Pharmacological Treatment of Endocrinopathies

Transcription

1 Pharmacological Treatment of Endocrinopathies

2 Progress in Basic and Clinical Pharmacology Vol. 5 Series Editors P. Lomax, Los Angeles, Calif. E.S. Vesell, Hershey, Pa. KARGER Basel München Paris. London NewYork New Delhi Bangkok. Singapore. Tokyo Sydney

3 Pharmacological Treatment of Endocrinopathies Bone Disease, Kidney Stones and Related Disorders Charles Υ Pak, Dallas, Tex. with contributions by Bruce Ettinger, Clare D. Edman, and Stanley Wallach 31 figures and 18 tables, 1991 KARG E R Basel. München Pans London NewYork New Delhi Bangkok. Singapore. Tokyo. Sydney

4 Charles Y.C. Pak, PhD Center for Mineral Metabolism and Clinical Research, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX (USA) Bruce Ettinger, MD Department of Medicine, Kaiser Permanente Medical Center, 2200 O'Farrell Street, San Francisco, CA (USA) Clare D. Edman, MD Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX (USA) Stanley Wallach, MD Medical Service, VA Medical Center, Bay Pines, FL (USA) Library of Congress Cataloging-in-Publication Data Pak, Charles Y.C. Pharmacological treatment of endocrinopathies : bone disease, kidney stones, and other disorders/charles Y. Pak with contributions by Bruce Ettinger, Clare D. Edman, and Stanley Wallach. (Progress in basic and clinical pharmacology; vol. 5) Includes bibliographic references. Includes index. 1. Calcium - Metabolism - Disorders - Chemotherapy. 2. Cystinuria - Chemotherapy. 3. Osteoporosis - Chemotherapy. 4. Kidneys - Calculi - Chemotherapy. I. Title. [DNLM: 1. Cystinu a - drug therapy. 2. Kidney Calculi - drug therapy. 3. Osteoporosis, Postmenopausal - drug therapy. WI PR666GK v. 5 / WJ 356 Pl 52ρ] RC632.C26P ' dc20 ISBN Drug Dosage The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Φ Copyright 1991 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland) ISBN

5 Contents Preface IX 1 Sodium Cellulose Phosphate for the Treatment of Absorptive Hypercalciuria Historical 1 Chemistry of Calcibind 1 Pathophysiology of Absorptive Hypercalciuria 2 Mechanism of Calcibind Action 4 Physiological Action of Calcibind 4 Physicochemical Action of Calcibind 8 Ind cat ons and Treatment Guidelines 9 Response to Therapy 10 Studies at NIH 10 Studies at Dallas 11 Studies by Other Workers 11 Hazards of Calcibind Therapy 12 Effect on Parathyroid Function and Bone Metabolism 12 Effect on Magnesium and Oxalate Metabolism 13 Effect of Calcibind on Trace Metals and Creatinine Clearance 13 Nonspecific Side Effects 13 References 14 Bruce Ettinger 2 Allopurinol for the Treatment of Uric Acid and Calcium Calculi.. 16 Pharmacology of Allopurinol 16 Pathophysiology of Urate Lithiasis 20 Treatment of Uric Acid Lithiasis 22 Changing Diet and Fluid Intake 22 Alkali Therapy 22 Allopurinol Therapy for Uric Acid Lithiasis 23 Hyperuricosuric Calcium Oxalate Lithiasis 25 Epidemiology 25 Allopurinol Treatment of Calcium Oxalate Lithiasis 26 Mechanisms of Allopurinol's Protection against Calcium Oxalate Lithiasis 28

6 Contents VI Hazards of Allopurinol Therapy 29 Conclusions 32 References 33 3 Potassium Citrate for the Treatment of Calcium and Uric Acid Nephrolithiasis 37 Historical Considerations 37 Pathophysiology 37 Uric Acid Nephrolithiasis 38 Hypocitraturic Calcium Nephrolithiasis 38 Mechanism of Action of Potassium Citrate 40 Physiological Action of Potassium Citrate 40 Physicochemical Action of Potassium Citrate 41 Uniqueness of Potassium Citrate from Other Alkali 42 Treatment Guidelines 43 Hypocitraturic Calcium Nephrolithiasis 43 Gouty Diathesis 45 Response to Therapy 45 Hazards 45 Endoscopie Examination of Upper Gastrointestinal Mucosa 46 Adverse Reactions 47 References 47 4 Alpha-Mercaptopropionylglycine for the Prevention of Cystinuria 49 Historical Considerations 49 Pathophysiology 49 Cystinuria 49 Pathogenetic Role of Cystinuria in Stone Formation 50 Mechanism of Action of Thiola 50 Chemistry 50 Pharmacokinetics and Bioavailability 50 Dose-Response Relationship 51 Effect of Thiola on Renal Excretion of Other Dibasic Amino Acids 52 Effect of Short-Term Thiola Withdrawal 52 Long-Term Action of Thiola on Cystine Excretion 53 Physicochemical Action of Thiola 53 Treatment Guidelines 54 Specific Therapies Other Than Thiola 54 Alpha-Mercaptopropionylglycine 56 Response to Thiola Therapy 57 Remien et al 57 Hautmann 57 Miano et al. 57 Linari et al. 58 Multiclinic Trial in the United States 58

7 Contents VII Hazards of Thiola Therapy 58 Multiclinic Trial in the United States 58 Other Reports 59 References 61 5 Thiazide for the Treatment of Hypercalciuric Nephrolithiasis Historical Considerations 63 Pathophysiology of Renal Hypercalciuric 63 Mechanism of Action of Thiazide 66 Physiological Action of Thiazide 66 Physicochemical Action of Thiazide 68 Indications and Treatment Guidelines 70 Indications 70 Treatment Guidelines 70 Response to Thiazide Therapy 71 Effectiveness of Combined Thiazide and Potassium Citrate 71 Hazards of Thiazide Therapy 71 References 73 6 Calcium Citrate for the Prevention of Postmenopausal Osteoporosis 76 Historical Considerations 76 Pathophysiology of Postmenopausal Osteoporosis 77 Classification of Osteoporosis 77 Pathogenesis of Postmenopausal Osteoporosis 78 Mechanism of Action of Calcium Supplementation 81 Physiological Action 81 Evidence that Calcium Citrate is an Optimum Calcium Supplement 81 Clinical Responses to Calcium Supplementation 88 Review of Literature 89 Hazards of Calcium Citrate Supplementation 90 Hypercalcemia 90 Renal Stones 91 Aluminum Toxicity 92 References 92 Clare D. Edman 7 Estrogens for Prevention of Postmenopausal Osteoporosis 96 Pathophysiology 96 Mechanism of Action 99 Guidelines to Therapy 100 Type of Estrogen and Route of Administration 101 Minimally Effective Dose 101 Duration of Use 102

8 Contents VIII Estrogens and Calcium 102 Estrogen and Progestin Therapy 103 Uterine Bleeding 104 References 105 Stanley Wallach 8 Calcitonin Treatment of Osteoporosis 108 Historical Considerations 108 Calcitonin Peptides 109 Actions of Calcitonin 109 Calcitonin in Osteoporosis 111 Experimental Results 112 Practical Aspects 114 Side Effects 115 Bone Mass Measurements 116 Coherence and Intermittent Programs Using Calcitonin 117 Calcitonin in Secondary Osteoporosis 119 Calcitonin in Osteoporosis Prevention 120 References Diphosphonate in the Management of Stone and Bone Disease 125 Chemistry 125 Metabolism 125 Physicochemistry 126 Physiological Effects on the Skeleton 127 Inhibition of Bone Mineralization 127 Inhibition of Bone Resorption 127 Varying Skeletal Effects of Diphosphonates 128 Renal Effects of Diphosphonates 129 Intestinal Effects of Diphosphonates 130 Clinical Uses of Diphosphonates 130 Disorders of High Bone Resorption 130 Heterotopic Calcification 133 Miscellaneous Conditions 134 References 135 Subject Index 139

9 Preface Considerable progress has been made recently in the management of nephrolithiasis and osteoporosis. This advance has become largely possible from the evolving pathophysiologic elucidation of these conditions. Thus, treatment modalities could be identified which are capable of correcting the underlying metabolic derangement for various causes of kidney stones and osteoporosis. This book summarizes the clinical pharmacology of nine drugs which are currently available for the management of renal stones and osteoporosis. They are sodium cellulose phosphate for absorptive hypercalciuria, allopurinol for hyperuricosuric calcium nephrolithiasis, potassium citrate for hypocitraturic calcium nephrolithiasis and gouty diathesis, alpha-mercaptopropionylglycine (MPG) for cystinuria, thiazide for hypercalciuric calcium nephrolithiasis, calcium citrate as a general calcium supplement for osteoporosis, estrogen for postmenopausal osteoporosis, calcitonin for `high turnover' osteoporosis, and diphosphonate as an effective antiresorptive agent. Chapters corresponding to the above drugs were written by authors who played key roles in the drug approval by the United States Food and Drug Administration, or who have an extensive personal experience with their use. Each chapter dealing with a separate drug is organized to include a historical perspective, pathophysiology of the treated condition, mechanism of drug action, indication and treatment guidelines, response to treatment, and hazards of treatment. An attempt has been made to describe other treatment options. However, it is acknowledged that the views expressed are those of the authors, which may not always be representative of the beliefs of others in the fields. Moreover, the recommended treatment options are not meant to be definitive. With the continuing evaluation of pathophysiologic elucidation and drug development, it is fully expected that refined, more effective drugs will be formulated in the future. This book is intended for students of endocrinology, urology or mineral metabolism, comprised of medical students, physicians in training and those caring for patients with renal stones and osteoporosis. Charles Y.C. Pak

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