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  • So let's jump right in to pharmacokinetics.

  • So the first thing we want to do is be able to answer the question, what is pharmacokinetics and cover some basic definitions.

  • And the easiest way to understand pharmacokinetics is to differentiate it from pharmacodynamics.

  • So when you look at this word, pharmacokinetics, what is the first thing that you think of?

  • Well, you should say pharmaco that means drug and kinetics, you should be thinking motion.

  • And this is to differentiate pharmacokinetics from pharmacodynamics.

  • Now, pharmaco again means drug. Dynamics comes from this word dynamus which really means power.

  • So when I think of pharmacokinetics, I'm thinking of a drug and I'm thinking of that drug moving through our body.

  • So what happens as a drug moves through our body?

  • Well the concentration changes and that's really what pharmacokinetics is looking at.

  • PK, pharmacokinetics, is really answering the question of how does the drug concentration change as it moves through the different compartments of your body.

  • That is pharmacokinetics my friend.

  • This is different than pharmacodynamics. We're dealing with power.

  • When you think of somebody who is powerful, what can they do?

  • They can exert their power and change other people right?

  • So the same idea goes with pharmacodynamics.

  • It's how does the drug exert its effects on your body, how powerful is this drug, how potent is it?

  • So we deal with things like potency.

  • Potency is a component of pharmacodynamics but by enlarge, the big thing we're looking at with pharmacodynamics is drug receptor interactions.

  • Now we also look at efficacy of the effects of the drug. Potency refers to the you know how much of the drug is required to get a certain effect

  • but we'll cover all of that later.

  • Today we're really focused on pharmacokinetics.

  • Now before we move any further, I want to explain how many books define this and how it can be confusing.

  • So a lot of books define pharmacokinetics as what your body does to the drug

  • and conversely, they define pharmacodynamics as what the drug does to your body.

  • I always mix these things two up and I have to think about it and I always return back to my bread and butter right here.

  • Pharmacokinetics, oh that has to do with motion, that has to do with the drug concentration changing as it's moving through my body.

  • Pharmacodynamics, I think power. How does the drug exert its effects, drug receptor interactions, potency, efficacy - all that jack.

  • So when I think of kinetics, where is it moving?

  • Well drugs need to enter our body and so, half of pharmacokinetics is dealing with drugs entering our body

  • and the other half of it is dealing with drugs leaving our body.

  • They need to enter. They need to leave.

  • So, what are the components of pharmacokinetics?

  • So instead of writing enter and leave, I wrote in vs. out.

  • So there are 2 components of drugs coming into our body.

  • Those two components are represented with absorption (A) and distribution (D).

  • I'm just going to write an A here and a D there.

  • So what is absorption?

  • Well, here's a book definition. Absorption is the process of a substance entering the blood circulation.

  • It's okay. How can we make this definition a little better?

  • Well, instead of saying our blood circulation, let's say it's the process of a substance entering the systemic circulation.

  • and the reason I like to say systemic is because absorption is everything that happens before this drug enters our systemic circulation.

  • So maybe I'll even add a little before right here.

  • And if you think about, you take a drug orally, it goes through your intestines.

  • It needs to go through your portal circulation before it gets to your liver and then it finally gets into your IVC then it's in our systemic circulation.

  • So everything before that is what we call absorption.

  • Now, to differentiate that from distribution, after it's in our systemic circulation, that drug can now be distributed to the rest of the body.

  • So what is distribution?

  • Well, here's a definition that is nothing special.

  • The dispersion of well, maybe a substance throughout fluids and tissues of the body.

  • It makes sense. You know you don't need a definition for distribution. It's going from one place to another.

  • So those are the 2 ins. What are the 2 outs?

  • How do drugs leave our body?

  • Well one of them is metabolism and the other is elimination (E).

  • And so, I'm going to write those right here. A, D, M, E.

  • This is a little acronym that is commonly used to define the 4 components of pharmacokinetics.

  • Absorption, Distribution, Metabolism, Elimination.

  • So, what is metabolism?

  • So, here's a definition that I do like.

  • Metabolism is the irreversible transformation of parent compounds into daughter compounds.

  • So what do we mean?

  • Well, let's say I start with Drug A. I transform Drug A - it's the parent - into a very structurally similar daughter compound that is Drug B.

  • Now, this doesn't mean that I am actually breaking down the drug. In pharmacology, it's actually the opposite.

  • Many times we don't actually break down the drug but we actually add something to it

  • and we add 1 or 2 molecules and the reason we do that is to make it more polar.

  • And so, the reason we make it more polar is to help us eliminate it.

  • Now before we move on to the next step, what are we doing here?

  • We're taking a biologically active molecule and we're transforming it.

  • So, a common name for metabolism is biotransformation.

  • And so, what is doing this biotransformation?

  • This is being done by enzymes.

  • And the reason we do it again is to make it more polar to get it ready for elimination.

  • Now this isn't the only reason that this happens but it's the big one

  • and right now, we're focused on the big picture.

  • So, elimination. What is elimination?

  • Elimination is the removal of substances from the body.

  • Now, the definition is not bad but the word itself is something I don't like. I don't like calling this elimination. Here's why.

  • Look at what we did to Drug A right here. We started with Drug A, we biotransformed it and now we have Drug B.

  • So in essence, what have we done with Drug A?

  • Well, we've eliminated it right?

  • And we no longer have Drug A. It goes bye-bye and now, we have Drug B.

  • So metabolism is in a sense elimination

  • and instead of calling this elimination, let's call this excretion.

  • Now a lot of books mess this up and confuse these two.

  • You might see this in your book written as elimination. Don't let yourself get confused but make sure you differentiate elimination from excretion.

  • So it's important to know these definitions but it's even more important to know where these things are occurring in the body. So, let's do that.

  • So where are you excreting or how do you excrete most of you know foreign substances in your body, most drugs?

  • And most of the time, this is happening in your renal circulation. Let's write renal, let's write this is happening in your kidney.

  • So when you see a kidney, a renal in some sort of exam question dealing with pharmacology, you can be thinking about excretion.

  • Whereas metabolism, where is most biotransformation occurring?

  • Let me ask you a question. Do you guys remember unconjugated bilirubin which came from red blood cells?

  • Well, what was the problem with unconjugated bilirubin right?

  • It needed to be conjugated and become direct bilirubin so that we can excrete it.

  • Now where did that occur?

  • Well that occurred in the liver. The same place where metabolism is occurring here.

  • This is occurring in the liver.

  • When you think liver, you should be thinking metabolism.

  • Now, I'm going to note. We don't always do this to make it more polar.

  • In some cases, we actually metabolize drugs to activate them and we've seen this in the body too.

  • Where else have you seen the liver activate certain endogenous substances?

  • Well, what about zymogens right?

  • How did those get activated?

  • Well those were metabolized and maybe not necessarily in the liver

  • but you know we go from trypsinogen to trypsin, pepsinogen to pepsin.

  • So metabolism, the definition is irreversible transformation of a parent compound to a daughter compound

  • but when we deal with pharmacology, our goal is to do that to eliminate it.

  • Distribution - so distribution was we're dealing with things going from one place to another after they're in our systemic circulation.

  • So, where is this occurring?

  • Well, what I want you to attach to distribution, I want you to think the first place it starts is in our vascular space.

  • What's our vascular space?

  • That's our blood or our plasma.

  • And from this vascular space, it's going to our extravascular space.

  • So what does that mean?

  • This could be fat. This could be muscles. This could be your interstitial space, the space between your cells.

  • And so, I'm not the best artist but let's just draw a little picture because pictures help.

  • Let's assume this is our blood vessel so this is our vascular space.

  • And out here is our extravascular space.

  • What distribution is, is the process of going from our vascular space to our extravascular space.

  • So if I had - if this was a drug, when it goes from here out there, that is distribution.

  • Now this is a little bit different than absorption.

  • Absorption was everything before it got to our systemic circulation.

  • So where is absorption occurring and I'll have to cop out just a little bit and say this depends.

  • If we take a drug orally, we're talking our GI tract. If we use an inhaler, we're talking our lungs.

  • If we use an injection intravenously, we are you know actually not really absorbing it. We have 100% absorption.

  • So when you think absorption, I want you to think of this depends on the route of administration.

  • It depends on the route of administration so when you see the route of administration, think absorption.

  • Now let's use this knowledge and apply it to something.

  • So let's look at the title of a paper from a clinical journal and this journal is the International Journal of Antimicrobial Agents.

  • Well, let's see if we can understand this.

  • The title of the paper is "Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy."

  • Sounds tough. Let's break it down.

  • Pharmacokinetics, we know what that means right?

  • Pharmacokinetics is the change in concentration of a drug as it moves to the different compartments of your body.

  • So that's really the big point of this paper.

  • Now, of a loading dose. So a loading dose, we're kind of referring to a route of administration here

  • and we'll talk about you know what a loading dose is but we're really dealing with absorption.

  • And what a loading is (I'll just tell you now) is we give a higher dose of things in order to avoid a slow absorption

  • and a slow increase in drug concentration in the plasma.

  • So, loading dose - we're dealing with absorption - of amikacin (Amikacin is just an antibiotic) in septic patients undergoing continuous renal replacement therapy.

  • So we see this word renal, that should be going ding, ding, ding, ding in your head.

  • We just covered that right? When I think renal, I should be thinking what?

  • I should be thinking excretion.

  • So, a patient who is on continuous renal replacement therapy.

  • What this is, is a blood filtering mechanism. Hemofiltration mechanism for patients who have renal failure.

  • So acute renal failure.

  • So, we know that there's probably some excretion component of pharmacodynamics that might be tested here

  • and finally, this one is not as obvious and so, let's use a different color.

  • Septic patients. So, when they're talking about septic patients, they're saying a patient who is in septic shock.

  • And so, one of the things about septic shock is you get massive vasodilation, you get hypotension

  • and what does that mean? How does that relate to what we're talking about?

  • Well, if we think about a capillary endothelium that's been vasodilated, those individual cells are now spaced further apart than they were in the past.

  • So what I'm drawing here is a capillary endothelium that's been vasodilated.

  • This is our vascular space.

  • And so, if distribution was a process of going from our vascular space to our extravascular space,

  • can we assume that because that we have a septic patient, that might change?

  • And the answer is yes. We have a septic patient so that's changing distribution

  • or the process of drugs going from intravascular to extravascular.

  • So here, the only thing missing distribution is it didn't really have anything to indicate metabolism

  • but 3 out of those 4 components of pharmacokinetics are addressed here.

  • Makes sense?

  • I hope so.

  • So before we move on to the next section, I want you to just stop, think and repeat some of the core concepts that we've covered here and do these on your own

  • And once you've got this down, you can move on to the next section

  • or if you're feeling adventurous, you can just move on without doing it.

  • In the next section, what we're going to be doing is covering absorption in detail.

  • I hope to see you there.

  • Subtitles by the Amara.org community

So let's jump right in to pharmacokinetics.

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薬物動態学とは?ADME -講義1 (What is Pharmacokinetics? ADME -Lect 1)

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    Yu Syuan Luo に公開 2021 年 01 月 14 日
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