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 okay so 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 looka trans 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 to fatty acid tails so lipid tails which does 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 a ragged donek acid okay a record Dalek 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 a rack idiotic acid and a rack idiotic 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 drawn up on this side of the whiteboard these prostaglandins are also involved in maintaining stomach or GI T integrity so what I can write up here is increased GI T 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 po2 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 T integrity ok 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 from boxing 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 you're 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 high quantities in a 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 waters 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 cops once danced 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 is going to reduce pain and reduce fever which means that it has an anti-inflammatory role and 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 cops 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 is not a what would call a normal nonsteroidal anti-inflammatory drug it isn't it is a NSAID like drug and the reason why is this because paracetamol yes play 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 to specific inhibitor it's one of the few Cox to 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 to 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 a sport 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 look a trained 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 Clawd echo steroids now the reason why they called corticosteroids is this Qualicum refers to the cortex the cortex of the adrenal gland and steroids are referring to the fact that that 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 okay and the major corticosteroids are hi Joe cortisone which we call clutter zone and cortisone now they're also known as glucocorticoids okay glucocorticoid so I'll get rid of 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 ecause 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 a record onic 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 out 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 hibbett 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 Luca Trent's and we mentioned histamine and Brady cannons 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