TAILIEUCHUNG - Color Atlas of Pharmacology (Part 6): Quantification of Drug Action

Quantification of Drug Action the dose at which one-half of the group has responded. The dose range encompassing the dose-frequency relationship reflects the variation in individual sensitivity to the drug. Although similar in shape, a dose-frequency relationship has, thus, a different meaning than does a dose-effect relationship. The latter can be evaluated in one individual and results from an intraindividual dependency of the effect on drug concentration. The evaluation of a dose-effect relationship within a group of human subjects is compounded by interindividual differences in sensitivity. To account for the biological variation, measurements have to be carried out on a. | 52 Quantification of Drug Action Dose-Response Relationship The effect of a substance depends on the amount administered . the dose. If the dose chosen is below the critical threshold subliminal dosing an effect will be absent. Depending on the nature of the effect to be measured ascending doses may cause the effect to increase in intensity. Thus the effect of an antipyretic or hypotensive drug can be quantified in a graded fashion in that the extent of fall in body temperature or blood pressure is being measured. A dose-effect relationship is then encountered as discussed on p. 54. The dose-effect relationship may vary depending on the sensitivity of the individual person receiving the drug . for the same effect different doses may be required in different individuals. Interindividual variation in sensitivity is especially obvious with effects of the all-or-none kind. To illustrate this point we consider an experiment in which the subjects individually respond in all-or-none fashion as in the Straub tail phenomenon A . Mice react to morphine with excitation evident in the form of an abnormal posture of the tail and limbs. The dose dependence of this phenomenon is observed in groups of animals . 10 mice per group injected with increasing doses of morphine. At the low dose only the most sensitive at increasing doses a growing proportion at the highest dose all of the animals are affected B . There is a relationship between the frequency of responding animals and the dose given. At 2 mg kg one out of 10 animals reacts at 10 mg kg 5 out of 10 respond. The dose-frequency relationship results from the different sensitivity of individuals which as a rule exhibits a log-normal distribution C graph at right linear scale . If the cumulative frequency total number of animals responding at a given dose is plotted against the logarithm of the dose abscissa a sigmoidal curve results C graph at left semilogarithmic scale . The inflection point of the curve lies at the .

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