphene, being detectable in plasma 1 month following its administration (10). -
Materializing Estrogen and Regulation Under Canada's Food and Drugs Act, 1939-1953 Lara Jessie Tessaro
Osgoode Hall Law School of York University Osgoode Digital Commons LLM Theses Theses and Dissertations 8-27-2018 Toxic Enactments: Materializing Estrogen and Regulation Under Canada's Food and Drugs Act, 1939-1953 Lara Jessie Tessaro Follow this and additional works at: https://digitalcommons.osgoode.yorku.ca/llm Part of the Legal History Commons TOXIC ENACTMENTS: MATERIALIZING ESTROGEN AND REGULATION UNDER CANADA’S FOOD AND DRUGS ACT, 1939-1953 LARA TESSARO A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF LAWS GRADUATE PROGRAM IN LAW OSGOODE HALL LAW SCHOOL, YORK UNIVERSITY TORONTO, ONTARIO August 2018 © Lara Tessaro, 2018 ABSTRACT The study describes how estrogen was standardized in Canada, in the 1940s and early 1950s, under the Food and Drugs Act. Contributing to interdisciplinary conversations, it provides an empirical case of how regulatory practices enact material realities. Using archival material, the study describes how estrogen was achieved, in part, through heterogeneous practices of the Canadian Committee on Pharmacopoeial Standards, National Health, and government solicitors. These regulators disagreed on whether, how, and by whom estrogens should be standardized. Rather than resolve these disagreements, Canada enacted multiple regulations purporting to standardize estrogen, and government solicitors practiced “techniques of validating” to render the regulations as lawful. I argue that these regulatory enactments materialized estrogen as a potent, unpredictable, and multiple object. Further, I show how estrogen spawned novel regulatory techniques in Canada, particularly the use of consumer product labels. In this way, estrogen catalyzed an early example of risk regulation in Canada. -
Pp375-430-Annex 1.Qxd
ANNEX 1 CHEMICAL AND PHYSICAL DATA ON COMPOUNDS USED IN COMBINED ESTROGEN–PROGESTOGEN CONTRACEPTIVES AND HORMONAL MENOPAUSAL THERAPY Annex 1 describes the chemical and physical data, technical products, trends in produc- tion by region and uses of estrogens and progestogens in combined estrogen–progestogen contraceptives and hormonal menopausal therapy. Estrogens and progestogens are listed separately in alphabetical order. Trade names for these compounds alone and in combination are given in Annexes 2–4. Sales are listed according to the regions designated by WHO. These are: Africa: Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, South Africa, Swaziland, Togo, Uganda, United Republic of Tanzania, Zambia and Zimbabwe America (North): Canada, Central America (Antigua and Barbuda, Bahamas, Barbados, Belize, Costa Rica, Cuba, Dominica, El Salvador, Grenada, Guatemala, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago), United States of America America (South): Argentina, Bolivia, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Guyana, Paraguay, -
Clomifene Or Letrozole Ovulation Induction Treatment
What happens next? For most women (once the correct dose has been established) we would encourage you to continue for six months without having to be scanned. After this, if you are still not pregnant, please ring your Fertility Nurse for advice. If, during the time you are receiving treatment, your periods become irregular ie. longer than 33-34 days, or you lose over a stone in weight (gaining is not an option!), please contact your Fertility Nurse. Clomifene or Letrozole Good Luck (Please call if you are pregnant!) Ovulation Induction Cornwall Centre for Reproductive Medicine treatment Wheal Unity Clinic Administrator – 01872 253044 Fertility Nurses – 01872 252061 If you would like this leaflet in large print, braille, audio version or in another language, please contact the General Office on 01872 252690 RCHT 557 © RCHT Design & Publications 2002 Revised 12/2018 V3 Review due 12/2021 What is clomifene? There is also a theoretical, but not proven, concern that prolonged use may Clomifene citrate or Letrozole are the most commonly used drug in the make the development of ovarian cancer more likely. Therefore it is treatment of women who fail to ovulate (produce an egg) regularly. Clomifene recommended to be taken for a year only, taking it for any longer is unlikely to or Letrozole drugs have the effect of boosting the production of those give any significant benefit. hormones that stimulate eggs to grow. When and how is it taken? Does it work for everyone? Take clomifene/letrozole for four days starting the day after your period starts Over half of women will respond to clomifene/letrozole treatment (more so if (ie. -
6. Endocrine System 6.1 - Drugs Used in Diabetes Also See SIGN 116: Management of Diabetes, 2010
1 6. Endocrine System 6.1 - Drugs used in Diabetes Also see SIGN 116: Management of Diabetes, 2010 http://www.sign.ac.uk/guidelines/fulltext/116 Insulin Prescribing Guidance in Type 2 Diabetes http://www.fifeadtc.scot.nhs.uk/media/6978/insulin-prescribing-in-type-2-diabetes.pdf 6.1.1 Insulins (Type 2 Diabetes) 6.1.1.1 Short Acting Insulins 1st Choice S – Insuman ® Rapid (Human Insulin) S – Humulin S ® S – Actrapid ® 2nd Choice S – Insulin Aspart (NovoRapid ®) (Insulin Analogues) S – Insulin Lispro (Humalog ®) 6.1.1.2 Intermediate and Long Acting Insulins 1st Choice S – Isophane Insulin (Insuman Basal ®) (Human Insulin) S – Isophane Insulin (Humulin I ®) S – Isophane Insulin (Insulatard ®) 2nd Choice S – Insulin Detemir (Levemir ®) (Insulin Analogues) S – Insulin Glargine (Lantus ®) Biphasic Insulins 1st Choice S – Biphasic Isophane (Human Insulin) (Insuman Comb ® ‘15’, ‘25’,’50’) S – Biphasic Isophane (Humulin M3 ®) 2nd Choice S – Biphasic Aspart (Novomix ® 30) (Insulin Analogues) S – Biphasic Lispro (Humalog ® Mix ‘25’ or ‘50’) Prescribing Points For patients with Type 1 diabetes, insulin will be initiated by a diabetes specialist with continuation of prescribing in primary care. Insulin analogues are the preferred insulins for use in Type 1 diabetes. Cartridge formulations of insulin are preferred to alternative formulations Type 2 patients who are newly prescribed insulin should usually be started on NPH isophane insulin, (e.g. Insuman Basal ®, Humulin I ®, Insulatard ®). Long-acting recombinant human insulin analogues (e.g. Levemir ®, Lantus ®) offer no significant clinical advantage for most type 2 patients and are much more expensive. In terms of human insulin. The Insuman ® range is currently the most cost-effective and preferred in new patients. -
Index to the NLM Classification 2011
National Library of Medicine Classification 2011 Index Disease see Tyrosinemias 1-8 5,12-diHETE see Leukotriene B4 1,2-Benzopyrones see Coumarins 5,12-HETE see Leukotriene B4 1,2-Dibromoethane see Ethylene Dibromide 5-HT see Serotonin 1,8-Dihydroxy-9-anthrone see Anthralin 5-HT Antagonists see Serotonin Antagonists 1-Oxacephalosporin see Moxalactam 5-Hydroxytryptamine see Serotonin 1-Propanol 5-Hydroxytryptamine Antagonists see Serotonin Organic chemistry QD 305.A4 Antagonists Pharmacology QV 82 6-Mercaptopurine QV 269 1-Sar-8-Ala Angiotensin II see Saralasin 7S RNA see RNA, Small Nuclear 1-Sarcosine-8-Alanine Angiotensin II see Saralasin 8-Hydroxyquinoline see Oxyquinoline 13-cis-Retinoic Acid see Isotretinoin 8-Methoxypsoralen see Methoxsalen 15th Century History see History, 15th Century 8-Quinolinol see Oxyquinoline 16th Century History see History, 16th Century 17 beta-Estradiol see Estradiol 17-Ketosteroids WK 755 A 17-Oxosteroids see 17-Ketosteroids A Fibers see Nerve Fibers, Myelinated 17th Century History see History, 17th Century Aardvarks see Xenarthra 18th Century History see History, 18th Century Abate see Temefos 19th Century History see History, 19th Century Abattoirs WA 707 2',3'-Cyclic-Nucleotide Phosphodiesterases QU 136 Abbreviations 2,4-D see 2,4-Dichlorophenoxyacetic Acid Chemistry QD 7 2,4-Dichlorophenoxyacetic Acid General P 365-365.5 Organic chemistry QD 341.A2 Library symbols (U.S.) Z 881 2',5'-Oligoadenylate Polymerase see Medical W 13 2',5'-Oligoadenylate Synthetase By specialties (Form number 13 in any NLM -
QSAR Modeling
Best practices for developing predictive QSAR models Alexander Tropsha Laboratory for Molecular Modeling and Carolina Center for Exploratory Cheminformatics Research School of Pharmacy UNC-Chapel Hill OUTLINE • Introduction: Brief outline of the QSAR approach • Why models fail (bad practices) • Good practices. – Predictive QSAR Modeling Workflow – Examples of the Workflow applications – Emerging applications of QSAR: chemocentric informatics • Conclusions: QSAR modeling is a decision support The rumors of QSAR demise have been greatly exaggerated 100,000 4500 90,000 4000 number of QSAR 80,000 Number of compounds papers in PubMed 3500 70,000 in CAS (in 1000s) 3000 60,000 2500 50,000 2000 40,000 Number of protein 1500 Structures in PDB 30,000 1000 20,000 500 10,000 0 0 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 Graphs are courtesy of Prof. A. Cherkasov Principles of QSAR modeling Introduction O N C 0.613 O O N 0.380 A -0.222 O D C M N O E 0.708 N S O Quantitative 1.146 T P N C O R 0.491 N Structure I O I 0.301 O P Activity N 0.141 V U O T Relationships N O 0.956 I N O R N 0.256 S D 0.799 T O 1.195 N Y S 1.005 Principles of QSAR/QSPR modeling Introduction O N C 0.613 O O N 0.380 P -0.222 O D R M N O E 0.708 N S O Quantitative 1.146 O P N C O R 0.491 N Structure P O I 0.301 O P Property N 0.141 E U O T Relationships N O 0.956 R N O R N 0.256 S D 0.799 T O 1.195 N Y S 1.005 The utility of QSAR models CHEMICAL -
Conjugated Estrogens Sustained Release Tablets) 0.3 Mg, 0.625 Mg, and 1.25 Mg
PRODUCT MONOGRAPH PrPREMARIN® (conjugated estrogens sustained release tablets) 0.3 mg, 0.625 mg, and 1.25 mg ESTROGENIC HORMONES ® Wyeth Canada Date of Revision: Pfizer Canada Inc., Licensee December 1, 2014 17,300 Trans-Canada Highway Kirkland, Quebec H9J 2M5 Submission Control No: 177429 PREMARIN (conjugated estrogens sustained release tablets) Page 1 of 46 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION .........................................................3 SUMMARY PRODUCT INFORMATION ...........................................................................3 INDICATIONS AND CLINICAL USE ................................................................................3 CONTRAINDICATIONS ......................................................................................................4 WARNINGS AND PRECAUTIONS ....................................................................................4 ADVERSE REACTIONS ....................................................................................................14 DRUG INTERACTIONS ....................................................................................................20 DOSAGE AND ADMINISTRATION ................................................................................23 OVERDOSAGE ...................................................................................................................25 ACTION AND CLINICAL PHARMACOLOGY ...............................................................25 STORAGE AND STABILITY ............................................................................................28 -
Electrochemical Behaviour and Quantitative Determination Of
Int J Pharma Res Health Sci. 2017; 5 (6): 2014-18 DOI:10.21276/ijprhs.2017.06.22 Reddy et al CODEN (USA)-IJPRUR, e-ISSN: 2348-6465 International Journal of Pharma Research and Health Sciences Available online at www.pharmahealthsciences.net Original Article Electrochemical Behaviour and Quantitative Determination of Clomifene in Pharmaceutical Formulations C Nageswara Reddy1,*, P Sandhya 3, P R Prasad 2, N Y Sreedhar 2 1Department of Chemistry, Govt. Degree & P.G. College, Puttur-517 583, A.P., India. 2Electroanalytical Lab, Department of Chemistry, Sri Venkateswara University, Tirupati-517 502, A.P, India. 3Department of Chemistry, Sri Padmavati Mahila Visvavidyalayam, Tirupati-517 502, A.P, India. ARTICLE INFO ABSTRACT Received: 11 Nov 2017 The electrochemical behaviour of clomifene was studied and determined in pharmaceutical Accepted: 18 Dec 2017 formulations. The drug of clomifene was electrochemically examined by cyclic and differential pulse voltammetry using a glassy carbon electrode (GCE). The obtained results showed that, the Britton Robinson buffer with pH 4.0 was the best medium for reduction of clomifene on the glassy carbon electrode at the peak potential -1.01 V. The range of linearity was found to be from 0.20 μg mL-1 to 60.0 μg mL-1 (R2 = 0.994) with limit of detection (LOD) 0.168 μg mL-1 and limit of quantification (LOQ) was 0.511 μg mL-1. Differential pulse voltammetric method was successfully applied for the electrochemical determination of clomifene in pharmaceutical formulations ______ Keywords: Clomifene, drug, voltammetry, pharmaceutical formulations. 1. INTRODUCTION An alkenyl group containing molecules play a vital role in drug chemistry.1 There are innumerable chemical reactions that involve or produce a carbon-carbon double bond group as an intermediate or as an end produce.1 Consequently the discovery of the first non-steroidal antiestrogen, several studies have been conducted to determine the mechanism of Corresponding author * action of this classes of compounds.