DOCSLIB.ORG

Over-The-Counter, Complementary and Alternative Agents Vitamins and Minerals, Herbal Products, Appearance and Performance Enhancing Supplements

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Over-The-Counter, Complementary and Alternative Agents Vitamins and Minerals, Herbal Products, Appearance and Performance Enhancing Supplements OVER-THE-COUNTER, COMPLEMENTARY AND ALTERNATIVE AGENTS VITAMINS AND MINERALS, HERBAL PRODUCTS, APPEARANCE AND PERFORMANCE ENHANCING SUPPLEMENTS INSTIs NNRTIs PIs RTI BICTEGRAVIR ELVITEGRAVIR/ DORAVIRINE EFAVIRENZ ATAZANAVIR • TENOFOVIR • TENOFOVIR (Biktarvy) COBICISTAT (Pifeltro, (Sustiva, Atripla) (Reyataz/Norvir, ALAFENAMIDE, DISOPROXIL, TDF (Stribild, Genvoya) Delstrigo) Evotaz) TAF (Descovy, (Viread,Truvada, DOLUTEGRAVIR ETRAVIRINE Biktarvy, Genvoya, Atripla, Complera, (Tivicay, Triumeq, RILPIVIRINE (Intelence) DARUNAVIR Odefsey, Symtuza) Delstrigo, Stribild) Juluca) (Edurant, (Prezista/Norvir, NEVIRAPINE Complera, Prezcobix, RALTEGRAVIR (Viramune) •ABACAVIR (Kivexa, Odefsey, Juluca) Symtuza) (Isentress) Ziagen, Triumeq) LOPINAVIR (Kaletra) VITAMINS AND MINERALS Vitamin D Potential for vitamin D Cations such as ↓ INSTI Potential for INSTI calcium, Raltegravir 600 mg magnesium, iron, HD tablets aluminum, zinc, including Raltegravir 400 mg supplements and OK with calcium multivitamins with high dose calcium, iron HERBAL PRODUCTS AND SUPPLEMENTS Echinacea Potential Potential for bictegravir NNRTI Dolutegravir, raltegravir INSTIs NNRTIs PIs RTI BICTEGRAVIR ELVITEGRAVIR/ DORAVIRINE EFAVIRENZ ATAZANAVIR • TENOFOVIR • TENOFOVIR (Biktarvy) COBICISTAT (Pifeltro, (Sustiva, Atripla) (Reyataz/Norvir, ALAFENAMIDE, DISOPROXIL, TDF (Stribild, Genvoya) Delstrigo) Evotaz) TAF (Descovy, (Viread,Truvada, DOLUTEGRAVIR ETRAVIRINE Biktarvy, Genvoya, Atripla, Complera, (Tivicay, Triumeq, RILPIVIRINE (Intelence) DARUNAVIR Odefsey, Symtuza) Delstrigo, Stribild) Juluca) (Edurant, (Prezista/Norvir, NEVIRAPINE Complera, Prezcobix, RALTEGRAVIR (Viramune) •ABACAVIR (Kivexa, Odefsey, Juluca) Symtuza) (Isentress) Ziagen, Triumeq) LOPINAVIR (Kaletra) Garlic Potential for INSTI Potential for INSTI Potential for Potential for Potential for PI Potential for TAF NNRTI NNRTI Ginkgo biloba Potential for Potential for Always use boosted NNRTI NNRTI PI Grapefruit juice Potential for rilpivirine Milk thistle Saw palmetto APPEARANCE AND PERFORMANCE ENHANCING SUPPLEMENTS (APES) Creatine Potential additive ↑ Potential additive ↑ Rilpivirine: Potential additive ↑ Tenofovir DF: Scr without Scr without potential additive ↑ Scr without Potential additive impacting renal impacting renal Scr without impacting renal nephrotoxicity function function impacting renal function (rare) function Testosterone (oral Potential for Potential for Potential for IM, topical) testosterone testosterone testosterone INSTIs NNRTIs PIs RTI BICTEGRAVIR ELVITEGRAVIR/ DORAVIRINE EFAVIRENZ ATAZANAVIR • TENOFOVIR • TENOFOVIR (Biktarvy) COBICISTAT (Pifeltro, (Sustiva, Atripla) (Reyataz/Norvir, ALAFENAMIDE, DISOPROXIL, TDF (Stribild, Genvoya) Delstrigo) Evotaz) TAF (Descovy, (Viread,Truvada, DOLUTEGRAVIR ETRAVIRINE Biktarvy, Genvoya, Atripla, Complera, (Tivicay, Triumeq, RILPIVIRINE (Intelence) DARUNAVIR Odefsey, Symtuza) Delstrigo, Stribild) Juluca) (Edurant, (Prezista/Norvir, NEVIRAPINE Complera, Prezcobix, RALTEGRAVIR (Viramune) •ABACAVIR (Kivexa, Odefsey, Juluca) Symtuza) (Isentress) Ziagen, Triumeq) LOPINAVIR (Kaletra) Anabolic steroids Oral: oxandrolone, stanozolol IM: nandrolone Selective androgen receptor modulators Andarine, ostarine Selective estrogen Potential for Potential for Potential for Potential for Potential for receptor tamoxifen to tamoxifen, possibly NNRTI tamoxifen and tamoxifen, possibly modulators (SERMS) bictegravir elvitegravir possibly NNRTI PI Clomiphene, tamoxifen Clomiphene OK Clomiphene OK Clomiphene OK Clomiphene OK Aromatase Potential for Potential for ↓ Cobicistat-boosted inhibitors aromatase inhibitor aromatase inhibitor PI: Potential for Letrozole, aromatase inhibitor anastrazole Ritonavir-boosted PI: potential for /↓ aromatase inhibitor Mechanism of Drug Interactions, Management and Monitoring Mechanism of Main interacting ARVs Management Monitoring Class interaction Cation-containing Chelation and All INSTIs Management recommendations In all cases, monitor for continued viral products, including decreased absorption vary according to specific INSTI: suppression. supplements and Bictegravir: Administer multivitamins Many Multivitamins bictegravir and polyvalent including once daily and cations simultaneously with especially those food, or separate by 2 hours. designed for women Dolutegravir: Administer with extra Calcium and dolutegravir and polyvalent iron, and those used cations simultaneously with during pregnancy, food, or take dolutegravir 2 contain enough cations hours before or 6 hours after to lead to chelation of polyvalent cations. the integrase inhibitors Elvitegravir/c : Stagger and limit their administration by at least 2 absorption. This results hours from mineral in lowered levels of the supplements. integrase inhibitor and Raltegravir: ONLY 400 MG BID could result in loss of dose may be used with calcium virologic suppression. carbonate; use with other polyvalent cations is not recommended. Do not use 600 mg HD tablet with any polyvalent cations. Echinacea May induce CYP3A4 Bictegravir, doravirine, Potential for decreased ARV Antiretroviral efficacy. (mild) rilpivirine concentrations, clinical significance unclear. Garlic May induce CYP3A4, All ARVs Avoid ingestion of large amounts of Antiretroviral efficacy. Pgp garlic (fresh, cooked or supplements) Ginkgo Biloba Ginkgo may induce bictegravir, unboosted Do not use unboosted atazanavir Antiretroviral efficacy. CYP3A4 atazanavir, NNRTIs, with Ginkgo. Mechanism of Main interacting ARVs Management Monitoring Class interaction Consider elvitegravir/cobicistat, dolutegravir or raltegravir instead of bictegravir. Avoid Ginkgo with NNRTI; switch to boosted INSTI or INSTI metabolized via UGT, or boosted PI. Grapefruit juice May inhibit CYP3A4, rilpivirine Clinical significance unclear; caution Pgp may be warranted if patient is on other drugs which inhibit CYP3A4 and/or have QT-prolonging effect Creatine Creatine is metabolized Cobicistat, ritonavir, Increases in serum creatinine Monitor renal function. to creatinine, and may dolutegravir, secondary to inhibition of renal lead to higher serum bictegravir, rilpvirine tubular transporters generally occur creatinine without soon after starting these necessarily impacting antiretrovirals and remain stable renal function. thereafter. Use of creatine Potential additive effect supplements may enhance this when combined with effect. If additional significant ARVs which inhibit renal increases in serum creatinine occur tubular secretion of after patient is stable on creatinine. antiretrovirals, explore other causes of potential nephrotoxicity. Potential additive risk Tenofovir disoproxil Some cases of renal impairment Monitor renal function. of renal toxicity. after use of creatinine have been reported. Aromatase inhibitors Anastrazole: substrate Protease inhibitors, Potential for increased or decreased Monitor for efficacy, toxicity of aromatase (anastrozole, letrozole) of CYP3A4, UGT elvitegravir/cobicistat concentrations of aromatase inhibitors. Letrozole: substrate of (inhibition of CYP3A4, inhibitors. CYP3A4, 2A6 ritonavir may induce UGT), NNRTIs (induction of CYP3A4) Selective estrogen Clomiphene: no Bictegravir, Less interaction potential with Efficacy/toxicity of tamoxifen. receptor modulators metabolism/transporter elvitegravir/cobicistat, clomiphene versus tamoxifen. Antiretroviral efficacy. effects. PIs, NNRTIs Mechanism of Main interacting ARVs Management Monitoring Class interaction Tamoxifen: substrate If using tamoxifen, consider using and inducer of CYP3A4 an unboosted integrase inhibitor with minimal CYP3A4 involvement Potential for increased such as dolutegravir or raltegravir. tamoxifen with boosted regimens or decreased tamoxifen with enzyme inducing NNRTIs. Potential for decreased ARV concentrations via CYP3A4 induction by tamoxifen. Legend: No dose adjustment required. Use combination with caution. Adjustment in drug dose or frequency or additional/more frequent monitoring may be required. May wish to consult with a pharmacist knowledgeable in HIV drug interactions. Contraindicated/avoid combination. .
Load more

Recommended publications
  • Aromasin (Exemestane)
    HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------------------ADVERSE REACTIONS------------------------------­ These highlights do not include all the information needed to use • Early breast cancer: Adverse reactions occurring in ≥10% of patients in AROMASIN safely and effectively. See full prescribing information for any treatment group (AROMASIN vs. tamoxifen) were hot flushes AROMASIN. (21.2% vs. 19.9%), fatigue (16.1% vs. 14.7%), arthralgia (14.6% vs. 8.6%), headache (13.1% vs. 10.8%), insomnia (12.4% vs. 8.9%), and AROMASIN® (exemestane) tablets, for oral use increased sweating (11.8% vs. 10.4%). Discontinuation rates due to AEs Initial U.S. Approval: 1999 were similar between AROMASIN and tamoxifen (6.3% vs. 5.1%). Incidences of cardiac ischemic events (myocardial infarction, angina, ----------------------------INDICATIONS AND USAGE--------------------------- and myocardial ischemia) were AROMASIN 1.6%, tamoxifen 0.6%. AROMASIN is an aromatase inhibitor indicated for: Incidence of cardiac failure: AROMASIN 0.4%, tamoxifen 0.3% (6, • adjuvant treatment of postmenopausal women with estrogen-receptor 6.1). positive early breast cancer who have received two to three years of • Advanced breast cancer: Most common adverse reactions were mild to tamoxifen and are switched to AROMASIN for completion of a total of moderate and included hot flushes (13% vs. 5%), nausea (9% vs. 5%), five consecutive years of adjuvant hormonal therapy (14.1). fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased • treatment of advanced breast cancer in postmenopausal women whose appetite (3% vs. 6%) for AROMASIN and megestrol acetate, disease has progressed following tamoxifen therapy (14.2). respectively (6, 6.1). ----------------------DOSAGE AND ADMINISTRATION----------------------- To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at Recommended Dose: One 25 mg tablet once daily after a meal (2.1).
    [Show full text]
  • Physiologic and Pathophysiologic Roles of Extra Renal Cyp27b1: Case Report T and Review ⁎ Daniel D
    Bone Reports 8 (2018) 255–267 Contents lists available at ScienceDirect Bone Reports journal homepage: www.elsevier.com/locate/bonr Physiologic and pathophysiologic roles of extra renal CYP27b1: Case report T and review ⁎ Daniel D. Bikle , Sophie Patzek, Yongmei Wang Department of Medicine, Endocrine Research Unit, Veterans Affairs Medical Center, University of California San Francisco, United States ARTICLE INFO ABSTRACT Keywords: Although the kidney was initially thought to be the sole organ responsible for the production of 1,25(OH)2D via CYP27b1 the enzyme CYP27b1, it is now appreciated that the expression of CYP27b1 in tissues other than the kidney is Immune function wide spread. However, the kidney is the major source for circulating 1,25(OH)2D. Only in certain granulomatous Cancer diseases such as sarcoidosis does the extra renal tissue produce sufficient 1,25(OH)2D to contribute to the cir- Keratinocytes culating levels, generally associated with hypercalcemia, as illustrated by the case report preceding the review. Macrophages Therefore the expression of CYP27b1 outside the kidney under normal circumstances begs the question why, and in particular whether the extra renal production of 1,25(OH)2D has physiologic importance. In this chapter this question will be discussed. First we discuss the sites for extra renal 1,25(OH)2D production. This is followed by a discussion of the regulation of CYP27b1 expression and activity in extra renal tissues, pointing out that such regulation is tissue specific and different from that of CYP27b1 in the kidney. Finally the physiologic significance of extra renal 1,25(OH)2D3 production is examined, with special focus on the role of CYP27b1 in regulation of cellular proliferation and differentiation, hormone secretion, and immune function.
    [Show full text]
  • A Randomized, Controlled Trial of High Dose Vs. Standard Dose Vitamin D for Aromatase-Inhibitor Induced Arthralgia in Breast Cancer Survivors
    A Randomized, Controlled Trial of High Dose vs. Standard Dose Vitamin D for Aromatase-Inhibitor Induced Arthralgia in Breast Cancer Survivors Protocol Number H-33261 Protocol Chair Mothaffar Rimawi, M.D. Baylor College of Medicine One Baylor Plaza BCM 600 Houston, TX 77030 Phone: (713) 798-1311 Fax: (713) 798-8884 Email: [email protected] IND Number: 120053 NCT Number: NCT01988090 Additional Sites Washington University Site PI: Foluso Ademuyiwa, MD High Dose Vitamin D for AIA Rimawi A Randomized, Controlled Trial of High Dose vs. Standard Dose Vitamin D for Aromatase- Inhibitor Induced Arthralgia in Breast Cancer Survivors - Protocol Revision Record – Original Protocol: April 18, 2013 Revision 1: July 22, 2013 Revision 2: September 3, 2013 Revision 3: November 18, 2013 Revision 4: July 14, 2015 Vitamin D for AIA TABLE OF CONTENTS 1. BACKGROUND ............................................................................................................................................ 5 1.1 TREATMENT OF HORMONE RECEPTOR POSITIVE BREAST CANCER..................................................................... 5 1.2 MUSCULOSKELETAL SIDE EFFECTS OF HORMONAL THERAPY ........................................................................... 6 1.3 MANAGEMENT OF AIA ......................................................................................................................... 8 1.4 VITAMIN D AND BREAST CANCER............................................................................................................. 9 1.5 VITAMIN D BACKGROUND
    [Show full text]
  • Aromatase Inhibitors
    FACTS FOR LIFE Aromatase Inhibitors What are aromatase inhibitors? Aromatase Inhibitors vs. Tamoxifen Aromatase inhibitors (AIs) are a type of hormone therapy used to treat some breast cancers. They AIs and tamoxifen are both hormone therapies, are taken in pill form and can be started after but they act in different ways: surgery or radiation therapy. They are only given • AIs lower the amount of estrogen in the body to postmenopausal women who have a hormone by stopping certain hormones from turning receptor-positive tumor, a tumor that needs estrogen into estrogen. If estrogen levels are low to grow. enough, the tumor cannot grow. AIs are used to stop certain hormones from turning • Tamoxifen blocks estrogen receptors on breast into estrogen. In doing so, these drugs lower the cancer cells. Estrogen is still present in normal amount of estrogen in the body. levels, but the breast cancer cells cannot get enough of it to grow. Generic/Brand names of AI’s As part of their treatment plan, some post- Generic name Brand name menopausal women will use AIs alone. Others anastrozole Arimidex will use tamoxifen for 1-5 years and then begin exemestane Aromasin using AIs. letrozole Femara Who can use aromatase inhibitors? Postmenopausal women with early stage and metastatic breast cancer are often treated with AIs. After menopause, the ovaries produce only a small amount of estrogen. AIs stop the body from making estrogen, and as a result hormone receptor-positive tumors do not get fed by estrogen and die. AIs are not given to premenopausal women because their ovaries still produce estrogen.
    [Show full text]
  • At the X-Roads of Sex and Genetics in Pulmonary Arterial Hypertension
    G C A T T A C G G C A T genes Review At the X-Roads of Sex and Genetics in Pulmonary Arterial Hypertension Meghan M. Cirulis 1,2,* , Mark W. Dodson 1,2, Lynn M. Brown 1,2, Samuel M. Brown 1,2, Tim Lahm 3,4,5 and Greg Elliott 1,2 1 Division of Pulmonary, Critical Care and Occupational Medicine, University of Utah, Salt Lake City, UT 84132, USA; [email protected] (M.W.D.); [email protected] (L.M.B.); [email protected] (S.M.B.); [email protected] (G.E.) 2 Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center, Salt Lake City, UT 84107, USA 3 Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; [email protected] 4 Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA 5 Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA * Correspondence: [email protected]; Tel.: +1-801-581-7806 Received: 29 September 2020; Accepted: 17 November 2020; Published: 20 November 2020 Abstract: Group 1 pulmonary hypertension (pulmonary arterial hypertension; PAH) is a rare disease characterized by remodeling of the small pulmonary arteries leading to progressive elevation of pulmonary vascular resistance, ultimately leading to right ventricular failure and death. Deleterious mutations in the serine-threonine receptor bone morphogenetic protein receptor 2 (BMPR2; a central mediator of bone morphogenetic protein (BMP) signaling) and female sex are known risk factors for the development of PAH in humans.
    [Show full text]
  • Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway
    International Journal of Molecular Sciences Article Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway Patricia Rodríguez Castaño 1,2, Shaheena Parween 1,2 and Amit V Pandey 1,2,* 1 Pediatric Endocrinology, Diabetology, and Metabolism, University Children’s Hospital Bern, 3010 Bern, Switzerland; [email protected] (P.R.C.); [email protected] (S.P.) 2 Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland * Correspondence: [email protected]; Tel.: +41-31-632-9637 Received: 5 September 2019; Accepted: 16 September 2019; Published: 17 September 2019 Abstract: Turmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of the Curcuma longa and is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wound healing, anti-inflammatory, and anti-carcinogenic activities. While curcuminoids have been studied for many years, not much is known about their effects on steroid metabolism. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the effect of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. When using 10 µg/mL of curcuminoids, both the 17α-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, only a mild reduction in CYP21A2 activity was observed. Furthermore, CYP19A1 activity was also reduced up to ~20% of control when using 1–100 µg/mL of curcuminoids in a dose-dependent manner. Molecular docking studies confirmed that curcumin could dock onto the active sites of CYP17A1, CYP19A1, as well as CYP21A2.
    [Show full text]
  • Interrelationships Between Aromatase and Cyclooxygenase-2 and Their Role in the Autocrine and Paracrine Mechanisms in Breast Cancer
    INTERRELATIONSHIPS BETWEEN AROMATASE AND CYCLOOXYGENASE-2 AND THEIR ROLE IN THE AUTOCRINE AND PARACRINE MECHANISMS IN BREAST CANCER DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Edgar S. Díaz-Cruz, M.S. ∗∗∗∗∗ The Ohio State University 2005 Dissertation Committee: Approved By Robert W. Brueggemeier, Ph.D., Adviser Robert S. Coleman, Ph.D. _____________________ Karl A. Werbovetz, Ph.D. Adviser Graduate Program in Pharmacy Pui-Kai Li, Ph.D. ABSTRACT Breast cancer is the most common cancer among women, and ranks second among cancer deaths in women. Approximately 60% of all breast cancer patients have hormone-dependent breast cancer, which contains estrogen receptors and requires estrogen for tumor growth. Estradiol is biosynthesized from androgens by the cytochrome P450 enzyme complex called aromatase. Previous studies suggest a strong association between aromatase (CYP19) gene expression and the expression of cyclooxygenase (COX) genes. Our hypothesis is that higher levels of COX-2 expression result in higher levels of prostaglandin E2 (PGE2), which in turn increases CYP19 expression through increases in intracellular cyclic AMP levels and activation of promoter II. This biochemical mechanism may explain the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer. The effects of NSAIDs (ibuprofen, piroxicam, and indomethacin), a COX-1 selective inhibitor (SC- 560), and COX-2 selective inhibitors (celecoxib, niflumic acid, nimesulide, NS-398, and SC-58125) on aromatase activity and expression were studied. To determine if aromatase activity is decreased by COX inhibitors, SK-BR-3 cells were treated for 24 hours with the different concentrations of the inhibitors.
    [Show full text]
  • Association Study of Aromatase Gene
    Int. J. Med. Sci. 2008, 5 29 International Journal of Medical Sciences ISSN 1449-1907 www.medsci.org 2008 5(1):29-35 © Ivyspring International Publisher. All rights reserved Research Paper Association Study of Aromatase Gene (CYP19A1) in Essential Hypertension Masanori Shimodaira1, Tomohiro Nakayama2, Naoyuki Sato3, Kosuke Saito2,4, Akihiko Morita5, Ichiro Sato6, Teruyuki Takahashi7, Masayoshi Soma8, Yoichi Izumi8 1. MD Program, Nihon University School of Medicine, Tokyo, Japan 2. Division of Receptor Biology, Advanced Medical Research Center, Tokyo, Japan 3. Division of Genomic Epidemiology and Clinical Trials, Advanced Medical Research Center, Tokyo, Japan 4. Department of Applied Chemistry, Toyo University School of Engineering, Tokyo, Japan 5. Department of Neurology, Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan 6. Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan 7. Department of Neurology, Graduate School of Medicine, Nihon University, Tokyo, Japan 8. Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan Correspondence to: Tomohiro Nakayama, MD, Division of Receptor Biology, Advanced Medical Research Center, Nihon University School of Medicine, Ooyaguchi-kamimachi, 30-1 Itabashi-ku, Tokyo 173-8610, Japan. Tel: +81 3-3972-8111 (ext.8205); Fax: +81 3-5375-8076; E-mail: [email protected] Received: 2007.10.21; Accepted: 2008.02.05; Published: 2008.02.07 Background: As aromatase-deficient mice, which are deficient in estrogens, reportedly have reduced blood pressure, the aromatase gene (CYP19A1) is thought to be a susceptibility gene for essential hypertension (EH). The aim of the present study was to investigate the relationship between CYP19A1 and EH by examining single nucleotide polymorphisms (SNPs).
    [Show full text]
  • Aromatase Inhibitors Produce Hypersensitivity In
    AROMATASE INHIBITORS PRODUCE HYPERSENSITIVITY IN EXPERIMENTAL MODELS OF PAIN: STUDIES IN VIVO AND IN ISOLATED SENSORY NEURONS Jason Dennis Robarge Submitted to the faculty of the University Graduate School in partial fulfillment of the requirements for the degree Doctor of Philosophy in the Department of Pharmacology and Toxicology, Indiana University September 2014 Accepted by the Graduate Faculty, of Indiana University, in partial fulfillment of the requirements for the degree of Doctor of Philosophy. ___________________________________ David A. Flockhart, M.D., Ph.D., Chair ___________________________________ Jill C. Fehrenbacher, Ph.D. Doctoral Committee ___________________________________ Rajesh Khanna, Ph.D. ___________________________________ Todd C. Skaar, Ph.D. June 9, 2014 ___________________________________ Michael R. Vasko, Ph.D. ii DEDICATION For Dad iii ACKNOWLEDGEMENTS This scientific endeavor was possible with the support, guidance, and collaboration of many individuals at Indiana University. Foremost, I am grateful for the mentorship of two excellent scientists, Dr. David Flockhart and Dr. Michael Vasko, who encouraged me to pursue scientific questions with thoughtful ambition. For the rest of my scientific career, I will always ask two critical questions: “What’s the clinical impact?” and “What’s the question?”. I am also equally thankful for the friendship and mentorship of many members of the Vasko lab family. I enjoyed so many enlightening conversations about scientific and non-scientific matters alike with Dr. Djane Duarte, Dr. Ramy Habashy, Behzad Shariati, and others. I thank Dr. Todd Skaar, Dr. Rajesh Khanna, and Dr. Jill Fehrenbacher for their encouragement and fair critique as members of my committee. I would especially like to thank my family. To my parents, who provided me with every opportunity to pursue higher education and were unwavering in their support and confidence in me.
    [Show full text]
  • Antenatal Treatment for Classic 21-Hydroxylase Forms of Congenital Adrenal Hyperplasia and the Issues
    July/August 1999 ·Vol. 1 ·No. 5 invitedreview 1cmeartlcle Antenatal treatment for classic 21-hydroxylase forms of congenital adrenal hyperplasia and the issues Julie Trm•it::, MS 1 and DanielL. Metzger, MIY 3 8 This paper discusses perinatal issues specific to the classi­ tal folds, and a rugated scrotal sac. ·6- Fetal androgens can cal 21-hydroxylase deficiency forms of congenital adrenal also inhibit downgrowth of the vesicovaginal septum in hyperplasia including: prenatal testing, detection, risks, and females, 1 and thus severely virilized females may have a sin­ limitations of such procedures; and prenatal treatment, its gle perineal orifice consisting of a fused vagina and urethra potential benefits to the affected female fetus, and risks to both (urogenital sinus). 3 This urogenital sinus may appear as per­ the fetus and the mother. The information may be important ineoscrotal or phallic hypospadias or even as a "normal male" for a family to have before and during a pregnancy in order urethra. Such females may require clitoroplasty in infancy, and to make an informed decision about what course of action vaginoplasty and vaginal dilation in young adulthood. Inter­ they might want to pursue. nal female sexual organs develop normally because they are 6 8 INTRODUCTION not influenced by androgens. • Because the male fetus is normally exposed to high levels The 21-0H deficiency form of CAH (for this paper, the of testicular androgens, affected newborn males will not have abbreviation CAH will be used to describe congenital adrenal apparent genital deformities but may present with slight hyper­ hyperplasia due to 21-0H deficiency only) affects the devel­ pigmentation of the external genitalia due to excess ACTH opment of genetic females by virilization of the external gen­ and related peptides.
    [Show full text]
  • Human Cytochrome P450 2E1: Functional Comparison to Cytochromes P450 2A13 and 2A6
    Human Cytochrome P450 2E1: Functional Comparison to Cytochromes P450 2A13 and 2A6 by Melanie A. Blevins B.S., Graceland University, 2002 Submitted to the Department of Medicinal Chemistry and the Faculty of the Graduate School of the University of Kansas in partial fulfillment of the requirements for the degree of Master’s of Science. Dissertation Committee: Major Professor Committee Date Defended: April 24, 2008 The Thesis Committee for Melanie Blevins certifies that this is the approved Version of the following thesis: Human Cytochrome P450 2E1: Functional Comparison to Cytochromes P450 2A13 and 2A6 Committee: _______________________________ Chairperson* _______________________________ _______________________________ ii Abstract The cytochrome P450 (CYP) superfamily of enzymes plays the predominant role in human phase I xenobiotic metabolism. These enzymes participate in the metabolism of a greater part of the drugs in present clinical use and have been linked to the activation of carcinogens and other toxins. The CYP2 family, in particular, is known for it extensive Phase I metabolism of a majority of the xenobiotic compounds [1]. The goal of this project is to determine the structural foundation for the substrate selectivities of the CYP2A6 and CYP2A13 enzymes versus CYP2E1. Because these enzymes metabolize both common, as well as unique, small molecule substrates, it is likely that only few key residue-substrate interactions are responsible for those metabolic capabilities that differ between them. Amino acid residues in regions of the CYP2E1 protein likely to contact ligands and that differ between CYP2E1 and the CYP2A enzymes were examined by site-directed mutagenesis. The resulting mutated CYP2E1 proteins were characterized for their ability to hydroxylate the reportedly selective CYP2E1 substrates p-nitrophenol (pNP) [2] and chlorzoxazone (CZN) [3], but none showed significant differences in activity from the CYP2E1 wild type enzyme.
    [Show full text]
  • Aromatase Inhibitors Medication Teaching
    Aromatase Inhibitors Medication Teaching The Center for Breast Cancer Mass General Cancer Center Topics to Discuss • What are Aromatase Inhibitors? How do they work in the body? • Reasons for taking an Aromatase Inhibitor • Types of Aromatase Inhibitors • How Aromatase Inhibitors are taken • Storage, Handling, and Disposal • Drug Interactions • Side Effects & How to Manage • Supportive Care Resources • Your Breast Cancer Team • When to Call and Important Phone Numbers 2 What are Aromatase Inhibitors? How do they work in the body? • Aromatase Inhibitors are a class of medications which suppress estrogen in the body. • They inactivating aromatase, an enzyme which converts androgens to estrogens. • Aromatase Inhibitors lower the level of estrogen in the body. This: – decreases the chance of breast cancer returning (recurrence) – decreases tumor size – delays hormone receptor positive tumors from spreading (progression) 3 Reasons for taking an Aromatase Inhibitor • Because you have a personal history of hormone receptor positive breast cancer or DCIS (ductal carcinoma in situ). – Generally given to post-menopausal females – Can be given to pre-menopausal females if administered with Lupron or Goserelin for ovarian suppression • Your care team will talk with you about how long you will need to take this therapy. – It is common to be on therapy for 5-10 years. 4 Types of Aromatase Inhibitors • There are several types of of aromatase inhibitors. They can cause similar side effects. – Femara (letrozole)- 1 tablet a day (2.5 mg) – Arimidex (anastrozole)- 1 tablet a day (1 mg) – Aromasin (exemestane)- 1 tablet a day (25 mg) 5 How are Aromatase Inhibitors taken? • Aromatase Inhibitors can be taken morning or night • It is important to take at the same time each day • Aromasin should be taken within 30 minutes after a meal • Arimidex and Femara may be taken without regard to meals • Swallow whole with water and do not break, chew, or crush your tablet • If you miss a dose, skip the dose.
    [Show full text]