Drug dosage

Drug dosage can be of five main kinds:

• Fixed dose. The effect that is desired can be obtained at well below the toxic dose (many mydriatics, diuretics, analgesics, oral contraceptives, antimicrobials) and enough drug can be given to render individual variation clinically insignificant.

• Variable dose—with crude adjustments. Here fine adjustments make comparatively insignificant differences and the therapeutic end-point may be hard to measure (depression, anxiety), may change only slowly (thyrotoxicosis), or may very because of pathophysiological factors (analgesics, adrenal steroids for suppressing disease).

• Variable dose—with fine adjustments. Here a vital function (blood pressure, blood sugar), that often changes rapidly in response to dose changes and can easily be measured repeatedly, provides the end-point. Adjustment of dose must be accurate. Adrenocortical replacement therapy falls into this group, whereas adrenocortical pharmacotherapy falls into the group above.

• Maximum tolerated dose is used when the ideal therapeutic effect cannot be achieved because of the occurrence of unwanted effects (anticancer drugs; some antimicrobials). The usual way of finding this is to increase the dose until unwanted effects begin to appear and then to reduce it slightly, or to monitor the plasma concentration.

• Minimum tolerated dose. This concept is not so common as the one above, but it applies to long-term adrenocortical steroid therapy against inflammatory or immunological conditions, e.g. in asthma and some cases of rheumatoid arthritis, when the dose that provides symptomatic relief may be so high that serious adverse effects are inevitable if it is continued indefinitely. The patient must be persuaded to accept incomplete relief on the grounds of safety. This can be difficult to achieve.

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