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Azathioprine
Last reviewed: 23.04.2024
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There are two main purine analogues - 6-mercaptopurine and azathioprine, but in clinical practice at present only the latter is used.
6-mercaptopurine is an analogue of hypoxanthin, in which the 6-OH radical is replaced by a thiol group. In turn, azathioprine represents a molecule that differs from 6-mercaptopurine by the inclusion of the imidazole ring in the S-position. Compared with 6-mercaptopurine, azathioprine is better absorbed when taken orally and has a longer duration of action. In the body, azathioprine is metabolized in erythrocytes and the liver with the formation of biologically active molecules (6-thioguanine and 6-thioinosinic acids), excreted by the kidneys.
[Tactics of treatment
By eliminating the acute hypersensitivity reaction to azathioprine, treatment should be started with a trial dose of 25-50 mg per day during the first week.
Then the dose is increased by 0.5 mg / kg per day every 4 to a week. The optimal dose is 1-3 mg / kg per day. At the beginning of treatment, it is necessary to perform a regular blood test (with a determination of the number of platelets) on a regular basis (every 1 week), and once a stable dose is reached, the laboratory control should be performed every 6-8 weeks. It must be remembered that the effect of azathioprine begins to manifest no earlier than 5 12 months from the start of therapy. The dose of azathioprine should be significantly reduced (by 50-75%) in patients receiving allopurinol or who have renal failure.
General characteristics
On the mechanism of action, azathioprine refers to a class of substances called "antimetabolites." It has the ability to be included as a "false base" and a DNA molecule and thus violate its replication. Azathioprine is considered as a phase-specific drug that affects cells in a particular phase of growth, mainly in the G phase. In higher doses, azathioprine disrupts the synthesis of RNA and protein in the G1 and G2 phases. Unlike alkylating agents, azathioprine does not have cytotoxic, but cytostatic activity.
The mechanism of action of azathioprine
Azathioprine causes peripheral T- and B-lymphopenia, in high doses reduces the level of T-helpers, with long-term administration reduces the synthesis of antibodies. However, since T-suppressors are particularly sensitive to the action of azathioprine, against the background of taking low doses of the preparation, the synthesis of antibodies can somewhat increase. Azathioprine is characterized by inhibition of the activity of EK cells and K cells, which are involved in the development of naturally and antibody-dependent cellular cytotoxicity, respectively.
Clinical use
The effectiveness of azathioprine at a dose of 1.25-3 mg / kg / day in RA was confirmed and a series of controlled studies. In general, the clinical efficacy of azathioprine in rheumatoid arthritis is comparable to that of cyclophosphamide, parenterally administered preparations of gold, D-penicillamine and antimalarial drugs. It is suggested that with rheumatoid arthritis azathioprine should be prescribed to elderly patients with a start option reminiscent of rheumatic polymyalgia, when a steroid-saving effect is required.
In systemic lupus erythematosus, according to short-term observation (1-2 years), there are no significant differences in clinical efficacy between groups of patients receiving only glucocorticoids or glucocorticoids in combination with azathioprine. But when assessing the results of treatment after 5-15 years, it was found that combination therapy has certain advantages, including slowing the progression of kidney damage, reducing the number of exacerbations and the possibility of using a lower maintenance dose of glucocorticoids. However, in patients receiving azathioprine, the frequency of various side effects significantly increases, including infectious complications (especially herpes zoster), ovarian failure, leukopenia, liver damage, and an increased risk of tumors.
In idiopathic inflammatory myopathies, about a third of patients resistant to glucocorticoids respond to the usual dose of azathioprine (2-3 mg / kg / day), and a steroid-saving effect is observed in half of the cases, which is somewhat worse than with methotrexate. The maximum clinical and laboratory effect in the treatment of azathioprine occurs only after 6-9 months. The maintenance dose of the drug is 50 mg / day.
The results of small controlled studies indicate the effectiveness of azathioprine in psoriatic arthritis, Reiter's syndrome, Behcet's disease.
Attention!
To simplify the perception of information, this instruction for use of the drug "Azathioprine" translated and presented in a special form on the basis of the official instructions for medical use of the drug. Before use read the annotation that came directly to medicines.
Description provided for informational purposes and is not a guide to self-healing. The need for this drug, the purpose of the treatment regimen, methods and dose of the drug is determined solely by the attending physician. Self-medication is dangerous for your health.