Azathioprine
Introduction
Azathioprine (AZA) is a medication used primarily in the treatment of certain autoimmune diseases, including Rheumatoid arthritis and Systemic lupus erythematosus. It is an immunosuppressive drug, meaning it reduces the activity of the immune system. Azathioprine is also used in organ transplantation to prevent organ rejection.
Pharmacology
Azathioprine is a prodrug, which means it is converted in the body into its active form. It is metabolized in the liver and red blood cells into 6-mercaptopurine (6-MP), which is then converted into active metabolites that incorporate into DNA and RNA, inhibiting their synthesis and function. This results in a decrease in the proliferation of immune cells, which leads to its immunosuppressive effects.
Clinical Uses
Azathioprine is used in the treatment of a variety of autoimmune diseases. These include rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, and autoimmune hepatitis. It is also used in the prevention of organ rejection following kidney, liver, and heart transplants.
Side Effects and Adverse Reactions
Like all medications, azathioprine has potential side effects. The most common include nausea, vomiting, and diarrhea. More serious side effects can include liver toxicity, bone marrow suppression, and an increased risk of infections due to its immunosuppressive effects. There is also a small increased risk of certain types of cancer, particularly skin cancer and lymphoma.
Contraindications and Interactions
Azathioprine should not be used in patients with known hypersensitivity to the drug or its metabolites. It should also be used with caution in patients with liver disease, as it is metabolized in the liver. Certain medications can interact with azathioprine, including allopurinol, which can increase the levels of azathioprine's active metabolites and increase the risk of toxicity.
Dosage and Administration
The dosage of azathioprine is individualized based on the patient's condition and response to therapy. It is typically started at a low dose and gradually increased as needed. Regular blood tests are required to monitor for side effects and to ensure the medication is working effectively.
History
Azathioprine was first synthesized in the 1950s and was initially used in the prevention of kidney transplant rejection. It was later found to be effective in the treatment of autoimmune diseases and has since become a mainstay of treatment for these conditions.
Future Directions
Research is ongoing into the use of azathioprine in other conditions, as well as into ways to minimize its side effects. There is also interest in the development of new drugs that work in a similar way but may be more effective or have fewer side effects.