HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Frattarelli, D. A. C. Search for Related Content PubMed PubMed Citation Articles by Frattarelli, D. A. C. Social Bookmarking                   What's this?

Adverse Drug Reactions and Avalanches: Life at the Edge of Chaos

From Wayne State University School of Medicine, Division of Clinical Pharmacology and Toxicology, Children's Hospital of Michigan, Detroit.

Although many reports have described the incidence of adverse drug reactions, none have explained their variable severity or why they happen. Because human physiology shares many of the features of other complex adaptive systems, reactions to drug therapy were examined mathematically for specific patterns to show (1) that the severity of adverse drug reactions follows a distribution seen in other complex adaptive systems, called a power law distribution, and (2) that preventable reactions occurred for reasons fundamentally different from those that underlie the nonpreventable reactions. Two reports detailing adverse drug reaction incidence and severity were evaluated: a meta-analysis of prospective adverse drug reaction studies and a prospective cohort study. Incidence of drug reaction was plotted as a function of severity and fit to an equation. The incidences of overall and nonpreventable drug reaction, plotted as a function of severity, followed a similar power law distribution regardless of sample size or the nature of the population or drugs studied. An exception to this was the preventable reactions, which were described by a different type of equation. Response to pharmacotherapy exhibits many properties of systems with self-organized criticality. An exception to this is the preventable reactions, which seem to be fundamentally different from the nonpreventable ones. These observations suggest that the presence and the distribution of severity of reaction to pharmacotherapy is a consequence of our adaptation as biological systems, and although adverse reactions can be made less frequent, a certain percentage will not be preventable.

Key Words: Adverse drug reactions • power laws • complex systems • systems biology

Address for reprints: Daniel A. C. Frattarelli, MD, Wayne State University School of Medicine, Division of Clinical Pharmacology and Toxicology, Children's Hospital of Michigan, 3901 Beaubien, Detroit, MI 48201.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Dokoumetzidis and P. Macheras A comment on "adverse drug reactions and avalanches: life at the edge of chaos". J. Clin. Pharmacol., September 1, 2006; 46(9): 1057 - 1058. [Full Text] [PDF]

				D. A. Frattarelli Author's Response J. Clin. Pharmacol., September 1, 2006; 46(9): 1059 - 1060. [Full Text] [PDF]