Principles of Pharmacodynamics and Toxicodynamics

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Pharmacodynamics and toxicodynamics relate doses of an agent to the characteristics, quantity, and time-course of its biological effect. Together with pharmacokinetic considerations, the mechanism of action is a key determinant of effect and toxicity. This chapter reviews the terminology, theory, and graphical representation of receptor occupancy by a drug/toxin (Scatchard, sigmoidal log-dose response), and then compares them with graded dose-effect relationships. A brief review of signal transduction mechanisms introduces a more detailed discussion of receptor agonism and antagonism using the reversible two-state receptor theory. Dynamic receptor phenomena leading to hyporeactivity and hyperreactivity are explained through signal transduction and other physiological mechanisms. Finally, methods of estimating drug selectivity and safety (therapeutic index) are summarized. The increasing importance of non-monotonic dose-effect curves, such as those characterized by endocrine disruption, is highlighted. Finally, principles of pharmacokinetic/pharmacodynamic (PK/PD) modeling are outlined as a way of improving clinical trial design. © 2013

Original languageEnglish (US)
Title of host publicationHaschek and Rousseaux's Handbook of Toxicologic Pathology
PublisherElsevier Inc.
Pages61-76
Number of pages16
ISBN (Print)9780124157590
DOIs
StatePublished - Aug 29 2013

Keywords

  • Agonist
  • Antagonist
  • Efficacy
  • Hyperreactivity
  • Hyporeactivity
  • Modeling
  • Potency
  • Receptor
  • Selectivity
  • Transduction

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Ferguson, D. C. (2013). Principles of Pharmacodynamics and Toxicodynamics. In Haschek and Rousseaux's Handbook of Toxicologic Pathology (pp. 61-76). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-415759-0.00003-0