Learn about the pharmacology of TNF alpha inhibitors
We shall be talking about 200 horses factor-alpha inhibitor drugs in this lecture the drugs i shall be studying our eterna sept infliximab a dilemma map certainly zoo map goo lima map so before we begin let’s understand exactly what two men across this factor alpha is my support well the summary of it is basically it’s involved in inflammation however to necrosis
Factor-alpha is actually a cytokine center to many aspects of inflammatory response macrophages marcelles and activated t helper cells secrete tumor necrosis factor-alpha tumor necrosis factor-alpha stimulates macrophages to produce saito tatsuo tab light thereby increasing focus eyelid killing activity so here you can see a stimulus activated motorcyclist on
Macrophage and then it produces to my necrosis factor-alpha however here it has a lot of effects on different parts of the body first of all it has effects on osteoclasts in the bone which lead to a buret activation of us a class formation while you remember osteoclast activity caused breakdown of bone if this happens in the joint examine cause you to have increased
Bone resorption joint space narrowing causing a lot of information also it affects a deeper site which interfere with the metabolism also affects monocytes which increases their differentiation and also causes and will fill ourselves to increase self infiltration and increased energy genesis which is formation of new blood vessels it also has effects on myocytes
Which is in the cardiac muscles which leads to my kradic dysfunction cardiac myocyte death it also has effects on glial cells which causes modification of synaptic transmission and also affects on fibroblasts which leads to apoptosis now when it binds to a parasite it leads to increased acute phase response which leads to increased inflammation that causes increased
Formation of c-reactive protein which you know is a marker of inflammation in the body this can be detected in the blood stream in the serum where you can test for a patient that has increased information from any inflammatory conditions and you can for crp levels and that’s because of the effects of this tumor necrosis factor-alpha it also binds to b cells which
Leads to formation of antibodies and t-cells which comes more t-cell proliferation which can eventually lead to inflammation so as you can see here it has a lot of effects but you also need to understand that it causes cachexia in malignancy so patient often components are having losing weight right the patient has a small cell carcinoma of the lung or has a rid
Of cell carcinoma often pretty cause complaints of weight loss well the reason why they’re losing weight is that they have this tumor necrosis factor it caused the necrosis which is death and because it’s involved in that in cancer cells this patient eventually develop cachexia and started losing weight remember in tuberculosis the ability of the dalai lama to stay
Stable is because of the effect of 200 crores factor alpha so that’s how macrophages are able to be entrapped the micro bacterium tuberculosis organism and form a granuloma inside the log so it’s very very important now in sepsis interleukin 1 interleukin 6 and too many courses factor alpha also can mediate sepsis now that we’ve seen the effects of too many courses
Factor alpha now we can further understand how drugs such as internships work but what is it turn acept where a tender cept is actually it’s produced by recombinant dna now let’s study a turn of something a little more detailed here first you have to realize on the cell membrane we have the tumor necrosis factor receptor which is the p55 kilodalton right here now
That has to bind to to my necrosis factor-alpha now also we have the second receptor for tumor necrosis factor alpha which is the tumor necrosis factor receptor 2 which is p 75 because it’s a 75 kilo dalton protein now when two hundred persons factor alpha are killed bind to its receptors it has pro-inflammatory cytokines and basically initiates the pathology causes
That we had talked about earlier with like increased inflammation activation of poor version of b cells or t cells b cells making two bodies just like we talked about earlier or even effects on the liver for example in transformation of c-reactive protein which is a marker of inflammation so now the time except on the other hand was discovered and it was created
By actually having identical receptors of the domain of the human p75 tnf receptor so what they did is they took this tnf receptor itself create an identical copy and then combined it to the igg g1 fc portion of the human antibody see right there so now we have like a partial antibody binding to this receptor and that’s what it turn acceptors and you see this is
The fc region of the human eye gg one antibody so using that that’s why it’s called it’s called it’s produced by recombinant dna now the important thing is that now that the turnus app can actually bind to to mana croesus factor alfred that is how it works that’s negative action c so once it binds well tomato crosses factor can no longer bind to its receptor on
The cells which mean there’s no more signal transduction you can have that massive inflammatory response patients get and there’s no effects on our co classic activity or chondrocytes there’s no inflammation in the joint impatient psyche to feel better so what do we use a timer set for what to use to treat patient’s have inflammatory conditions such as rheumatoid
Arthritis psoriasis and ankylosing spondylitis right remember these are all inflammatory conditions patient abdomens arthritis or would have joint pain right because they constantly have a massive information a sufficient upon closing spine lights always having back pain right so in psoriasis they usually develop a rash but they can also develop psoriatic arthritis
Right so you can see ids i despise us all about information about this condition so how do you remember this for the board exam well it’s just spell out at the time except and look at the t and the capital n intercepts tnf so etanercept with t and intercepts tomorrow necrosis factor-alpha now let’s take a look monoclonal antibodies well excuse me look at the word
Mono means one quantum is basically the cloning single antibodies right so these are basically antibodies so we’ve got infliximab add a little map sir – loser map in gulu moon map well they’re making the – is pretty straightforward there are when you freeze whenever you see the word em a b right ma b basically stands for monoclonal antibody so on the board exam
Once you see map you know we’re talking i’m gonna call an antibody so it’s pretty straightforward but what they do is they are anti tumor necrosis factor-alpha a monoclonal antibodies so here side by side you can see this is infliximab right it’s a chimeric antibody right and it’s a little bit different from a tennyson right so if you look here we have the heavy
Chain and the light chain of the human antibody right that’s the constant regions of the human antibody right and they bind here they will bind to tumor necrosis factor-alpha and basically negate the effects on the cell membrane so they don’t buy into that tumor necrosis factor alpha receptors now if you look at infliximab a deliverer map and good limu map there
Are monoclonal antibody however so the laser map is a peggle which is a pegylated fa b fragment okay still works by binding to tumor necrosis factor-alpha if you come compare that at nsf which we talked about earlier which is a suitable receptor see it has basically that to learn necrosis factor receptor here which is used to form the first portion of it and it’s
Not combined with the fc fragment of the human eye gg1 antibody segment okay that’s what makes it separated from all this monoclonal antibody now it’s used to treat the pair disease that’s what i call a pair which is psoriasis ankylosing spondylitis inflammatory bowel disease such as crohn’s disease or ulcerative colitis or rheumatoid arthritis these are all have
The same pathology right it’s all about inflammation so if you can decrease inflammation the patient’s body they have less pain and they feel better this is why we treat patients women on antibodies on the board exam remember pai r that’s the mnemonic to be able t for diseases that we treat this monoclonal antibodies so you’re probably thinking to yourself alright
Penis how am i gonna be able to remember all this monoclonal antibodies but we’ve got a beautiful mnemonic for you here so the way you remember it is i dow got certified by inflicting pain on tnn wow that is easy right so well you have to look at it ignore the last couple of regular remember it’s basically a map right they all have map in them so it’s very easy
To remember remember that part it’s now trying to keep track of which one of them when you’ve been tested on the usmle of the comics of which i’m supposed to pick right so i can know which one is being used well i dow is the name of the guy in order for him to get certified he’s gotta be able to win the championship right he’s got to be win the match what the match
Is the the battle between patients a half pain right all these patients have pain rheumatoid arthritis complete of pain right knee pain joint pain back pain ankylosing spondylitis right inflammatory bodies they have abdominal pain right they have blood in your stool depending if you have ulcerative colitis right because they have an oscillation oscillation in the
Bowel is to see the amount of pain now so i dow is the main guy he’s a guy who’s got another fighting to get certified it’s got to inflict pain on tnf once we inflict pain on tnf we give him a chemical knockout i’ll punch him in the face and now the patient feels better right so now that’s how we get certified so i the limo map guglielmo map certainly zoom out
And in flicks in it right that is how you remember these for the board exam okay so if you really enjoyed this lecture we’d like you to click below on the icon to subscribe to our channel and also we like you to visit smash usmle comm to be able to watch over 300 hours of usmle and comma to review lecture videos such as this to be able to do well on your board exam
Thank you very much for watching have a by
Transcribed from video
TNF-a inhibitors Simplified for the USMLE and COMLEX By Dr. Adeleke Adesina DO
