Effective and lethal doses

Posted onJuly 9, 2019

These are the last two terms that are introduced here to describe the effects of drugs. They arose from the fact that individual reactions to the same dose of the drug are very diverse. As a result, to determine the effect produced by a given dose, it is not enough to examine one person. The effect is often described in comparative terms or in a quantitative ratio of people who have this effect at a certain dose.
Figure 4-6 shows the dose lines of action for two effects. The difference of this graph from the previous ones is that on the vertical axis is not the magnitude of the effect of the drug, but the percentage of people who have this effect. This change is made to better illustrate effective and lethal doses. These terms clearly define the effect. We consider the change in the percentage of people experiencing this effect, with an increase in the dose of the drug.

The effective dose (ED) is the percentage of people who have the desired effect at a given dose. This can also be expressed as the dose at which a given number of people have an effect of interest to us. To find the ED on our graph, you need to draw a line from a certain percentage of people to the dose curve and then lower the other line to the horizontal axis. The point of intersection will give us an ED for a given percentage of people. Figure 4-6 shows the standard pharmacological term ED 50, in this case for the sedative effect of a certain drug. ED 50 means that 50% of people who have received a given dose of a drug will be sleepy. Similarly, you can define an ED for any other percentage. Figure 4-6 shows two more such effective doses.

Lethal dose (LD) is a specific case of an effective dose. As the name implies, the effect of interest in this case is death, and thus, LD represents the percentage of animals (people in experiments with lethal doses, of course, are not used) who die from a given dose of a drug over time. Pharmacological standard and here 50%. LD 50 is the dose at which 50% of the animals that received it die during a given time. The dose of LD 50 for humans is determined by extrapolating data obtained from animals. In Figure 4-6, the LD 50 of our imaginary drug is presented on the right line.
Knowledge of these two doses is very important. For example, medical institutions need to know what the discrepancy is between the ED and LD of a given substance. If the discrepancy is small, then the risk of unintentional suicides of people who use these substances not in therapeutic purposes. For some drugs, say caffeine and marijuana, the difference between ED and LD is large. But other drugs pose big problems. Occasional death from a heart attack while taking cocaine. Another example is alcohol. If a person weighing 70 kg and has an average tolerance for alcohol, drink 100 grams per hour on an empty stomach, he will feel relaxed. LD 50 for such a person will be 0.75 liters of whiskey per hour. Such doses are used much more often than you can imagine, and lead to severe poisoning and death. Moreover, if you mix drugs (say, alcohol and barbiturates), then the total ED and LD get very close together and the risk of death increases.

And the last note: the divergence of these doses is always taken into account when prescribing drugs for medical purposes. Doctors are looking for substances, a certain dose of which would produce the desired therapeutic effect (that is, was an effective dose) for all patients, did not give side effects and thus was not fatal. The therapeutic index is displayed: this is the LD 50 / ED 50 ratio for the drug. The most common ED is to relieve the symptoms of any illness or poisoning. You see, the higher the therapeutic index of a substance, the bolder it can be used in medicine. As a rule, the steeper the slope of the dose line, the lower the therapeutic index of the substance. Knowing the therapeutic index of the drug, the doctor can easily determine whether to prescribe it in this case.

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