{"id":8428,"date":"2021-11-25T19:22:33","date_gmt":"2021-11-25T17:22:33","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/rheumatology\/therapeutic-approach-in-rheumatology-nsaid-corticosteroid-disease-modifying-drugs-dmard-conventional-sysnthetic-biological-and-targeted-synthetic-dmards\/"},"modified":"2022-07-19T01:48:50","modified_gmt":"2022-07-18T23:48:50","slug":"therapeutic-approach-in-rheumatology-nsaid-corticosteroid-disease-modifying-drugs-dmard-conventional-sysnthetic-biological-and-targeted-synthetic-dmards","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/rheumatology\/therapeutic-approach-in-rheumatology-nsaid-corticosteroid-disease-modifying-drugs-dmard-conventional-sysnthetic-biological-and-targeted-synthetic-dmards\/","title":{"rendered":"Therapeutic approach in rheumatology: NSAID, corticosteroid, disease modifying drugs (DMARD): conventional sysnthetic, biological and targeted synthetic DMARDS"},"content":{"rendered":"<span class=\"block-heading\" id=\"header_1\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">NSAIDs<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<p class=\"wp-block-paragraph\">NSAIDs are widely used for reducing inflammation, analgesia, and reducing fever.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>NSAIDs can be administered systemically (oral, IV, suppository), or locally (gel, ointment).<\/li><li>The combination of two systemic NSAIDs is contraindicated.<\/li><\/ul>\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\">Mechanism of action<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<p class=\"wp-block-paragraph\">They work by inhibiting the activity of COX and LOX enzymes, which reduces the production of prostaglandins and leukotrienes, leading to a reduction in inflammation.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>There are three isoforms of the COX enzyme, with the important ones being COX-1 and COX-2.<\/li><li>COX-1 enzyme is important for many physiological processes required for the maintenance of homeostasis, while COX-2 is mostly involved in inflammation.<\/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\">Selectivity and examples<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<p class=\"wp-block-paragraph\">There are a variety of groups of NSAIDs, and they are generally classified based on whether they are <strong>non-selective <\/strong>(deactivate both COX-1 and COX2), or <strong>selective <\/strong>(higher affinity to COX-2).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Examples for non-selective NSAIDs:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Paracetamol (500mg, max 4g\/day)<\/li><li>Ibuprofen (200mg, max 1200mg\/day)<\/li><li>Diclofenac (50mg, max 150mg\/day)<\/li><li>Naproxen (max 1500mg\/day)<\/li><li>Piroxicam (max 20mg\/day)<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Selective COX-2 inhibitors (COXIBs) have a significantly reduced risk for gastric ulcers but they have a higher risk of cardiovascular adverse effects, and some of them have been withdrawn due to that (for example, VIOXX).<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Etodolac (400mg, max 1200mg\/day)<\/li><li>Celecoxib (max 400mg\/day)<\/li><li>Etoricoxib (max 120mg\/day)<\/li><\/ul>\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\">Adverse effects<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<ul class=\"wp-block-list\"><li>Gastrointestinal bleeding<\/li><li>Fatal cardiovascular events<\/li><li>Bronchospasm in patients with asthma<\/li><li>Renal damage<\/li><li>Tocolytic effect<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Patients undertaking chronic NSAID therapy should be supplemented with PPIs to reduce the risk for gastric ulceration.<\/p>\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\">Drug interactions<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<ul class=\"wp-block-list\"><li>Increase the effect of coumarin and oral antidiabetics<\/li><li>Decrease the effect of ACE inhibitors and beta-blockers<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_6\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Corticosteroids<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_6\">\n\n\n<p class=\"wp-block-paragraph\">Corticosteroids were first used in patients with RA, dramatically improving their symptoms. They are used as first-line therapy to this day for a variety of inflammatory conditions.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>They can be used systemically (PO, IV) or locally (topical, intra-articular, epidural), and are available at different potencies.<\/li><li>In case of arthritis in one or two joints, an intra-articular injection is a good choice of treatment to reduce the side-effects; in polyarthropathy, however, systemic administration is required.<\/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\">Mechanism of action<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_7\">\n\n\n<p class=\"wp-block-paragraph\">Corticosteroids exert their actions by both acting as a transcription factor inducing anti-inflammatory genes, and by inactivating pro-inflammatory transcription factors.<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_8\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Examples<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_8\">\n\n\n<ul class=\"wp-block-list\"><li>Short-acting, low potency<ul><li>Cortisone (25mg)<\/li><li>Cortisol (20mg)<\/li><\/ul><\/li><li>Medium-acting, medium potency<ul><li>Presnisolone (5mg)<\/li><li>Methylprednisolone (4mg)<\/li><li>Triamcinolone (4mg)<\/li><\/ul><\/li><li>Long-acting, high potency<ul><li>Dexamethasone (0.5mg)<\/li><li>Bethamethasone (0.5mg)<\/li><\/ul><\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The doses written are the minimal doses that can be used for long-term therapy (months-indefinitely). They can be increased if the treatment is planned for a few days (for example, 250mg prednisone as bolus therapy).<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_9\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Adverse effects<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_9\">\n\n\n<ul class=\"wp-block-list\"><li>Fluid retention and edema<\/li><li>Hypertension<\/li><li>Osteoporosis<\/li><li>Gastric ulcers<\/li><li>Glaucoma<\/li><li>Diabetes<\/li><li>Myopathy<\/li><li>Psychosis<\/li><li>Infections<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_10\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">DMARDs<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_10\">\n\n\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><span class=\"block-heading\" id=\"header_11\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Classification<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_11\">\n\n\n<p class=\"wp-block-paragraph\">DMARDs are divided into <strong>synthetic<\/strong> DMARDs (<strong>sDMARDs<\/strong>) which are human-made chemical compounds, and <strong>biologic<\/strong> DMARDs (<strong>bDMARDs<\/strong>), 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 <strong>conventional<\/strong>, and <strong>targeted <\/strong>synthetic DMARDs:<\/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_12\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Conventional synthetic DMARDs and methotrexate<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_12\">\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\n<p class=\"wp-block-paragraph\">Methotrexate is an example for a csDMARD. It 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 a 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<\/span><span class=\"block-heading\" id=\"header_13\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Targeted synthetic DMARDs and tofacitinib<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_13\">\n\n\n<p class=\"wp-block-paragraph\">tsDMARDs are a relatively new group of synthetics DMARDs (although some erroneously refer to them as biological DMARDs) consisting of small molecules that specifically target intracellular transduction pathways such as kinases and phosphodiesterases.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Tofacitinib is an example for a tsDMARD. It is a kinase inhibitor used for the treatment of RA as well as psoriatic arthritis, and ulcerative colitis.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Mechanism of action.<\/strong> Tofacitinib inhibits JAK3 and JAK1, interfering with the JAK-STAT signaling, which are key components in the inflammation pathway.<\/li><li><strong>Dosing<\/strong>. 5mg x2\/day.<\/li><li><strong>Adverse effects<\/strong>. Diarrhea, headaches, hypertension, pulmonary embolism, and increased susceptibility to infections and cancer.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_14\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Biological DMARDs<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_14\">\n\n\n<p class=\"wp-block-paragraph\">bDMARDs, or simply biologics, are drugs produced by living organisms. Most of the bDMARDs are monoclonal antibodies that bind to cytokines or receptors on T or B cells and inhibit their activity. <\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"pure-table\"><thead><tr><th>Target<\/th><th>Examples<\/th><\/tr><\/thead><tbody><tr><td>TNF-alpha<\/td><td>Infliximab<br>Adalimumab<\/td><\/tr><tr><td>IL-1<\/td><td>Canakinumab<br>Anakinra<\/td><\/tr><tr><td>IL-6<\/td><td>Tocilizumab<br>Sarilumab<\/td><\/tr><tr><td>B-cells<\/td><td>Rituximab<br>Belimumab<\/td><\/tr><\/tbody><\/table><figcaption><strong>Table 1. Examples of biologics<\/strong><\/figcaption><\/figure>\n\n\n\n<ul class=\"wp-block-list\"><li>The names of biologics which are <strong>m<\/strong>onoclonal <strong>a<\/strong>nti<strong>b<\/strong>odies all end in -mab.<\/li><li>Biologics are contraindicated for patients with TB or hepatitis. Live and inactivated vaccines are also contraindicated.<\/li><li>Before starting the therapy, bloodwork, liver tests, and a mantoux test (for TB) are required, and they should be repeated every several months.<\/li><li><strong>Adverse effects. <\/strong>Are usually mild, such as irritation in the site of injection, respiratory tract infections, and rarely, malignancy.<\/li><\/ul>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">NSAIDs<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Mechanism of action<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Selectivity and examples<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Adverse effects<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Drug interactions<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Corticosteroids<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Mechanism of action<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Examples<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Adverse effects<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">DMARDs<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Classification<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Conventional synthetic DMARDs and methotrexate<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Targeted synthetic DMARDs and tofacitinib<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Biological DMARDs<\/h4><\/div>","protected":false},"excerpt":{"rendered":"<p>NSAIDs NSAIDs are widely used for reducing inflammation, analgesia, and reducing fever. NSAIDs can be administered systemically (oral, IV, suppository), or locally (gel, ointment). The combination of two systemic NSAIDs is contraindicated. Mechanism of action They work by inhibiting the activity of COX and LOX enzymes, which reduces the production of prostaglandins and leukotrienes, leading [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":8424,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-8428","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>Therapeutic approach in rheumatology: NSAID, corticosteroid, disease modifying drugs (DMARD): conventional sysnthetic, biological and targeted synthetic DMARDS &#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\/rheumatology\/therapeutic-approach-in-rheumatology-nsaid-corticosteroid-disease-modifying-drugs-dmard-conventional-sysnthetic-biological-and-targeted-synthetic-dmards\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"5 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\\\/rheumatology\\\/therapeutic-approach-in-rheumatology-nsaid-corticosteroid-disease-modifying-drugs-dmard-conventional-sysnthetic-biological-and-targeted-synthetic-dmards\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/rheumatology\\\/therapeutic-approach-in-rheumatology-nsaid-corticosteroid-disease-modifying-drugs-dmard-conventional-sysnthetic-biological-and-targeted-synthetic-dmards\\\/\",\"name\":\"Therapeutic approach in rheumatology: NSAID, corticosteroid, disease modifying drugs (DMARD): conventional sysnthetic, biological and targeted synthetic DMARDS &#8211; 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