Hey, what’s up guys, it’s Jessica, and
welcome to CritIC: the pharmacokinetics series. In these series I’ll take you through the
pharmacokinetic steps of absorption, distribution, metabolism and excretion, with a separate
video on clearance and half-life. I’m making these videos with young physicians
in mind, focusing on why these steps are important and how you can apply them in daily clinic
life. And also as a step up for future videos. Now, lettuce commence ;) When you prescribe a drug to your patient,
you’d want that drug to have a certain clinical effect. Let’s take a look at metoprolol, a selective
beta-1-receptor blocker. Beta-1-receptors increase heart rate and heart
contractility, and promote renin release, which leads to an increase in blood pressure. So, blocking these would cause a decrease
in heart rate, a decrease in contractility and a decrease blood pressure, making the
heart a bit more energy efficient. Unfortunately for us, the patient isn’t
taking this drug directly on their beta-1-receptor, but usually through the mouth. You can image that the dose the patient takes,
isn’t directly corresponding with the dose on the receptors. The drug undergoes some changes. This is pharmacokinetics: not what the drug
will do to the body, but what the body does to the drug. And we’ll talk about this step by step. Starting with how the drug gets in to the
bloodstream (in absorption), how it is distributed throughout the body (in distribution), and
how it is cleared by the body, either through metabolism, through excretion or by a combination
of both. I’ve broken these down into separate videos,
so be sure to check these out. My goal is that after these series, you’ll
be able to look at your patient’s medication, and for each drug, you’ll be able to do
the following if needed: Let’s look at metoprolol. And let’s say our patient uses 50mg two
times a day (meaning not slow release). The bioavailability is 50-70% by great first
pass effect The volume of distribution is 5.5L/kg. That’s quite large, so it must be low in
protein binding (it is, it’s only 12%) and it’s probably lipid soluble. If it is, it will probably be metabolized
by the liver greatly, because it cannot be excreted by the kidney directly. For metabolism: metoprolol is a primarily
substrate of CYP2D6, so I should pay attention to 2D6 inhibitors (like prozac) and inducers. Also, 2D6 has high genetic variability. However, my patient uses 100mg a day with
good clinical effect, so that most likely isn’t an issue. Excretion is performed by the kidney. About 5% is unchanged, the rest are metabolites. So renal injury isn’t a problem with metoprolol. Concluding: possible problem with metoprolol:
comedication that influences CYP2D6, and liver failure. At first, it will take quite some time to
do this for your patients list of medication, but after a while, you’ll be able to do
a lot if this by heart. So please go through the next couple of videos
on absorption, distribution, clearance and half-life, metabolism and excretion. If you like these series, please share them
and give them a thumbs up. Also, let me know in the comments what you
would like to see more of. Thanks so much.