To determine the dose of a substance, you need to know the magnitude of the effect it produces. Above, you saw that the narcotic effect depends on the dose taken. There may be hundreds of dose sizes, and it would be rather difficult to understand the various effects. Therefore, we need a tool that will present the data clearly and definitely, to the extent possible. In pharmacology, such a tool is a dose action line. This is a common form of image effects obtained from taking different doses. Several groups of people will take different doses of alcohol and after a certain time they will be asked to describe the degree of their relaxation. From the average data for each group, a schedule is compiled, which will be the dose action line.
In fig. 4-2 shows a sample of such a line. Vertical presents the changes of interest to us, let us designate them as the “effect size”. The nature of the changes to which special attention is paid in this book is determined by generally accepted methods for measuring the mood, behavior or functioning of the nervous system. Examples are memory testing, mood assessment, measurement of physiological parameters such as pulse. Doses are marked on the horizontal axis (often their logarithms). The studies cover at least three doses. After that, it remains to plot the data on the strength of the effect of the studied drug on people who have received a certain dose. Either different doses are given to different groups of people, or the same group receives these doses over several days.In both cases, we get the average effect of each dose studied.
Thus, the graph depicts the functional dependence of the magnitude of the effect on the dose of the drug.
From Figure 4-2, it can be seen that the effect varies with dose change. The shape of the line suggests that an accurate dose is needed to accurately determine the magnitude of the effect. For example, the larger the dose of the drug in Figure 4-2, the greater the effect it produces. But there is a limit: at the highest doses, the schedule tends to move to a horizontal line. This means that increasing the dose over a certain level does not enhance the effect. You can illustrate this with the effect of alcohol on the time it takes a person to have a simple reaction, for example, say yes or no in response to the presence or absence of any stimulus, say light. For an “average” drinking person, taking two 0.33-liter doses of beer per hour had practically no effect on the reaction time. After four doses, the time required for a response has increased markedly.After five doses, responses began to be given even more slowly. If a person took nine or more doses of beer per hour, he was very sleepy, and thus measuring the further deterioration of the reaction as alcohol was consumed would be simply useless. At this point, when a person has to make great efforts not to disconnect, the possibilities and benefits of such a measurement will tend to zero. After a ninefold dose, the line of action will take a horizontal position on the graph.the possibilities and benefits of such a measurement will tend to zero. After a ninefold dose, the line of action will take a horizontal position on the graph.the possibilities and benefits of such a measurement will tend to zero. After a ninefold dose, the line of action will take a horizontal position on the graph.
This experience with alcohol and the time of a simple reaction shows that the question is not what effect a particular drug produces at all, but how much the effect is at a particular dose.
Variation of dose action lines. Graphs of the effect of dose size may differ from that shown in Figure 4-2. One option is a biphasic narcotic effect. This means that up to a certain point with increasing dose, the effect increases, but then, despite the continued increase in dose, it falls. This case is shown in the figure.
The magnitude of the effect here increases with increasing doses from small to moderate. At higher doses, the line changes direction, noting a decrease in the narcotic effect. In this example, the magnitude of the effect returns almost to the original level obtained at the lowest doses. Pulse is one of the biphasic effects of alcohol and marijuana.
Any drug produces many effects, the strength of which is measurable, and therefore a dose action line can be constructed for any such effects. Many lines have similarities, and as a rule they belong to the type shown in Figure 4-2. Nevertheless, some dose lines of a single drug may look completely different. It depends on what effects to compare with each other.
We know that the line of action of the dose depends on the magnitude of the measured effect. This is illustrated in Figure 4-4, representing the results of laboratory studies of how sexual arousal feelings change in female students (first effect) and physiological parameters (blood flow to the genitals) of their arousal (second effect) when they consume small and moderate doses of alcohol. A negative narcotic effect is also shown on the vertical axis. According to the schedule, with an increase in the dose of alcohol to moderate, the students felt an increase in sexual arousal (large doses were not studied). At the same time, the physiological parameters of female sexual arousal decreased with increasing dose.
Slope, maximum effect and power of action. These are terms used in pharmacology to describe in more detail the action of a drug. They are presented in Figure 4-5, where dose action lines for two drugs, A and B, are constructed. Graphs have a slope, its characteristic is steepness. It is associated with time passing to achieve a strong effect. This inclination is taken into account in practical activities: in drafting a prescription for drugs or predicting life-threatening effects of drugs. An example of the latter is the sedative effect of barbiturates or the effect that the simultaneous use of benzodiazepines and alcohol gives. In Figure 4-5, line A has a steeper slope than line B, and since these curves then take a horizontal direction, this dose of drug A produces a greater effect.
Figure 4-5 also presents two other concepts: maximum effect and strength of action of a drug. The maximum effect of this drug corresponds to the highest point of the dose action line. In the figure, this is the moment when the curves stop growing. In this case, we have two drugs with the same maximum effect. The power of action – the dose of the drug, giving this maximum effect. If you draw a line from the point of maximum effect down to the horizontal axis, the point of intersection will be the force of action of the given drug for a particular effect.