A theory of drug tolerance and dependence II: the mathematical model

Peper, A.

doi:10.1016/j.jtbi.2004.04.009

Cited by 17 publications

(35 citation statements)

References 5 publications

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“…In addition to this dynamic action, a lasting shift in functioning develops. In the mathematical model described previously, these two activities are modelled with a fast and a slow regulator respectively (Peper et al 1987(Peper et al , 1988Peper 2004aPeper , 2004b, illustrating the twofold effect of drugs. A drug not only causes a direct, relatively short lasting effect, but it also fundamentally changes the level of functioning of the processes involved.…”

Section: A Dynamic Model Of the Dose-response Relationmentioning

confidence: 99%

“…As the model is a general model of tolerance development and does not describe a specific process, the vertical axes in the figures are in arbitrary units. an exogenous substance of the same composition (see Peper 2004b). The diagram comprises the digestive tract, the bloodstream, the process, the process regulator and an adaptive regulator.…”

Section: A Dynamic Model Of the Dose-response Relationmentioning

confidence: 99%

“…The capacity of the body to suppress disturbances-in the model domain represented by the open loop gain of the regulation loop (Peper et al 1988;Peper 2004b)-is of major importance. The latter parameter is not fixed but depends on health and age (Mitchell et al 1970;Verveen 1978Verveen , 1983Peper et al 1987Peper et al , 1988Peper 2004a;).…”

Section: Sensitization and Other Paradoxical Effectsmentioning

confidence: 99%

“…In previous publications, a model of drug tolerance and dependence was presented (Peper et al 1987(Peper et al , 1988Peper and Grimbergen 1999;Peper 2004aPeper , 2004b. The two 2004 papers present an advanced mathematical model of intermittent adaptation describing the mechanism of tolerance development and elaborate the theory underlying the model (Peper 2004a(Peper , 2004b.…”

Section: Introductionmentioning

confidence: 99%

“…Feedback systems lack the capacity for learning, which is a vital tool in the development of tolerance to repeated drug administrations (Thorpe 1956, Siegel 1983, Peper et al 1987. Learning is the domain of adaptive processes and in earlier work it was argued that the development of tolerance is an adaptive process (Peper et al 1988;Peper 2004aPeper , 2004b. Although adaptive processes generally also use feedback, they constitute a class of regulated processes essentially different from and much more complex than feedback processes and the two should be kept distinct.…”

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confidence: 99%

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Aspects of the Relationship between Drug Dose and Drug Effect

Peper

2009

Dose-Response

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ᮀ It is generally assumed that there exists a well-defined relationship between drug dose and drug effect and that this can be expressed by a dose-response curve. This paper argues that there is no such clear relation and that the dose-response curve provides only limited information about the drug effect. It is demonstrated that tolerance development during the measurement of the dose-response curve may cause major distortion of the curve and it is argued that the curve may only be used to indicate the response to the first administration of a drug, before tolerance has developed. The precise effect of a drug on an individual depends on the dynamic relation between several variables, particularly the level of tolerance, the dose anticipated by the organism and the actual drug dose. Simulations with a previously published mathematical model of drug tolerance demonstrate that the effect of a dose smaller than the dose the organism has developed tolerance to is difficult to predict and may be opposite to the action of the usual dose.

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Section: A Dynamic Model Of the Dose-response Relationmentioning

confidence: 99%

Section: A Dynamic Model Of the Dose-response Relationmentioning

confidence: 99%