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What does Ibuprofen or medications like it do to the human body?

This is a very common medication that I'm sure many of you have probably used for things

like pain, inflammation, a fever, or maybe even something like period or menstrual cramps

but could this medication cause any harm or potential side effects?

Maybe you've heard it could affect the liver, the stomach, or other organs throughout the

human body.

So, in this video, we're going to take a look at those organs by utilizing the body's behind

me, and of course, talk about how this medication works on you.

So, let's do this.

So, at some point, we're going to need to take this and get it into the various digestive

system structures so that eventually the medication can get absorbed into the body so that it

can take its effect.

But first, what is Ibuprofen?

Ibuprofen commonly known as some other brand names like Advil or Motrin is classified as

a non-steroidal anti-inflammatory drug or an NSAID.

Now, there are some steroidal anti-inflammatories.

Maybe you've heard of things like prednisone or dexamethasone but those steroidal anti-inflammatories

work a little differently and so we'll save those for a different video and focus on these

non-steroidal anti-inflammatory like Ibuprofen.

Now, Ibuprofen has some pretty common uses.

It's commonly used as an analgesic which is a pain reliever and antipyuretic, which is

a fever reducer and obviously as an anti-inflammatory.

Now, is Ibuprofen the only inset out there?

Absolutely not.

Some of you have probably used some others or heard of them.

Things like Aleve, also known as deproxin.

Some of my patients have also used a topical one called Voltaren Gel or Diclofenac gel

that's kind of this generic versus brand name thing and there are variety of prescription

strength insets and for the most part, they all have this similar mechanism of action

or in other words, how they work in the body and so, we'll focus on Ibuprofen as kind of

our baseline inset because it's one of the most commonly used.

So, let's finally get this thing into the body to figure out how it works.

So, I've got my 200 milligram tablet of Ibuprofen which you probably you can't see very well.

So, I'll put it in my tweezers here and we'll trace it into the body.

Here's a sagittal cut of a head.

So, essentially, like so and most of us first put the pill in the mouth or the oral cavity

here.

Now, we often say the oral cavity or the mouth is where digestion begins but this pill isn't

going to spend a lot of time in there.

We pop it in there, put some water in and swallow it quickly down into the pharynx here

and then to the next part of the tube would be the esophagus here.

The esophagus is the food tube or posterior to the windpipe or the trachea here and that

tablet would then move down the esophagus and I can show you on an anterior or a front

view of the esophagus on this dissection, moving down into the stomach here.

Now, many of you have probably heard that Ibuprofen can be harmful to the stomach and

there's definitely truth to that but first, let's get it absorbed into the body and figure

out what it's supposed to do and then we can talk about its potential side effects.

So, in the stomach, it's going to start mixing with the gastric juices.

Those gastric juices essentially include things like the stomach acid, digestive enzymes,

and even some of the stomach mucus.

Now, that's where the pill or the tablet is actually going to start to dissolve and it's

active ingredients are going to be released or to a point where they can start to be absorbed.

Now, some of it can get absorbed into the stomach or through the bloodstream through

that mucosal line that we'll show you later in the video but the majority of it still

going to pass into the small intestine and this is where the majority of the medication

will actually be absorbed.

Small intestine has tons and tons of blood vessels to absorb nutrients or in this case

a medication and this whole timeline of where absorption can start to take place is about

30 to 60 minutes depending on things like the contents of the stomach.

But now that we're in the bloodstream, we essentially can think or say that the medications

going to be distributed to potentially everywhere and now we can talk about how it takes its

effect.

So, Ibuprofen works by inhibiting certain enzymes called Cyclooxygenase 1 in Cyclooxygenase

2 or Cox1 and Cox2.

But what in the world does that mean?

Well these enzymes, cox 1 and cox2 normally get involved in synthesizing other substances

called Prostaglandins.

Prostaglandins are extremely important to this discussion because these prostaglandins

are involved in multiple physiological processes throughout the body.

Some of these include things like inflammation.

Another is they're involved in pain and essentially stimulating certain pain receptors.

You find a lot of Prostaglandins in areas of infection and tissue damage.

They're also involved with interacting with this structure in the central core the brain

called the hypothalamus.

The hypothalamus does a lot of things but one of the things that gets involved in is

body temperature and even the fever response.

We also see Prostaglandins influencing uterine contractions.

Say like during menstrual cramping.

It can cause that smooth muscle in the uterus to contract.

Other things are influencing blood flow into these cool little organs that we call the

kidney.

You can see this artery right here, blood would go in but it really influences some

of these microscopic vessels that you'd find on the cortex or the outer portion of the

kidney here.

And the last thing that I want to mention that the prostaglandins get involved in - if

I take this other dissection of the stomach is the prostaglandins also get involved in

aiding in the mucosal lining of the stomach or the inside lining of the stomach here producing

mucus and also helps to regulate stomach acid.

So, I want you to kind of think about the huge list that we just created of all the

things that the prostaglandins are involved in and if I can take a medication like Ibuprofen

that inhibits Cox1 and Cox2, these enzymes that produce prostaglandins, I'm going to

lower the number of prostaglandins that are circulating throughout the body and so therefore,

I could help potentially reduce inflammation, help reduce pain, help reduce the fever, and

even help reduce like menstrual cramping and a lot of you've probably used these medications

with some level of success with varying degrees depending on the pain levels and what was

actually going on with your body.

But what about the side effects?

Let's discuss those by going to another cadaver.

So, let's talk about some of the potential side effects of Ibuprofen.

Whenever we take a medication, we kind of have to do this pros versus cons, the pros

of the therapeutic benefits of the medication versus the cons or those side effects of the

medication.

So, with Ibuprofen, could it affect the liver, the stomach, or other organs throughout the

human body?

Well, let's start with the liver.

If you take a look at this section here, I've got the diaphragm in my hands here and after

I reflect this diaphragm or this muscle back or upwards, you can see this huge organ that

we call the liver.

The liver is the second largest organ in the human body, second to the skin and it's located

in the right upper quadrant of the abdomen.

Now, the liver does a ton of amazing things for the human body.

One of which is to metabolize a lot of different drugs or medications and what do we mean by

metabolize drugs and medications?

Well, let's think about the Ibuprofen circulating throughout the bloodstream.

Eventually, that Ibuprofen is going to pass through the liver.

And when it passes to the liver, the liver contains certain enzymes that are going to

actually convert the Ibuprofen into more of an inactivated form and what they would refer

to as metabolite and that metabolite, that converted form of Ibuprofen, will then continue

on its merry little way through the bloodstream but eventually make it to the kidneys, get

filtered out and will just pee it out hopefully into the toilet.

But the question is, during that conversion process in the liver, does that cause any

potential harm to the liver?

For the most part, no.

Ibuprofen is relatively safe for the liver.

You can always find cases where there's certain situations where people have had some harm

to the liver from taking Ibuprofen, but again, for the most part, it's relatively safe.

But if we compare that to the potential side effects of the stomach, that might be a little

bit of a different story.

So, let's take a look at this other dissection here.

So, I've actually got two stomachs here.

I've overlaid two thirds of the stomach because we cut it right here as you can see and I

just wanted to kind of give you the comparison of the full stomach but the reason we show

people this stomach is we love to show people the amazing inside lining of the stomach.

This inside lining that I'm touching with my thumbs here is called the tunica mucosa,

called the tunica mucosa because it helps produce mucus.

Now, one of the reasons why our stomach doesn't eat itself alive with its own acid or irritate

itself is because we have that coating or that protective barrier of mucus between the

acid and the actual lining of the stomach So, you think here's the inside lining of

the stomach, mucus, and then we've got that acid but remember our discussion about Prostaglandins

and what they could do earlier.

Prostaglandins also got involved in helping the stomach produce mucus and even regulating

the stomach acid.

So, if I take a medication that reduces the amount of Prostaglandins, Ibuprofen, then

I reduce the potential amount of stomach mucus on that inside lining and so, I could thin

out that protective barrier and make it more risky or at least create a situation where

the acid could irritate the stomach more easily because that mucus being thinner or less produced.

And so, that's essentially how Ibuprofen could affect the stomach or cause stomach irritation.

Now, in general, people who take Ibuprofen every once in a while, even if you take Ibuprofen

for a few days to help with the fever from like the flu or some other illness, for the

most part, you're not going to have major stomach issues.

We're more concerned about those who maybe on Ibuprofen every single day to help manage

a chronic condition say like maybe arthritis or we might be more concerned with patients

who have a history of gastritis which is inflammation of this inside lining or maybe somebody who

has peptic ulcer disease.

But what about other organs like the kidneys?

I mentioned the kidneys a little bit earlier when we talked about the Ibuprofen passing

through the liver, getting converted to a more inactive form that we referred to as

a metabolite and then those metabolites eventually made it to the kidneys and got excreted in

the urine.

Let's talk a little bit more about the details of that process and see if Ibuprofen can have

an effect on the kidneys.

So, here's a really cool dissection that we briefly saw earlier in the video but more

context, this is a frontal cut so we could see the internal anatomy of the kidneys and

the first thing I want to mention is this structure here called the renal artery.

Renal just mean - means kidney and this renal artery is going to take blood into the kidney

and it'll branch multiple times but go back to that story of that metabolite of the Ibuprofen.

Eventually, it's going to enter through this blood vessel and get distributed throughout

the kidneys and like I mentioned, those blood vessels will continue to branch and branch

and branch until the point where when they get into the cortex here, the outer portion

of the kidney, they're microscopic.

Can't see 'em with the naked eye.

So, if we zoomed in and zoomed in to the renal cortex, we'd see these awesome functional

units referred to as a nephron.

A nephron is a combination of urinary tubules as well as some tiny little blood vessels

and this is where we're going to see this filtration process between the cardiovascular

system and the urinary system.

In essence, we're going to create urine here.

So, there's going to be a fluid component from the cardiovascular system that's going

to pass into these urinary tubules and it'll take these waste products including some of

these metabolites into the urinary tubules.

So, we've moved from the cardiovascular system now into the urinary system and if we come

back to this really cool kidney dissection, you can see these areas right here that I'm

highlighting with the probe here and these are referred to as renal pyramids.

Now, these are full of tiny, tiny, little collecting tubules that are collecting essentially

urine and they're going to take them out and funnel them into this process or I should

say this larger tube here called the renal pelvis which then goes and becomes the ureter

down to the bladder and hopefully again out into the toilet.

So, it's a really cool process that's happening 24 hours a day, seven days a week, but does

that process of that metabolite from Ibuprofen passing from the cardiovascular system into

the urinary system cause a problem?

Not so much but there is a potential side effect with the kidneys and Ibuprofen.

It doesn't have to do with the process that I just went through and mentioned, it's weird,

has to do with again what the prostaglandins do.

Last thing, we'll refer to back to the beginning of the video.

Remember the prostaglandins they did have an effect on the kidney, a vasodilator or

in other words, they help the tiny little blood vessels in that renal cortex vasodilate

or stay open a little bit.

And if you take Ibuprofen and suppress Prostaglandins synthesis, you no longer have quite as much

influence to vasodilate those blood vessels and they can start to vasoconstrict.

Now, in what context would that be a problem?

Somebody again, who's taking Ibuprofen every once in a while or for short periods of time,

who's staying well hydrated isn't going to have a much, much of a problem with that kind

of vaso constrictive effect of taking the Ibuprofen, but let's say again, we go back

to that example, somebody who's taking it multiple times a day, every day to help try

to manage arthritis or in a sense - maybe somebody has kidney disease.

If somebody already has kidney disease and uveso constrict those blood vessels, you might

exacerbate that problem even further.

So, when I'm in the clinic and I'm talking about managing people's pain or inflammation

or fevers with Ibuprofen, we often will have a discussion around what their kidney status

is.

Do they have a history of kidney disease?

Sometimes, I'll even pull up their previous labs and see what their kidney function looks

like.

So, those are some considerations that we have to do with say Ibuprofen and if I run

into some of those problems, I may have to consider using some other pain medication

to help manage their pain or their inflammation or their fevers.

So, it's probably enough detail on Ibuprofen and it's potential therapeutic effects versus

its potential side effects.

Now, granted there are some side effects we didn't discuss but we really wanted to focus

on the main or the most common side effects in this video.

Those others we can talk about in a future video.

But I do want to mention one last thing about a really cool phrase that one of my pharmacology

professors mentioned when I was still in medical training and that was in regards to us giving

medications to patients and she would often say this phrase, "start low and go slow".

In other words, start at the lowest therapeutic dose and slowly titrate up till you get the

therapeutic response and then you can stop there.

In other words, you don't necessarily have to say jump like to 800 milligrams of Ibuprofen

if say someone's pain and inflammation could be controlled with 2 to 400 milligrams.

Now, granted everyone situations different, the pain levels, the condition you're treating,

all of that matters when you're picking a medication as well as dosing, but I thought

that was a really cool phrase.

At least that could be used as a general rule for clinicians and even for people who are

going to manage their own health with over-the-counter medications.

Now, in this video, we put so many little puzzle pieces together.

We put the pieces of human physiology and how they would interact with Ibuprofen.

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