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Azathioprine: Pharmacology, Clinical Applications, and Safety Profile

At a Glance

Title: Azathioprine: Pharmacology, Clinical Applications, and Safety Profile

Total Categories: 7

Category Stats

  • Azathioprine: Fundamental Properties and Classification: 9 flashcards, 5 questions
  • Pharmacology: Mechanism of Action and Metabolism: 9 flashcards, 8 questions
  • Clinical Applications and Therapeutic Uses: 14 flashcards, 13 questions
  • Adverse Effects, Risks, and Monitoring: 12 flashcards, 12 questions
  • Pharmacogenomics and Drug Interactions: 8 flashcards, 7 questions
  • Special Populations: Pregnancy and Lactation: 3 flashcards, 3 questions
  • Historical Development and Comparative Therapeutics: 11 flashcards, 12 questions

Total Stats

  • Total Flashcards: 66
  • True/False Questions: 30
  • Multiple Choice Questions: 30
  • Total Questions: 60

Instructions

Click the button to expand the instructions for how to use the Wiki2Web Teacher studio in order to print, edit, and export data about Azathioprine: Pharmacology, Clinical Applications, and Safety Profile

Welcome to Your Curriculum Command Center

This guide will turn you into a Wiki2web Studio power user. Let's unlock the features designed to give you back your weekends.

The Core Concept: What is a "Kit"?

Think of a Kit as your all-in-one digital lesson plan. It's a single, portable file that contains every piece of content for a topic: your subject categories, a central image, all your flashcards, and all your questions. The true power of the Studio is speed—once a kit is made (or you import one), you are just minutes away from printing an entire set of coursework.

Getting Started is Simple:

  • Create New Kit: Start with a clean slate. Perfect for a brand-new lesson idea.
  • Import & Edit Existing Kit: Load a .json kit file from your computer to continue your work or to modify a kit created by a colleague.
  • Restore Session: The Studio automatically saves your progress in your browser. If you get interrupted, you can restore your unsaved work with one click.

Step 1: Laying the Foundation (The Authoring Tools)

This is where you build the core knowledge of your Kit. Use the left-side navigation panel to switch between these powerful authoring modules.

⚙️ Kit Manager: Your Kit's Identity

This is the high-level control panel for your project.

  • Kit Name: Give your Kit a clear title. This will appear on all your printed materials.
  • Master Image: Upload a custom cover image for your Kit. This is essential for giving your content a professional visual identity, and it's used as the main graphic when you export your Kit as an interactive game.
  • Topics: Create the structure for your lesson. Add topics like "Chapter 1," "Vocabulary," or "Key Formulas." All flashcards and questions will be organized under these topics.

🃏 Flashcard Author: Building the Knowledge Blocks

Flashcards are the fundamental concepts of your Kit. Create them here to define terms, list facts, or pose simple questions.

  • Click "➕ Add New Flashcard" to open the editor.
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Create a bank of questions to test knowledge. These questions are the engine for your worksheets and exams.

  • Click "➕ Add New Question".
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  • The Explanation field is a powerful tool: the text you enter here will automatically appear on the teacher's answer key and on the Smart Study Guide, providing instant feedback.

🔗 Intelligent Mapper: The Smart Connection

This is the secret sauce of the Studio. The Mapper transforms your content from a simple list into an interconnected web of knowledge, automating the creation of amazing study guides.

  • Step 1: Select a question from the list on the left.
  • Step 2: In the right panel, click on every flashcard that contains a concept required to answer that question. They will turn green, indicating a successful link.
  • The Payoff: When you generate a Smart Study Guide, these linked flashcards will automatically appear under each question as "Related Concepts."

Step 2: The Magic (The Generator Suite)

You've built your content. Now, with a few clicks, turn it into a full suite of professional, ready-to-use materials. What used to take hours of formatting and copying-and-pasting can now be done in seconds.

🎓 Smart Study Guide Maker

Instantly create the ultimate review document. It combines your questions, the correct answers, your detailed explanations, and all the "Related Concepts" you linked in the Mapper into one cohesive, printable guide.

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Generate unique assessments every time. The questions and multiple-choice options are randomized automatically. Simply select your topics, choose how many questions you need, and generate:

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Step 3: Saving and Collaborating

  • 💾 Export & Save Kit: This is your primary save function. It downloads the entire Kit (content, images, and all) to your computer as a single .json file. Use this to create permanent backups and share your work with others.
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You're now ready to reclaim your time.

You're not just a teacher; you're a curriculum designer, and this is your Studio.

This page is an interactive visualization based on the Wikipedia article "Azathioprine" (opens in new tab) and its cited references.

Text content is available under the Creative Commons Attribution-ShareAlike 4.0 License (opens in new tab). Additional terms may apply.

Disclaimer: This website is for informational purposes only and does not constitute any kind of advice. The information is not a substitute for consulting official sources or records or seeking advice from qualified professionals.


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Study Guide: Azathioprine: Pharmacology, Clinical Applications, and Safety Profile

Study Guide: Azathioprine: Pharmacology, Clinical Applications, and Safety Profile

Azathioprine: Fundamental Properties and Classification

Azathioprine is an immunosuppressive medication primarily used to increase the activity of the body's immune system.

Answer: False

Azathioprine is an immunosuppressive medication, meaning it functions to reduce, not increase, the activity of the body's immune system.

Related Concepts:

  • What are the primary medical conditions for which Azathioprine is prescribed?: Azathioprine is primarily used to treat autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus. It is also used in kidney transplants to help prevent the body from rejecting the new organ.
  • What is Azathioprine, and what are some of its common brand names?: Azathioprine is an immunosuppressive medication, meaning it works to reduce the activity of the body's immune system. It is sold under various brand names, including Imuran and Jayempi, and is also known by the abbreviation AZA.

Azathioprine belongs to the antimetabolites family of medications and is classified as a purine analogue.

Answer: True

Azathioprine is indeed classified as a purine analogue within the broader family of antimetabolite medications, reflecting its mechanism of interfering with purine metabolism.

Related Concepts:

  • What is the classification of Azathioprine within the family of medications?: Azathioprine belongs to the purine analogues subclass, which is part of the antimetabolites family of medications. Antimetabolites interfere with the normal metabolic processes of cells, often by mimicking natural substances.

Which of the following is NOT a common brand name or abbreviation for Azathioprine?

Answer: Cyclosporin

Imuran and Jayempi are common brand names for Azathioprine, and AZA is a common abbreviation. Cyclosporin is a different immunosuppressive medication.

Related Concepts:

  • What is Azathioprine, and what are some of its common brand names?: Azathioprine is an immunosuppressive medication, meaning it works to reduce the activity of the body's immune system. It is sold under various brand names, including Imuran and Jayempi, and is also known by the abbreviation AZA.

To which family of medications does Azathioprine belong?

Answer: Antimetabolites

Azathioprine is classified as an antimetabolite, specifically a purine analogue, due to its mechanism of interfering with cellular metabolic processes.

Related Concepts:

  • What is the classification of Azathioprine within the family of medications?: Azathioprine belongs to the purine analogues subclass, which is part of the antimetabolites family of medications. Antimetabolites interfere with the normal metabolic processes of cells, often by mimicking natural substances.

What is the chemical formula of Azathioprine?

Answer: C9H7N7O2S

The chemical formula for Azathioprine is C9H7N7O2S, reflecting its molecular composition.

Related Concepts:

  • What are the physical and chemical properties of Azathioprine?: Azathioprine is a pale yellow solid with a slightly bitter taste. It has a melting point ranging from 238 to 245 degrees Celsius (460 to 473 degrees Fahrenheit). Chemically, it is a thiopurine linked to an imidazole derivative via a thioether. It is practically insoluble in water and only slightly soluble in lipophilic solvents like chloroform, ethanol, and diethyl ether. However, it dissolves in alkaline aqueous solutions, where it undergoes hydrolysis to form 6-mercaptopurine (6-MP).
  • What is the chemical formula and molar mass of Azathioprine?: The chemical formula for Azathioprine is C9H7N7O2S, and its molar mass is 277.26 grams per mole.
  • What does the image of 'Azathioprine.svg' represent in the source material?: The source material includes an image titled 'Azathioprine.svg' which depicts the chemical structure of Azathioprine.

Pharmacology: Mechanism of Action and Metabolism

Azathioprine is exclusively administered by injection directly into a vein.

Answer: False

Azathioprine can be administered orally, typically in tablet form, in addition to intravenous injection.

Related Concepts:

  • How is Azathioprine typically administered to patients?: Azathioprine can be administered either by mouth, usually in tablet form, or by injection directly into a vein.

Azathioprine exerts its immunosuppressive effects by directly stimulating the production of RNA and DNA.

Answer: False

Azathioprine's immunosuppressive action involves disrupting, not stimulating, the normal synthesis of RNA and DNA by interfering with purine metabolism.

Related Concepts:

  • How does Azathioprine exert its immunosuppressive effects at a cellular level?: Azathioprine works by being converted in the body into 6-thioguanine, which then disrupts the normal process of making RNA and DNA by cells. This interference with nucleic acid synthesis is key to its immunosuppressive action.
  • What is the primary mechanism by which Azathioprine achieves immunosuppression?: Azathioprine primarily achieves immunosuppression by inhibiting purine synthesis. Purines are essential building blocks required for the production of DNA and RNA. By disrupting purine synthesis, Azathioprine reduces the amount of DNA and RNA available for the synthesis of white blood cells, thereby suppressing the immune system.
  • How do Azathioprine's metabolites interfere with DNA replication and purine biosynthesis?: Azathioprine's metabolites, specifically the nucleotides formed from 6-mercaptopurine and 6-thioguanine, are incorporated into newly synthesized DNA, rendering it nonfunctional and halting DNA replication. These nucleotides also act as inhibitors of glutamine-phosphoribosyl pyrophosphate amidotransferase (GPAT), an enzyme crucial for purine biosynthesis, through a process called product inhibition. This dual action particularly affects actively replicating cells, such as cancer cells and immune system cells like T and B cells.

Azathioprine is absorbed from the gut at approximately 50%, with high variability among patients.

Answer: False

Azathioprine is absorbed from the gastrointestinal tract at an approximate rate of 88%, though its overall bioavailability can vary due to hepatic inactivation.

Related Concepts:

  • How is Azathioprine absorbed and distributed in the body?: Azathioprine is absorbed from the gut at approximately 88%. Its bioavailability, which is the proportion of the drug that enters the circulation, varies significantly among patients, ranging from 30% to 90%, due to partial inactivation in the liver. While circulating in the bloodstream, 20% to 30% of the drug is bound to plasma proteins.
  • What are the plasma concentrations and half-lives of Azathioprine and its metabolites?: The highest blood plasma concentrations, including both the drug itself and its metabolites, are typically reached within 1 to 2 hours after administration. The average plasma half-life for Azathioprine itself is 26 to 80 minutes, while for the drug plus its metabolites, it is 3 to 5 hours.

The active form of Azathioprine, 6-mercaptopurine, is formed through enzymatic conversion in the liver.

Answer: False

Azathioprine is converted to 6-mercaptopurine (6-MP) through reductive cleavage, a process mediated by glutathione and similar compounds in the intestinal wall, liver, and red blood cells, without the need for enzymes.

Related Concepts:

  • How is Azathioprine metabolized in the body, and what are its end products?: Azathioprine is a prodrug, meaning it is converted into an active form within the body. Initially, it is slowly and almost completely converted to 6-mercaptopurine (6-MP) through reductive cleavage, a process mediated by glutathione and similar compounds in the intestinal wall, liver, and red blood cells, without the need for enzymes. 6-MP is then metabolized similarly to natural purines, forming thioinosine monophosphate (TIMP) and other intermediates, eventually leading to thioguanosine triphosphate (TGTP) and thiodeoxyguanosine triphosphate (TdGTP). Additionally, the sulfur atom of 6-MP and TIMP undergoes methylation. The final metabolic products, including thiouric acid (38%) and various methylated and hydroxylated purines, are excreted via the urine.
  • What is the role of the thiopurine S-methyltransferase (TPMT) enzyme in Azathioprine's metabolism?: The enzyme thiopurine S-methyltransferase (TPMT) plays a crucial role in both the activation and deactivation steps of Azathioprine's mechanism of action. Specifically, TPMT is responsible for methylating 6-mercaptopurine (6-MP), an initial metabolite of Azathioprine, into the inactive metabolite 6-methylmercaptopurine, thereby preventing 6-MP from being further converted into active, cytotoxic thioguanine nucleotide (TGN) metabolites.

Azathioprine's immunosuppressive action primarily involves inhibiting purine synthesis, which is crucial for DNA and RNA production.

Answer: True

Azathioprine primarily achieves immunosuppression by inhibiting purine synthesis, thereby disrupting the production of DNA and RNA necessary for immune cell proliferation.

Related Concepts:

  • What is the primary mechanism by which Azathioprine achieves immunosuppression?: Azathioprine primarily achieves immunosuppression by inhibiting purine synthesis. Purines are essential building blocks required for the production of DNA and RNA. By disrupting purine synthesis, Azathioprine reduces the amount of DNA and RNA available for the synthesis of white blood cells, thereby suppressing the immune system.
  • How does Azathioprine exert its immunosuppressive effects at a cellular level?: Azathioprine works by being converted in the body into 6-thioguanine, which then disrupts the normal process of making RNA and DNA by cells. This interference with nucleic acid synthesis is key to its immunosuppressive action.
  • How do Azathioprine's metabolites interfere with DNA replication and purine biosynthesis?: Azathioprine's metabolites, specifically the nucleotides formed from 6-mercaptopurine and 6-thioguanine, are incorporated into newly synthesized DNA, rendering it nonfunctional and halting DNA replication. These nucleotides also act as inhibitors of glutamine-phosphoribosyl pyrophosphate amidotransferase (GPAT), an enzyme crucial for purine biosynthesis, through a process called product inhibition. This dual action particularly affects actively replicating cells, such as cancer cells and immune system cells like T and B cells.

How does Azathioprine primarily achieve its immunosuppressive effect at a cellular level?

Answer: By disrupting the normal process of making RNA and DNA

Azathioprine's immunosuppressive action is primarily achieved by its metabolites interfering with purine synthesis and being incorporated into DNA, thereby disrupting the production and function of RNA and DNA.

Related Concepts:

  • How does Azathioprine exert its immunosuppressive effects at a cellular level?: Azathioprine works by being converted in the body into 6-thioguanine, which then disrupts the normal process of making RNA and DNA by cells. This interference with nucleic acid synthesis is key to its immunosuppressive action.
  • What is the primary mechanism by which Azathioprine achieves immunosuppression?: Azathioprine primarily achieves immunosuppression by inhibiting purine synthesis. Purines are essential building blocks required for the production of DNA and RNA. By disrupting purine synthesis, Azathioprine reduces the amount of DNA and RNA available for the synthesis of white blood cells, thereby suppressing the immune system.
  • How do Azathioprine's metabolites interfere with DNA replication and purine biosynthesis?: Azathioprine's metabolites, specifically the nucleotides formed from 6-mercaptopurine and 6-thioguanine, are incorporated into newly synthesized DNA, rendering it nonfunctional and halting DNA replication. These nucleotides also act as inhibitors of glutamine-phosphoribosyl pyrophosphate amidotransferase (GPAT), an enzyme crucial for purine biosynthesis, through a process called product inhibition. This dual action particularly affects actively replicating cells, such as cancer cells and immune system cells like T and B cells.

What is the approximate absorption rate of Azathioprine from the gut?

Answer: Approximately 88%

Azathioprine is absorbed from the gastrointestinal tract at an approximate rate of 88%, though its overall bioavailability can vary due to hepatic inactivation.

Related Concepts:

  • How is Azathioprine absorbed and distributed in the body?: Azathioprine is absorbed from the gut at approximately 88%. Its bioavailability, which is the proportion of the drug that enters the circulation, varies significantly among patients, ranging from 30% to 90%, due to partial inactivation in the liver. While circulating in the bloodstream, 20% to 30% of the drug is bound to plasma proteins.
  • What are the plasma concentrations and half-lives of Azathioprine and its metabolites?: The highest blood plasma concentrations, including both the drug itself and its metabolites, are typically reached within 1 to 2 hours after administration. The average plasma half-life for Azathioprine itself is 26 to 80 minutes, while for the drug plus its metabolites, it is 3 to 5 hours.
  • How is Azathioprine metabolized in the body, and what are its end products?: Azathioprine is a prodrug, meaning it is converted into an active form within the body. Initially, it is slowly and almost completely converted to 6-mercaptopurine (6-MP) through reductive cleavage, a process mediated by glutathione and similar compounds in the intestinal wall, liver, and red blood cells, without the need for enzymes. 6-MP is then metabolized similarly to natural purines, forming thioinosine monophosphate (TIMP) and other intermediates, eventually leading to thioguanosine triphosphate (TGTP) and thiodeoxyguanosine triphosphate (TdGTP). Additionally, the sulfur atom of 6-MP and TIMP undergoes methylation. The final metabolic products, including thiouric acid (38%) and various methylated and hydroxylated purines, are excreted via the urine.

What is the average plasma half-life for Azathioprine itself?

Answer: 26 to 80 minutes

The average plasma half-life of Azathioprine itself is relatively short, ranging from 26 to 80 minutes.

Related Concepts:

  • What are the plasma concentrations and half-lives of Azathioprine and its metabolites?: The highest blood plasma concentrations, including both the drug itself and its metabolites, are typically reached within 1 to 2 hours after administration. The average plasma half-life for Azathioprine itself is 26 to 80 minutes, while for the drug plus its metabolites, it is 3 to 5 hours.
  • How is Azathioprine absorbed and distributed in the body?: Azathioprine is absorbed from the gut at approximately 88%. Its bioavailability, which is the proportion of the drug that enters the circulation, varies significantly among patients, ranging from 30% to 90%, due to partial inactivation in the liver. While circulating in the bloodstream, 20% to 30% of the drug is bound to plasma proteins.
  • How is Azathioprine metabolized in the body, and what are its end products?: Azathioprine is a prodrug, meaning it is converted into an active form within the body. Initially, it is slowly and almost completely converted to 6-mercaptopurine (6-MP) through reductive cleavage, a process mediated by glutathione and similar compounds in the intestinal wall, liver, and red blood cells, without the need for enzymes. 6-MP is then metabolized similarly to natural purines, forming thioinosine monophosphate (TIMP) and other intermediates, eventually leading to thioguanosine triphosphate (TGTP) and thiodeoxyguanosine triphosphate (TdGTP). Additionally, the sulfur atom of 6-MP and TIMP undergoes methylation. The final metabolic products, including thiouric acid (38%) and various methylated and hydroxylated purines, are excreted via the urine.

Clinical Applications and Therapeutic Uses

One of Azathioprine's primary uses is to prevent the rejection of transplanted organs, such as kidneys.

Answer: True

Azathioprine is indeed primarily used in organ transplantation, including kidney transplants, to prevent the recipient's immune system from rejecting the allograft.

Related Concepts:

  • How is Azathioprine typically used in organ transplantation to prevent rejection?: Azathioprine is used to prevent the rejection of kidney or liver allografts (transplanted organs from another individual), usually in combination with other immunosuppressive therapies such as corticosteroids and local radiation therapy. Its administration typically begins at the time of transplantation or within two days following the procedure.
  • What are the primary medical conditions for which Azathioprine is prescribed?: Azathioprine is primarily used to treat autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus. It is also used in kidney transplants to help prevent the body from rejecting the new organ.
  • For which specific conditions is Azathioprine approved by the Food and Drug Administration (FDA) in the United States?: In the United States, the Food and Drug Administration (FDA) has approved Azathioprine for use in kidney transplantation from human donors and for the treatment of rheumatoid arthritis.

The World Health Organization does not include Azathioprine on its List of Essential Medicines.

Answer: False

Azathioprine is included on the World Health Organization's List of Essential Medicines, signifying its importance in a basic health system.

Related Concepts:

  • What is Azathioprine's status on the World Health Organization's List of Essential Medicines?: Azathioprine is included on the World Health Organization's List of Essential Medicines, which identifies the most important medications needed in a basic health system.

In 2018, Azathioprine was among the top 100 most commonly prescribed drugs in the United States.

Answer: False

In 2018, Azathioprine ranked as the 358th most commonly prescribed drug in the United States, not among the top 100.

Related Concepts:

  • What was the prevalence of Azathioprine prescriptions in the United States in 2018?: In 2018, Azathioprine was a widely prescribed medication in the United States, ranking as the 358th most commonly prescribed drug, with over 800,000 prescriptions issued.

The FDA has approved Azathioprine for use in kidney transplantation and the treatment of rheumatoid arthritis.

Answer: True

The U.S. FDA has specifically approved Azathioprine for use in kidney transplantation from human donors and for the treatment of rheumatoid arthritis.

Related Concepts:

  • For which specific conditions is Azathioprine approved by the Food and Drug Administration (FDA) in the United States?: In the United States, the Food and Drug Administration (FDA) has approved Azathioprine for use in kidney transplantation from human donors and for the treatment of rheumatoid arthritis.
  • What are the primary medical conditions for which Azathioprine is prescribed?: Azathioprine is primarily used to treat autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus. It is also used in kidney transplants to help prevent the body from rejecting the new organ.
  • How is Azathioprine typically used in organ transplantation to prevent rejection?: Azathioprine is used to prevent the rejection of kidney or liver allografts (transplanted organs from another individual), usually in combination with other immunosuppressive therapies such as corticosteroids and local radiation therapy. Its administration typically begins at the time of transplantation or within two days following the procedure.

Azathioprine is typically used as a standalone therapy for organ transplantation, without other immunosuppressants.

Answer: False

Azathioprine is typically used in combination with other immunosuppressive therapies, such as corticosteroids, to prevent organ rejection.

Related Concepts:

  • How is Azathioprine typically used in organ transplantation to prevent rejection?: Azathioprine is used to prevent the rejection of kidney or liver allografts (transplanted organs from another individual), usually in combination with other immunosuppressive therapies such as corticosteroids and local radiation therapy. Its administration typically begins at the time of transplantation or within two days following the procedure.

Combining Azathioprine with other DMARDs is generally recommended for adult rheumatoid arthritis.

Answer: False

While Azathioprine can be combined with NSAIDs and corticosteroids for rheumatoid arthritis, combining it with other disease-modifying antirheumatic drugs (DMARDs) is not recommended.

Related Concepts:

  • How is Azathioprine utilized in the management of adult rheumatoid arthritis?: As a disease-modifying antirheumatic drug (DMARD), Azathioprine is used to manage the signs and symptoms of adult rheumatoid arthritis. It can be combined with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, but combining it with other DMARDs is not recommended.

Azathioprine's onset of action for Crohn's disease is rapid, often showing clinical response within days.

Answer: False

Azathioprine has a slow onset of action for Crohn's disease, often requiring several months for a clinical response.

Related Concepts:

  • What is the role of Azathioprine in treating inflammatory bowel disease, specifically Crohn's disease?: Azathioprine is used in the management of moderate to severe chronically active Crohn's disease. It helps maintain clinical remission (absence of disease activity) in patients who are dependent on corticosteroids and can benefit individuals with fistulizing Crohn's disease. However, its onset of action is slow, often requiring several months for a clinical response.

Azathioprine is considered a 'steroid-sparing' agent because it allows for a reduction in the required dose of steroids.

Answer: True

Azathioprine is used as a 'steroid-sparing' agent in various autoimmune conditions, enabling a reduction in steroid dosage and thus minimizing steroid-related side effects.

Related Concepts:

  • How does Azathioprine function as a 'steroid-sparing' agent in conditions like pemphigus and myasthenia gravis?: Azathioprine is used as an add-on therapy for conditions like pemphigus and myasthenia gravis when oral steroid therapy is given. It acts as a 'steroid-sparing' agent, meaning it helps reduce the required dose of steroids, thereby minimizing steroid-related side effects.
  • When is Azathioprine sometimes used in systemic lupus erythematosus?: Azathioprine is sometimes used in systemic lupus erythematosus, particularly for patients who require a maintenance dose of 15 mg or higher of prednisone and experience recurrent flares of the disease.
  • How is Azathioprine utilized in the management of adult rheumatoid arthritis?: As a disease-modifying antirheumatic drug (DMARD), Azathioprine is used to manage the signs and symptoms of adult rheumatoid arthritis. It can be combined with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, but combining it with other DMARDs is not recommended.

Azathioprine is primarily used to treat which of the following conditions?

Answer: Autoimmune diseases and organ transplant rejection

Azathioprine's primary therapeutic applications are in the management of various autoimmune diseases and in preventing the rejection of transplanted organs.

Related Concepts:

  • What are the primary medical conditions for which Azathioprine is prescribed?: Azathioprine is primarily used to treat autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus. It is also used in kidney transplants to help prevent the body from rejecting the new organ.
  • Beyond its primary uses, what other autoimmune diseases can Azathioprine be used to treat?: In addition to its primary uses, Azathioprine can treat a range of autoimmune diseases including pemphigus, Behçet's disease, other forms of vasculitis, autoimmune hepatitis, atopic dermatitis, myasthenia gravis, neuromyelitis optica (Devic's disease), and restrictive lung disease.
  • When is Azathioprine sometimes used in systemic lupus erythematosus?: Azathioprine is sometimes used in systemic lupus erythematosus, particularly for patients who require a maintenance dose of 15 mg or higher of prednisone and experience recurrent flares of the disease.

Which organization includes Azathioprine on its List of Essential Medicines?

Answer: The World Health Organization (WHO)

The World Health Organization (WHO) includes Azathioprine on its List of Essential Medicines, recognizing its importance for global health systems.

Related Concepts:

  • What is Azathioprine's status on the World Health Organization's List of Essential Medicines?: Azathioprine is included on the World Health Organization's List of Essential Medicines, which identifies the most important medications needed in a basic health system.

For which specific conditions has the U.S. FDA approved Azathioprine?

Answer: Kidney transplantation and rheumatoid arthritis

The U.S. Food and Drug Administration (FDA) has specifically approved Azathioprine for use in kidney transplantation from human donors and for the treatment of rheumatoid arthritis.

Related Concepts:

  • For which specific conditions is Azathioprine approved by the Food and Drug Administration (FDA) in the United States?: In the United States, the Food and Drug Administration (FDA) has approved Azathioprine for use in kidney transplantation from human donors and for the treatment of rheumatoid arthritis.
  • What are the primary medical conditions for which Azathioprine is prescribed?: Azathioprine is primarily used to treat autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus. It is also used in kidney transplants to help prevent the body from rejecting the new organ.
  • When is Azathioprine sometimes used in systemic lupus erythematosus?: Azathioprine is sometimes used in systemic lupus erythematosus, particularly for patients who require a maintenance dose of 15 mg or higher of prednisone and experience recurrent flares of the disease.

How is Azathioprine typically used in organ transplantation to prevent rejection?

Answer: In combination with other immunosuppressive therapies like corticosteroids

Azathioprine is typically used in combination with other immunosuppressive agents, such as corticosteroids, to effectively prevent organ rejection in transplant recipients.

Related Concepts:

  • How is Azathioprine typically used in organ transplantation to prevent rejection?: Azathioprine is used to prevent the rejection of kidney or liver allografts (transplanted organs from another individual), usually in combination with other immunosuppressive therapies such as corticosteroids and local radiation therapy. Its administration typically begins at the time of transplantation or within two days following the procedure.

In the context of conditions like pemphigus and myasthenia gravis, what does it mean for Azathioprine to be a 'steroid-sparing' agent?

Answer: It helps reduce the required dose of steroids, minimizing side effects.

As a 'steroid-sparing' agent, Azathioprine allows for a reduction in the dosage of concomitant steroid therapy, thereby mitigating the adverse effects associated with long-term steroid use.

Related Concepts:

  • How does Azathioprine function as a 'steroid-sparing' agent in conditions like pemphigus and myasthenia gravis?: Azathioprine is used as an add-on therapy for conditions like pemphigus and myasthenia gravis when oral steroid therapy is given. It acts as a 'steroid-sparing' agent, meaning it helps reduce the required dose of steroids, thereby minimizing steroid-related side effects.
  • Beyond its primary uses, what other autoimmune diseases can Azathioprine be used to treat?: In addition to its primary uses, Azathioprine can treat a range of autoimmune diseases including pemphigus, Behçet's disease, other forms of vasculitis, autoimmune hepatitis, atopic dermatitis, myasthenia gravis, neuromyelitis optica (Devic's disease), and restrictive lung disease.

Adverse Effects, Risks, and Monitoring

Bone-marrow suppression is a common side effect of Azathioprine, particularly in individuals with a genetic deficiency of the TPMT enzyme.

Answer: True

Bone-marrow suppression is a well-documented common side effect of Azathioprine, with increased incidence and severity in patients with reduced or absent TPMT enzyme activity due to genetic variations.

Related Concepts:

  • Why is bone-marrow suppression a particular concern with Azathioprine, and in whom is it more common?: Bone-marrow suppression is a significant concern because Azathioprine inhibits the bone marrow's ability to produce blood cells, potentially leading to conditions like anemia and increased susceptibility to infection. This side effect is especially common in individuals who have a genetic deficiency of the enzyme thiopurine S-methyltransferase (TPMT).
  • How do genetic variations in the TPMT gene affect patients receiving Azathioprine?: Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity. Individuals who are homozygous or heterozygous for these variations may experience increased levels of active thioguanine nucleotide (TGN) metabolites, which significantly raises their risk of severe bone-marrow suppression, also known as myelosuppression, when treated with Azathioprine.
  • What testing methods can identify patients at risk due to TPMT activity, and what is the FDA's recommendation?: Patients with reduced TPMT enzyme activity can be identified through an assay of TPMT activity in red blood cells or by a TPMT genetic test. The FDA-approved drug label for Azathioprine recommends testing for TPMT activity to identify patients at risk for myelotoxicity, making it one of the few examples of pharmacogenetics integrated into routine clinical care.

Hypersensitivity reactions like dizziness, diarrhea, and rashes are not known adverse effects of Azathioprine.

Answer: False

Hypersensitivity reactions, including dizziness, diarrhea, fatigue, and rashes, are indeed known adverse effects of Azathioprine.

Related Concepts:

  • What are some other adverse effects of Azathioprine besides bone-marrow suppression and vomiting?: Other adverse effects of Azathioprine can include hypersensitivity reactions such as dizziness, diarrhea, fatigue, and rashes. Hair loss is often observed in transplant patients receiving the drug, though it is rare for other indications. Acute pancreatitis can also occur, particularly in patients with Crohn's disease.
  • What are the most common side effects associated with Azathioprine treatment?: Common side effects of Azathioprine include bone-marrow suppression, which can lead to reduced production of blood cells, and vomiting. Nausea is also a frequent adverse effect, particularly at the start of treatment.

The International Agency for Research on Cancer (IARC) classifies Azathioprine as a Group 1 carcinogen.

Answer: True

The International Agency for Research on Cancer (IARC) classifies Azathioprine as a Group 1 carcinogen, indicating it is considered carcinogenic to humans.

Related Concepts:

  • How is Azathioprine classified by the International Agency for Research on Cancer (IARC) and the National Toxicology Program (NTP)?: The International Agency for Research on Cancer (IARC) lists Azathioprine as a group 1 carcinogen, meaning it is considered carcinogenic to humans. Similarly, the National Toxicology Program (NTP) of the U.S. Department of Health and Human Services lists it as 'known to be a human carcinogen' based on sufficient human evidence.
  • What warnings has the U.S. FDA required regarding Azathioprine and cancer risks?: Since August 2009, the U.S. Food and Drug Administration (FDA) has mandated that warnings be placed on Azathioprine packaging to inform users and clinicians about the increased risks of certain cancers associated with its use.

Transplant patients taking Azathioprine have a significantly lower risk for skin cancer compared to the general population.

Answer: False

Transplant patients taking Azathioprine are at a significantly higher risk for skin cancer, with incidence rates 50 to 250 times greater than the general population.

Related Concepts:

  • Why are transplant patients taking Azathioprine at a significantly higher risk for skin cancer?: In transplant patients, skin cancer is 50 to 250 times more common than in the general population, with 60-90% of patients affected 20 years post-transplantation. This increased risk is linked to immunosuppressive medications like Azathioprine, which causes the accumulation of 6-thioguanine (6-TG) in patients' DNA. This accumulation can then trigger cancer when the patient is exposed to ultraviolet A (UVA) light, to which they become abnormally sensitive.
  • What factors influence the cancer risks associated with Azathioprine, and how do risks differ between patient groups?: The cancer risks associated with Azathioprine appear to be related to both the duration and the dosage of the drug. Patients previously treated with an alkylating agent may face an excessive risk of cancers if subsequently treated with Azathioprine. While transplant patients generally have higher risks of non-Hodgkin lymphoma, squamous cell carcinomas of the skin, hepatobiliary carcinomas, and mesenchymal tumors, those receiving Azathioprine for rheumatoid arthritis may have a lower risk compared to transplant recipients.

Long-term overdose of Azathioprine primarily causes severe headaches and muscle cramps.

Answer: False

Long-term overdose of Azathioprine primarily manifests as infections of unclear origin, mouth ulcers, and spontaneous bleeding, stemming from bone-marrow suppression.

Related Concepts:

  • What are the symptoms of a long-term overdose of Azathioprine?: The main symptoms of long-term overdosing with Azathioprine are infections of unclear origin, mouth ulcers, and spontaneous bleeding, all of which are consequences of its bone-marrow suppression.
  • How well are large, single doses of Azathioprine generally tolerated?: Large, single doses of Azathioprine are generally well tolerated. For instance, a patient who took 7.5 grams of Azathioprine (equivalent to 150 tablets) at once experienced no significant symptoms other than vomiting, a slight decrease in white blood cell count, and minor changes in liver function parameters.

What is a significant concern related to Azathioprine's effect on the bone marrow?

Answer: Reduced production of blood cells, leading to conditions like anemia

Azathioprine can cause bone-marrow suppression, which impairs the production of blood cells, potentially resulting in conditions such as anemia, leukopenia, and thrombocytopenia.

Related Concepts:

  • Why is bone-marrow suppression a particular concern with Azathioprine, and in whom is it more common?: Bone-marrow suppression is a significant concern because Azathioprine inhibits the bone marrow's ability to produce blood cells, potentially leading to conditions like anemia and increased susceptibility to infection. This side effect is especially common in individuals who have a genetic deficiency of the enzyme thiopurine S-methyltransferase (TPMT).
  • What monitoring is recommended for patients undergoing Azathioprine treatment due to its effect on bone marrow?: Because Azathioprine suppresses the bone marrow, regular monitoring of the patient's blood count is recommended during treatment to detect potential issues like anemia or increased susceptibility to infection.
  • What are the most common side effects associated with Azathioprine treatment?: Common side effects of Azathioprine include bone-marrow suppression, which can lead to reduced production of blood cells, and vomiting. Nausea is also a frequent adverse effect, particularly at the start of treatment.

What is a potential risk associated with Azathioprine treatment for inflammatory bowel disease?

Answer: Increased risk of lymphoma

Azathioprine treatment for inflammatory bowel disease is associated with an increased risk of lymphoma, including the rare but aggressive hepatosplenic T-cell lymphoma.

Related Concepts:

  • What is the potential risk associated with Azathioprine treatment for inflammatory bowel disease, and what is unclear about this risk?: Azathioprine treatment for inflammatory bowel disease is associated with an increased risk of lymphoma. However, it is unclear whether this increased risk is directly due to the drug itself or if it is related to a predisposition caused by Crohn's disease.
  • What are some other adverse effects of Azathioprine besides bone-marrow suppression and vomiting?: Other adverse effects of Azathioprine can include hypersensitivity reactions such as dizziness, diarrhea, fatigue, and rashes. Hair loss is often observed in transplant patients receiving the drug, though it is rare for other indications. Acute pancreatitis can also occur, particularly in patients with Crohn's disease.
  • What specific type of lymphoma has been reported in patients treated with Azathioprine, particularly those with inflammatory bowel disease?: Cases of hepatosplenic T-cell lymphoma, a rare and aggressive type of lymphoma, have been reported in patients treated with Azathioprine. The majority of these cases occurred in individuals with inflammatory bowel disease, predominantly adolescents and young adult males, and were often fatal.

Which of the following is NOT listed as an adverse effect of Azathioprine?

Answer: Increased blood clotting

Dizziness, hair loss (in transplant patients), and acute pancreatitis are listed as adverse effects of Azathioprine. Increased blood clotting is not mentioned as an adverse effect.

Related Concepts:

  • What are some other adverse effects of Azathioprine besides bone-marrow suppression and vomiting?: Other adverse effects of Azathioprine can include hypersensitivity reactions such as dizziness, diarrhea, fatigue, and rashes. Hair loss is often observed in transplant patients receiving the drug, though it is rare for other indications. Acute pancreatitis can also occur, particularly in patients with Crohn's disease.
  • What are the most common side effects associated with Azathioprine treatment?: Common side effects of Azathioprine include bone-marrow suppression, which can lead to reduced production of blood cells, and vomiting. Nausea is also a frequent adverse effect, particularly at the start of treatment.
  • Why is bone-marrow suppression a particular concern with Azathioprine, and in whom is it more common?: Bone-marrow suppression is a significant concern because Azathioprine inhibits the bone marrow's ability to produce blood cells, potentially leading to conditions like anemia and increased susceptibility to infection. This side effect is especially common in individuals who have a genetic deficiency of the enzyme thiopurine S-methyltransferase (TPMT).

What monitoring is recommended for patients undergoing Azathioprine treatment due to its effect on bone marrow?

Answer: Regular monitoring of the patient's blood count

Due to the risk of bone-marrow suppression, regular monitoring of the patient's complete blood count is essential during Azathioprine therapy to detect potential hematologic abnormalities.

Related Concepts:

  • What monitoring is recommended for patients undergoing Azathioprine treatment due to its effect on bone marrow?: Because Azathioprine suppresses the bone marrow, regular monitoring of the patient's blood count is recommended during treatment to detect potential issues like anemia or increased susceptibility to infection.
  • Why is bone-marrow suppression a particular concern with Azathioprine, and in whom is it more common?: Bone-marrow suppression is a significant concern because Azathioprine inhibits the bone marrow's ability to produce blood cells, potentially leading to conditions like anemia and increased susceptibility to infection. This side effect is especially common in individuals who have a genetic deficiency of the enzyme thiopurine S-methyltransferase (TPMT).
  • What are the most common side effects associated with Azathioprine treatment?: Common side effects of Azathioprine include bone-marrow suppression, which can lead to reduced production of blood cells, and vomiting. Nausea is also a frequent adverse effect, particularly at the start of treatment.

What is the classification of Azathioprine by the International Agency for Research on Cancer (IARC)?

Answer: Group 1 carcinogen (carcinogenic to humans)

The International Agency for Research on Cancer (IARC) classifies Azathioprine as a Group 1 carcinogen, indicating sufficient evidence of carcinogenicity in humans.

Related Concepts:

  • How is Azathioprine classified by the International Agency for Research on Cancer (IARC) and the National Toxicology Program (NTP)?: The International Agency for Research on Cancer (IARC) lists Azathioprine as a group 1 carcinogen, meaning it is considered carcinogenic to humans. Similarly, the National Toxicology Program (NTP) of the U.S. Department of Health and Human Services lists it as 'known to be a human carcinogen' based on sufficient human evidence.
  • What is the classification of Azathioprine within the family of medications?: Azathioprine belongs to the purine analogues subclass, which is part of the antimetabolites family of medications. Antimetabolites interfere with the normal metabolic processes of cells, often by mimicking natural substances.
  • What warnings has the U.S. FDA required regarding Azathioprine and cancer risks?: Since August 2009, the U.S. Food and Drug Administration (FDA) has mandated that warnings be placed on Azathioprine packaging to inform users and clinicians about the increased risks of certain cancers associated with its use.

Why are transplant patients taking Azathioprine at a significantly higher risk for skin cancer?

Answer: Due to the accumulation of 6-thioguanine in DNA, triggering cancer with UVA light exposure.

The increased risk of skin cancer in transplant patients on Azathioprine is attributed to the accumulation of 6-thioguanine in their DNA, which makes them abnormally sensitive to UVA light and can trigger carcinogenesis upon exposure.

Related Concepts:

  • Why are transplant patients taking Azathioprine at a significantly higher risk for skin cancer?: In transplant patients, skin cancer is 50 to 250 times more common than in the general population, with 60-90% of patients affected 20 years post-transplantation. This increased risk is linked to immunosuppressive medications like Azathioprine, which causes the accumulation of 6-thioguanine (6-TG) in patients' DNA. This accumulation can then trigger cancer when the patient is exposed to ultraviolet A (UVA) light, to which they become abnormally sensitive.
  • What factors influence the cancer risks associated with Azathioprine, and how do risks differ between patient groups?: The cancer risks associated with Azathioprine appear to be related to both the duration and the dosage of the drug. Patients previously treated with an alkylating agent may face an excessive risk of cancers if subsequently treated with Azathioprine. While transplant patients generally have higher risks of non-Hodgkin lymphoma, squamous cell carcinomas of the skin, hepatobiliary carcinomas, and mesenchymal tumors, those receiving Azathioprine for rheumatoid arthritis may have a lower risk compared to transplant recipients.
  • What are some other adverse effects of Azathioprine besides bone-marrow suppression and vomiting?: Other adverse effects of Azathioprine can include hypersensitivity reactions such as dizziness, diarrhea, fatigue, and rashes. Hair loss is often observed in transplant patients receiving the drug, though it is rare for other indications. Acute pancreatitis can also occur, particularly in patients with Crohn's disease.

What are the main symptoms of a long-term overdose of Azathioprine?

Answer: Infections of unclear origin, mouth ulcers, and spontaneous bleeding

Long-term Azathioprine overdose primarily manifests as symptoms related to severe bone-marrow suppression, including unexplained infections, oral ulcerations, and spontaneous hemorrhage.

Related Concepts:

  • What are the symptoms of a long-term overdose of Azathioprine?: The main symptoms of long-term overdosing with Azathioprine are infections of unclear origin, mouth ulcers, and spontaneous bleeding, all of which are consequences of its bone-marrow suppression.
  • How well are large, single doses of Azathioprine generally tolerated?: Large, single doses of Azathioprine are generally well tolerated. For instance, a patient who took 7.5 grams of Azathioprine (equivalent to 150 tablets) at once experienced no significant symptoms other than vomiting, a slight decrease in white blood cell count, and minor changes in liver function parameters.
  • What are the most common side effects associated with Azathioprine treatment?: Common side effects of Azathioprine include bone-marrow suppression, which can lead to reduced production of blood cells, and vomiting. Nausea is also a frequent adverse effect, particularly at the start of treatment.

Pharmacogenomics and Drug Interactions

Allopurinol can increase the toxicity of Azathioprine by inhibiting an enzyme responsible for its breakdown.

Answer: True

Allopurinol inhibits xanthine oxidase, an enzyme that metabolizes Azathioprine, thereby increasing Azathioprine's concentration and potential toxicity.

Related Concepts:

  • How does allopurinol interact with Azathioprine, and what are the implications?: Allopurinol, another purine analogue, inhibits xanthine oxidase, an enzyme responsible for breaking down Azathioprine. This inhibition can increase the toxicity of Azathioprine. However, low doses of allopurinol have also been shown to safely enhance the efficacy of Azathioprine, especially in inflammatory bowel disease patients who do not respond well to the drug, though this combination requires careful monitoring due to potential lower lymphocyte counts and higher infection rates.
  • How is Azathioprine metabolized in the body, and what are its end products?: Azathioprine is a prodrug, meaning it is converted into an active form within the body. Initially, it is slowly and almost completely converted to 6-mercaptopurine (6-MP) through reductive cleavage, a process mediated by glutathione and similar compounds in the intestinal wall, liver, and red blood cells, without the need for enzymes. 6-MP is then metabolized similarly to natural purines, forming thioinosine monophosphate (TIMP) and other intermediates, eventually leading to thioguanosine triphosphate (TGTP) and thiodeoxyguanosine triphosphate (TdGTP). Additionally, the sulfur atom of 6-MP and TIMP undergoes methylation. The final metabolic products, including thiouric acid (38%) and various methylated and hydroxylated purines, are excreted via the urine.
  • What is the role of the thiopurine S-methyltransferase (TPMT) enzyme in Azathioprine's metabolism?: The enzyme thiopurine S-methyltransferase (TPMT) plays a crucial role in both the activation and deactivation steps of Azathioprine's mechanism of action. Specifically, TPMT is responsible for methylating 6-mercaptopurine (6-MP), an initial metabolite of Azathioprine, into the inactive metabolite 6-methylmercaptopurine, thereby preventing 6-MP from being further converted into active, cytotoxic thioguanine nucleotide (TGN) metabolites.

Azathioprine decreases the effects of both nondepolarizing and depolarizing muscle relaxants.

Answer: False

Azathioprine decreases the effects of nondepolarizing muscle relaxants but increases the effect of depolarizing muscle relaxants.

Related Concepts:

  • What are the effects of Azathioprine on the anticoagulation drug warfarin and muscle relaxants?: Azathioprine decreases the effects of the anticoagulant warfarin. It also decreases the effects of nondepolarizing muscle relaxants but increases the effect of depolarizing muscle relaxants.

Genetic variations in the TPMT gene can lead to increased TPMT enzyme activity, reducing the risk of bone-marrow suppression with Azathioprine.

Answer: False

Genetic variations in the TPMT gene typically lead to *decreased* or *absent* TPMT enzyme activity, which *increases* the risk of severe bone-marrow suppression with Azathioprine.

Related Concepts:

  • How do genetic variations in the TPMT gene affect patients receiving Azathioprine?: Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity. Individuals who are homozygous or heterozygous for these variations may experience increased levels of active thioguanine nucleotide (TGN) metabolites, which significantly raises their risk of severe bone-marrow suppression, also known as myelosuppression, when treated with Azathioprine.
  • What testing methods can identify patients at risk due to TPMT activity, and what is the FDA's recommendation?: Patients with reduced TPMT enzyme activity can be identified through an assay of TPMT activity in red blood cells or by a TPMT genetic test. The FDA-approved drug label for Azathioprine recommends testing for TPMT activity to identify patients at risk for myelotoxicity, making it one of the few examples of pharmacogenetics integrated into routine clinical care.
  • Why is bone-marrow suppression a particular concern with Azathioprine, and in whom is it more common?: Bone-marrow suppression is a significant concern because Azathioprine inhibits the bone marrow's ability to produce blood cells, potentially leading to conditions like anemia and increased susceptibility to infection. This side effect is especially common in individuals who have a genetic deficiency of the enzyme thiopurine S-methyltransferase (TPMT).

How does allopurinol interact with Azathioprine?

Answer: It inhibits an enzyme that breaks down Azathioprine, potentially increasing its toxicity.

Allopurinol inhibits xanthine oxidase, an enzyme involved in Azathioprine's metabolism, which can lead to increased levels of Azathioprine and heightened toxicity.

Related Concepts:

  • How does allopurinol interact with Azathioprine, and what are the implications?: Allopurinol, another purine analogue, inhibits xanthine oxidase, an enzyme responsible for breaking down Azathioprine. This inhibition can increase the toxicity of Azathioprine. However, low doses of allopurinol have also been shown to safely enhance the efficacy of Azathioprine, especially in inflammatory bowel disease patients who do not respond well to the drug, though this combination requires careful monitoring due to potential lower lymphocyte counts and higher infection rates.
  • How is Azathioprine metabolized in the body, and what are its end products?: Azathioprine is a prodrug, meaning it is converted into an active form within the body. Initially, it is slowly and almost completely converted to 6-mercaptopurine (6-MP) through reductive cleavage, a process mediated by glutathione and similar compounds in the intestinal wall, liver, and red blood cells, without the need for enzymes. 6-MP is then metabolized similarly to natural purines, forming thioinosine monophosphate (TIMP) and other intermediates, eventually leading to thioguanosine triphosphate (TGTP) and thiodeoxyguanosine triphosphate (TdGTP). Additionally, the sulfur atom of 6-MP and TIMP undergoes methylation. The final metabolic products, including thiouric acid (38%) and various methylated and hydroxylated purines, are excreted via the urine.
  • What are the effects of Azathioprine on the anticoagulation drug warfarin and muscle relaxants?: Azathioprine decreases the effects of the anticoagulant warfarin. It also decreases the effects of nondepolarizing muscle relaxants but increases the effect of depolarizing muscle relaxants.

What severe interaction has been reported between Azathioprine and niacin (vitamin B3)?

Answer: Pellagra and fatal medullary aplasia

A severe interaction between Azathioprine and niacin has been reported, leading to pellagra and fatal medullary aplasia, a critical bone marrow failure.

Related Concepts:

  • What severe interaction can occur between Azathioprine and niacin (vitamin B3)?: Azathioprine can interfere with niacin (vitamin B3), which has resulted in at least one reported case of pellagra and fatal medullary aplasia, a severe bone marrow failure.

What is the role of the thiopurine S-methyltransferase (TPMT) enzyme in Azathioprine's metabolism?

Answer: It is responsible for methylating 6-mercaptopurine into an inactive metabolite.

The TPMT enzyme plays a critical role in the deactivation of 6-mercaptopurine, an Azathioprine metabolite, by methylating it into an inactive form, thereby preventing its conversion to cytotoxic thioguanine nucleotides.

Related Concepts:

  • What is the role of the thiopurine S-methyltransferase (TPMT) enzyme in Azathioprine's metabolism?: The enzyme thiopurine S-methyltransferase (TPMT) plays a crucial role in both the activation and deactivation steps of Azathioprine's mechanism of action. Specifically, TPMT is responsible for methylating 6-mercaptopurine (6-MP), an initial metabolite of Azathioprine, into the inactive metabolite 6-methylmercaptopurine, thereby preventing 6-MP from being further converted into active, cytotoxic thioguanine nucleotide (TGN) metabolites.
  • How is Azathioprine metabolized in the body, and what are its end products?: Azathioprine is a prodrug, meaning it is converted into an active form within the body. Initially, it is slowly and almost completely converted to 6-mercaptopurine (6-MP) through reductive cleavage, a process mediated by glutathione and similar compounds in the intestinal wall, liver, and red blood cells, without the need for enzymes. 6-MP is then metabolized similarly to natural purines, forming thioinosine monophosphate (TIMP) and other intermediates, eventually leading to thioguanosine triphosphate (TGTP) and thiodeoxyguanosine triphosphate (TdGTP). Additionally, the sulfur atom of 6-MP and TIMP undergoes methylation. The final metabolic products, including thiouric acid (38%) and various methylated and hydroxylated purines, are excreted via the urine.
  • How do genetic variations in the TPMT gene affect patients receiving Azathioprine?: Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity. Individuals who are homozygous or heterozygous for these variations may experience increased levels of active thioguanine nucleotide (TGN) metabolites, which significantly raises their risk of severe bone-marrow suppression, also known as myelosuppression, when treated with Azathioprine.

What is the approximate frequency of TPMT polymorphisms that lead to decreased enzyme activity in many ethnicities?

Answer: Approximately 5%

TPMT polymorphisms resulting in decreased or absent enzyme activity are observed in approximately 5% of many ethnic populations, with about 0.25% being homozygous for these variants.

Related Concepts:

  • What is the approximate frequency of TPMT polymorphisms that result in decreased enzyme activity in many ethnicities?: In many ethnicities, TPMT polymorphisms that lead to decreased or absent TPMT activity occur with a frequency of approximately 5%. This means that about 0.25% of patients are homozygous for these genetic variants.

Special Populations: Pregnancy and Lactation

A 2003 study indicated that Azathioprine use during pregnancy was associated with a seven-fold increase in fetal abnormalities.

Answer: True

A 2003 population-based study in Denmark reported a seven-fold increase in fetal abnormalities associated with Azathioprine and related mercaptopurine use during pregnancy.

Related Concepts:

  • What are the known risks of Azathioprine use during pregnancy?: Azathioprine can cause birth defects. A 2003 population-based study in Denmark indicated that the use of azathioprine and related mercaptopurine resulted in a seven-fold increase in fetal abnormalities and a twenty-fold increase in miscarriage. Birth defects have also been reported in children whose fathers were taking Azathioprine. Animal studies have shown teratogenesis (developmental malformations) at doses equivalent to human dosages.

Transplant patients should discontinue Azathioprine if they become pregnant due to severe contraindications.

Answer: False

Transplant patients already on Azathioprine are generally advised not to discontinue the medication upon becoming pregnant, unlike other immunosuppressants that are strictly contraindicated.

Related Concepts:

  • Should transplant patients discontinue Azathioprine if they become pregnant?: No, transplant patients who are already on Azathioprine should not discontinue the medication upon becoming pregnant, contrasting with other drugs like tacrolimus and mycophenolate, which are contraindicated during pregnancy.

What is the recommendation for transplant patients regarding Azathioprine use during pregnancy?

Answer: They should not discontinue the medication upon becoming pregnant.

For transplant patients already on Azathioprine, it is generally recommended not to discontinue the medication during pregnancy, unlike certain other immunosuppressants.

Related Concepts:

  • Should transplant patients discontinue Azathioprine if they become pregnant?: No, transplant patients who are already on Azathioprine should not discontinue the medication upon becoming pregnant, contrasting with other drugs like tacrolimus and mycophenolate, which are contraindicated during pregnancy.
  • How is Azathioprine typically used in organ transplantation to prevent rejection?: Azathioprine is used to prevent the rejection of kidney or liver allografts (transplanted organs from another individual), usually in combination with other immunosuppressive therapies such as corticosteroids and local radiation therapy. Its administration typically begins at the time of transplantation or within two days following the procedure.

Historical Development and Comparative Therapeutics

Azathioprine was first synthesized in the early 1980s.

Answer: False

Azathioprine was first synthesized in 1957, not the early 1980s.

Related Concepts:

  • When was Azathioprine first developed?: Azathioprine was first synthesized in 1957.
  • Who were the scientists credited with synthesizing Azathioprine?: Azathioprine was synthesized by George Herbert Hitchings and Gertrude Elion in 1957.
  • What was the initial intended use of Azathioprine after its synthesis?: After its synthesis, Azathioprine (originally named BW 57-322) was initially used as a chemotherapy drug.

A 2007 Cochrane review found that Azathioprine increased the number of relapses in the first year of treatment for multiple sclerosis patients.

Answer: False

A 2007 Cochrane review actually found that Azathioprine reduced the number of relapses in the first year of treatment for multiple sclerosis patients.

Related Concepts:

  • What did a 2007 Cochrane review conclude about Azathioprine for multiple sclerosis?: A 2007 Cochrane review found that Azathioprine reduced the number of relapses in the first year of treatment and slowed disease progression in the first two to three years for multiple sclerosis patients. The review did not find an increase in cancer, but noted the need for direct comparisons with interferon beta and acknowledged the potential for long-term risks.

Robert Schwartz's research in 1958 showed that 6-mercaptopurine enhanced antibody formation in rabbits.

Answer: False

Robert Schwartz's 1958 research demonstrated that 6-mercaptopurine profoundly suppressed, rather than enhanced, antibody formation in rabbits.

Related Concepts:

  • How did Robert Schwartz's research contribute to the understanding of 6-mercaptopurine's effects?: In 1958, Robert Schwartz investigated the effect of 6-mercaptopurine (6-MP), a metabolite of Azathioprine, on the immune response. He discovered that when administered to rabbits along with antigens, 6-MP profoundly suppressed the formation of antibodies, highlighting its immunosuppressive properties.

Sir Roy Calne initially introduced cyclosporin as an experimental immunosuppressant for transplantation before Azathioprine.

Answer: False

Sir Roy Calne initially introduced 6-mercaptopurine (a metabolite of Azathioprine) as an experimental immunosuppressant, and later Azathioprine itself. Cyclosporin was introduced much later, in 1978.

Related Concepts:

  • Who introduced 6-mercaptopurine and subsequently Azathioprine as experimental immunosuppressants for transplantation?: Sir Roy Calne, a British pioneer in transplantation, introduced 6-mercaptopurine as an experimental immunosuppressant for kidney and heart transplants. When he sought related compounds, Gertrude Elion suggested Azathioprine, which Calne later found to be superior due to its comparable effectiveness and lower toxicity to the bone marrow.
  • What was the standard antirejection regimen for many years, and what drug eventually replaced some of Azathioprine's use?: For many years, the standard antirejection regimen involved dual therapy with Azathioprine and glucocorticoids. However, cyclosporin, introduced into clinical practice by Roy Calne in 1978, eventually replaced some of Azathioprine's use, particularly in heart-related transplantations, due to its association with longer survival times.

Mycophenolate mofetil is increasingly preferred over Azathioprine in organ transplantation due to its lower cost and similar side effect profile.

Answer: False

Mycophenolate mofetil is increasingly favored despite being more expensive, due to its association with less bone-marrow suppression, fewer opportunistic infections, and a lower incidence of acute rejection, not a similar side effect profile.

Related Concepts:

  • Why is mycophenolate mofetil increasingly being used instead of Azathioprine in organ transplantation?: Mycophenolate mofetil is increasingly favored over Azathioprine in organ transplantation, despite being more expensive, because it is associated with less bone-marrow suppression, fewer opportunistic infections, and a lower incidence of acute rejection.

When was Azathioprine first synthesized?

Answer: 1957

Azathioprine was first synthesized by George Herbert Hitchings and Gertrude Elion in 1957.

Related Concepts:

  • Who were the scientists credited with synthesizing Azathioprine?: Azathioprine was synthesized by George Herbert Hitchings and Gertrude Elion in 1957.
  • When was Azathioprine first developed?: Azathioprine was first synthesized in 1957.
  • What was the initial intended use of Azathioprine after its synthesis?: After its synthesis, Azathioprine (originally named BW 57-322) was initially used as a chemotherapy drug.

What did a 2012 study conclude about a therapy combining Azathioprine with prednisone and N-acetylcysteine for idiopathic pulmonary fibrosis?

Answer: It produced worse outcomes compared to a placebo.

A 2012 study demonstrated that the combination therapy including Azathioprine for idiopathic pulmonary fibrosis resulted in worse outcomes than a placebo, leading to a reevaluation of this treatment approach.

Related Concepts:

  • What was the outcome of a 2012 study regarding Azathioprine's use in idiopathic pulmonary fibrosis?: A 2012 study showed that a widely used therapy for idiopathic pulmonary fibrosis, which combined azathioprine with prednisone and N-acetylcysteine, actually produced worse outcomes compared to a placebo.

Who were the scientists credited with synthesizing Azathioprine?

Answer: George Herbert Hitchings and Gertrude Elion

Azathioprine was synthesized by the Nobel laureates George Herbert Hitchings and Gertrude Elion in 1957.

Related Concepts:

  • Who were the scientists credited with synthesizing Azathioprine?: Azathioprine was synthesized by George Herbert Hitchings and Gertrude Elion in 1957.
  • When was Azathioprine first developed?: Azathioprine was first synthesized in 1957.
  • How is Azathioprine synthesized?: Azathioprine is synthesized by combining 5-chloro-1-methyl-4-nitro-1H-imidazole and 6-mercaptopurine in dimethyl sulfoxide (DMSO). The synthesis of 5-chloro-1-methyl-4-nitro-1H-imidazole begins with an amide derived from methylamine and diethyl oxalate, which is then cyclized and chlorinated using phosphorus pentachloride, and finally, a nitro group is introduced with nitric and sulfuric acid.

What was the initial intended use of Azathioprine after its synthesis?

Answer: As a chemotherapy drug

Upon its synthesis, Azathioprine was initially developed and used as a chemotherapy agent.

Related Concepts:

  • What was the initial intended use of Azathioprine after its synthesis?: After its synthesis, Azathioprine (originally named BW 57-322) was initially used as a chemotherapy drug.
  • When was Azathioprine first developed?: Azathioprine was first synthesized in 1957.

What did Robert Schwartz discover about 6-mercaptopurine's effect on the immune response in rabbits?

Answer: It profoundly suppressed antibody formation.

Robert Schwartz's research in 1958 revealed that 6-mercaptopurine, a metabolite of Azathioprine, profoundly suppressed antibody formation in rabbits, indicating its immunosuppressive properties.

Related Concepts:

  • How did Robert Schwartz's research contribute to the understanding of 6-mercaptopurine's effects?: In 1958, Robert Schwartz investigated the effect of 6-mercaptopurine (6-MP), a metabolite of Azathioprine, on the immune response. He discovered that when administered to rabbits along with antigens, 6-MP profoundly suppressed the formation of antibodies, highlighting its immunosuppressive properties.

When did successful human kidney allotransplantation become possible using Azathioprine and prednisone?

Answer: 1962

Successful human kidney allotransplantation, utilizing regimens that included Azathioprine and prednisone, was first achieved in April 1962.

Related Concepts:

  • When did successful human kidney allotransplantation become possible with Azathioprine and prednisone?: Successful allotransplantation (transplantation between genetically different individuals of the same species) of human kidneys was achieved for the first time in April 1962, using regimens that combined Azathioprine and prednisone.
  • What was the standard antirejection regimen for many years, and what drug eventually replaced some of Azathioprine's use?: For many years, the standard antirejection regimen involved dual therapy with Azathioprine and glucocorticoids. However, cyclosporin, introduced into clinical practice by Roy Calne in 1978, eventually replaced some of Azathioprine's use, particularly in heart-related transplantations, due to its association with longer survival times.

Why is mycophenolate mofetil increasingly favored over Azathioprine in organ transplantation?

Answer: It is associated with less bone-marrow suppression and fewer opportunistic infections.

Mycophenolate mofetil is increasingly preferred in organ transplantation due to its more favorable safety profile, including less bone-marrow suppression and a reduced incidence of opportunistic infections and acute rejection, despite its higher cost.

Related Concepts:

  • Why is mycophenolate mofetil increasingly being used instead of Azathioprine in organ transplantation?: Mycophenolate mofetil is increasingly favored over Azathioprine in organ transplantation, despite being more expensive, because it is associated with less bone-marrow suppression, fewer opportunistic infections, and a lower incidence of acute rejection.

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