Selective Toxicity. (Fifth Edition)

Selective Toxicity is an exposition of the many chemical and biological principles that allow drugs to act selectively. To incorporate both pharmacodynamics and chemotherapy into the discussion, a rather broad definition of "selective toxicity" is adopted ..."the injury of one kind of living matter without harming another kind...."); thus propranolol is viewed as a reversible antagonist (injurer) of A-receptors and penicillin as an irreversible injurer of gram-positive bacteria. Chapters are built around the mechanisms of and principles behind selectivity, and examples are chosen from past and present pharmacopoeias to illustrate the reduction of theory to practice. For instance, the penicillins are discussed in the chapters on comparative cytology (structure of bacterial cell walls), principles of chemotherapy (problem of resistant organisms), covalent bonds (details of acylation of cell wall components), and steric factors (reactivity of the ,3-lactam ring). Albert's writing is crisp and remarkably jargon-free. The readability of Selective Toxicity is commendable, but occasionally mechanisms are summarized too tersely, neatly, and uncritically, and the novice may be led to believe that drugs are more selective than they really are. Cardiac glycosides are said to have a "direct and selective action on heart muscle"; no discussion of their neurotoxic side effects appears. Chloramphenicol is said to "specifically inhibit protein synthesis in bacterial ribosomes"; the occasional action on human bone marrow leading to aplastic anemia is not mentioned. As for drug design gone awry, thalidomide's teratogenic action is only mentioned once, in passing, in one sentence in the book. Specialists and careful readers will find a few technical errors in the text. Notable ones occur in the discussion of Lineweaver-Burk plots (Km is not "shown at the intersection of slope and ordinate") and in the chapter on steric factors (after a lucid discussion of the rectus/sinister convention, the structures of ephedrine and pseudoephedrine are drawn correctly, but the configurations are misassigned). Selective Toxicity is not a comprehensive treatment of either medicinal chemistry or pharmacology and cannot be recommended as the principal text in a course in either discipline. But selected chapters are highly recommended as stimulating supplementary reading. Albert's book illustrates, over and over again, how seemingly irrelevant work in organic chemistry and comparative biochemistry can lead to medical advances. In an era of diminished funds for basic research, this point cannot be made too often.