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- Every drug administered in our body has to pass the blood-brain barrier. Do gastric medicines also reach brain for treatment or they simply work in gastrointestinal track?(1 vote)
- Hey, so only a limited amount of drugs can pass through the blood-brain barrier. They are ultra-hydrophobic structures. 5-ASA, one of the main drugs for IBD, is polar and does not cross that barrier... so it just stays mostly in the colon and the portion absorbed by the body passes through the kidneys and is excreted.(1 vote)
- What about other kinds of colitis, such as collagenous colitis? I have it AND IBSD, resulting in diarrhea even while asleep at night and malnutrition.(1 vote)
- [Voiceover] Inflammatory bowel disease is a chronic inflammatory disease, as its name suggests. And both types of the disease, both Crohn's disease and ulcerative colitis, usually last throughout one's life after they're diagnosed. And if they're not properly managed, they can result in many serious or potentially even life-threatening complications. So, let's briefly talk about the clinical course of inflammatory bowel disease and how it relates to treating IBD. So let's create a timeline of the severity of inflammatory bowel disease. So, on the X axis, we have time, so this is going to be over a period of years to decades. And then, on the Y axis, we'll have the severity of disease. And we'll classify the severity kind of in three categories here, with mild, moderate, and severe. So, you'll notice that early on in the disease process, it starts out fairly mild. In fact, during this period, someone may not necessarily realize that they have inflammatory bowel disease. But then, it's going to spike. And these spikes are known as relapses or IBD flares. And it's during this first inflammatory bowel disease flare typically when the disease is diagnosed. But then it's treated, and the severity goes back down, and it will go back down close to, hopefully, close to their baseline severity. But what you'll notice is, over time, there'll be more and more of these flares and relapses. And occasionally, when the relapse resolves, the severity of the disease, the new baseline, gets worse and worse over time. So, these peaks are known as flares or relapses. And then these valleys, these baseline periods, are known as remissions. So, this disease pattern is known as relapsing-remitting. And it's very characteristic of both types of inflammatory bowel disease. But how does this all relate to the treatment of inflammatory bowel disease? Well, there are three goals to the treatment of inflammatory bowel disease, and they have to do with these relapses and remissions. So, the first goal is to induce remission. The second goal is to maintain remission, or you can think about it as preventing relapses. And the last goal is to prevent and treat complications. Now, to understand how we can accomplish these goals, I think it's helpful to think about the mechanism of inflammatory bowel disease as having three steps. And the first step is the immune response. And this is a drawing of a macrophage, which is one of the main types of immune cells in inflammatory bowel disease that causes the inflammation, which is the second step in the mechanism. Then, it's the inflammation that results in the complications. Now, we can use these three steps as a framework to develop a better understanding of how the different medications used to treat inflammatory bowel disease will achieve these three goals. Now, it is important to note that many of these treatments are effective for both Crohn's disease and ulcerative colitis. So I'm going to talk about them together. However, the efficacy of some of the medications may vary depending on the condition, whether it's ulcerative colitis or Crohn's disease, as well as it can vary from individual to individual. Now, since inflammatory bowel disease most frequently presents from a medical evaluation during this first or second flare, let's start by discussing how to achieve this first goal of inducing remission. So, you can think of an inflammatory bowel disease flare as this immune response kind of getting out of control, and it results in a ton of inflammation. And it's this inflammation that's causing all of the pain and discomfort for someone with inflammatory bowel disease. And because of this, the primary mechanism by which we can induce remission is to directly treat this inflammation with anti-inflammatory medications. And the type of medication that's going to be used will likely depend on this severity here. So, for flares that are mild to moderate in severity, the primary anti-inflammatory medication that's going to be used to induce remission is a group of medications known as aminosalicylates. Then, for moderate to severe flares, the type of medication that's primarily used is corticosteroids. Now, corticosteroids are very effective and powerful anti-inflammatories, but the reason they're reserved for some of the more moderate to severe cases of inflammatory bowel disease is because they can have many different side effects, and they shouldn't be taken for long periods of time. So, they're really only used when necessary. And there are some other drugs that can be used as anti-inflammatory medications over the aminosalicylates, and corticosteroids are by far the most common anti-inflammatories. But this isn't the only type of medication that can be used to treat an acute flare. The other group of medications are known as immunomodulators. So, this immune response is largely mediated by these signaling proteins that are released by inflammatory cells such as macrophages. And one of these signaling proteins is a protein known as tumor necrosis factor alpha, which is abbreviated TNF alpha, and it is one of the signaling proteins that's responsible for the inflammation. Fortunately, we have medications that can target TNF alpha and prevent its effect. So, one of the most common types of immunomodulators used to treat an acute flare of inflammatory bowel disease are the TNF alpha inhibitors. Now, once an acute flare has been overcome and the medications for inducing remission have been successful, the next step is to maintain that remission. Now, fortunately, the medications used to maintain remission are a lot of the same medications that are used to induce remission. However, in the induction, the anti-inflammatories are the primary focus because it's the inflammation that's causing all of the pain and discomfort. During the maintenance phase, it's the immunomodulators that are a little bit more stressed, but they're still taken at slightly less doses often than they would be taken during the induction of remission. Then, another treatment category that's important to mention during this kind of remission phase is lifestyle modifications. And although the effect of some of these lifestyle modifications can be kind of small, they have been shown to decrease the rate of relapse. So, one of the lifestyle modifications is smoking cessation. And this is especially important in Crohn's disease. And another one to mention is diet. Now, there's no evidence that certain diets actually cause inflammatory bowel disease. However, some foods may aggravate the symptoms of inflammatory bowel disease and should be limited or avoided as much as possible. And these include things like dairy, high-fat foods, as well as high-fiber foods. And then, the last lifestyle modification is stress reduction, which can be achieved through meditation or routine exercise. All right. So, the last goal in treating inflammatory bowel disease is preventing and treating complications. So, let's start with the prevention. And there's two main areas we focus on, and that is infection and cancer. So, someone with inflammatory bowel disease during an acute flare is much more likely to develop a severe abdominal infection. So, sometimes, during these relapses or flares, prophylactic or preventative antibiotics will be prescribed. And the other is cancer, specifically colorectal cancer. So, inflammatory bowel disease is associated with a much higher risk of developing colorectal cancer. Now, it's higher for both Crohn's disease and ulcerative colitis, but it's significantly higher much more so in ulcerative colitis. So, anyone with ulcerative colitis is recommended to start having a routine colorectal screening with a colonoscopy starting eight years after they're diagnosed with ulcerative colitis or by the age of 40, whatever comes first. All right. So, we'll start with abscesses. And what an abscess is is it's a localized walled-off pocket of infection. And on its own, an abscess isn't necessarily that bad of a complication, but it has a risk of rupturing, and if it ruptures, it can cause a life-threatening infection of the abdominal cavity called peritonitis. To prevent an abscess from rupturing and to treat it, what happens is the individual will be starting on IV antibiotics and then the abscess is going to be drained. And drainage most commonly is accomplished by having a needle inserted through the abdominal wall into that pocket of inflammation, and this is typically done under x-ray guidance in order to make sure that the needle gets right into the right spot. And then, the fluid is aspirated out of the abscess, and then it tends to heal down on its own. The next complication is known as a fistula. So, a fistula is kind of like a tunnel between two structures that aren't supposed to be connected. So, imagine in this drawing here, you have the bladder and it's kind of right up next to a loop of the small bowel. Well, if that loop of the small bowel becomes inflamed within inflammatory bowel disease lesions such as in Crohn's disease, and that's right up next to the bladder, well, unfortunately, over time, that inflammation can extend through the wall of the bladder and form this kind of tunnel into the bladder. So, the bladder is usually a sterile space, and so now it's exposed to all the bacteria and inflammation of the small intestine, and you can get a pretty bad bladder infection. So, fistulas are also treated with antibiotics because of this infection risk, and then also they typically will require surgery. Now, there are a number of other complications that can occur with Crohn's disease and ulcerative colitis. But the abscesses and the fistulas are two of the most common. Unfortunately, a lot of the complications do require surgery. So, about one-third of individuals who have inflammatory bowel disease will eventually need surgery for the treatment of some sort of complication. And, unfortunately, surgery is not curative. So, if you think once again about this three-step mechanism of inflammatory bowel disease, the surgery really only treats the complications. It doesn't really affect the inflammation or this immune response. So, if you look at this clinical course over time, unfortunately, surgery isn't going to affect it that much because it doesn't focus on the underlying mechanism. There is one exception to this, and that is with ulcerative colitis. So, because ulcerative colitis never extends outside of the colon, someone who has inflammation of the entire colon known as total colitis, they can have a procedure known as a proctocolectomy where their entire rectum and colon is removed. And this can actually be curative of ulcerative colitis because there's no longer the large intestine to become inflamed. However, this is not something that's typically done unless it absolutely needs to, because it is a very big surgery. So, if you can remember, the inflammatory bowel disease is a relapsing, remitting disease. It's caused by this inappropriate immune response resulting in inflammation throughout the gastrointestinal tract. You can remember that you can use anti-inflammatory medications or these immunomodulators to treat inflammatory bowel disease.