Introduction

Systems therapeutics defines where pharmacologic processes and pathophysiologic processes interact to produce a clinical therapeutic response. A systems therapeutics diagram has been constructed (1), consisting of two rows of four parallel systems components for pharmacologic and pathophysiologic processes, representing the four different biologic levels of interactions between these two processes, i.e., at the molecular level, the cellular level, the tissue/organ levels, and the clinical level, culminating in a therapeutic response. The interactions at these different biologic levels then determine the four different systems therapeutics categories, Categories I – IV. The above referenced summary only named therapeutic class examples for each of the four systems therapeutics categories, but did not include representative illustrative examples for each of these categories.

The purpose of this post is to provide an illustrative example for one of the systems therapeutics categories, Category II, where the pivotal interaction between the pharmacologic and pathophysiologic processes involves a fundamental biochemical mechanism at the cellular level, related to the disease evolution, although not necessarily an etiologic pathway. The illustrative example chosen for Category II involves Proton Pump Inhibitors for Gastroesophageal Reflux Disease (GERD) and Peptic Ulcer Disease (PUD). Future communications will provide illustrative examples for the other systems therapeutics categories.

Illustrative Example for Category II

The chart below (click for a larger view) illustrates the individual systems components for pharmacologic and pathophysiologic processes for Proton Pump Inhibitors for Gastroesophageal Reflux Disease (GERD) and Peptic Ulcer Disease (PUD), culminating in a therapeutic response.

This chart follows the design of the systems therapeutics diagram previously referenced (1), which includes definitions of the individual systems therapeutics categories and a glossary of the individual systems components. The chart was developed using OmniGraffle (The Omni Group, Seattle, WA). The bold connection between pharmacologic and pathophysiologic processes represents the pivotal interaction between these processes, which here is at the cellular level (Category II). The descriptions for the individual systems components were generated from generally available textbooks of pharmacology, pathophysiology and medicine, and other sources, but with an emphasis on a separation of pharmacologic and pathophysiologic concepts and processes, culminating in a therapeutic response.

Comments

The systems therapeutics framework referenced above (1), including a diagram, four categories, definitions and a glossary, was constructed with the goal of serving to facilitate discussion and understanding of the different types of FDA approved drugs. Importantly, this framework attempts to illustrate the pharmacologic processes and the pathophysiologic processes separately, rather than exhibiting a singular pharmacotherapeutic process, in contrast to previously published attempts, thus enabling highlighting at what level the pharmacologic process engages with the pathophysiologic process. It has previously been noted that this systems-based framework does not explicitly address interpatient variability in therapeutic response, although this framework clearly suggests that variabilities in pharmacologic processes and pathophysiologic processes both contribute to the overall variability in therapeutic response. A general commentary on variabilities in pharmacologic processes (pharmacokinetics and pharmacodynamics) and pathophysiologic processes (disease initiation and disease progression) has been previously published (2).

The chart presented in this publication has provided a representative illustrative example for one of the four systems therapeutics categories (Category II). It is hoped that this illustration will serve as a useful example of how the systems therapeutics framework can provide a framework for facilitating discussions concerning various aspects of different therapeutics, as well as suggesting areas in need of future research and better understanding.

References

1. Systems Therapeutics: Where Pharmacologic and Pathophysiologic Processes Interact. Therapeutics Research Institute, February 2017.
   This post summarizes the systems therapeutics framework, including the systems therapeutics diagram, its four categories, related definitions, as well as a glossary. Note the example presented above for Category II was initially named as Category III.
2. Systems Therapeutics: Variabilities. Therapeutics Research Institute, May 2016. 
   This post discusses variability in pharmacologic processes (pharmacokinetics and pharmacodynamics) and pathophysiologic processes (disease initiation and disease progression). Note the systems therapeutics diagram in this post represents an earlier version of the diagram.