British Journal of Anaesthesia, 2003, Vol. 91, No. 5 764-765
© 2003 The Board of Management and Trustees of the British Journal of Anaesthesia
Book Review |
Pharmacology, 5th Edn
Oxford, UK
Pharmacology, 5th Edn.
H. P. Rang, M. M. Dale, J. M. Ritter and P.K. Moore.
Published by Churchill Livingstone, Edinburgh.
Pp. 797; indexed; illustrated. Price £38.99. ISBN 0443071454.
This new edition contains a number of major changes in both format and style, with the addition of colour to the figures (many of which stand on their own without referral to the accompanying text), and tables throughout the text. One key improvement has been the addition of an overview section at the beginning of each chapter, allowing the reader a clear summary of the breadth of the content. Other new innovations are the addition of ‘small print’ sections in most chapters (not too many of them, and not always where you think they might be most useful), and extensive lists of references and further reading. The latter has clearly been reviewed at the proof stage of this book, as several chapters have references relating to papers published in 2001 and 2002.
The book is divided into six sections: General Principles; Chemical Mediators; Drugs Affecting Major Organ Systems; the Nervous System; Drugs Used in the Treatment of Infections and Cancer; and Special Topics. Three of these sections are worthy of specific further comment.
Section 1 (General Principles) has a new introductory chapter and also includes two chapters on cellular mechanisms. All three are first rate, and should be usefully read by all Primary FRCA candidates. Similarly, the chapters on absorption and distribution of drugs and drug elimination and pharmacokinetics are not overwhelmed by mathematical equations, and again offer much to the anaesthetist studying for the various examinations.
In Section 6 (Special Topics), there are good chapters on individual variation and drug interactions, the adverse effects of drugs, and the use of gene therapy as a treatment modality. A further chapter examines the various stages that go into a drug’s discovery and development by the pharmaceutical industry. The cost of this process is put at about £250–500 million per drug (does this include the cost of the pre-clinical screening of potential compounds?), and goes some way to explaining why the rate of introduction of new drugs world-wide has declined since the peak of around 60 new drugs per year at the end of the 1970s. There is new information on use of disease models such as transgenic animals in drug testing.
In Section 2 (Chemical Mediators), there is considerable information on control of nitric oxide synthesis and other endothelial-derived mediators, as well as neuromuscular blocking drugs (Chapter 10) and autonomic nervous system (Chapter 9). The latter two chapters integrate physiology and pharmacology, and again deserve to be widely read by trainee anaesthetists.
Within the section on the effects of drugs on the major organ systems, there are useful and up-to-date chapters covering the treatment of cardiac failure, the use of statins and their effects on lipid metabolism, as well as full coverage (again integrating physiology and pharmacology) of the control of and effects of drugs on blood glucose (including detailed discussion of the thiazolinediones), and treatments of obesity. Bone metabolism is expanded with new information on the interaction between osteoblasts and osteoclasts (although sadly here is an example of incomplete editing as it appears as Chapter 30 in the text not 32 as cited in the introductory preface!). Similar misquoting occurs in regard to Chapter 46 on antiviral agents (not 47 as in the preface).
Of special interest to anaesthetists should be the chapters on anaesthetic drugs and their mechanisms of action (Chapter 35) and local anaesthetics (Chapter 43), although there are no obvious drug concentration–effect relationships defined for the common local anaesthetic agents. The reasons for the high cardiotoxicity of bupivacaine are not delineated (these include high tissue binding, high affinity to the myocyte membrane, and low systemic clearance), and there is an unfortunate error in figure 36.4 where nordiazepam appears as nordazepam!
I was disappointed, however, by the chapter on volatile and i.v. hypnotic drugs (Chapter 35). There is still considerable discussion of the Meyer-Overton theory as a mechanism for anaesthesia, without mentioning the limitations of this model (such as the relationship between the lipid:gas solubility coefficient for anaesthetic agents and those volatile compounds with similar physicochemical properties but without activity or being less potent than might be predicted from their lipophilicity, and hence described as non-immobilizers and transitional compounds, respectively, by Eger and colleagues1). The authors make little comment on the role of chirality studies in defining the possible site of anaesthetic action, nor much on anaesthetic–protein and anaesthetic protein–lipid interactions.
There is discussion on all the current volatile agents, but the section on Intravenous Drugs focuses mainly on thiopental, with etomidate limited to 12 lines, and surprisingly, propofol dismissed in nine lines! The pharmacology of ketamine and midazolam are both brief, with no comment on the place or role of S(+) ketamine. Nowhere is there discussion of how these i.v. drugs may work (there are now papers showing the effects of clinically relevant drug concentrations on a number of model systems including the Xenopus oocyte). However, to be fair to the editors, mention of the effects of benzodiazepines on GABA-A receptors does occur in the following chapter on anxiolytic and hypnotic drugs, where they also discuss the concept of benzodiazepine inverse agonists and antagonists.
Chapter 15 (Local Hormones, Inflammation and Immune Reactions) is another good chapter for the anaesthetist to read, but although anaphylaxis is discussed, there is no clear didactic account of its management until page 735 (and then only relating to the effects on the cardiovascular system and ignoring the need to consider the airway and oxygenation).
Overall, there is no doubt that this new edition of a classic text represents a key reference volume for the clinician. If I was asked about its use as a text for the Primary FRCA, I would have to feel there were better volumes for that particular examination. However, if all anaesthetists were to rightly view the pivotal role of pharmacology in our daily activities, then this volume (at a very modest price for a major textbook) should be on everyone’s bookshelves. Certainly I expect my copy to be widely used!
References
1 Fang Z, et al. Effects of inhaled nonimmobilizer, proconvulsant compounds on desflurane minimum alveolar anesthetic concentration in rats. Anesth Analg 1997; 85: 1149–53[Abstract]
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