Module 49 Flashcards
What has been the most important advance in the treatment of diarrhea?
- Oral rehydration solutions are the most important advance in the treatment of diarrhea. Patients die from severe diarrhea caused by infections such as cholera because of dehydration. Young children are especially vulnerable. IV fluids can be used to keep up with the fluid loss, but in many parts of the world such treatment is not available for everyone.
However, there is an active sodium-glucose transporter that results in the absorption of water that can keep up with fluid loss even with severe diarrhea. There are many versions of the oral rehydration solutions, but the basic requirement is sodium and glucose. These solutions have saved many lives. They are also used in Canada mainly to treat diarrhea in infants (e.g. Pedialyte) so that IV fluids are not required.
How is the mechanism by which oral hydration solutions overcome major water loss in the intestine related to a common treatment for type II diabetes
- The oral rehydration solutions work by active transport of water via the sodium/glucose transporter protein 1 (SGLT1) and the gliflozin-type drugs such as empagliflozin work by inhibiting SGLT2.
Narcotics are known to cause constipation and are often used to treat diarrhea. Why is diphenoxylate (Lomotil) a restricted narcotic while loperamide (Imodium) can be purchased without a prescription?
Both are basic amines that are mostly ionized, but that does not keep them out of the brain. However, loperamide is a good substrate for p-glycoprotein, and this limits the brain concentration and CNS effects.
What are the major agents used to treat inflammatory bowel disease?
- The treatment of inflammatory bowel disease is similar to the treatment of other immune-mediated diseases such as rheumatoid arthritis, but there are also differences.
○ Corticosteroids are useful for acute disease flairs, but there are too many side-effects for them to be used chronically.
○ Fluticasone enemas for ulcerative colitis can limit systemic effects to some degree because of their local administration and large first pass effect- Mexalazine (5-aminosalicylic acid) is more useful for ulcerative colitis than for Crohn’s disease, while anti-TNFa antibodies (e.g. infliximab), azathioprine, and methotrexate are more useful for Crohn’s disease.
- Ulcerative colitis can be treated with a total colectomy, but the small intestine is necessary for absorption of nutrients, etc; therefore, removal of the small intestine is very problematic.
- A section of small intestine about 5 feet long is required, and without that severe malabsorption results (it also depends on what portion of the small bowel is resected). It is even more complex in that some inflammatory bowel disease fits somewhere between classic ulcerative colitis and Crohn’s disease. The microbiome is likely important, but, other than antibiotics, the efficacy of treatments involving the microbiome have yet to be clearly demonstrated.
What nonpharmacologic treatment shows some evidence of efficacy for the treatment of inflammatory bowel disease?
- I don’t know how effective it will turn out to be, but there have been experiments with things such as the eggs of the pig whipworm, which do not survive in humans, but appear to have an effect on the immune system to suppress inflammation.
- It is basically the opposite of the hygiene hypothesis. These are interesting ideas, but it is too early to tell how effective they will be.
What common habit affects inflammatory bowel disease, and what is the effect?
- Smoking decreases the risk of ulcerative colitis, but it increases the risk of Crohn’s disease. This is strange because they are sometime difficult to differentiate. I once had a patient tell me he smoked, but he had to. Then he recounted the story of how he stopped smoking because it became socially unacceptable. He then developed ulcerative colitis, but he did not make the connection between stopping smoking and the onset of ulcerative colitis.
- He always drove to Florida in the winter, but with the ulcerative colitis he started driving at night so that he could pull over and go off in the bushes when he needed to because the urgency was too great to make it to the next rest stop. Then on one occasion he was falling asleep, and he remembered he had cigarettes in the glove compartment and thought they might help him stay awake. He lit up and made it all the way to Florida without having to pull over. However, I would not recommend smoking for the treatment of ulcerative colitis, and nicotine patches do not appear to be effective.
If a patient has a history of an allergic reaction to sulfasalazine, what other drugs would they also have to be careful with?
sulfasalazine is reduced by gut bacteria to aminosalicylic acid and sulfapyridine. Therefore, you have to be careful with both sulfonamide antibiotics and aminosalicylic acid. In addition, aminosalicylic acid is an NSAID related to aspirin so you have to also be careful with aspirin and even other NSAIDs
Is a gluten-free diet more healthy?
- If a person has coeliac disease (gluten enteropathy) it is very important to avoid gluten. However, this is an uncommon disease, and for most people it is not important to avoid gluten and, in fact, avoiding gluten can lead to a less healthy diet with less fiber.
- On the other hand many people suffer from irritable bowel syndrome, which is not life-threatening as is celiac disease; however, it can be quite distressful. The cause of irritable bowel syndrome is not well understood, and medications are not very effective and have significant side-effects.
- One possible cause of irritable bowel disease is a sensitivity to FOMAPS (fermentable oligo- di- mono-saccharides and polyols). These short-chain carbohydrates are poorly absorbed, pull water into the intestine via osmosis and can be fermented to produce gas. This can cause significant symptoms.
There is some overlap between a gluten free diet and a diet low in FOMAPS. So if someone says they feel better on a gluten free diet it may be true. However, it would be much better to specifically limit FOMAPS if this is the real cause of their discomfort.
