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What is the primary mechanism of action of thiopurines?
What side effect is NOT commonly associated with glucocorticoids?
Which thiopurine metabolite is an active nucleotide involved in the drug's action?
When should 6-mercaptopurine be taken?
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What dietary adjustments should patients taking glucocorticoids consider?
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Which of the following is a boxed warning for thiopurines?
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What is the mechanism of action of low-dose thiopurines?
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Which anti-TNF-alpha agent is coded as a chimeric monoclonal antibody?
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How should the dose of 6-TGN be adjusted for poor metabolizers?
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Which of the following side effects is associated with anti-TNF-alpha agents?
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Which medication must be monitored for potential interactions with thiopurines?
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What is one of the serious side effects of thiopurines?
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Why are infliximab and adalimumab more potent than certolizumab?
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Which drug can cause adverse effects related to immunosuppression?
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What is a common adverse reaction of thiopurines?
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What is the recommended management to prevent renal toxicity during thiopurine therapy?
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Which of the following is not an indication for thiopurines?
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Which classification of drugs is certolizumab categorized under?
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Which adverse reaction is specifically noted for higher doses of thiopurines?
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What is the significance of monitoring liver function tests (LFTs) during thiopurine therapy?
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What type of immunity is primarily activated in ulcerative colitis?
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Which of the following drugs is classified as an aminosalicylate used to treat IBD?
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What is the mechanism of action of sulfasalazine in treating IBD?
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Which adverse drug reaction is most commonly associated with sulfasalazine?
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Which inflammatory bowel disease can affect any part of the gastrointestinal tract?
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What is a major side effect of glucocorticoids used in IBD treatment?
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Which drug class includes azathioprine and 6-mercaptopurine?
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What is the active compound of sulfasalazine responsible for its therapeutic effects?
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Which janus kinase inhibitor is used in the treatment of IBD?
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Which drug is a glucocorticoid commonly used to treat IBD?
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What is the primary therapeutic effect of natalizumab?
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Which adverse effect is common to both natalizumab and vedolizumab?
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How does tofacitinib exert its therapeutic effects in treating IBD?
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What is a side effect associated with vedolizumab?
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What is the mechanism of action of integrin receptor antagonists like natalizumab?
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In the case of an allergic reaction during natalizumab treatment, what immediate action should be taken?
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Which of the following drugs is primarily used for rheumatoid arthritis but also shows benefits in IBD?
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What is a common management step for infusion reactions when using natalizumab?
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Which of these is NOT a side effect of tofacitinib?
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If there is no therapeutic benefit from natalizumab treatment after 12 weeks, what should be done?
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Match the following brand names with their generic equivalents:
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Match the following generic names with their categories:
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Match the following mechanisms of action with their corresponding drug:
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Match the common side effects with their occurrence:
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Match the therapeutic uses with their respective conditions:
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Match the side effects to the appropriate classification:
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Match the following drugs to their side effects:
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Match the generic names with their potential off-label uses:
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Match the following brand names with their generic equivalents:
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Match the following generic names with their primary function:
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Match the following brand names with their administration forms:
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Match the following generic names with their brand counterparts:
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Match the following brands with their formulations:
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What are the primary uses of aminosalicylates?
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Which metabolite of mesalamine is known for its anti-inflammatory effects?
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What is a common side effect associated with sulfasalazine?
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Where is mesalamine primarily absorbed in the body?
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What is a significant consideration for patients taking aminosalicylates?
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Match the following mechanisms of action with their corresponding effects of glucocorticoids:
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Match the following side effects of glucocorticoids with their description:
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Match the following classes of drugs with their characteristics in comparison to glucocorticoids:
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Match the following long-term management strategies with their descriptions:
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Match the common short-term side effects of glucocorticoids to their potential impact:
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Match the following glucocorticoid effects with their specific outcomes:
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Match the following long-term treatment options with their benefits:
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Match the common risks associated with long-term use of glucocorticoids:
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Match the following side effects of glucocorticoids with their long-term implications:
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Match the following treatment strategies with their goals:
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Match the following glucocorticoids with their brand names:
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Match the following brand names with their generic equivalents:
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Match the following thiopurines with their primary therapeutic use:
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Match the following generic glucocorticoids with their dosage forms:
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Match the following glucocorticoids with their indication in IBD:
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Match the following thiopurine medications with their brand names:
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Match the following brand names with their thiopurine generic equivalents:
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Match the following glucocorticoid generics with their primary action:
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Match the thiopurines with their commonly known side effects:
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Match the thiopurines with their routes of administration:
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Which of the following is a brand name for azathioprine?
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What is the generic name for the drug marketed under the brand name Purixan?
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Which of the following is NOT a thiopurine used for inflammatory bowel disease?
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Which of the following brand names corresponds to thioguanine?
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Which thiopurine is available as an oral medication for inflammatory bowel disease?
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Match the following immunosuppressive drugs with their generic names:
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Match the following classes of drugs with their examples:
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Match the following anti-TNF alpha drugs with their characteristics:
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Match the following biological therapies to their mechanisms:
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Match the following drug classes used for IBD with their actions:
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Match the following immunosuppressive drugs with their descriptions:
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Match the following anti-TNF alpha drugs with their brand names:
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Match the following classes of drugs to their corresponding examples:
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Match the following drug classes with their therapeutic targets:
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Match the following adhesion molecule antagonists with their brand names:
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What is the mechanism of action of sulfasalazine in the treatment of IBD?
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What is a common adverse drug reaction associated with sulfasalazine?
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Which active compound of sulfasalazine is responsible for its therapeutic effects?
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What supplementation is commonly needed for patients taking sulfasalazine?
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Which of the following is NOT a side effect associated with sulfasalazine therapy?
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What is a common adverse drug reaction associated with thiopurines like azathioprine and 6-mercaptopurine?
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Which metabolite of thiopurines is crucial for their pharmacological activity?
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How do slow metabolizers typically respond to thiopurine therapy?
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What is a significant drug-drug interaction (DDI) effect that can impact thiopurine metabolism?
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Which condition is primarily treated with thiopurines such as azathioprine and 6-mercaptopurine?
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What is the primary therapeutic use of methotrexate in the treatment of IBD?
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Which of the following is a common adverse drug reaction (ADR) associated with methotrexate?
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What is the mechanism of action (MOA) of methotrexate?
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What is the antidote used in cases of methotrexate overdose?
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At high doses, methotrexate is primarily associated with which of the following risks?
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What is the primary mechanism of action of methotrexate in the treatment of IBD?
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Which of the following is a common adverse drug reaction (ADR) associated with methotrexate?
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What is the primary use of low-dose methotrexate?
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What is the antidote for a methotrexate overdose?
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At high doses, what serious adverse reaction can methotrexate cause?
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Which anti-TNF α agent is classified as a chimeric monoclonal antibody?
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Which drug among the anti-TNF α agents is known for its higher potency?
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What is a common adverse drug reaction (ADR) associated with anti-TNF α agents?
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Which of the following anti-TNF α agents is pegylated?
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Which of the following statements is true regarding the mechanism of action (MOA) of anti-TNF α agents?
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Which anti-TNF α agent is a chimeric monoclonal antibody?
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Which anti-TNF α agent has the highest potency in treating inflammatory bowel disease?
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What common adverse effect is associated with the use of anti-TNF α agents?
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Which of the following best describes Certolizumab Pegol?
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If a drug is shown to have more potency, what characteristic can contribute to this potency?
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Which drug is classified as an integrin receptor antagonist?
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What is the primary drug name for the Janus kinase inhibitor used in IBD treatment?
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Which formulation of cyclosporine has better bioavailability?
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Ustekinumab is categorized as an antagonist of which interleukins?
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What is the main issue regarding the bioavailability of the oral formulation of cyclosporine?
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Which type of inflammatory bowel disease primarily involves humoral mediated immunity?
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Which drug class is NOT considered an anti-inflammatory treatment for IBD?
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What is a common adverse reaction associated with the use of sulfasalazine?
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What type of immunity is primarily activated in Crohn's disease?
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Which of the following drugs is an example of a Janus kinase inhibitor used for treating IBD?
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What is the primary mechanism of action of thiopurines?
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Which side effect is specifically linked to long-term use of glucocorticoids?
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How should the dose of azathioprine be adjusted for patients taking allopurinol for gout?
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Which of the following dietary recommendations is crucial for patients on glucocorticoids?
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What must be monitored in patients on thiopurines to prevent serious side effects?
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Study Notes
Thiopurine Mechanism of Action
- Thiopurines like azathioprine and 6-mercaptopurine act by inhibiting purine synthesis, a critical step in DNA and RNA production.
- This slows down the rate of cell division, particularly in inflammatory cells, helping to reduce inflammation in conditions like Inflammatory Bowel Disease (IBD).
- 6-thioguanine (6-TGN) is the active metabolite of thiopurines, directly interfering with DNA synthesis.
Thiopurine Administration & Dosage
- 6-mercaptopurine should be taken on an empty stomach, ideally at bedtime, for optimal absorption.
- Dosage adjustments are necessary for poor metabolizers of 6-TGN, requiring lower amounts.
Thiopurine Side Effects & Monitoring
- Common side effects of thiopurines include bone marrow suppression leading to decreased white blood cell count, nausea, vomiting, and diarrhea.
- Serious adverse effects of thiopurines include hepatotoxicity (liver damage) and pancreatitis.
- Monitoring liver function tests (LFTs) is essential during thiopurine therapy to detect early signs of potential liver complications.
- Renal toxicity is another concern, so prophylactic measures like hydration and monitoring of renal function are crucial.
Glucocorticoids in IBD
- Glucocorticoids like prednisone are often used to manage IBD due to their potent anti-inflammatory properties.
- A common side effect of glucocorticoids is weight gain, NOT associated with them is hypoglycemia.
- Patients on glucocorticoids should adjust their diet to control weight gain and maintain blood sugar balance.
Anti-TNF-alpha Agents in IBD
- Infliximab, adalimumab, and certolizumab are anti-TNF-alpha agents commonly used in IBD.
- Infliximab and adalimumab are more potent than certolizumab because they are fully human monoclonal antibodies, while certolizumab is a chimeric antibody.
- Common adverse effects of anti-TNF-alpha agents include infusion reactions, infections, and reactivation of latent tuberculosis.
- Anti-TNF-alpha agents are associated with increased risk of lymphoma, a serious side effect.
- Monitoring for interactions with thiopurines is crucial when using anti-TNF-alpha agents.
Other IBD Medications
- Sulfasalazine, an aminosalicylate, is used in treating IBD.
- It works by inhibiting the synthesis of prostaglandins, inflammatory mediators, and also acts as an antimicrobial agent against specific gut bacteria.
- The most common side effect associated with sulfasalazine is nausea and vomiting.
- Mesalamine, a metabolite of sulfasalazine, is particularly effective in its anti-inflammatory action.
- Aminosalicylates are typically absorbed in the ileum (last part of the small intestine).
- Tofacitinib, a janus kinase inhibitor, is used to treat IBD by blocking specific enzymes involved in inflammation.
- Natalizumab and vedolizumab are integrin receptor antagonists that target adhesion molecules involved in leukocyte migration, reducing inflammation.
IBD Treatment Strategies & Considerations
- The most common type of immunity activated in ulcerative colitis is cell-mediated immunity, involving T lymphocytes.
- Ulcerative colitis can affect any part of the gastrointestinal (GI) tract, unlike Crohn's disease which can affect any part of the GI tract from the mouth to the anus.
- Treatment of IBD aims to achieve remission (control inflammation), maintain remission, and improve patient quality of life.
- Long-term treatment with glucocorticoids can lead to osteoporosis, cataracts, and Cushing's syndrome, serious implications.
- Infusion reactions during natalizumab treatment require immediate action. The infusion should be stopped and appropriate medical assistance sought.
- Methotrexate, primarily used for rheumatoid arthritis, can also be beneficial in treating IBD.
- If no therapeutic benefit is observed from natalizumab treatment within 12 weeks, alternative therapies should be considered.
Drug Groups & Classifications
- Thiopurines include azathioprine and 6-mercaptopurine, and their main use is for IBD.
- Glucocorticoids include prednisone, methylprednisolone, and hydrocortisone, which are commonly used for IBD treatment.
- Aminosalicylates include sulfasalazine and mesalamine, used for their anti-inflammatory actions in IBD.
- Anti-TNF-alpha agents include infliximab, adalimumab, and certolizumab, used for their ability to block TNF-alpha, a key inflammatory mediator.
- Integrin receptor antagonists include natalizumab and vedolizumab, used for their ability to block adhesion molecules, preventing leukocyte migration.
- Janus kinase inhibitors include tofacitinib, which blocks specific enzymes involved in inflammation.
Drug-Specific Information:
- Purixan is the brand name for azathioprine.
- Thioguanine is marketed under the brand name Thioguanine.
- Azathioprine and 6-mercaptopurine are available as oral medications for IBD.
- Sulfasalazine is commonly used by patients suffering from both Crohn's disease and ulcerative colitis, the two primary forms of IBD.
- The mechanism of action of sulfasalazine is based on both its anti-inflammatory properties and its antibacterial effects.
- 6-Mercaptopurine can cause serious side effects such as myelosuppression, leading to low blood cell counts, including anemia, leukopenia, and thrombocytopenia.
- The active metabolite of thiopurines responsible for their therapeutic effect is 6-thioguanine (6-TGN).
- Folic acid supplementation is often necessary for patients taking sulfasalazine to prevent potential deficiencies.
- Sulfasalazine can cause hepatotoxicity (liver damage), a serious side effect.
- Sulfasalazine is often not recommended for patients with sulfa allergies.
Thiopurines: Key Facts
- Azathioprine is an immunosuppressant that blocks purine synthesis.
- 6-Mercaptopurine is a purine analog that disrupts DNA synthesis.
- 6-Thioguanine is a thiopurine used for IBD.
- Thiopurines can cause adverse effects like myelosuppression, hepatotoxicity, and pancreatitis.
Glucocorticoids: Essential Information
- Glucocorticoids are anti-inflammatory medications commonly used for IBD.
- They modulate the immune system by suppressing the production of inflammatory mediators.
- Glucocorticoids can have significant side effects, including osteoporosis, cataracts, Cushing's syndrome, and weight gain.
- Long-term use of glucocorticoids can increase the risk of infections and other complications.
Ulcerative Colitis vs. Crohn's Disease
- Ulcerative colitis (UC): Mucosal inflammation affecting the rectum and colon. Humoral mediated immunity (B cells) are involved.
- Crohn's disease (CD): Transmucosal inflammation affecting any part of the body, from mouth to anus. Cell mediated immunity (T cells) are involved.
- Common symptom: Bloody diarrhea
Drug Classes for Treating IBD
-
Anti-inflammatory drugs: Aminosalicylates, such as 5-ASA (5-aminosalicyclic acid), are commonly used.
- Azo-containing 5-ASA drugs: Azulfidine, Dipentum, Colazal
- Mesalamine (5-ASA) drugs: Pentasa, Azacol, Rowasa, Canasa, Lialda
-
Other drugs:
- Glucocorticoids: Prednisone, prednisolone, budesonide, methylprednisone
- Thiopurines: Azathioprine, 6-mercaptopurine
- Immunosuppressives: Methotrexate, cyclosporine
- Anti-TNF-alpha agents: Infliximab, adalimumab, certolizumab pegol, natalizumab
- IL-receptor antagonist: Ustekinumab
- Janus kinase inhibitors: Tofacitinib
Sulfasalazine: MOA, ADRs, Active Compounds, Supplementation
- Mechanism of action (MOA): Inhibits prostaglandin synthesis (anti-inflammatory). Azo component is broken down to 5-ASA, the active compound.
- Side effects: Sulfa allergy, headache, rash, nausea, vomiting, diarrhea, bone marrow suppression, yellow-orange discoloration of skin and urine.
- Active compounds: Mesalamine = 5-ASA
- Drug-drug interactions (DDIs): Folic acid deficiency may occur, requiring supplementation (1 mg/day).
- Important note: Sulfasalazine has the most side effects but is also the least expensive.
Glucocorticoids: MOA and ADRs
- MOA: Inhibit production of cytokines.
- Side effects: Cushing's syndrome, adrenal suppression, insomnia, behavioral changes, peptic ulcers, hyperglycemia, impaired wound healing, immunosuppression, osteoporosis, increased intraocular pressure, hypertension, hypokalemia.
- Pregnancy considerations: All are pregnancy category C, EXCEPT budesonide (pregnancy category B).
- Important notes: Patients should follow high protein and potassium-rich diets due to hypokalemia. Abrupt discontinuation should be avoided. Patients unresponsive to glucocorticoids cannot take them, and patients dependent on glucocorticoids must take a small dose for life.
Thiopurines: MOA, ADRs, and DDI Effects
- MOA: 6-TG (active compound) suppresses purine nucleotide metabolism and DNA synthesis, thereby inhibiting cell division and proliferation, and it inhibits B and T cell function.
- Side effects: Nausea, vomiting, hepatotoxicity, lymphoma, leukopenia, thrombocytopenia.
- Boxed warning: Lymphoma, leukopenia, thrombocytopenia.
- DDIs: Allopurinol is a xanthine oxidase inhibitor, which can increase thiopurine levels. Careful monitoring of CBC and LFTs is essential. In patients with both gout and IBD, high-dose allopurinol is still needed, requiring a decrease in the dose of 6-TGN (azathioprine).
Thiopurine Metabolism: Slow and Fast Metabolizers
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Metabolism pathways: Azathioprine and 6-MP are metabolized through three pathways:
- Oxidative pathway: XO to 6-TU (inactive)
- S-methylation: TPMT to 6-MMP (inactive)
- HGPRT: Active nucleotide 6-TGN
- Slow metabolizers: Patients lacking TPMT are at increased risk of bone marrow suppression. Reduce the dose of thiopurines.
- Fast metabolizers: Increased dose may be required.
Methotrexate: MOA, ADRs, Uses, and Antidote
- MOA: Low dose inhibits AICAR, inhibiting IL-2 and decreasing inflammation. High dose inhibits cell-mediated immunity, decreasing inflammation in cancer.
- Uses: Crohn's disease, autoimmune diseases (rheumatoid arthritis, psoriasis, lupus, dermatomyositis), cancers, immunosuppressant.
- Side effects: Myelosuppression, oral ulceration/stomatitis, renal effects, nausea, vomiting, increased LFTs, pneumonitis, photosensitivity, alopecia, crystalluria (high dose).
- Antidote: Leucovorin.
- Important notes: Monitor LFTs and stay hydrated to prevent renal toxicity. Make urine basic using bicarbonate.
Anti-TNF-alfa Agents: MOA, Drug Names, and ADRs
- MOA: Inhibit TNF-alpha, decreasing cytokine release.
- Drug names: Infliximab, adalimumab, certolizumab, golimumab.
- Side effects: Increased infections, reactivation of latent TB, hepatitis B, lymphoma.
-
Important notes: Avoid use in immunocompromised patients.
-
Monoclonal antibody nomenclature:
- "-mab" or "-monab" indicates monoclonal antibody.
- The letter before "mab" indicates antibody source: "o" = mouse, "u" = human, "xi" = chimeric.
- The internal letter indicates therapeutic use: "tu" = tumor, "vi" = virus, "ci" = circulation.
- Example: Rituximab is a chimeric human-murine monoclonal antibody.
-
Monoclonal antibody nomenclature:
Potency of Anti-TNF-alpha Agents
- Infliximab and Adalimumab: More potent due to the presence of an Fc portion that activates the complement pathway. The Fc portion binds to membrane-bound TNF, activating the complement pathway and increasing potency.
- Certolizumab: Less potent due to the lack of the Fc portion.
Integrin Receptor Antagonist, Janus Kinase Inhibitor, Cyclosporine, and IL-12/23 Inhibitors
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Integrin receptor antagonists: Humanized monoclonal antibodies that block lymphocyte migration.
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Natalizumab: Blocks the interaction of alpha-4-beta-7 integrin with MadCAM-1, inhibiting migration of memory T cells into inflamed GI tissue.
- Side effects: Infusion reactions, headache, fatigue, brain infection (PML).
-
Vedolizumab: Similar MOA to natalizumab.
- Side effects: Nasopharyngitis, headache, arthralgia, brain infection (PML).
- Important notes: For infusion reactions, take Tylenol or Benadryl. If an allergic reaction occurs, stop treatment. Discontinue natalizumab if no therapeutic benefit is seen after 12 weeks.
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Natalizumab: Blocks the interaction of alpha-4-beta-7 integrin with MadCAM-1, inhibiting migration of memory T cells into inflamed GI tissue.
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Janus kinase inhibitor: Inhibits Janus kinase, inhibiting immune cell functions.
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Tofacitinib (Xeljanz):
- Side effects: Increased LFTs, increased lipids, infusion reactions, infections.
- Important notes: Not a monoclonal antibody, but a small molecule taken orally. Primarily used for rheumatoid arthritis but demonstrates benefits in IBD.
-
Tofacitinib (Xeljanz):
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Cyclosporin: Immunosuppressive agent that inhibits calcineurin, a key enzyme in T cell activation.
- Adverse effects: Increased risk of infections, kidney dysfunction, hypertension, hair growth, tremor.
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Inhibitors of IL-12/23: Block the production of IL-12 and IL-23, cytokines that contribute to inflammation in IBD.
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Ustekinumab:
- Side effects: Headache, nausea, injection site reactions, infections.
- Important notes: This drug is approved for the treatment of moderate to severe Crohn's disease and plaque psoriasis.
-
Ustekinumab:
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Description
This quiz covers the basics of Inflammatory Bowel Disease (IBD), focusing on the two major types: Ulcerative Colitis and Crohn's Disease. It also explores various medications used to treat IBD, including anti-inflammatory drugs and immunosuppressives. Test your knowledge on symptoms, treatments, and the pathophysiology of these conditions.