비스테로이드성 항염증제의 이해

### 염증 화학적 매개체, NSAID, 류코트리엔 길항제 및 스테로이드
* 염증은 혈관 조직의 손상이나 부상에 대한 반응으로 발생하며, **혈관 반응으로 시작하여 발적, 열, 부기, 통증의 네 가지 주요 징후**가 특징입니다.
* 💊 프로스타글란딘과 류코트리엔과 같은 염증성 화학 매개체는 **혈관 확장 및 내피 수축**을 유도하여 염증을 촉진합니다.
* 💊 아라키돈산에서 유래한 프로스타글란딘은 기능에 따라 크게 **위장관의 완전성을 유지하고 응고를 촉진하는 프로스타글란딘**과 **활액 관절에 다량으로 존재하며 혈소판 응집을 감소시키는 두 가지 그룹**으로 분류할 수 있습니다.
* 💊 아스피린, 이부프로펜, 파라세타몰, 셀레콕시브와 같은 비스테로이드성 항염증제(NSAID)는 **프로스타글란딘 합성에 관여하는 COX 효소(COX-1 또는 COX-2)를 억제**하는 방식으로 작용합니다.
* 또 다른 염증 매개 물질 그룹인 류코트리엔은 **염증, 기도의 점액 생성 증가, 기관지 수축**에 관여하여 **천식의 주요 원인 물질**입니다.
* 💊 류코트리엔 수용체 길항제는 **류코트리엔 수용체에 경쟁적으로 결합**하여 염증, 점액 생성 및 기관지 수축을 감소시킵니다.
* 💉 스테로이드계 항염증제 또는 하이드로코르티손과 같은 글루코코르티코이드는 **아라키돈산과 염증 유발 유전자의 합성을 억제**하여 강력한 항염증제로 작용합니다.

비스테로이드성 항염증제는 프로스타글란딘과 류코트리엔을 억제하여 염증, 통증, 발열을 줄여줍니다.

so I stated, in this video, we're going to have a look at three major learning objectives. The first of which is going to have a look at some of the chemical mediators of inflammation. And then we're going to have a look at some of the drugs used to mitigate inflammation or reduce the inflammatory process. And we've broken that up into two major objectives. Course objective 2 or the learning objective 2 for this is looking at the non-steroidal anti-inflammatory medications. And the third is to have a look at the stoical anti-inflammatory medications. So let's just first go back and just have a quick recap of what Graham was talking about in the inflammatory process. Remember that inflammation will occur any time damage has been inflicted or injury has been inflicted on vascularized tissue because you know that the inflammatory process first starts off with a vascular response. And the inflammatory process is basically seen through the four cardinal signs. Okay, the four cardinal signs of inflammation, which is redness, heat, swelling, and pain. Now the reason why we

get redness, heat, swelling, and pain is because of the vascularized response. So when that damage occurs, what you'll find is that the blood vessels in that area will dilate, increasing the amount of blood flow get into the injured site and the endothelial cells. So remember what that means if you take a blood vessel, the cells that line the inside of that blood vessel are called endothelial cells, and that these inflammatory pro-inflammatory agents or chemical mediators of inflammation, they can tell these endothelial cells to contract and get smaller, which means that the space between one and athili or sell in the next gets larger. And what that means is the blood flow that's coming through those vessels can be pushed out of the blood vessel into the surrounding tissue at the area where it's injured. And this can be because it wants to dilute out what's going on, wants to increase the leukocytes or the white blood cells to that area. It wants to wash away any potential foreign agent that is built up.

the vascular response the inflammatory spots is vasodilation and endothelial constriction, and the reason why these two things occur is because of these chemical mediators of inflammation. They have been released from surrounding cells, and some of these chemical mediators, including Grable, have spoken about these in the previous video: prostaglandins, leukotrienes, nitric oxide, Brady cannons, histamine, and cytokines. So, these are all chemical mediators that promote this process that we just spoke about. So, what that means is, if we want to mitigate or we want to reduce the inflammatory process, we need certain drugs or compounds that stop these chemicals from having that function. Okay, in this video, we're going to talk about two major chemical mediators of inflammation: prostaglandins and leukotrienes. And the reason why we're talking about those two is because they're part of the same cascading pathway. So, let's first start off with this: if you take the cells in your body, you know that those cells are surrounded

by a phospholipid bilayer, and this phospholipid bilayer is made up of phospholipids. And if we were to draw a phospholipid, you know that it has a phosphate head, which loves water, so it's hydrophilic, and two fatty acid tails, so lipid tails, which do not like water, so they're hydrophobic. Okay, now the reason why I'm bringing this up is if you were to take a twenty-carbon portion of this fatty acid tail, right, just take a small portion of this fatty acid tail, that actually is what we call arachidonic acid. Okay, arachidonic acid. Now, arachidonic acid is important because it produces prostaglandins and leukotrienes. Okay, so from phospholipids, you have the fatty acid tails. Taking a twenty-carbon portion of that fatty acid tail, we can create arachidonic acid. And arachidonic acid, like I said, will create prostaglandins and leukotrienes, both of

which are chemical mediators of inflammation. What that means is they promote vasodilation, and then promote endothelial constriction, amongst others. Now let's first focus on the prostaglandins because many prostaglandins exist within the body. And yes, a lot of them have a pro-inflammatory role and a role in producing pain and fever. But also, prostaglandins play many other roles within the body. And these many different roles can be broken up into two major categories. And that's what we're going to focus on today. We're going to break up all the individualized prostaglandins into two major categories and focus on those. So let's break prostaglandins up. So both of these prostaglandins will promote, like I stated, inflammation. Both types of prostaglandins will promote pain. Both types of prostaglandins will promote fever, all of which we know are involved in that whole inflammatory process. But prostaglandins aren't just involved in these things. They're

involved in other processes. So, for example, the prostaglandins that will be drawn up on this side of the whiteboard. These prostaglandins are also involved in maintaining stomach or GI tract integrity. So, what I can write up here is increased GI tract integrity. Now, what am I referring to here? You know that in your stomach you have a mucous lining. Okay, now this mucous lining has bicarbonate and mucus, and it protects our stomach from the acid that it creates. Okay, because we know that we create hydrochloric acid, and there's a very low pH around about 1.5 to 3, which is sufficient to break down the tissue of our stomach. But this mucous lining protects us. It is prostaglandins that help us create this mucous lining and increase or maintain GI tract integrity. Okay, so that's a very important point put across. These prostaglandins on this side also produce something called thromboxane. So, let's write thromboxane. Now, thromboxane you may see written as T.

X a to and from boxing is involved in the clotting pathway natural fact from boxing promotes platelet aggregation from boxing promotes platelet aggregation, which means it promotes clotting. Okay, so the prostaglandins on this side are involved in inflammation, pain, and fever, maintaining stomach integrity, and increasing the clotting pathway so increasing platelet aggregation. If we ever look on the other side of these prostaglandins again, they are involved in inflammation and pain and fever, but some other processes. For example, you'll find that these prostaglandins are in high quantities in synovial fluid. Now, why is this important to note? Because think about where we find the synovial fluid if either AB synovial joints. Okay, so that includes the knee, for example. Now, if you increase the amount of these prostaglandins in the knee or the son of your fluid there at the knee, it's going to promote inflammation of pain and can also lead through to rheumatoid arthritis. So these prostaglandins do play a role.

in rheumatoid arthritis. Okay. In addition to that, we saw that over here, these prostaglandins or this side of the pathway that involves thromboxane promotes platelet aggregation. Over on this side, they reduce platelet aggregation. So, very different. So, what do these prostaglandins have in common? Both are involved in inflammation, both involved in pain, both involved in fever. However, the prostaglandins on this side maintain the mucous lining of our stomach and also promote clotting. On this side, yes, inflammation, pain, fever, but these prostaglandins are present in high quantities in synovial joints and therefore can play a role in rheumatoid arthritis. And they reduce platelet aggregation. Now, these are all important because we need or we have drugs that can reduce our inflammatory response. Okay. Now, some of these drugs are called the non-steroidal anti-inflammatory drugs. So, let's write that up. These drugs, which we call NSAIDs. So, let's just write answers which like I said of the

non-steroidal anti-inflammatory drugs. They're non-steroidal, okay, so steroidal drugs often have their effect as signaling molecules, okay, in this manner because they're a steroid, they can easily pass through the phospholipid bilayer of cells, okay, because they have a lipid base to them, okay. Remember, lipids love lipids. What the lipids hate, they hate water, they hate anything that's polar, okay. Polar means it's charged. Lipids hate charged things and water's charged, but lipids like other lipids which are not charged like steroids. Now, what that means is that steroid hormones, if they come across a cell, they can just move straight into the cell and go straight to the nucleus where the DNA is, and that means that many steroids exert their effect by altering the transcription of our DNA, meaning it tells what genes to be expressed and what genes not to be expressed, okay. So, in this scenario, we're talking about the non-steroidal anti-inflammatory drugs. All that means is that these drugs do not exert their

effect via this means. Okay, now you've heard of these most oral anti-inflammatory drugs before. The major ones include aspirin, ibuprofen, paracetamol, and celecoxib. They're the four major ones we're going to talk about today. So what I'm going to do is this: if I break these two sides of the prostaglandins up and discuss aspirin, ibuprofen, paracetamol, and celecoxib, what you'll find is that they either work by inhibiting these types of prostaglandins or these types of prostaglandins. But how do they do it? Well, in order to produce the prostaglandins on this side, we need a particular enzyme that turns them all on. Okay, what is this enzyme? This enzyme is called cox-1. Cox-1 stands for cyclooxygenase one. So this is an enzyme that comes along and promotes these prostaglandins and through bakso to have these functions in the body. On this side, cox-2 is the enzyme and cox-2 promotes

these prostaglandins to have these particular functions, and these nonsteroidal anti-inflammatory drugs. How do they work? Well, they'll inhibit these Cox enzymes. Okay, so let's first start with aspirin. What you'll find is aspirin inhibits both Cox-1 and Cox-2. So, I can draw aspirin right in the middle here. But we will also find is aspirin more specifically, slightly more specifically, will inhibit Cox-1. Now let's talk about what that means. If aspirin inhibits the Cox enzymes, specifically more so Cox-1, it's going to reduce inflammation, it's going to reduce pain, and reduce fever, which means that it has an anti-inflammatory role, an analgesic role, and an antipyretic role. But what that also means, it's going to reduce GI t in temporary, so it's going to reduce our ability to maintain the mucous lining of our stomach. And what that means is that the acid that's present in our stomach will more likely irritate our stomach and can cause

damage to it. So that's why you've probably heard of doctors or nurses stating, Take your aspirin on a full stomach to reduce this sort of stomach irritation. But in addition to that, what you'll find is aspirin, even though it's an NSAID and anti-inflammatory medication, one of the other most common means or uses of aspirin, I should say, is for individuals who have cardiovascular disease or increased likelihood of stroke or heart attack. Why? Because taking a small amount of aspirin, have a look down here, will reduce platelet aggregation. Because it's inhibiting this side, it's going to inhibit platelet aggregation. So it's going to reduce the likelihood on their blood to clot. And that's why aspirin is often handed out to patients who are likely to have strokes and heart attacks and so forth. Okay, so the next one I want to talk about is ibuprofen. And ibuprofen, again, inhibits both COX-1 and COX-2, and therefore has a very similar effect.

anti-inflammatory effect as aspirin paracetamol, which we call an acetaminophen. Okay, so paracetamol is an acetaminophen. It is not what we would call a normal nonsteroidal anti-inflammatory drug. It isn't. It is an NSAID-like drug, and the reason why is this, because paracetamol, yes, plays around somewhere in this pathway. It is a very efficient analgesic and antipyretic, but paracetamol is actually not very good at reducing inflammation. Okay, and so if it was to work upon blocking cox-1 and cox-2, it should be good as an anti-inflammatory drug, but it's not, which gives us an indication that it may not actually inhibit cox-1 and cox-2, but it may actually inhibit a third cox isoform called cox 3. However, we do not have enough proof to demonstrate that this is the case, but we just put paracetamol in as an NSAID, okay, because it has a very similar effect.

it's very good as an analgesic and antipyretic, but it's quite a poor anti-inflammatory drug. So let's write paracetamol, and the last instead I want to discuss, we call celecoxib. You may hear of it by its name on the market, which is celebrex. And celecoxib, you can see I've drawn just on the cox-2 side, which means celecoxib is a Cox-2 specific inhibitor. It's one of the few Cox-2 specific inhibitors available on the market in Australia. There were some others, but they've been taken off the market. Now let me tell you why celecoxib is good as an anti-inflammatory, as an OG zyk, as an antipyretic. It is used in cases of rheumatoid arthritis to reduce the amount of prostaglandins in synovial fluid. But many of those cox-2 specific inhibitors, if the normal prostaglandins in this pathway reduce platelet aggregation, if you were to block it.

you're going to increase platelet aggregation, which increases clotting, which meant that a lot of the previous cox-2 inhibitors. Cox to specific inhibitors promoted clotting and increase the patient's likelihood to clot, which isn't good because it's going to increase their likelihood of myocardial infarction, stroke, and so forth. Okay, but so far celecoxib has not shown to have this effect but has shown to be an efficient anti-inflammatory, analgesic, antipyretic, and reduce rheumatoid arthritis. So these are the non-steroidal anti-inflammatory drugs. Okay, now if we move over to the Luca trends. Luca trends yes are involved in inflammation. So again, I can write down inflammation for one of the roles of Luca trends because we knew that, but Luca trends also increase mucus secretion, specifically in the Airways, or I should say more so in the Airways, and increases bronchoconstriction. Now I want you to have a look at these three major effects of Luca drinks. Luca drinks promotes inflammation, increases mucus production

more so in the Airways and increases bronchoconstriction. What do you think? What process or what disease process do you think this plays a big role in asthma? So you'll find that Luca trains are involved in the inflammatory process involved in asthma because asthma is a reversible inflammatory disease. So inflammation is the crux of asthma, and Luca trains are involved in this process. So how do we stop these Luca trends from having their effect? Well, we don't necessarily stop the synthesis of the Luca trends, but we stop the Luca trains from binding to Luca tree receptors. So we have drugs that come in, which are called leukotriene receptor antagonists, Luca train receptor antagonists. So that will competitively bind at that receptor spot against Luca trains and therefore reduce inflammation, mucus production of bronchial constriction. Okay, now the very last point I want to talk about are the steroidal anti-inflammatory drugs. So a lot of us have taken steroids at some point, such as hydrocortisone, cortisol, called it.

just normal cortisone for many different reasons because we know that they have a very strong anti-inflammatory role, but also have other systemic effects. Okay, but we're just going to talk about the anti-inflammatory role of these steroids. Now, these steroids we call corticosteroids, so let's write that up. Corticosteroids. Now, the reason why they're called corticosteroids is this: cortico refers to the cortex, the cortex of the adrenal gland, and steroids are referring to the fact that they are steroids. Okay, now remember you have your kidneys and on the kidneys you have your adrenal gland, adrenal meaning near kidney or on kidney, and that adrenal gland has an outer portion called the cortex and an inner portion called the medulla, and different hormones are produced in different layers. Okay, in the cortical layer we produce the corticosteroids, and the major corticosteroids are hydrocortisone, which we call cortisol, and cortisone. Now, they're also known as glucocorticoids. Glucocorticoid.

corticosteroids and right glucocorticoids because you probably see them as either corticosteroids or glucocorticoids. Let's write glucocorticoids gluco corty coins because glucose cortex steroids. Now the gluco portion refers to the fact that these steroid hormones here, what they do is they promote the release of glucose into our bloodstream. Okay, this doesn't necessarily play a role in our anti-inflammatory picture here. Okay, call the cow again cortex and again refer to the steroid portion. Now how do glucocorticoids such as hydrocortisone because Oh play an anti-inflammatory role? Well, first point is this, they can actually come into this area here and then can stop phospholipid phospholipids from turning into arachidonic acid. Okay, so glucocorticoids can stop phospholipids from turning into arachidonic acid. It means that they stop this entire cascading process right here. They stop these prostaglandins from being produced. They can stop these Luca trains

from being produced, so-called glucocorticoids, a very potent anti-inflammatory drugs. But that's not the only role they play, because again, there's steroids, which means that predominately, they have their function by moving into a cell and altering the transcription of genes. And the genes that they can alter the transcription of, a pro-inflammatory gene. So, there's many, all these interleukins and cytokines, glucocorticoids can reduce their expression or inhibit their expression, therefore inhibiting inflammation. Okay, so I hope that this makes sense, talking about some of the pro-inflammatory agents, okay, such as prostaglandins, leukotrienes, and we mentioned histamine and bradykinins and cytokines and so forth. We spoke about the non-steroidal anti-inflammatory drugs, such as aspirin, ibuprofen, paracetamol, and celecoxib, and the fact that they work by inhibiting prostaglandins from being made, either from COX-1 or COX-2 or both. And we spoke about the non-steroid about the

steroidal anti-inflammatory drugs, the glucocorticoids, and they play a role in inhibiting the production of a catana Cassatt, but also inhibit the synthesis of pro-inflammatory genes. So I hope that all made sense.

Anti-inflammatory drugs (NSAIDs and steroids)

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염증 과정은 혈관 반응에 의해 시작되며 프로스타글란딘, 류코트리엔, 산화질소, 히스타민, 사이토카인과 같은 화학적 매개체에 의해 매개됩니다.

이러한 매개 물질은 혈관 확장, 내피 수축, 손상된 조직으로의 혈류 증가를 촉진하여 염증의 특징적인 징후를 유발합니다.

이러한 화학적 매개체, 특히 프로스타글란딘과 류코트리엔을 억제할 수 있는 약물은 염증 과정을 줄이는 데 매우 중요합니다.

인지질에서 추출한 아라키돈산은 프로스타글란딘과 류코트리엔 생성의 핵심 성분으로, 항염증제의 표적이 됩니다.

염증에서 프로스타글란딘의 역할

프로스타글란딘은 신체의 염증, 통증, 발열을 촉진하는 화학적 매개체입니다.

또한 위장의 완전성을 유지하고, 응고 경로를 증가시키며, 활액에 존재하여 류마티스 관절염에 기여하는 역할을 합니다.

비스테로이드성 항염증제(NSAID)는 프로스타글란딘과 관련된 염증 반응을 줄이기 위해 사용됩니다.

비스테로이드성 항염증제의 역할

비스테로이드성 항염증제(NSAID)는 세포막을 쉽게 통과하지 않고 DNA 전사를 변화시키지 않기 때문에 스테로이드 약물과는 다른 방식으로 작용합니다.

아스피린, 이부프로펜, 파라세타몰, 셀레콕시브 등 주요 NSAID는 콕스-1 및 콕스-2 효소를 억제하여 염증, 통증, 발열을 감소시키지만 위장 자극을 유발할 수도 있습니다.

통증 및 염증 관리에서 아스피린, 이부프로펜, 파라세타몰, 셀레콕시브의 역할

아스피린은 일반적으로 혈액 응고 위험을 줄이기 위해 사용되며 심장마비 및 뇌졸중 위험이 있는 사람에게 처방됩니다.

이부프로펜은 아스피린과 마찬가지로 COX-1과 COX-2를 억제하여 항염증 효과가 있습니다.

파라세타몰은 진통 및 해열에 효과적하지만 염증을 줄이는 데는 그다지 효과적이지 않으며, 세 번째 COX 동형체를 억제하는 방식으로 작용할 수 있습니다.

셀레브렉스로 알려진 셀레콕시브는 류마티스 관절염 관리를 위해 활액의 프로스타글란딘 수치를 낮추는 데 사용되는 COX-2 특이적 억제제입니다.

혈소판 응집은 염증과 통증을 줄이는 데 효과적인 셀레콕시브를 제외한 COX-2 억제제에 의해 증가합니다.

류코트리엔은 천식에서 염증을 촉진하고 점액 생성을 증가시키며 기관지 수축을 유발하는 역할을 하는데, 류코트리엔 수용체 길항제로 이를 해결할 수 있습니다.

하이드로코르티손과 코르티솔과 같은 코르티코스테로이드는 부신 피질에 작용하는 강력한 항염증제입니다.

항염증 치료에서 글루코코르티코이드의 역할

글루코코르티코이드는 포도당 방출을 촉진하고 프로스타글란딘과 류코트리엔의 생성을 중단하여 강력한 항염증제 역할을 합니다.

또한 전 염증성 유전자의 전사를 변화시켜 인터루킨과 사이토카인의 발현을 감소시켜 염증을 억제합니다.

따라서 비스테로이드성 항염증제와 구별되는 항염증 치료의 중요한 부분입니다.