Principles of Pharmacodynamics and Toxicodynamics

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Pharmacodynamics (PD) and toxicodynamics relate doses of an agent to the characteristics, quantity, and time course of its biological effect. Together with pharmacokinetic (PK) 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 nonmonotonic dose-effect curves, such those characterized by endocrine disruption, is highlighted. Finally, principles of PK/PD modeling are outlined as a way of improving clinical trial design.

Original languageEnglish (US)
Title of host publicationFundamentals of Toxicologic Pathology
EditorsMatthew A Wallig, Wanda M Haschek, Colin G Rousseaux, Brad Bolon
PublisherAcademic Press
Pages47-58
Number of pages12
Edition3
ISBN (Electronic)9780128098424
ISBN (Print)9780128098417
DOIs
StatePublished - Jan 1 2018

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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