Lack of Response to a Drug: A System Theory Approach

Abstract

It seems necessary to consider the functioning of biological systems on the basis of agonistic and antagonistic actions of a couple of elements. Here, the adrenal postpituitary system is considered. We show how such a view allowed us to give an account of diverse phenomena, noticeably the lack of response to Cortisol. It gave also rise to “paradoxical” therapies in the sense that both hormones had to be administered in case of an imbalance. A mathematical model helps one to become accustomed to these notions and, perhaps, is able to directly improve therapeutical strategies.

Agonistic Antagonistic Systemics: An Introduction To Bilateral — and Paradoxically Unilateral — Strategies

“…In order to explain the gap between the in vitro and the in vivo effects of adrenal hormones, we proposed the intuitive (and experimentally verified) notion of a "neuropostpituitary response to an adrenocortical load" that increases again the already increased secretion of VP. We called this phenomenon "pathological homeostasis" of Type I [24].…”

“…The purpose of BT is as follows: owing to the complex intricacy of negative and positive feedback, direct or crossed, the administration of AA agents should also provoke the restoration of a normal balance where the sum of endogenous secretion of CT and administered CT would match the sum of VP secreted and administered. Our first uses of such a combination were performed in 1954, concerning pathological brain hydration [25], and in 1959, concerning brain malignant processes [24,26].…”

Integrative System Theory of Hippocampal-Hypothalamic-Pituitary-Adrenal Axis for Cortisol Feedback Dysfunctions and Feedback Drug Therapies

“…In the 90s, Bernard-Weil and Claude were pioneering what was probably the first clinical therapeutical application of system theory in clinical neuroendocrinology (13,14).…”

“…The HPA block diagram and model can also be expanded to include aldosterone (17) and arginine vasopressin (AGV) (13,14) for various clinical therapeutic applications given the connections between these and cortisol.…”

“…The immediate merit of a mathematical system theoretic approach in neuroendocrinology is the revelation of a new typology and classification of dysfunctions/pathologies based on the feedback and feedforward circuitry as well as the revelation of sometimes new and even counter-intuitive drug therapies or therapeutic strategies to fix those dysfunctions (13,14,21,25,32).…”