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17 Şubat 2017 Cuma


Leflunomide, when taken orally, is rapidly absorbed and transforms into the active form of teriflunomide.                          Türkçe
The major effect of teriflunomide is inhibition of ribonucleotide uridine pyrinamide (rUMP) synthesis.
Leflunomide reduces rUMP synthesis by inhibiting dihydroorotate dehydrogenase, a mitochondrial enzyme
Thus, active cells cannot pass from the G1 phase to the S phase by activating the p52 pathways of apoptotic selection.
Those who prefer to give a loading dose of 100 mg / day for 3 days have not been shown to be superior to start with a dosage of 20 mg / day without loading. Moreover, loading is accompanied by more side effects.
The serum half-life of leflunomide is approximately 15 days. Leflunomide enters enterohepatic recirculation. It is equally eliminated from the kidneys and GIS. Drug clearance is about 38% higher in smokers.
Plasma levels of the active metabolite are potentially risky for pregnancy as they can last up to 2 years at levels of 0.02 mg / L. The cholestyramine can be used for rapid clearance of the drug.
Biological effects
Leflunomide inhibits adhesion to vascular endothelial cells of leukocytes. Thus preventing the homing of leukocytes to the synovial endothelium.
Leflunomide has selective activities on some self-reactive lymphocytes such as Memory T cells.
Teriflunomid dentritik hücre fonksiyonlarını bozmak suretiyle antijen prezentasyonunu bozmuş olur.
Leflunomid, lenfositlerin ve Tip 1 sinoviyositlerin sinoviyayı infiltre etmesini anlamlı şekilde azaltır.
Teriflunamide blocks the proinflammatory consequences of NF-kappaB depending on the dose and time, blocking the two steps necessary for the activation of NF-kappaB.
Teriflunamide inhibits protein tyrosine kinases Jak1 and Jak3.
These kinases increase T cell stimulation through IL-2 receptors.
Teriflunamide decreases the response of B cells to IL-4. IL-10 and IL-11 secretion are also reduced.
Teriflunamide increases TGF-beta synthesis. This cytokine, in some cases, has a repressive effect on the immune system.
In an animal model, leflunomide has been reported to be protective against acetaminophen toxicity. This effect is exerted via the acetaminophen-induced activation of c-jun NH2-terminal kinase.
Potential side effects
Hypertension; It is estimated that teriflunamid is involved in the separation of NSAID from albumin and is associated with an increase in NSAID activity. A few patients develop HT.
Diarrhea and nausea can develop in 10-15% of patients.
It has been reported that up to 13% of patients can have up to 3 times more liver function tests. Patients who have had fatal liver damage have also been reported, although they generally respond well to dose reduction or drug withdrawal.
Leflunomide should not be used in patients with known liver disease, those with high liver function tests, those using other toxic drugs to liver, those with acute or chronic viral hepatitis, and those with autoimmune hepatitis.
KCFT should be checked very closely.
Leukopenia is rare.
Klinik pratikte Leflunomid, MTX ile kombine olarak daha çok kullanılır. Tek başına da kullanılabilir.

Although leflunomide is claimed to be associated with interstitial lung disease, this issue is still controversial.
Peripheral neuropathy is partially remedied by stopping the drug.
Rash and alopecia are not very serious (10-15%).
Leflunomide may increase the effectiveness of warfarin.
The use of this drug during pregnancy and lactation is contraindicated.

Leflunomide is used more frequently in combination with MTX in clinical practice. It can also be used alone. Leflunomide therapy is preferred in patients who are not suitable for combined triple therapy of MTX-hydroxychloroquine-sulfasalazine and are not suitable for biological agents.

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