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[immunosuppressive drug, wikipedia]
- Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:
- Prevent the rejection of transplanted organs and tissues (e.g., bone marrow, heart, kidney, liver)
- Treat autoimmune diseases or diseases that are most likely of autoimmune origin (e.g., rheumatoid arthritis, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, focal segmental glomerulosclerosis, Crohn’s disease, Behcet’s Disease, pemphigus, and ulcerative colitis).
- Treat some other non-autoimmune inflammatory diseases (e.g., long term allergic asthma control).
- These drugs are not without side-effects and risks. Because the majority of them act non-selectively, the immune system is less able to resist infections and the spread of malignant cells. There are also other side-effects, such as hypertension, dyslipidemia, hyperglycemia, peptic ulcers, liver, and kidney injury. The immunosuppressive drugs also interact with other medicines and affect their metabolism and action. Actual or suspected immunosuppressive agents can be evaluated in terms of their effects on lymphocyte subpopulations in tissues using immunohistochemistry.
It is used to treat leukemia, pediatric non-Hodgkin’s lymphoma, polycythemia vera, psoriatic arthritis, and inflammatory bowel disease (such as Crohn’s disease and ulcerative colitis)
It has demonstrated some in vitro effectiveness against Mycobacterium paratuberculosis.
6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism. This alters the synthesis and function of RNA and DNA. Mercaptopurine interferes with nucleotide interconversion and glycoprotein synthesis.
Some of the adverse reactions of taking mercaptopurine might include diarrhea, nausea, vomiting, loss of appetite, fatigue, stomach/abdominal pain, weakness, skin rash, darkening of the skin, or hair loss. Serious adverse reactions include mouth sores, fever, sore throat, easy bruising or bleeding, pinpoint red spots on the skin, yellowing of eyes or skin, dark urine, and painful or difficult urination. Unlikely but serious side-effects include: black or tarry stools (melena), bloody stools, and bloody urine.
Symptoms of allergic reaction to mercaptopurine include rash, itching, swelling, dizziness, trouble breathing, and pancreatitis.
Mercaptopurine causes myelosuppression, suppressing the production of white blood cells and red blood cells. It may be toxic to bone marrow. Weekly blood counts are recommended for patients on mercaptopurine. The patient should stop taking the medication at least temporarily if there is an unexplained, abnormally large drop in white blood cell count, or any other blood count.
Patients exhibiting myelosuppression or bone marrow toxicity should be tested for thiopurine methyltransferase (TPMT) enzyme deficiency. Patients with TPMT deficiency are much more likely to develop dangerous myelosuppression. In such patients, it may be possible to continue using mercaptopurine, but at a lower dose.
Allopurinol inhibits xanthine oxidase, the enzyme that breaks down mercaptopurine. Those taking allopurinol (often used to prevent gout) are at risk for mercaptopurine toxicity. The dose should be reduced or allopurinol should be discontinued.
Mercaptopurine can lower the body’s ability to fight off infection. Those taking mercaptopurine should get permission from a doctor in order to receive immunizations and vaccinations. It is also recommended that, while on the drug, one should avoid those having recently received oral polio vaccine.
This drug is traditionally not recommended during pregnancy, but this issue has been debated, and current evidence indicates that pregnant women on the drug show no increase in fetal abnormalities. However, women receiving mercaptopurine during the first trimester of pregnancy have an increased incidence of miscarriage. Davis et al. 1999 found that mercaptopurine, compared to methotrexate, was ineffective as a single-agent abortifacient; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a suction abortion.
Mercaptopurine causes changes to chromosomes in animals and humans, though a study in 1990 found that, “while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal.” Another study in 1999 noted an increased risk of developing leukemia when taking large doses of 6-MP together with other cytotoxic drugs.
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