the videos are an escape from ecology is this about helping you sends any drugs that we didn't cover thus far one of the drugs most efficient has to stay in muscle contraction muscle cramp and can't relax we can give them a muscle relaxant we give them benzos but we want to know a little bit more specific we don't want to skimp and over eye candy so we give a muscle relaxant and these include things like back with him and cyclo pentene they work in the brain they work kind of like benzos actually becomes with less side effects of in does it work like then those that will mainly work on GABA so they are GABA agonist in particular gaba type B receptors about working on is to kill your receptors they think this is what gives them muscle relaxing without all the other things that come with benzos all right so that's muscle relaxing let's say they don't have a sustained muscle cramp or just have muscular pain or pain in general an entire video talking about these autoimmune disorders that cause you know there's systemic pain and we want to treat that pain we start conservatively trying to exercise try and reduce any triggers and then you start moving slowly slow into things like and says things like core codes and then you might move a little bit further but we always want to try the more conservative ralpherz and they're slowly build up so we're going to talk about things like answers and things like corticosteroids oh we can't talk about those without talking about the pathway so what causes that initial pain and inflammation to start with well in your plasma membrane the membrane it holds something called arachidonic acid this kinda like emergency alarm stab like you know the emergency boxes this is break glass here if there's an emergency you break the glass pull the alarm in it sounds real I was the exact same thing so you have a little box to present a number and inside you have a record I said any sign of damage and kind of break that glass electrode as it comes out just ring that breaks that glass it's gonna be fossil lipase a - judging by the name it works on phospholipids and it kind of cuts the phospholipids and it cuts out that arachidonic acid that iraq nadaya gas is free to leave the plasma membrane so it leaves a pleasant numbering now it's free and there's two routes it can go to you can go to look between route I'll just write leave the train route and it makes the katrin's the initial enzyme that works on is going to be lipo oxygenation and this becomes precursors like v h PE t and LG a for an LTL will eventually become things like LT b4 ltc4 d 4e for LC before is the main one because we're talking about things like pain so this is a chemotactic agent for neutrophils it's no tactic for neutrophils that may be neutrophils brings in the pain LTC that e these are all things that cause bronchospasms bronchospasms hopefully you remember its pathway in our earlier talks but information even in there talked about in our respiratory block because because this carbonyl spasm is seen as a causative agent in things like asthma and so we have a lot of drugs that block this when we're talking about asthma if you're tall we can block we're gonna bug Lucien binding with montelukast or juice box halfway out right by blocking light for oxygenase with things like by lutein and so the last use is respiratory drugs that help with asthma a little aside because we're talking about how much K in this block but just remember everything kind of builds on itself so don't forget these important facts but Ltd for is the pinnacle routine target agents new triple to come in to pay now what's the other pathway you can go on what can go on another pathway an enzyme works on this is a cyclo oxygenase also known as Cox Cox one and cox-2 and similar to here it makes a precursor called prostaglandin h2 prostaglandin h2 can make a ton of things you can make you can go to platelets and platelets will turn into TX pay to put on boxing a tune and that causes platelets to come together go to the aggregation it can also make prostaglandin proper so these are the actual prostaglandins that we usually think about when we talk about prostaglandins the prostaglandins P G e1 pge2 P g s2 these causes the pain the fever the inflammation that we are accustomed to talking about abundance it can also turn into pgi2 and pgic was like the mortal enemy of TX a to the PGI to actually causes platelets to not aggregate cells a decreased platelet aggregation and causes vasodilation again makes it harder for the playlists aggregates and that is your cyclooxygenase now there's something else would possibly doing there has a life outside of inflammation the classic the prostaglandins also help maintain your gastric mucosa so it's good for that also helps maintain renal function we might we need that right renal function I mean how does it do that well why do you think we have cox-1 and cox-2 why why would we need to end dental cox one is the thing that helps maintain these normal functions maintain functions so maintaining your Mukul your gastric mucosa maintain your renal function costumes more inflammatory fellow than these and this end down is the one that causes the employee so it's a fine balance yeah I has a life outside of inflammation and by using different enzymes at different locations we can achieve that balance so we're looking for one last thing I want talk about [Music] something else works on cyclooxygenase and kind of revs up this cycle and then there's a protein complex this protein complex called nf-kb our protein complex and helps mediate inflammation so it can also rebel cyclooxygenase that is a rundown on the pathway analyses how would you manipulate is we kind of reduce that pain to reduce that inflammation some big drugs will be your corticosteroids corticosteroids they do a ton of things through a ton of different mechanisms but because we're talking about inflammation because we're talking about this particular pathway corticosteroids are so potent and reducing inflammation because they block the enzyme do you need the motor block the first enzyme awesome life is a TSO fossil lipase into a blog now you don't have a pathway simple that so that's why there's so pwned you can also what else do we have that source of power and if maybe they'll block that too so they block everything every possible thing you think of so locks FK be how does it do that it creates inhibitory okay so you can you can guess what that does I didn't have this and that KB sounds very inhibit so by blocking the two main players and you still have the pathway and that's why it's so potent so they're corticosteroids now if we don't want to jump to close the stairs because we have so much space we can give something a little bit milder things you can find out ready carry these would be things like Cox inhibitors these are things called NSAIDs non-steroidal anti-inflammatory drugs how perfectly I name right so and says no sir or doesn't necessarily actually and these work bucking cyclooxygenase they can block both cox-1 and cox-2 and by blocking that you get to reduce pain you get to reduce inflammation get rid of these fever so I'll just write to do signs but you can imagine like I said things like pasta glands have a life outside of information do you have that maintain your guess we both have to retain your real function so side effects you can imagine include things like GI t upset ulcers bleeding renal failure because you can know a lot of maintain that renal function if you recall a positive going to help dilate your efferent arterial so if you don't have that you can constrict and reduce renal functions so you know function here ya know and said it is from there ibuprofen you have more specialized ones like aspirin aspirin blocks both why is it different then because it irreversibly blocks it bye see you later it just means putting a seal group on it a simulation and at low doses really likes a blog TX a2 so it kind of stops that segregation and so we use that for preventing clots so low doses stops clubs and our medium high doses then they start working on things like inflammation fever stuff like that inflammation fever some side effects well general side effects of GI upset renal failure also seems to be toxic to your cranial nerve eight that's for auditory so cn8 alright to new this also an overdose and you can have hyperventilation and causes respiratory alkalosis risk alkalosis and then one thing you should and never ever forget do not give aspirin for kids that have some refuse and inflammation it's a common enough drug that you have in the back of the label so don't give it it for kids because you give it to kids it can have liver failure we call our Reye's syndrome Reye's syndrome overly these terms are kind of ring about we talked about it earlier so it can cause arise syndrome that's aspirin there's another special end said and this is celecoxib until I talk to is talks to explicit if fake so blocks talks to that's the one that seemed more inflammation and by doing that great we have reduce inflammation without all the other side effects so reduce inflammation less gid side effects however seems to particularly like the block pgi2 about blocking pgi2 and leaving kind of TXA in place you have more platelet aggregation more clods and less of this counter and less of this counter regulatory brother TDI - and good we have more clots that effectiveness is increased risk of thrombosis you absolutely need to know that the increases of CVS disease risk from BOCES all that stuff because you have increased clots and that's analogies it isn't so for GERD so there's a sulphur algae then I ask you what drug you want to take try and do NSAIDs instead alright you might you might get enticed because it says those CIT problems but it's a sulphur drugs all the other social reaction so you just do general NSAIDs last thing I want to talk about is going to be a diminution that's tylenol that is one of the oldest the most most classic drug for acetaminophen now see the benefit seems to block talks also both seem to block it preferentially in the CNS in the brain it seems to be inactivated peripherally or so it works in the brain you can figure that it will reduce things like fever so reduce fever and paying because things can be centrally controlled by doesn't really work too much for inflammation if you have information from here from all these inflammatory cells coming in and creating cytokines and I'd gunk if it works in the brain is not going to really work on that information so I was right doesn't really work well with inflammation so these Morpher fever for pain why would you get Messina mention of you have fever is the other kid that Steve on pain he said wait wait wait Mike just said I can't give him aspirin so was an alternative acetaminophen would be an all time so you can give this for kids to avoid Reye's syndrome [Music] I've already arrived some from some side effects when acetaminophen is metabolized that crease is really really dangerous for your article called and a pqi the full name is in my notes and this is pretty cool and gone to your living a little freaked out and thankfully for us we have free radical scavengers especially gluta biome now glutathione is a great as is is very limited so glutathione will pick up the NA P Q PI but if you're overdosing on every taking too much with and you know let it read a file will run out when it runs out and this going to have like this free radical has prevailed really just destroys your liver so how do we counteract that what's the answer that we can give n-acetylcysteine NS 0 60 district punishes that glutathione and kind of allows them to do this job again so that's the mechanism you need to know the mechanism of that Antico because a lot of times the transfer key they might get say they gave them an MS in cysteine and how did it work did it increase renal excretion no that's not where does is the increase Gita fishing no that doesn't that does it what conversion know that yeah it just increase accrued of file okay so that's the mechanism of it those are your drugs hope there are so many loose ends in our msk pharmacology and I hope you enjoyed the video things