Dose

Because all effects of drugs are quantitative by nature, the dose of a drug is a central theme in pharmacology. Dose is the quantity of a drug in units of mass that is, or should be, used to elicit an expected effect. In experimental pharmacology, one often refers to concentrations rather than doses, but in many in vivo conditions, and especially in treatment of patients, one has to rely on quantities. Nevertheless, drug levels in body fluids are expressed in concentration units. These depend on the dose, but also a number of principles of pharmacokinetics.

Both the main, desired effects and the side effects of drugs depend upon the dose. Drug development aims at drugs that would not elicit side effects at the doses used for treatment purposes, but this has not always been possible. Thus, with some drugs, therapeutic doses elicit unwanted effects as well, at least in a significant fraction of treated subjects. With other drugs, side effects usually occur at higher doses. When side effects occur, it is thus frequently possible to reduce the dose but continue the treatment. This is not always the case, however, especially when allergic reactions are involved.

Because every drug is capable of producing multiple effects, selectivity refers to the degree to which a drug acts upon a given site relative to all possible sites of action. In experimental pharmacology, this can be expressed in terms of concentration measures, but in a clinical setting where the health of a patient is at stake, one needs a simple indicator of the drug's safety. Basic textbooks suggest the therapeutic index as a simple means to provide a quantitative assessment of a drug's relative benefits and risks. This is customarily calculated by dividing the dose that produces toxic effects by the dose that produces the desired therapeutic effect in 50 percent of the treated population. A drug with a higher therapeutic index would appear a safer drug. Unfortunately, calculation of a therapeutic index is more complicated than that, and therefore even though textbooks suggest its use, they do not provide a table of values of therapeutic index for a series of drugs. The easiest way to explain the infeasibility of a single therapeutic index for any given drug is to recall that drugs have multiple therapeutic effects and multiple toxic effects. Nevertheless, there are safer drugs and more dangerous drugs. Therefore, thinking in terms of ratios between toxic and therapeutic doses is useful even if we fail to put it into precise calculations.

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