01.07 Pharmacokinetics

When we talk about Pharmacokinetics, we’re talking about what the body does to a drug from start to finish. Think “what I do to the drug”.

There are four major components of pharmacokinetics. Absorption, distribution, metabolism, and excretion. Let's look at each one of these in a little bit more detail.

The first part of the pharmacokinetics process is absorption. Absorption is when the drug particles begin making their way into our systemic circulation. Typically when I say systemic circulation I'm talking about the arterial circulation, because that's when we know it's going to get out to the right place. Two things that affect rate of absorption are solubility and route of administration. If the drug is fat soluble, it may be better given Subcutaneously. But water solubility means it can be given in more ways and still be absorbed well. Now, when we look at route of administration - what we’re looking at is the time it takes to get into that arterial circulation. So, if we give a med orally - it goes into the gut. Then it gets absorbed and processed by the liver, then goes into the venous circulation. From there it goes through the heart, to the lungs, back to the heart, and THEN to the arterial circulation. So we can see that giving a med PO takes long to get full absorption than it would if we gave it intravenously. And, if we give something via the inhalation route, it gets there even faster. So that’s how route of administration affects the rate of absorption.

One thing I want to mention while we’re talking about absorption is something called the first-pass effect or first-pass metabolism. Basically what happens is we give a drug orally, it is absorbed in the gut, then metabolized by the liver and we end up with not enough drug left to produce any therapeutic effects. Not all drugs experience this effect, but for those that do, we typically will need to increase the dose orally in order to produce an effect. For some drugs that have very strong first-pass metabolism, it’s often better to give it through a different route, like intravenously, to avoid the gut and prevent having to give such high doses.

The next part in the pharmacokinetics process is distribution. This is when the drug particles have made it into the arterial circulation and are now making their way into various body compartments and out to their target organs. Now, When I say body compartments I'm talking about things like the blood plasma, the fat, the intracellular fluid and extracellular fluid, and other various compartments like the peritoneum or the intracranial fluid etc. When I talk about Target organs I mean the place where the drug is supposed to take effect. So if the drug is supposed to affect the pancreas then that would be its Target organ. There are a couple of factors that affect distribution, one of which is protein binding. If the drug has to be bound to a protein in order to be distributed throughout the body, but that protein is not as available as it should be, then that will affect our ability to distribute the drug. Like we talked about with absorption we also see solubility affection the route of administration and where the target organ is. And then, of course, if we don’t have sufficient blood flow, we can’t get the drug to the place it’s trying to go. We tend to see quick distribution to the heart, liver, and kidneys, and much slower distribution to other internal organs, the skin, and the muscles.

The next step is metabolism. Don’t forget about the first-pass effect here - if we metabolize so much of the drug in the liver that it can’t produce a therapeutic effect, we need to consider non-oral administration. So - what the heck is metabolism anyways. Metabolism is the process of making a drug ACTIVE so that it can work in the body AND/OR making it able to be excreted. Usually this happens by binding the drug to another chemical or molecule so that the body can process it. This process is completed by the Cytochrome P450 system. This system contains hundreds of different enzymes that work on specific drugs in order to metabolize them. We aren’t going to get into super deep specifics here. Just know that if we don’t activate it, it can’t work. And, if we don’t metabolize it to make it excretable, it will build up in our system.

Speaking of excretion - that is the final step in the pharmacokinetics process. This is the process of getting the drugs OUT of the system. There are two main ways we excrete drugs or their metabolites. One is the hepatobiliary system. The Liver excretes the drug into the bile and the bile is excreted in the stool. The second way is renal excretion, or through the kidneys. Remember you have a glomerulus and a nephron. The drug gets filtered through the glomerulus into the nephron, then it goes out through the collecting duct and is excreted in the urine. Here’s the big thing I want you to see here - if we aren’t filtering blood well through the glomerulus - so our glomerular filtration rate or GFR is low - meaning our kidneys aren’t working well - then we won’t be able to get the drug out and it will just continue to build up in our system. In the same way, if our Liver isn’t working right, we will struggle with this excretion process as well. If we have slow excretion, we’re at risk for toxicity. There are two things we can do - either decrease the dose or decrease how often we give it to prevent those cumulative effects and possible toxicity.

One thing that comes into play when we talk about excretion is clearance - clearance is just how quickly we can get the drug out of the system. It is dependent on how much drug is in the blood - the more drug in the system, the more will be being cleared, assuming everything else is working correctly. It is also dependent on the rate of urine production - again our GFR - how well are we filtering the blood to make urine. It is also dependent on that Cytochrome P450 system. If we have so much drug in our system that those enzymes are saturated - then they aren’t working to prepare the drug to be excreted. That means we have an increased concentration in our system - again causing a risk for toxicity.

I also want to review some timings you need to know. Half-life is the time it takes for our bodies to metabolize and excrete HALF of the drug - so the concentration is cut in half. The longer a drug’s half-life, the less frequent we will dose it, the shorter the half-life, the more frequent - to make sure we maintain consistent therapeutic levels. Onset is the time it takes for the drug to START working. Peak is the time until the concentration is the highest, so you’ll see the strongest effects. And duration is the total time that we will see any therapeutic effects. These three timings are really important when it comes to insulin administration - so make sure you check out the insulin lesson.

Finally, I want to kind of show you a timeline of the drug from getting into our body to getting out. First is the drug being made soluble - like dissolving in stomach acid. That’s the Pharmaceutics part of the process. Then the drug gets into circulation, that’s absorption. Then we have the drug getting to the target organ in its active form - that’s distribution and metabolism. Then the drug produces its effect - that’s where pharmacodynamics comes in. Then the drug is excreted out of the body. These steps here are all of the pharmacokinetics steps. So you can see how these processes all work together to get the therapeutic effects we want from drugs.

So, let’s recap - Pharmacokinetics is what I do to the drug - so how the body works on the drug. The 4 steps in that process are absorption, which is getting the drug into the system, distribution - getting it to the target organs, Metabolism - which is making the drug active and/or excretable, and finally excretion - getting the drug out of the system. Remember to consider our liver and kidney function when it comes to metabolism and excretion - because without good metabolism or clearance, we can see toxicity. And don’t forget that some drugs experience a first-pass effect when given orally - that means they’re absorbed and metabolized so much that we can’t even get a good effect from them. We usually switch to IV at that point.

So that’s it for pharmacokinetics. Make sure you check out all the resources attached to this lesson. Now, go out and be your best selves today. And, as always, happy nursing!!