Dose Response Relationship

Abstract

Drugs act either by receptor or non-receptor-mediated mechanism. A receptor is usually a macromolecule of a cell with which an endogenous substance or a drug interacts (through specific recognition of binding domain) and elicits its effect (through transduction of signal into response). The intensity of response generally increases with plasma drug concentrations (reflected by doses administered), yielding a sigmoidal curve when the response is plotted against logarithmic values of drug concentrations or doses. The linear slope indicates the range of doses in direct proportion to the intensity of response, while the maximum indicates that receptors are fully occupied by the drug, and doses given close to and more than this response point can potentially cause overdose toxicity. A drug that is able to elicit a maximal response of a receptor is called a full agonist, while the response elicited by a partial agonist is submaximal. In the presence of a partial agonist, the effect of a full agonist can be reduced and the condition may precipitate a withdrawal syndrome for drugs like narcotic opiates. A drug that blocks the action of an agonist is called an antagonist; increasing the agonist concentration may overcome the blockade caused by a competitive antagonist (i.e. regaining the maximal response), but not that caused by a non-competitive antagonist (the response achieved is always below the maximum). Understanding of the relationship between drug dose and response as well as the effect of agonist and antagonist is important for dosing optimization. Dose-dependent adverse effect can be avoided with finely tailored drug dosages for patients, especially those with impaired organ function. Therapeutic index serves as an indicator to estimate the safety margin of a drug over a range of dose.