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Azathioprine - everything you need to know at a glance
Last updated on May 1, 2020 at 8:24 PM
What is azathioprine and how does it work?
Azathioprine is a Immunosuppressant. This means that it makes the immune system less active. At Autoimmune diseases The body's immune system not only attacks hostile intruders, but also the body's own tissue. This leads to inflammatory reactions and chronic diseases.
In addition, the active ingredient helps to one Organ transplant To avoid rejection reactions so that the receiving organ can carry out its functions.
Azathioprine affects the growth of immune cells and reduces the number of immune cells as a whole. To do this in detail:
These effects need one deep Incision in the physical processes and functions. Azathioprine is a prodrug. That means there is a hardly any active substance is. It is only converted into its active form through metabolism. After ingestion it will be in the liver to 6-mercaptopurine metabolized, which in cancer therapy often takes the form of a Chemotherapy as a cytostatic is administered. The cytostatic effect occurs through azathioprine only from one high Dosage on.
Further metabolic processes turn 6-mercaptopurine into an active metabolite and two inactive metabolites. Metabolites are substances that arise from intermediate stages or breakdown products of metabolic processes.
The metabolites from the metabolism of azathioprine affect the Duplication of DNA and RNA. This is because 6-mercaptopurine is a purine analogue, which is antimetabolic due to its purine-like structure Adenine and Guanine works. These two are 2 of the 4 bases for DNA and RNA.
The DNA denotes the Deoxyribonucleic acid and is Carrier of the genetic information. It is from this information that proteins are formed. The RNA is that Ribonucleic acid. It is contained in the nucleus and cytoplasm of every cell. She delivers that Instructions for protein formation.
The inhibition of adenine and guanine causes 6-mercaptopurine to be incorporated into DNA and RNA. This creates a great change in the human body. Due to the changed information, the Formation of immune cells and the Differentiation of the lymphocytes inhibited.
In addition, the cell division of T lymphocytes, natural killer cells and B lymphocytes is reduced. This is where the immunosuppressive effect comes about - the immune reactions against one's own body and invading pathogens are curbed because the number of immune cells is reduced overall.
The full effect of azathioprine is only visible afterwards 2 to 5 months regular intake. This is why this time is often bridged with an additional immunosuppressant, such as cyclosporine, until azathioprine alone can “keep the immune system in check”.
For which diseases is azathioprine used?
By inhibiting the immune system, azathioprine is released after a Organ transplant used. Also at Autoimmune diseases and others chronic diseases is it used:
Azathioprine is also involved in curing the Tight junctions involved in what Leaky good Syndrome is relevant.1 Intestinal cells are firmly connected to one another so that there are no gaps through which intestinal contents can get into the free abdominal cavity. These connections from proteins are called Tight junctions.
At the Leaky good Syndrome tear these connections open, so that microorganisms (and their components) from the Intestinal flora and allergens in the body reach. Often gluten is a cause of this. The consequences of the holey intestine include allergies, autoimmune diseases and inflammation of the liver or pancreas.
How is azathioprine used?
The immunosuppressant is used in Tablets offered with 25, 50, 75 or 100 mg azathioprine. The typical trade names are for example: Azafalk, Azaimun, Azamedac, Imurel or Aza-Q.
They differ depending on the reason for the application recommended dosagesn. For transplants, the starting dose is up to 5 mg / kg body weight. This dose is reduced to around 1 to 3 mg / kg body weight as soon as the active ingredient has the desired effect.
For other clinical pictures, the starting dose is between 1 and 3 mg / kg body weight. Increasing the doses in smaller increments can cause some Prevent side effectswhich is why the slow weekly increase is very popular.
The film-coated tablets are supposed to whole and taken in one piece with a meal. In some cases it is necessary to cut the tablets in half. The direct skin or mucous membrane contact with the powder or the break point, as these can be cytotoxic. If the tablet is undamaged, this precaution does not apply.
1-10% of users can only metabolize the active ingredient slowly due to a genetic change ("slow metabolizer"), So that the risk of a Overdose is increased. For this reason, the enzyme thiopurine methyltransferase should be tested before the first use. If there is a deficiency or decreased activity, this is a sign that azathioprine should be taken in a lower dose.
In ulcerative colitis, the Duration of intake at least 4 years. If there is no acute flare-up during this time, the risk of a new flare-up is about as high as without the azathioprine therapy.2 To avoid a Organ rejection should be the immune system permanent be suppressed.
When should azathioprine not be used?
Patients with Lesch-Nyhan syndrome should not take azathioprine because those affected lack an enzyme that prevents the drug from working properly.
In addition, it shouldn't be for one Hypersensitivity be taken against azathioprine, 6-mercaptopurine or other components of the tablet. Lie severe infections, Liver and bone marrow disorders, cancer or pancreatitis, the intake should be checked carefully.
The Risk-benefit factor should also be carefully considered if patients are pregnant or breastfeeding their child. In lupus erythematosus, azathioprine can lower the risk of newborn lupus or pregnancy risks such as high blood pressure.3
Special precautions apply in combination with these drugs:
- Allopurinol, Oxipurinol and Thiopurinol
- Mesalazine, olsalazine and sulfasalazine
- ACE inhibitors, co-trimoxazo, cimetidine and indomethacin
- Cytotoxic and myelosuppressive drugs
- Tubocurarine and suxamethonium
- Live vaccines
Side effects of azathioprine
Possible side effects and frequency in percent (9):
- Pancreatitis (3.3%)
- Bone marrow suppression (2%)
- Allergies (2%)
- Heptatitis (0.3%)
- Infections (7.4%)
- Neoplasms (3.1%)
Because immunosuppressants like azathioprine the Suppress the immune system, some side effects are possible.
The Risk of infection against bacteria and other pathogens increases. This can lead to more infections. In order to minimize the risk of infectious diseases, it is recommended to consider vaccination against the following pathogens before therapy. Please speak to your treating doctor in this regard:
- Hepatitis A, B
- (if possible) herpes zoster and varicella zoster (live vaccinations)
Deficiencies in red and white blood cells and platelets are also common. Occasionally, hypersensitivity reactions such as dizziness, nausea, vomiting or rashes occur.
A so-called AZA-induced occurs occasionally in patients with IBD acute pancreatitis. The most common outbreak occurs when smoking is in addition to ingestion.4 If taken after an organ transplant, bleeding in the gastrointestinal tract, ulcer or diverticulitis may occur.
Leukopenia, i.e. a severe deficiency in white blood cells, can occur and can be recognized by the symptoms of coughing, inflammation in the genital area, headache, nausea, swelling of the lymph nodes and a generally poor sense of wellbeing.
Will the drug overdosed, the most common side effect of this is the Bone marrow suppression with symptoms such as fever, bruising, or tiredness.
Neoplasms (cell growths) are an equally serious side effect that should be considered. This corresponds to benign tumors, which in rare cases can turn into malignant (malignant) tumors. The absolute risk of malignant tumors is very low, but neoplasms must also be considered by doctors.
When should the intake be stopped?
The doctor should stop taking it if the following symptoms occur:
- Acute abdominal pain
- shortness of breath
- Fever flare-ups
- Gastrointestinal bleeding
- Muscle and joint pain
- Declining physical health
- Chronic fatigue
- Severe diarrhea
The Risks of Taking Azathioprine
Azathioprine not only weakens the defense against pathogens, but also changes the body's own cells. That's how it is Risk of cancer to get sick, increases. According to studies, this risk has been classified as very low in absolute terms.
The active ingredient is suspected of being used in Crohn's disease increased risk of liver cancer (hepatocellular carcinoma).5 The risk of developing lip cancer increases with the higher dose of azathioprine.6
In the case of patients treated with azathioprine, researchers noted altered chromosomes firmly. However, it has not yet been possible to research what role the active ingredient plays in this.
Summary: Azathioprine Therapy
- Azathioprine is an important component of treatment for chronic inflammatory bowel diseases and autoimmune hepatitis
- It is an effective drug for maintaining remission
- Azathioprine often enables a reduction in steroids such as cortisone or Bodenosid
- In the case of intestinal diseases, it may enable the intestinal barrier to regenerate
- Side effects are possible, but a low risk through close monitoring of the state of health and vaccinations (free of aluminum)
- It can lead to hypersensitivity and ("slow metabolizer") Accumulate the active ingredient, this must also be monitored.
- Regular laboratory tests are mandatory during therapy
- The risk of cancer is increased, but not as dramatic in absolute terms as is often claimed. The risk of neoplasia (approx. 3%) is significantly higher and must be taken into account.
- If you feel unwell or have concerns about taking azathioprine, please talk to your doctor about possible alternatives.
- In summary, azathioprine is an effective drug in the treatment of IBD and autoimmune hepatitis, but has more severe side effects than mesalazine, for example. It should therefore not be a first-line treatment.
Azathioprine in daily practice - Guidance for practical use in gastroenterology and hepatology (2017) Dr. J. Weismüller, Group Practice for Gastroenterology, Koblenz, on behalf of Dr. Falk Pharma GmbH
1: Khare V, Krnjic A, Frick A, Gmainer C, Asboth M, Jimenez K, Lang M, Baumgartner M, Evstatiev R, Gasche C. (2019): Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation . In: Sci Rep. 2019 Feb 26; 9 (1): 2842. doi: 10.1038 / s41598-019-39401-0.
2: Bouhnik Y, Lémann M, Mary JY, Scemama G, Taï R, Matuchansky C, Modigliani R, Rambaud JC. (1996): Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. In: Lancet. 1996 Jan 27; 347 (8996): 215-9.
3: Dalal DS, Patel KA, Patel MA. (2019): Systemic Lupus Erythematosus and Pregnancy: A Brief Review. In: J Obstet Gynaecol India. 2019 Apr; 69 (2): 104-109. doi: 10.1007 / s13224-019-01212-8. Epub 2019 Mar 12. https://www.ncbi.nlm.nih.gov/pubmed/30956462
4: Pond N, Mohl W, Bokemeyer B, Bündgens B, Büning J, Miehlke S, Hüppe D, Maaser C, Klugmann T, Kruis W, Siegmund B, Helwig U, Weismüller J, Drabik A, Stallmach A; German IBD Study Group. (2016): Azathioprine-Induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases – A Prospective Study on Incidence and Severity. In: J Crohn's Colitis. 2016 Jan; 10 (1): 61-8. doi: 10.1093 / ecco-jcc / jjv188. Epub 2015 Oct 13.
5: Heron V, Fortinsky KJ, Spiegle G, Hilzenrat N, Szilagyi A. (2016): Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on Azathioprine. In: Case Rep Gastroenterol. 2016 May 19; 10 (1): 50-6. doi: 10.1159 / 000444012. eCollection 2016 Jan-Apr.
6: Na R, Laaksonen MA, Grulich AE, Meagher NS, McCaughan GW, Keogh AM, Vajdic CM. (2016): High azathioprine dose and lip cancer risk in liver, heart, and lung transplant recipients: A population-based cohort study . In: J Am Acad Dermatol. 2016 Jun; 74 (6): 1144-1152.e6. doi: 10.1016 / j.jaad.2015.12.044. Epub 2016 Jan 30.
7: Anvil: Immunsuppressiva: URL: https://www.amboss.com/de/wissen/Immunsuppressiva accessed on April 17, 2019.
8: Ratiopharm GmbH: Azathioprin ratiopharm 25 mg / 50 mg URL: https://www.ratiopharm.de/index.php?eID=dumpFile&t=f&f=62886&g=-1&r=1894%2C1894&token=2859dd5f0eb9ff9a95a2db4da.815a.
9: Ann Intern Med. 1989 Oct 15; 111 (8): 641-9. 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Present DH1, Meltzer SJ, Krumholz MP, Wolke A, Korelitz BI.
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