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      Clinical Observations on the Mechanism of the Antidiuretic Action of Chlorpropamide in Vasopressin-Sensitive Diabetes insipidus and in Normal Subjects

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          Abstract

          The antidiuretic action of chlorpropamide has been amply confirmed since the observations of Arduino and his colleagues in Brazil (1966). We have studied the initial and long-term response of 21 patients with the syndrome of diabetes insipidus. There was a consistent decrease in free water clearance usually to a negative value, which was unaffected by salt restriction. Other clinical studies in these patients, including hypertonic saline infusion, vasopressin administration, water loading and the pharmacological administration of alcohol produced data consistent with the proposed mechanism of action, to potentiate the normal effect of circulating vasopressin on the distal nephron. Free water clearance also became increasingly negative in 4 of 5 normal subjects, but was unaffected in 2 patients with polyuria due to diabetes mellitus. There was a consistent decrease in fluid intake relative to urine output during the initial phase of treatment of diabetes insipidus, suggesting a possible effects via a thirst mechanism, but this effect was not clearly demonstrated in normal subjects. The subsequent clinical course over 3 years of these patients, emphasising the danger of hypoglycaemia in coincident hypopituitarism and in children is discussed.

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          Author and article information

          Journal
          HRE
          Horm Res Paediatr
          10.1159/issn.1663-2818
          Hormone Research in Paediatrics
          S. Karger AG
          1663-2818
          1663-2826
          1972
          1972
          21 November 2008
          : 3
          : 2
          : 77-96
          Affiliations
          The Metabolic Unit, Royal Victoria Hospital, Belfast
          Article
          178259 Hormones 1972;3:77–96
          10.1159/000178259
          71136442-a06c-440a-a5f1-1698b89368b9
          © 1972 S. Karger AG, Basel

          Copyright: 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. 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 changes 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. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          History
          Page count
          Pages: 20
          Categories
          Paper

          Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
          Free water clearance,Chlorpropamide,Mefruside,Central thirst centre,Diabetes insipidus,Osmolality,Hypothalamus,Diabetes mellitus,Vasopressin,Antidiuretic hormone (ADH)

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