Dose-Response Relationships

 I'm back, and this time we're going to be learning about the wonderful world of dose-reponse. In the words of John Timbrell: "There are no safe drugs, only safe ways of using them". In a high enough quantity any drug can be dangerous. But how do we assess what this threshold?

One problem is what the real dose is. Different chemicals are absorbed in different ways with different efficiencies, for example cyanide really has to be absorbed through the mouth to be dangerous, however thallium can be potent even when only applied to the skin. It is not only the method of absorption that affects the 'real dose', but also may be metabolised or excreted more or less rapidly.

however well the chemical is absorbed, metabolised or excreted, the higher the external dose, the higher the internal dose. Eventually the internal dose will reach a high enough level that the body's detoxification and excretion processes can not keep up and are overwhelmed, resulting in toxic levels of a chemical. It is particularly important to be familiar with the dangerous dose, as low doses may cause internal damage which is not detectable until it has progressed to the point where it compromises a bodily function.

According to the Paracelsus Principle, as the dose level rises the body cells will show an increasing level of dysfunction and damage up to a maximal effect (function completely inhibited).

As an example consider a drug that lowers blood pressure. The higher the dose of the drug the larger the decrease in blood pressure, up to a fatal decrease. This can be plotted as a sigmoid curve graph.

Another way in which dose-response relationships are represented is if the effect can be measured in a sort of binary way, either present or absent. The number of people displaying the measured effect at each dose is used to plot the graph.This relationship can represent both negative and beneficial effects.

So why does the larger the dose mean the greater the effect? Well for almost every effect in the human body caused by chemical, interaction with some kind of molecule is necessary, for example the receptor on an enzyme. In order for an effect to occur enough of the receptors must be occupied. The higher the concentration of drug, the more receptors are filled by the drug (this is especially important in competitive inhibitors, where they have to have a high concentration of drug in relation to whatever it is competing with). The threshold is where not enough of the receptors are occupied to have an effect. Ultimately this is what you have to think about when assessing the danger of a chemical. Ultimately the lower a dose required to cause the greater an effect the more potent the drug. 

Thanks for reading, over and out!