Why can the same drug heal or harm depending on the amount?

The amount decides what a drug does, because every drug has a dose-response curve. The old saying "the dose makes the poison" captures it: a small amount of a toxin can have no noticeable effect, while a large amount may be fatal. The same holds for medicines. A dose that does nothing, a dose that helps, and a dose that harms can be the same substance at three different amounts.

If you plot the dose on one axis and the response on the other, you typically get an S-shaped, or sigmoidal, curve: almost nothing at first, a steep rise in the middle, then a flattening. Pharmacologists draw such curves all the time in drug development.

To describe how forgiving a drug is, they use the therapeutic index, which compares the amount that causes toxicity with the amount that causes the therapeutic effect. In early toxicology it was worked out in animals as the dose lethal to half of them divided by the dose effective in half of them. A big ratio means a wide margin, called the therapeutic window. A small ratio means that the helpful amount and the harmful amount sit close together.

The numbers make the point. Diazepam has an index of 100:1 and morphine 70:1. Paracetamol, the drug sold as Tylenol or Panadol, has an index of 10:1, the same as ethanol, and digoxin sits at about 2:1. For drugs with a narrow window, doctors measure blood levels to keep them between too little and too much.