Drug Toxicity: Effective & Lethal Dose-Responses

Drug Toxicity: Effective & Lethal Dose-Responses
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  • 0:01 Drug Toxicity
  • 0:30 LD50
  • 2:45 ED50
  • 4:25 Therapeutic Index
  • 6:09 Lesson Summary
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Lesson Transcript
Instructor: Artem Cheprasov
In this lesson, you're going to learn about several important topics related to drug toxicity: the lethal dose 50, the effective dose 50, and the therapeutic index (margin of safety).

Drug Toxicity

How do you know how truly toxic a drug is? How can you tell if swallowing one more pill of a drug would kill you or not harm you at all? Drug toxicity, the adverse or lethal reaction to an administered dose of a medication is a difficult field to understand, and this lesson starts you off with three critical concepts related to drug toxicity: the LD50, ED50 and the therapeutic index.

LD50

A very important measure of drug toxicity is something known as the LD50, or lethal dose 50. The LD50 is the lethal dose for 50% of individuals tested. Put another way, at this dose we expect 50% of test animals who receive such a dose to die and 50% to survive. So, if we give drug X to 100 mice, at the given LD50, fifty mice would die as a result of that dose. That is easy to understand. Now for a not-so-intuitive point I need to get across. A drug with a small LD50 is more toxic than a drug with a high LD50. Why? Think about this: if the LD50 is small, that means we need to give a smaller dose to kill the same proportion of test subjects when compared to a drug with a higher LD50. Here's a concrete example: If drug X has an LD50 of 10mg/kg, 50 out of 100 test subjects will die at that dose. If drug Y has an LD50 of 100mg/kg, it will take ten times the dose of drug X to kill 50 out of 100 test subjects. Clearly, drug X is more toxic than drug Y. But here's another thing, my friends. You shouldn't assume that just because a drug has a larger LD50, that it's any less dangerous than a drug with a small LD50. This is because when looking at the LD50 we are essentially measuring lethality and ignoring non-lethal adverse effects. This means an illness or serious negative side effect may occur with a much smaller dose, even in a drug with a high LD50. That, and the risk of negative side effects, is largely determined by how the drug is used, in whom, and when, and less so by how toxic the drug is intrinsically. Just an example of what I mean by this, is the fact that the LD50 of a drug can vary markedly when taken orally versus intravenously.

ED50

Another critical concept related to a drug's usage is the ED50, or effective dose 50. Efficacy can be seen as the maximum effect a drug can cause at any given dose. The ED50 can be further delineated into one of two concepts. The ED50 can be seen either as the dose of a drug at which 50% of the potential maximum effect is produced, or it can alternatively be seen as the dose at which the desired effect is produced in 50% of the test subjects. Which one you choose depends on whether we're looking at this topic from an individual or population level respectively. The smaller the ED50, the more potent the drug. Potency is a word that refers to the relative dose that's necessary to produce a drug effect of a defined magnitude. Not sure as to the true difference between efficacy and potency? Look at the dose response curves on your screen. Do you see how drugs A and B have a 100% efficacy, while drug C does not? This means our efficacy can be seen as A=B, which are both greater than C. Note, however, that the potency is quite different. It takes a much higher dose of drug B and even more so of drug C to produce the same effect as drug A. Thus, drug A is the most potent, and drug C is the least potent drug in this example.

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