Transcript for:
Understanding Pharmacokinetics Processes

It’s Professor Dave, I wanna tell you about pharmacokinetics. In the previous tutorial, we learned about all of the different ways that drugs can be administered, or basically the ways that drugs can enter the body, whether in the mouth, through the skin, directly into the bloodstream, or otherwise. Now we want to talk about what happens next. Once drugs are inside your body, how do they move around, and get to where they need to go? Do they stay in the body indefinitely, or are they eventually removed from the body somehow? The study of pharmacokinetics deals with precisely these issues, and in learning about this, we can highlight four main processes. Those are absorption, distribution, metabolism, and excretion. Absorption generally describes the way the drug moves from its site of administration across one or more membranes, often into the bloodstream, if it was not administered there directly. Distribution describes its journey through the bloodstream to target cells and specific target molecules within. Metabolism describes the ways that it eventually gets modified by enzymes and rendered ineffective, and excretion describes the way it then exits the body, typically either through urine or feces. We want to understand each of these processes, as well as the ways that interactions with food, drink, other drugs, and additional factors can have an influence on them, so let’s get a closer look at these now. As we said, the first step is absorption. If a drug is administered topically, this could mean moving through the skin or a mucous membrane, and subsequently through the walls of nearby blood vessels. If administered orally, this would mean being absorbed through the lining of the stomach or intestines, a process which would be slowed by the presence of food. Some drugs will pass through the cells that comprise these membranes by passive transport, others by active transport, but one way or another they will make it through on the way to their destination. In describing this process, it will be appropriate to review the term “bioavailability”. This term describes the proportion of a drug that is successfully absorbed into systemic circulation. Next, we mentioned distribution. This is the way that drugs move through the bloodstream, after being absorbed into it, or injected into it. There are many factors that influence this, like the way that the drug interacts with the components of blood, such as plasma proteins. If the drug binds too tightly to these proteins, it will not be able to reach its target cells. Sometimes, a second drug is administered in conjunction with the first that has a higher affinity for these proteins than the first one does, thus serving the sole purpose of displacing the primary drug once bound to the protein, allowing it to be delivered to its destination. Beyond these blood elements, there are other factors that may hinder the movement of a drug. These are anatomical barriers found in certain organs. We have already discussed the blood-brain barrier in the biopsychology series. This prevents certain substances from passing out of the bloodstream into brain tissue. Some drugs will not be able to surpass this barrier, while others will, such as psychotropic drugs, or those affecting the mind. There is also the blood-placental barrier, that regulates which substances can pass from the bloodstream of a pregnant woman into the fetus. There are, however, a number of substances that are able to pass through this barrier that can still do harm to the fetus, such as alcohol and certain medications. And then there is the blood-testicular barrier, which prevents many substances from reaching the male testes, therefore making disorders of the testes difficult to treat. After distribution, there is metabolism. This describes any chemical reactions that the drug may participate in, often aimed at inactivating it and targeting it for excretion. If a drug is traveling through the bloodstream, it is highly likely to be metabolized to some degree. For example, if a drug is taken orally, it will be absorbed through the intestinal wall, and for this reason, the part of the circulatory system it enters is a collection of blood vessels called the hepatic portal system. These carry blood directly to the liver, where they will be metabolized in some manner. This is called the first-pass effect, referring to the first pass of a drug through the liver, and this will typically greatly reduce the bioavailability of a drug. In certain cases, metabolism in the liver actually activates a drug, but this is less common, and the first pass effect can inactivate over 90 percent of an orally administered drug before it is able to reach general circulation. This must be taken into account when determining appropriate dosage. Of course, drugs eventually reach their target cells, but even then, after enough time elapses, they will be metabolized. There are many different enzymes in the body that perform these metabolic functions, which are very important, because the immune system is only good at dealing with large biological particles like viruses or bacteria. It has no defense against small molecules, so this detoxification mechanism aimed specifically at small molecules had to evolve for life to exist in a chemical world. Finally, after metabolization there is excretion, where the drug or its remnants exit the body. This is typically done via exhalation, sweating, urination, or defecation. The kidneys are heavily involved in this process, as they must remove harmful substances from the bloodstream. Some drugs are metabolized into gaseous form, and are thus easily exhaled. Some drugs are excreted through bile, a substance secreted by the liver to aid in digestion, as bile is recirculated back to the liver via enterohepatic recirculation, whereby most of the drug can then be excreted by the kidneys, and the rest will exit in the form of feces. And as we said, glands that produce fluids such as saliva and sweat can also promote excretion, though this method tends to be less effective. And with that, we have traced the journey of a drug into the body, around the body, and out of the body, which gives us a basic understanding of pharmacokinetics.