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"What we call the beginning is often the end, and to make an end is
to make a beginning. The end is where we start from." T. S. ELIOT,
"Geroniton" The discovery of endothelin-l was both an end and a
beginning. It is an end because this discovery has started a
plethora of investigations as to endothe1in's sites of production,
mode of action, it's normal and abnormal physiological role and its
involvement in a variety of pathological conditions ranging from
renal failure to myocardial infarction, cardiac hypertrophy,
hyperten sion, cyclosporine induced toxicity, mental depression,
renal failure, stress related illness, and even stroke and sudden
death. It is a beginning because no one can foresee where the
investigations will ultimately lead, or how they will end. The
discovery of the endothelins was a very recent event and soon
specialist books will start to appear dealing in detail with
different aspects of their chemistry, physiological role and
pathological importance. The present book is intended to act as a
guide and primer for those who are becoming intrigued by the many
endothelin related articles which are now appearing in the journals
but who as yet have not had the time or opportunity to be caught up
in the web of enthusiasm and excitement which is motivating those
more directly involved in the field of research.
"Those who choose to increase their knowledge still further by
reading ... will discover an exciting new world. " NOEL WHITTAKER,
in "Making Money Made Simple" 1989. The development of calcium
antagonists has recently been described as representing "one of the
major advances in cardiovascular thera peutics of the latter half
of the twentieth century" (Braunwald, 1990). However, although the
development of these drugs started in the mid nineteen sixties it
is only recently that their real potential has begun to be
appreciated. Even now the calcium antagonist saga is not complete,
since new compounds continue to appear and new therapeutic applica
tions emerge. Based on the experience gained in the clinics in
which these drugs have been used recognition is being given now to
the need to improve upon the prototypes of the group. Such
improvement is resulting in the development and production not only
of long-acting formulations of the prototypes (nifedipine,
verapamil and diltiazem) but also of new calcium antagonists with
improved tissue selectivity, potency and duration of action. To
those of us who are interested in this field such a development is
both exciting and rewarding. As far as the clinicians who prescribe
these drugs are concerned the long-acting nature of some of the
newer calcium antagonists should make the satisfactory management
of their patients an achievable goal."
"Another damned, thick, square book! Always scribble, scribble,
scribble! Eh! Mr. Gibbon?" From the Literary Memoirs of Willi am,
DUKE OF GLOUCESTER, 1743-1805 The foreword of any book is probably
the most difficult to write -not only because it stands at the
beginning of an exercise in writing and logic but because it is in
this chapter that areader can expect to find a clear and
unambiguous explanation of the author's reason for writing the book
and why some subject matter has been included and other subject
matter excluded. Potential readers ofthis book may not have an
inclination to question why some subject matter has been excluded
but instead may wonder why another book on calcium antagonists has
been published. However, it is arguable with some force that there
have been at least three recent developments in the field of
calcium antagonism which provide more than adequate support for the
view that another book on this topic is warranted. These
developments include: (i) an improved understanding of the chemical
structure, mode of action and architecture of the
voltage-activated, calcium antagonist-sensitive calcium channels
and their associated calcium-antagonist specific binding sites;
(ii) a more accurate appreciation ofhow and when the calcium
antagonists should be used in the management of a variety of
clinical dis orders including cerebral ischaemia atherosclerosis,
"mild" ischaemic heart disease, ventricular hyper trophy, impaired
ventricular relaxation and hypertension (to name but a few), and
(iii) the emergence of a second generation of calcium antagonists.
This is the first book to summarize experimental results from the
new, rapidly expanding field of research into the calcium channel
in cell membrane. Calcium is an ubiquitous messenger of various
cellular functions. Its fundamental role in the regulation of
cardiac contractions has long been recognized. Drugs counteracting
some actions of calcium ions, namely calcium antagonists, have
since become essential to research. In the last decade it has been
established that calcium ions reach their target intracellular
system by passing through specialized calcium channels in the
membrane. Recently improved experimental techniques combined with
the discovery of highly specific Ca channel ligands have
dramatically enlarged our knowledge of the molecular structure and
function of such channels. The contributions by leading world
specialists shed new light on both basic science and possible
clinical implications for cardiovascular pharmacology,
endocrinology and neuropharmacology.
Die Entwicklung von Calciumantagonisten wurde erst k}rzlich als
einer der gr] ten Fortschritte in der Therapie von kardiovaskul{ren
Erkrankungen in der 2. H{lfte des 20. Jahrhunderts beschrieben.
Obwohl die Entwicklung dieser Medikamente bereits Mitte der
sechziger Jahre begann, werden die therapeutischen M]glichkeiten
erst seit kurzem genutzt. Die Information, diein diesem Buch
geboten wird, ist zusammengestellt, um das Interesse des Lesers an
dem langwirksamen Calciumantagonisten Amlodipin zu wecken. Es
werden sowohl Eigenschaften von Amlodipin beschrieben als auch
Vorteile dieses Therapeutikums im Vergleich zu anderen
Calciumantagonisten herausgearbeitet. Das Buch ist besonders
interessant f}r klinisch t{tige rzte, die derartige Medikamente
verschreiben und eine optimale Therapieihrer Patienten anstreben.
Schon wieder so ein verdammtes, dickes, spiessiges Buch! Immer
kritzeln, kritzeln, kritzeln, nicht wahr, Mr. Gibbon! Aus den
Literarischen Memoiren von Herzog Wilhelm von Gloucester, 1743-1805
Bei jedem Buch ist das Vorwort wahrscheinlich das Schwierigste.
Nicht nur weil es am Beginn einer UEbung im Schreiben und im
folgerichtigen Denken steht, sondern weil der Leser an dieser
Stelle eine eindeutige Erklarung dafur erwarten kann, warum das
Buch uberhaupt geschrie- ben wurde und warum manche Themen
besprochen, andere hingegen weggelassen wurden. Mancher Leser wird
sich vielleicht keine Gedanken daruber machen, warum der eine oder
andere Punkt nicht erwahnt wurde; er wird sich vielmehr fragen,
warum schon wieder ein Buch uber Calciumantagoni- sten erscheint.
Ich glaube aber, es kann mit Fug und Recht behauptet werden, dass
auf diesem Gebiet in der letzten Zeit zumindest drei Ent-
wicklungen zu verzeichnen waren, welche die Veroeffentlichung eines
neuen Buches zu diesem Thema unbedingt gerechtfertigt erscheinen
las- sen: I. Wir wissen heute mehr uber die chemische Struktur, die
Wirkungs- weise und den Aufbau der spannungsempfindlichen, auf
Calcium- antagonisten ansprechenden Calcium-Kanale und ihre fur
Calcium- antagonisten spezifischen Bindungsstellen. II. Die
Anwendungsmoeglichkeiten von Calciumantagonisten zur Be- handlung
einer Vielfalt von Erkrankungen wie zerebrale Ischamie,
Atherosklerose, leichte ischamische Herzkrankheit, Linksherz-
hypertrophie, beeintrachtigte ventrikulare Relaxation und Hyper-
tonie, um nur einige zu nennen, koennen heute besser beurteilt wer-
den. 111. Eine zweite Generation von Calciumantagonisten ist jetzt
verfugbar.
Dieses Buch gibt einen hervorragenden Uberblick uber den Stand der
wissenschaftlichen Forschungen auf dem Gebiet der Pharmakologie der
Calcium-Antagonisten. Die Pharmakokinetik der verschiedenen
Calcium-Antagonisten wird ebenso beschrieben, wie die Anwendung in
der Praxis bei den verschiedensten Erkrankungen des
Herz-Kreislauf-Systems. Nebenwirkungen, Risiken und
Kontraindikationen sind ein weiteres wichtiges Thema. Zum Schluss
wird ein Ausblick auf die Zukunft dieses vielseitigen Medikamentes
gegeben.
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