Immunosuppressive Drugs: Overview

00:01 Welcome to Pharmacology by Lecturio.

00:04 Today, we’re gonna talk about a very complex topic called the biologic medications.

00:10 This deals with the pharmacology of inflammation.

00:13 Now from a real world perspective we would never categorize these drugs under one section but I’m just going to explain them to you so it makes a little bit more sense in the grand scheme of things.

00:23 You can then read about them later when you’re doing a system, say, respiratory.

00:28 Now, in general, when we talk about drugs that suppress the immune system, we divide them into intracellular mechanisms of action and extracellular mechanisms of action.

00:39 When we talk about intracellular, we talk about those that initiate the inflammation pathway so you can talk about antimetabolite drugs, you can talk about macrolides or you can talk about IMDs.

00:52 Now, an example of a antimetabolite is something like a azathioprine.

00:57 So we’ve actually talked about these drugs already in some of our viral lectures and some of our other inflammation lectures.

01:03 What this does is it inhibits or interrupts purine synthesis.

01:08 You can also interrupt pyrimidine synthesis so leflunomide is a great example of this particular mechanism of action.

01:16 Finally, you can have antifolate medications.

01:19 Methotrexate is a classic example of an antimetabolite that works intracellularly.

01:26 We also have macrolides, now the macrolides we commonly think of as antibiotics but these are also macrolides.

01:35 These drugs are like tacrolimus or other drugs in this drug class and what they do is they block a certain type of protein called calcineurin.

01:48 There are others as well in this drug class.

01:50 Finally, there are what we call the IMDs - these are angiogenesis inhibitors.

01:56 Great example is the thalidomide.

01:58 Thalidomide was made famous by patients who ended up being born with no arms and no legs because they were given to pregnant women.

02:07 Now the drug itself wasn’t the problem the problem was that during the manufacture of thalidomide, there was enantiomers.

02:14 Enantiomers are examples of my left and right hand, they're enantiomers of each other.

02:19 The wrong enantiomers were being mixed in the product and it was the enantiomer that was fetotoxic, the original drug was not.

02:28 The other type of intracellular agents are receptor antagonists.

02:32 So for example, you can have interleukin receptor antagonist or mTOR antagonists.

02:39 Now when you look at the mTOR antagonists you can see drugs that are very familiar to us and these are often used in transplant medicine to suppress the immune system so that you don’t have a reaction to your newly transported organ.

02:53 Extracellular immunosuppressive drugs are quite wide and varied and these are containing some of the most exciting drugs in history.

03:03 The antibody based extracellular drugs include polyclonal and monoclonal drugs.

03:09 So the polyclonal drugs are old, they’re the anti-thymocyte globulin and the anti-lymphocyte globulin - these are polyclonal in the sense that they are acting on multiple sites, they have multiple strains so it’s not a specified targeted kind of a drug like the monoclonal antibodies are.

03:27 The monoclonal antibodies are probably the most exciting thing to happen to medicine in the last 200 years.

03:34 Monoclonal antibodies are so specific and they are so relatively speaking free of a side effects that they are revolutionizing every single branch of medicine.

03:47 Now the monoclonal anti-bodies can target the serum, can target the cellular or can target any other area.

03:54 It’s a huge area and obviously, the schematic is not done to size because of monoclonal antibodies there are thousands of them where perhaps there are maybe 10 or 12 in the other categories.

04:06 For example, in terms of your serum targets you can have those drugs that target complement C5 or you can have those drugs that target IgE so omalizumab is a classic example of an IgE monoclonal antibody.

04:23 There’s interferon based treatments, there’s other types of interleukin 12 or interleukin 17A - there’s hundreds and hundreds of different targets that you can have in the serum.

04:35 Cellular targets are huge as well. You can have everything from CD 3 to CD 154.

04:42 Literally, there’re hundreds of the CD base cellular targets. Some of the more commonly once that we know about is the CD 20 targeter of rituximab which we’ll talk about in a minute.

04:56 Now we have other unsorted ones, so I’m not gonna go into all of them, I think that it’s just important to know that some of the monoclonal antibodies will have various targets, one of the one’s that I’m thinking of in particular is [inaudible 05:25] which is actually used in cholesterol control of all things, so monoclonal antibodies are wide and varied.

05:19 We're talking here about immunosuppressive drugs but they can be many different targets, they can also have immunosuppressive activity.

05:25 In terms of extracellular activity, we also have some fusion inhibitors which we commonly think of as viral treatments but we can also have immunosuppressive drugs that work in the same areas.

05:39 We also have agents that work against tumor necrosis factor so for example etanercept is an agent that works against TNFi.

05:51 So there you have it.

05:52 There’s an overall schemata of the inflammatory immunosuppressive agents.

05:58 There are a lot of them, there are hundreds of them but when you start talking about the individual agents in trying to figure out where they fit in into the schema, if you have schema like this to put it all together, it starts to make a little bit more sense.

06:11 Also have a look at my other lecture that went over the entire immune system sort of in three minutes and it’ll help.