A theory of drug tolerance and dependence I: a conceptual analysis

Journal of Theoretical Biology
Abraham Peper

Abstract

A mathematical model of drug tolerance and its underlying theory is presented. The model extends a first approach, published previously. The model is essentially more complex than the generally used model of homeostasis, which is demonstrated to fail in describing tolerance development to repeated drug administrations. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary only in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behavior to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity ...Continue Reading

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Citations

Jan 24, 2007·Psychopharmacology·Karl J KaiyalaDouglas S Ramsay
Apr 30, 2010·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Karl J Kaiyala, Douglas S Ramsay
Oct 4, 2006·Homeopathy : the Journal of the Faculty of Homeopathy·M Z Teixeira
Jun 23, 2009·Dose-response : a Publication of International Hormesis Society·Abraham Peper
Nov 26, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Karl J Kaiyala, Douglas S Ramsay
Sep 6, 2014·Behavioural Pharmacology·Juan D DeliusRita Leydel
Sep 4, 2019·Theoretical Biology & Medical Modelling·Vladimir N Melnikov
Nov 6, 2020·Communicative & Integrative Biology·Abraham Peper
Oct 15, 2020·Issues in Mental Health Nursing·Carrie N Lingerfelt, Sadie P Hutson

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