Antiemetic Therapy - J. Donnerer (Karger, 2003) WW

241 Pages·2003·5.42 MB·English

Antiemetic Therapy

www.anaesthesia-database.blogspot.com

Antiemetic Therapy

Basel · Freiburg · Paris · London · New York ·
Bangalore · Bangkok · Singapore · Tokyo · Sydney

Editor

Josef Donnerer
Graz

39 figures, 1 in color, and 28 tables, 2003

DrWael

Prof. Dr. Josef Donnerer
Institut für Experimentelle und
Klinische Pharmakologie
Karl-Franzens-Universität Graz (Austria)

Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and
Index Medicus.

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.

© Copyright 2003 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel
ISBN 3–8055–7547–5

Library of Congress Cataloging-in-Publication Data

Antiemetic therapy / editor, Josef Donnerer.
p. ; cm.
Includes bibliographical references and indexes.
ISBN 3–8055–7547–5 (hard cover : alk. paper)
1. Antiemetics. 2. Vomiting–Treatment. 3. Nausea–Treatment. I. Donnerer, Josef.
[DNLM: 1. Antiemetics–therapeutic use. 2. Vomiting–drug therapy. 3. Nausea–drug
therapy. 4. Nausea–physiopathology. 5. Vomiting–physiopathology. WI 146 A629 2003]
RB150.N38A58 2003
616�.047–dc21
2003040097

DrWael

Contents

VII Preface

1 The Emetic Reflex Arc
Donnerer, J. (Graz)

11 Receptive Mechanisms of Noxious Stimulation of Emesis
Lang, I.M. (Milwaukee, Wisc.)

22 5-HT3 Receptor Antagonists in Antiemetic Therapy
Donnerer, J.; Beubler, E. (Graz)

33 The Site of the Antiemetic Action of NK1 Receptor Antagonists
Fukuda, H.; Koga, T.; Furukawa, N.; Nakamura, E.; Harano, M.; Yanagihara, M.
(Kurashiki)

78 Potential of Substance P Antagonists as Antiemetics
Diemunsch, P. (Strasbourg); Grélot, L. (Marseille)

98 Neuronal Mechanisms and Treatment of Motion Sickness
Schmäl, F.; Stoll, W. (Münster)

113 Management of Opioid-Induced Nausea and Emesis
Aparasu, R.R. (Brookings, S. Dak.); Aparasu, A. (Sioux Falls, S. Dak.)

121 Prevention and Treatment of Postoperative Nausea and Vomiting
Kovac, A.L. (Kansas City, Kans.)

161 Metoclopramide for the Control of Postoperative Nausea and Vomiting
Henzi, I.; Tramèr, M.R. (Genève)

169 Prevention of Delayed Nausea and Emesis Induced by Chemotherapy
Roila, F. (Perugia)

179 Prophylaxis of Radiation-Induced Emesis
Maranzano, E. (Terni) DrWael

Contents
VI

192 Pharmacotherapy for Nausea and Vomiting in Early Pregnancy
Kus¸cu, N.K. (Manisa)

204 Hyperemesis gravidarum in the Clinical Setting
Eliakim, R. (Haifa); Abulafia, O.; Sherer, D.M. (Brooklyn, N.Y.)

226 Author Index

227 Subject Index

Preface

Prevention and treatment of nausea and emesis are very important issues
for the patient’s well-being under different clinical as well as outpatient situa-
tions. This multidisciplinary book on this topic should bridge the gap between
basic research and clinical practice, and we hope that many scientists will be
able to benefit from it. In this context I am very grateful to everybody who was
involved in the preparation and completion of this book.
Various and partly still unresolved pathomechanisms play roles in nausea
and emesis in humans, and appropriate animal models are not always available
for preclinical research on antiemetic drugs. Therefore, only the results from
studies in the clinical setting can decide a new compound’s utility. Basically, we
have a rather small number of drugs in the established treatment regimens, how-
ever some new interesting compounds are being studied in clinical trials.
The aim of this book on the one hand is to lead to a better understanding
of the pathophysiology of nausea and emesis under different conditions, and on
the other to provide an update of the treatment regimens. Specifically, the
increasing use of emetogenic anti-cancer chemotherapy needs the best preven-
tion and treatment strategies to control its nausea- and emesis-provoking side
effects. Vomiting might also be a complicating factor in radiation therapy and
surgery. On the other hand, in women affected by nausea and vomiting in early
pregnancy, the question of drug treatment versus non-treatment has to be
answered.
Essentially, this book should serve the clinician. In collecting the articles
we aimed at providing a ‘state-of-the-art’ overview of the selection of
antiemetic drugs available and their dosages and routes of administration under

VII

specific clinical conditions. After a few decades of intense research, we are in
the fortunate situation that in almost every relevant clinical condition of nausea
and emesis, a collection of investigations has put forward clear conclusions for
the best treatment modalities.
Whereas the main task of collecting these papers was to serve the clinician
when making the right choice for every patient’s needs, the book also pays
significant attention to the interests of scientists in basic research as well as
academic teachers.
Josef Donnerer
September 2002

Preface
VIII

Donnerer J (ed): Antiemetic Therapy.
Basel, Karger, 2003, pp 1–10

The Emetic Reflex Arc

Josef Donnerer

Institute of Experimental and Clinical Pharmacology, University of Graz, Austria

The emetic reflex is an autonomous defense reaction of the gastrointesti-
nal tract, aimed at eliminating noxious agents, in a similar way as the cough
reflex or sneezing is aimed at eliminating irritating particles from the respira-
tory tract. Therefore, in many instances, nausea and emesis are evoked by
ingestion of spoiled food, too much alcohol, or simply by eating too much.
Under these circumstances the ability to detect and to eject potential toxic sub-
stances from the gastrointestinal tract can be regarded as a useful reaction.
However, nausea and emesis can also represent general symptoms of a disease
or they are side effects of certain drug actions. Under these latter circum-
stances, the emetic reflex has to be regarded as a more general defense reaction
against potential toxic substances; the toxic substances are, however, in the
bloodstream and cannot be eliminated anymore by vomiting. These conditions
are very stressful for the patient and need efficient therapy. Examples represent
chemotherapeutic agents inducing nausea and emesis for hours and days with-
out eliminating any toxins from the body, postoperative nausea and vomiting,
hyperemesis gravidarum and nausea in the course of opioid therapy.

Neuronal Structures Involved in the Emetic Reflex Arc

The receptive pathway of the emetic reflex is a build-up of different sen-
sors and receptors in the periphery as well as within the CNS [1]. Sensory
impulses are conveyed by afferent neurons towards a medullary control center.
In the so-called ‘vomiting center’, impulses are integrated and transmitted onto
motor and autonomic output limbs to elicit either the feeling of nausea, retch-
ing or emesis. Although the receptive pathways may be different, all sensory
pathways converge on a common preprogrammed motor and autonomic output
to the digestive tract.

Many neurotransmitter receptors are present on this reflex arc, which can
be selectively influenced by antiemetic drugs. Depending on the noxious agents
and the anatomical location of the pathways, different receptors may be
involved and different therapeutic drugs are effective.
Within the CNS there are three structures that can be regarded as central
coordination areas of the emetic reflex (fig. 1). They are located in the medulla/
brainstem region. Vomiting is coordinated by a distributed medullary control
system rather than a unique, well-defined vomiting center. Neurons involved
are embedded in an arc of neurons radiating from the area postrema and nucleus
of the solitary tract (NTS) through the intermediate reticular zone of the lateral
tegmental field to the ventrolateral medulla. These functional areas are located
close to or are integrated into nuclei of the vagus nerve, the most important
input for the emetic reflex. The vomiting center represents the central connec-
tion between sensory afferents and motor and autonomic efferents [2–4].
The ‘chemoreceptor trigger zone’ (CTZ) of the area postrema is situated
nearby, which serves the central detection of noxious agents that circulate in the
bloodstream and in the cerebrospinal fluid. This area on the floor of the fourth
ventricle is on the one hand directly exposed to the cerebrospinal fluid, and can
detect noxious agents that are present in it, and on the other hand it contains
a dense vascular network of fenestrated capillaries. In this way, substances
circulating in the blood can be detected that would not penetrate the blood-brain
barrier. Chemoreceptors in the area postrema, which are outside the blood-
brain barrier, are sensitive to circulating emetic agents such as apomorphine,
cytotoxic drugs and dopamine.

Donnerer
2

Chemoreceptor
trigger zone

Vomiting center

Anatomical overview

Nucleus of the
solitary tract

(Vagus nerve)

Fig. 1. Structures within the CNS that can be regarded as central coordination areas of
the emetic reflex.