Methotrexate psoriasis

The main folate antagonist is methotrexate, an analogue of folic acid. Methotrexate competitively inhibits dihydrofolate reductase, the enzyme responsible for the synthesis of purine and pyramidine from folic acid. Trimetrexate, a methotrexate analogue, is useful in treating methotrexate-resistant tumours. It is also used to treat Pneumocystis carinii infections. Methotrexate is usually given orally, but may also be given intravenously or intrathecally. In addition to its use in cancer therapy, it is used in the treatment of psoriasis. Methotrexate can cause an obstructive nephropathy due to its precipitation in the renal calyx. 

Adalimumab (Humira ) is a folly human anti-TNF monoclonal antibody that is mainly used in combination with methotrexate to treat rheumatoid arthritis in adults [3]. Meanwhile, it is also used against arthritis of psoriasis and ankylosing spondylitis. Its therapeutic value in Crohn s disease is under clinical trial. 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Infliximab (Remicade) is a chimeric monoclonal antibody directed against TNF-a. Recently, its indications have been expanded to include psoriatic arthritis and treatment of adults with chronic severe plaque psoriasis. An advantage over other systemic psoriasis treatments is that infliximab does not adversely affect blood counts, hepatic enzyme levels, or kidney function. The recommended dose is 5 mg/kg as an IV infusion at weeks 0, 2, and 6, then every 8 weeks thereafter. For psoriatic arthritis, it may be used with or without methotrexate. Adverse effects include headaches, fever, chills, fatigue, diarrhea, pharyngitis, upper respiratory and urinary tract infec-... 

Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can be administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral folic acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

Thioguanine is a purine analog that has been used as an alternative treatment for psoriasis when conventional therapies have failed. The typical dose is 80 mg twice weekly, increased by 20 mg every 2 to 4 weeks the maximum dose is 160 mg three times a week. Adverse effects include bone marrow suppression, GI complications (e.g., nausea, diarrhea), and elevation of liver fimction tests. 6-Thioguanine may be less hepatotoxic and therefore more useful than methotrexate in hepatically compromised patients with severe psoriasis. 

Hydroxyurea inhibits cell synthesis in the S phase of the DNA cycle. It is used selectively in the treatment of psoriasis, especially in those with liver disease who would be at risk of adverse effects with other agents. However, it is less effective than methotrexate. The typical dose is 1 g/day, with a gradual increase to 2 g/day as needed and as tolerated. Adverse effects include bone marrow toxicity with leukopenia or thrombocytopenia, cutaneous reactions, leg ulcers, and megaloblastic anemia. 

UVB light (290 to 320 nm) therapy is an important phototherapeutic intervention for psoriasis. The most effective wavelength is 310 to 315 nm, which led to development of a UVB narrowband light source, in which 83% of the UVB emission is at 310 to 313 nm. Topical and systemic psoriatic therapies are used adj unctively to hasten and improve the response to UVB phototherapy. Emollients enhance efficacy of UVB and can be applied just before treatments. Combining short-contact anthralin, calcipotriene, or topical retinoids to UVB may also improve results. However, topical application should be done after or at least 2 hours before UVB therapy because phototherapy can inactivate the topical product. UVB phototherapy may also be more effective when added to systemic treatments such as methotrexate and oral retinoids. 

Methotrexate is an antimetabolite chemotherapeutic agent, which may also be used for severe resistant psoriasis. The dose is usually administered orally once a week. Haematological and biochemical parameters are monitored throughout treatment. 

Methotrexate is an antimetabolite of folic acid and has immunosuppressant properties. It inhibits the enzyme dihydrofolate reductase that is required for the synthesis of purines and pyrimidines. It is used in malignant disease, Crohn s disease, rheumatic disease and psoriasis. Folic acid is given with methotrexate to reduce the occurrence of side-effects particularly the risk of mucositis. 

Psoriasis Neoral and Gengraf are indicated for the treatment of adult, nonimmunocompromised patients with severe (ie, extensive and/or disabling), recalcitrant, plaque psoriasis who have failed to respond to at least 1 systemic therapy (eg, PUVA, retinoids, methotrexate) or in patients for whom other systemic therapies are contraindicated or cannot be tolerated. While rebound rarely occurs, most patients will experience relapse with Neoral or Gengraf as with other therapies upon cessation of treatment. 

Hypersensitivity to polyoxyethylated castor oil (injection only see Warnings and Administration and Dosage), cyclosporine, or any component of the products Gengraf and Neoral in psoriasis or RA patients with abnormal renal function, uncontrolled hypertension, or malignancies Gengraf and A/eora/concomitantly with PUVA or DVB, methotrexate or other immunosuppressive agents, coal tar or radiation therapy in psoriasis patients. 

Severe reactions Because of the possibility of severe toxic reactions (which can be fatal), fully inform patients of the risks involved and assure constant supervision. Deaths Use methotrexate only in life-threatening neoplastic diseases, or in patients with psoriasis or rheumatoid arthritis (RA) with severe, recalcitrant, disabling disease that is not adequately responsive to other forms of therapy. Deaths have occurred with the use of methotrexate in malignancy, psoriasis, and RA. Closely monitor patients for bone marrow, liver, lung, and kidney toxicities. 

Pregnancy Fetal death and/or congenital anomalies have occurred do not use in women of childbearing potential unless benefits outweigh possible risks. Pregnant women with psoriasis or RA should not receive methotrexate (see Contraindications). 

Metabolism - Methotrexate undergoes hepatic and intracellular metabolism. The terminal half-life reported is approximately 3 to 10 for patients receiving treatment for psoriasis, RA, or low-dose antineoplastic therapy (less than 30 mg/m ). 

In psoriasis and RA, stop methotrexate immediately if there is a significant drop in blood counts. 

Pleural effusions or ascites In patients with significant third space accumulations, evacuate the fluid before treatment and monitor plasma methotrexate levels. Psoriasis lesions Lesions of psoriasis may be aggravated by concomitant exposure to ultraviolet radiation. Radiation dermatitis and sunburn may be recalled by the use of methotrexate. 

As you might expect, the converse occurs, and the renal elimination of methotrexate, an anti-folate drug used to treat some malignancies as well as, recently, rheumatoid disease and florid psoriasis, may... 

Clinical applications include childhood acute lymphoblastic leukemia, choriocarcinoma, osteosar-com, non-Hodgkin s lymphoma and Burkitt s lymphoma. However methotrexate is also frequently used as an immunosuppressant in diseases such as psoriasis, rheumatoid arthritis and others. 

Of the DMARDs, methotrexate (Rheumatrex) is the most widely prescribed. It is indicated for the treatment of rheumatoid arthritis and psoriasis it is also used for psoriatic arthritis, systemic lupus erythematosus, and... 

Methotrexate is approved for use in severe disabling psoriasis recalcitrant to other less toxic treatments. The standard regimen is similar to low-dose therapy used for the treatment of rheumatoid arthritis (see Chapter 36). Although toxicities are similar to those described in the treatment of other diseases, hepatic cirrhosis and unexpected pancytopenia are of special concern given the chronicity of treatment. 

Methotrexate is one of the few anticancer drugs that can be safely administered intrathecally for the treatment of meningeal metastases. Its routine use as prophylactic intrathecal chemotherapy in acute lymphoblastic leukemia has greatly reduced the incidence of recurrences in the CNS and has contributed to the cure rate in this disease. Daily oral doses of methotrexate are used for severe cases of the nonneoplastic skin disease psoriasis (see Chapter 41), and methotrexate has been used as an immunosuppressive agent in severe rheumatoid arthritis. 

Folic Acid Antagonists. Folic acid antagonists block the biosynthesis of purine nucleotides. Methotrexate (7.76) is the prototypic fohc acid antagonist and functions by binding to the active catalytic site of dihydrofolate reductase, thereby interfering with the synthesis of the reduced form that accepts one-carbon units lack of this cofactor blocks the synthesis of purine nucleotides. As well as being used in the treatment of cancer, methotrexate has been used in the management of rheumatoid arthritis, psoriasis, and even asthma. 

Adalimumab is given subcutaneously and has a half-life of 10-20 days. Its clearance is decreased by more than 40% in the presence of methotrexate, and the formation of human antimonoclonal antibody is decreased when methotrexate is given at the same time. The usual dose in rheumatoid arthritis is 40 mg every other week, although increased responses may be evident at higher dosages. In psoriasis, 80 mg is given at week 0, 40 mg at week 1, and then 40 mg every other week thereafter. 

The compound is approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, plaque psoriasis, and Crohn s disease. It decreases the rate of formation of new erosions. It is effective both as monotherapy and in combination with methotrexate and other DMARDs. 

In patients with psoriasis treated with methotrexate, hepatic damage is common however, among patients with inflammatory bowel disease and rheumatoid arthritis, the risk is significantly lower. Renal insufficiency may increase risk of hepatic accumulation and toxicity. 

Methotrexate Folex, Rheumatrex - Rheumatoid arthritis, psoriasis... 

Although the most common methotrexate dosing regimens for the treatment of rheumatoid arthritis are 15 or 17.5 mg weekly, there is an increased effect up to 30 or 35 mg weekly. The drug decreases the rate of appearance of new erosions. Evidence supports its use in juvenile chronic arthritis, and it has been used in psoriasis, psoriatic arthritis, polymyositis, dermatomyositis, Wegener s granulomatosis, giant cell arteritis, subacute lupus erythematosus, and vasculitis. 

Methotrexate is also used in the treatment of rheumatoid arthritis (Chapter 36 Nonsteroidal Anti-Inflammatory Drugs, Disease-Modifying Antirheumatic Drugs, Nonopioid Analgesics, Drugs Used in Gout) and psoriasis. 

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