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Related Concept Videos

Drugs for Treatment of Ulcerative Colitis in IBD01:29

Drugs for Treatment of Ulcerative Colitis in IBD

Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide generation. 
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel Disease...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

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Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2 (COX-2),...
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Inflammatory Bowel Disease IV: Pharmacological Management

Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
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Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation
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Optimizing immunomodulator therapy for inflammatory bowel disease.

Marla C Dubinsky1

  • 1Pediatric IBD Center, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 1165W, Los Angeles, CA 90048, USA. dubinskym@csmc.edu

Current Gastroenterology Reports
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PubMed
Summary
This summary is machine-generated.

Personalized dosing of thiopurines using genetic and metabolite information can improve safety and effectiveness for inflammatory bowel disease (IBD) patients. This approach optimizes immunomodulator therapy by targeting specific drug metabolism and metabolite levels.

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Genetics

Background:

  • 6-Mercaptopurine (6-MP) and azathioprine (AZA) are key immunomodulators for maintaining steroid-free remission in inflammatory bowel disease (IBD).
  • Current dosing strategies for thiopurines are often empirical, based on weight or arbitrary choices.
  • Understanding inherited metabolic differences can lead to safer and more effective thiopurine therapy.

Purpose of the Study:

  • To explore the potential of pharmacogenetic and pharmacokinetic dosing for thiopurines in IBD.
  • To highlight the role of thiopurine methyltransferase (TPMT) in thiopurine metabolism and toxicity.
  • To emphasize the correlation between active 6-thioguanine (6-TGN) metabolite levels and therapeutic benefits.

Main Methods:

  • Review of existing literature on thiopurine metabolism, pharmacogenetics, and clinical outcomes in IBD.
  • Analysis of the role of TPMT enzyme activity in thiopurine disposition.
  • Correlation of 6-TGN metabolite concentrations with therapeutic response and toxicity.

Main Results:

  • TPMT enzyme activity significantly influences thiopurine metabolism and toxicity risk.
  • Therapeutic benefits of thiopurines are maximized when patients achieve optimal 6-TGN levels.
  • Pharmacogenetic and pharmacokinetic dosing strategies show promise for improving patient outcomes.

Conclusions:

  • Personalized dosing of 6-MP and AZA based on TPMT genotype and 6-TGN levels offers a safer and more effective alternative to traditional methods.
  • Optimizing immunomodulator therapy through pharmacogenetic and pharmacokinetic approaches can enhance treatment efficacy in IBD patients.
  • This novel approach provides a mechanism for tailoring thiopurine therapy to individual patient needs.