{"id":9340,"date":"2021-12-19T00:25:23","date_gmt":"2021-12-18T22:25:23","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/immunology\/immunosuppressive-immunomodulant-therapy-principles-products-metotrexate-azathio-prine-cyclosporine-a-cyclophosphamide-high-dose-ivig-side-effects\/"},"modified":"2022-09-09T15:18:47","modified_gmt":"2022-09-09T13:18:47","slug":"immunosuppressive-immunomodulant-therapy-principles-products-methotrexate-azathioprine-cyclosporine-a-cyclophosphamide-high-dose-ivig-side-effects","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/immunology\/immunosuppressive-immunomodulant-therapy-principles-products-methotrexate-azathioprine-cyclosporine-a-cyclophosphamide-high-dose-ivig-side-effects\/","title":{"rendered":"Immunosuppressive\/immunomodulant therapy (principles, products: methotrexate, azathioprine, cyclosporine-A, cyclophosphamide, high dose IVIG, side effects)"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Disease-modifying anti-rheumatic drugs are a heterogeneous group of drugs that acts on different components of the immune system. They suppress the immune system and slow down the progression of inflammatory and autoimmune diseases, through a variety of mechanisms.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">They were initially named anti-rheumatic for their potential treatment of RA, but they are useful for the treatment of many chronic inflammatory and autoimmune diseases.<\/p>\n\n\n<span class=\"block-heading\" id=\"header_1\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Classification<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<p class=\"wp-block-paragraph\">DMARDs are divided into <strong>synthetic<\/strong> (<strong>sDMARDs<\/strong>) which are human-made chemical compounds, and <strong>biologic<\/strong> (<strong>bDMARDs<\/strong>) DMARDs, which are substances (antibodies and other proteins) produced by living organisms (simply known as <strong>biologics<\/strong>).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">sDMARDs can be further subdivided into:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Conventional synthetic <\/strong>(<strong>csDMARDs<\/strong>)<\/li><li><strong>Targeted synthetic <\/strong>(<strong>tsDMARDs<\/strong>)<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Older DMARDs such as gold salts are no longer in use in most of the world, as newer, safer, and more effective drugs are available.<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Conventional synthetic DMARDs<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<p class=\"wp-block-paragraph\">This group of drugs includes small molecules, usually divided into <strong>cytotoxic<\/strong> and <strong>non-cytotoxic csDMARDs<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Cytotoxic agents<\/strong><ul><li>Methotrexate<\/li><li>Azathioprine<\/li><\/ul><ul><li>Cyclophosphamide<\/li><li>Leflunomide<\/li><li>Myphenolate mofetil<\/li><li>Chloroquine and hydroxychloroquine<\/li><\/ul><\/li><li><strong>Non-cytotoxic agents<\/strong><ul><li>Cyclosporine A<\/li><li>Tacrolimus<\/li><li>Sulfasalazine<\/li><li>Thalidomide<\/li><\/ul><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Methotrexate<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<p class=\"wp-block-paragraph\">Methotrexate is an antimetabolite that is considered the gold standard for the treatment of RA and other chronic inflammatory diseases. It is cheap and relatively safe.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Mechanism of action.<\/strong> MTX inhibits several key enzymes such as DHFR and AICAR, leading to the suppression of inflammatory reactions, T-cell apoptosis and reduced proliferation.<\/li><li><strong>Dosing<\/strong>. As an DMARD, methotrexate is used at a low dose (starting at 7.5mg\/week and slowly increased up to 15-25mg\/week). It is usually taken once-twice a week.<\/li><li><strong>Adverse effects<\/strong>. Nausea, mucosal ulceration, liver damage, anemia, and leukopenia.<\/li><li>Frequent TBC and liver function tests are required for monitoring for the adverse effects.<\/li><li>Folic acid supplementation is required to reduce the adverse effects.<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">References: https:\/\/www.nature.com\/articles\/s41584-020-0373-9<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_4\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Azathioprine<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<p class=\"wp-block-paragraph\">Azathioprine is a prodrug of mercaptopurine, a purine analog functioning as an antimetabolite, inhibiting lymphocyte proliferation. Used in inflammatory diseases and organ transplantation.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Mechanism of action.<\/strong> Inhibits purine synthesis.<\/li><li><strong>Dosing<\/strong>. 100-250mg\/day PO.<\/li><li><strong>Adverse effects<\/strong>. Bone marrow suppression, liver damage, GI disturbances.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_5\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Cyclosporin-A<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<p class=\"wp-block-paragraph\">Cyclosporin-A is an antibiotic used in autoimmune disorders, GVH disease, and organ transplantation.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Mechanism of action<\/strong>. Blocks T-cell activation<\/li><li><strong>Dosing.<\/strong> 125-200mg\/day PO.<\/li><li><strong>Adverse effects.<\/strong> Nephrotoxicity, liver damage, CNS toxicity, increased predisposition to cancer. <\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_6\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Cyclophosphamide<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_6\">\n\n\n<p class=\"wp-block-paragraph\">Cyclophosphamide is a highly-effective immunosuppressant acting against proliferating lymphocytes.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Mechanism of action<\/strong>. Alkylating agent. Adds alkyl groups to guanine bases leading to DNA cross-linking and damage.<\/li><li><strong>Adverse reations<\/strong>. Nausea, hemorrhagic cystitis, cardiotoxicity, electrolyte disturbances.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_7\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Tofacitinib (tsDMARD)<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_7\">\n\n\n<p class=\"wp-block-paragraph\">Tofacitinib is a small synthetic molecule that inhibits JAK (although some refer to it as biological). Most importantly, it inhibits JAK3 and JAK1, important components in the inflammation pathway.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is used for RA as well as other chronic inflammatory diseases.<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_8\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">High-dose IVIG<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_8\">\n\n\n<p class=\"wp-block-paragraph\">IVIG is a biological therapy consisting of pooled antibodies, used in immunodeficiencies, autoimmune disorders, and infections.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">High-dose IVIG is used in autoimmune disorders for the reduction of inflammation and immunomodulation.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Consists of antibodies of 1,000-100,000 donors, mostly IgG.<\/li><li>High-dose IVIG actively modulate the immune system by:<ul><li>Inhibit the activation of the innate immune system, and induction of anti-inflammatory cytokines. <\/li><\/ul><ul><li>Binding autoantibodies and neutralize them.<\/li><li>Binding complement proteins and sequestering them away from autoantibodies.<\/li><\/ul><\/li><li>For autoimmunity, high-dose IVIG is administered in doses of 1-3g\/kg bodyweight per month.<\/li><li>Adverse effects:<ul><li>Mild (headache, fever, chills, fatigue)<\/li><li>Moderate (vomiting, chest-pain)<\/li><li>Severe (anaphylaxis, acute renal failure, thromboemboli, arrhythmias)<\/li><\/ul><\/li><\/ul>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Classification<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Conventional synthetic DMARDs<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Methotrexate<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Azathioprine<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Cyclosporin-A<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Cyclophosphamide<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Tofacitinib (tsDMARD)<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">High-dose IVIG<\/h3><\/div>","protected":false},"excerpt":{"rendered":"<p>Disease-modifying anti-rheumatic drugs are a heterogeneous group of drugs that acts on different components of the immune system. They suppress the immune system and slow down the progression of inflammatory and autoimmune diseases, through a variety of mechanisms. They were initially named anti-rheumatic for their potential treatment of RA, but they are useful for the [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":9306,"menu_order":16,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-9340","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Immunosuppressive\/immunomodulant therapy (principles, products: methotrexate, azathioprine, cyclosporine-A, cyclophosphamide, high dose IVIG, side effects) &#8211; Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/immunology\/immunosuppressive-immunomodulant-therapy-principles-products-methotrexate-azathioprine-cyclosporine-a-cyclophosphamide-high-dose-ivig-side-effects\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/immunology\\\/immunosuppressive-immunomodulant-therapy-principles-products-methotrexate-azathioprine-cyclosporine-a-cyclophosphamide-high-dose-ivig-side-effects\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/immunology\\\/immunosuppressive-immunomodulant-therapy-principles-products-methotrexate-azathioprine-cyclosporine-a-cyclophosphamide-high-dose-ivig-side-effects\\\/\",\"name\":\"Immunosuppressive\\\/immunomodulant therapy (principles, products: methotrexate, azathioprine, cyclosporine-A, cyclophosphamide, high dose IVIG, side effects) &#8211; 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