Pharmacokinetic vs. Pharmacodynamic Tolerance

Instructor: Adrianne Baron

Adrianne has a master's degree in cancer biology and has taught high school and college biology.

We are going to look at what is happening in the body when we notice the development of drug tolerance. This lesson is going to discuss pharmacokinetic and pharmacodynamic tolerances as well as their similarities and differences.

Drug Tolerance

Your head hurts, you pop a pain pill and you feel pain-free. You feel depressed, you pop an anti-depressant and you feel happier. You want to relax from work, you drink a margarita and you are relaxed and ready for whatever comes next in your day. One day it hits you that you now have to take four pain pills rather than two, a higher dose of anti-depressants, and more than two margaritas in order to feel the way you used to feel with much less.

Your body has developed a drug tolerance for the drugs you take most often. Drug tolerance is when a drug becomes less effective in your body over a period of time of taking the drug. The usual reaction to drug tolerance is that you take more of the drug to get the same effect that it used to give you. There are several different types of drug tolerance that you can develop. Two of them are pharmacodynamic and pharmacokinetic.

Pharmacodynamic

Pharmacodynamic drug tolerance is the drug tolerance that develops from the drug being in your body for so long that it gets use to the drug and becomes less sensitive to its presence in your body. This usually happens after extended use of drugs. There are a few mechanisms that allow this type of drug tolerance to develop.

Let's just say that you drink margaritas, or any other alcoholic drink, every day after work. Eventually, your body will get used to having some amount of alcohol in it each day. The amount of alcohol you normally drink becomes a normal part of your body and therefore the cells in your body stop reacting to that normal amount of alcohol. If you increase the amount of alcohol you drink, then your cells will likely react to the alcohol and make you feel relaxed again.

Another possible way that pharmacodynamic drug tolerance occurs is by the body reducing the number of target sites available to react to the drug. In this case, you are still drinking your normal amount of alcohol, but because there are fewer sites available for the alcohol to bind to in the body, then the body does not give as strong of a reaction to the alcohol. As a result, you drink more alcohol so that more alcohol is available in the body to bind to the sites that are present and give you the desired reaction.

The last way that this type develops is by other substances competing for the same binding sites within the body. There are likely other drugs that bind to the same exact target sites that your favorite margarita binds to. If you take the other drug along with alcohol, then fewer sites will be available for the alcohol. Again, you drink more alcohol which allows more alcohol to be present to outcompete the other drug for the binding sites and then you get your relaxed feeling.

Pharmacokinetic

Now things happen differently in pharmacokinetic drug tolerance, which is drug tolerance that develops due to a smaller amount of the drug making it to the target sites in the body. So just how does that happen? Shouldn't the amount of anti-depressants you take be the same as the amount that reaches the target sites in the brain? Not always!

The majority of drugs, such as anti-depressants, which you take by mouth or by injection have to enter your body's bloodstream to be transported to their specific target sites in the body. Our blood is full of many other substances to include proteins called enzymes. Enzymes function by breaking down chemicals and other substances.

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