Aspects of the Relationship between Drug Dose and Drug Effect

Abstract

ᮀ 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.

Anticholinergic drugs and oral health-related quality of life in patients with schizophrenia: a pilot study

“…This dose-dependent therapeutic domain differs not only between drugs but also between patients. The effect of a certain dose of a certain drug on an individual is difficult to predict, as it depends on several and very different parameters, such as the magnitude of the compensatory response, the level of tolerance, the subject's state of health and the history of the drug administration [48].…”

Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial

“…It is therefore plausible to hypothesize that acute effects of sucralose on S I are different from chronic effects due to the development of compensatory responses (i.e., tolerance) to the consumption of sucralose. Typically, once tolerance to a substance has been developed, exposure to a smaller dose of such a substance, or to stimuli conditioned to the presence of the substance (such as its "taste") triggers the compensatory response, which is commonly opposite to the initial acute effects of the substance [38].…”

Hormesis and homeopathy: The artificial twins

“…Homeopathy claims a curative reaction from a small dose of a drug of which high doses cause symptoms similar to those from which the patient is suffering [ 1 ]. Homeopathy originated in 19 th century, prior to the acceptance of the germ and gene bases of disease; it has never been based on scientific evidence [ 2 ].…”

“…Hormesis has been defined as a biphasic dose-response relationship in which the response at low doses is opposite to the effect at high doses [ 1 ]. According to this concept, a small dose of a noxious agent can exert a beneficial action.…”