{"id":754,"date":"2020-02-17T21:57:56","date_gmt":"2020-02-17T16:27:56","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=754"},"modified":"2020-02-17T21:57:56","modified_gmt":"2020-02-17T16:27:56","slug":"drugs-used-in-psoriasis","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/drugs-used-in-psoriasis\/","title":{"rendered":"Drugs used in Psoriasis"},"content":{"rendered":"\n<p><strong>Drugs used in Psoriasis<\/strong><\/p>\n\n\n\n<p><strong>Psoriasis-<\/strong> <strong>autoimmune<\/strong> disease&nbsp;<\/p>\n\n\n\n<ul><li>five main types of psoriasis: <strong>plaque, guttate, inverse, pustular, and erythrodermic<\/strong>.<\/li><li><strong>Plaque<\/strong> psoriasis, also known as psoriasis vulgaris, makes up about <strong>90% of cases.<\/strong><\/li><li>Psoriasis is characterized by an <strong>abnormally excessive and rapid growth of the epidermal layer of the skin<\/strong>.<\/li><li>chronic, non-contagious disease of the skin, in which <strong>silvery white masses of epidermic scales<\/strong> are attached, more or less firmly to a reddish vascular base<\/li><li>Sites -knees, elbows, scalp, hands, feet, and lower back.<\/li><li><strong>Skin cells are replaced every 3\u20135 days<\/strong> in psoriasis rather than the usual 28\u201330 days.<\/li><li><strong>premature maturation of keratinocytes<\/strong> induced by an inflammatory cascade in the dermis involving dendritic cells, macrophages, and T cells<\/li><li>These immune cells move from the dermis to the epidermis and secrete <strong>inflammatory chemical signals (cytokines) such as tumor necrosis factor-\u03b1, IL-1\u03b2, IL-6, IL-36 and IL-22<\/strong>.<\/li><li>These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate.<\/li><\/ul>\n\n\n\n<p><strong>Topical corticosteroids<\/strong><\/p>\n\n\n\n<ul><li>Most frequently prescribed medications for treating mild to moderate psoriasis and initially even in severe cases<\/li><li>They <strong>slow cell turnover by suppressing the immune system, which reduces inflammation and itching<\/strong><\/li><li>Low-potency corticosteroid ointments are usually recommended for sensitive areas such as face or skin folds, and for treating widespread patches of damaged skin<\/li><li>Amcinonide 0.1%, betamethasone dipropionate, betamethasone valerate as 0.1%, 0.12% and 1% , halcinonide 0.1%, desoximetasone 0.25% and mometasone furoate<\/li><li><strong>Highest potency is clobetasol propionate 0.05%<\/strong><\/li><li>Systemic therapy with corticosteroids and\/or immunosuppressants is reserved for severe and refractory cases.<\/li><li>S\/e- Thinning of the skin, telangiectasia, systemic side effects such as diabetes, hypertension and HPA suppression<\/li><\/ul>\n\n\n\n<p><strong>Acitretin in Psoriasis<\/strong><\/p>\n\n\n\n<ul><li><strong>second-generation retinoid<\/strong> and a free acid form and active metabolite of its precursor <strong>etretinate.<\/strong><\/li><li>It has the advantage over its precursor of having a much <strong>shorter half-life.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Mechanism of Action<\/strong><\/p>\n\n\n\n<ul><li>acts by <strong>modulating the proliferation of epidermal keratinocytes.<\/strong><\/li><li>In psoriasis, this antiproliferative action <strong>reduces desquamation, erythema, and the overall thickness of the lesion.<\/strong><\/li><li>Acitretin <strong>binds to RAR and RXR nuclear receptors, activating all 3 subtypes (alpha, beta and gamma) and modulating the transcription of the genes<\/strong> that code for various proteins involved in the pathogenesis of psoriasis.<\/li><li>In addition to its direct mechanism of positive transcription, acitretin <strong>also exerts an indirect effect by inhibiting certain genes that regulate proliferation, angiogenesis, and inflammation in psoriasis<\/strong>.<\/li><\/ul>\n\n\n\n<p>Indications<\/p>\n\n\n\n<p>\u2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; severe extensive psoriasis that is resistant to other forms of therapy,<\/p>\n\n\n\n<p>\u2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; palmoplantar pustular psoriasis<\/p>\n\n\n\n<p>Acitretin is not indicated in the treatment of psoriatic arthritis.<\/p>\n\n\n\n<p><strong>Calcipotriene and Calcipotriol<\/strong><\/p>\n\n\n\n<ul><li>synthetic non-hypercalcaemic<strong> vit D analogue<\/strong> effective topically in plaque type psoriasis.<\/li><li>It <strong>binds to the intracellular vit D receptor in epidermal keratinocytes and suppresses their proliferation<\/strong> while enhancing differentiation.<\/li><li>Benefit in psoriasis is slow; but <strong>most cases respond in 4\u20138 weeks<\/strong>. Response is maintained till treatment is continued.<\/li><li><strong>Combination with a steroid is more effective<\/strong> than either drug alone.<\/li><\/ul>\n\n\n\n<p><strong>Tazarotene<\/strong><\/p>\n\n\n\n<ul><li><strong>synthetic retinoid<\/strong> applied as <strong>a topical gel (0.05\u20130.1%)<\/strong> is moderately effective in psoriasis.<\/li><li>Tazarotene Like other vitamin A derivatives, it normalizes DNA activity in skin cells and may decrease inflammation<\/li><li>Exerts <strong>antiproliferative and anti-inflammatory<\/strong> action by <strong>binding to the intracellular retinoic acid receptor<\/strong> and modification of gene function.<\/li><\/ul>\n\n\n\n<p><strong>Salicylic acid<\/strong><\/p>\n\n\n\n<ul><li>Promotes sloughing of dead skin cells and reduces scaling<\/li><li>Sometimes it&#8217;s combined with other medications, such as topical corticosteroids or coal tar, to increase its effectiveness.<\/li><li>Medicated shampoos and scalp solutions to treat scalp psoriasis<\/li><\/ul>\n\n\n\n<p><strong>Coal tar<\/strong><\/p>\n\n\n\n<ul><li>Thick, black byproduct obtained through distillation of bituminous coal<\/li><li>The polycyclic aromatic hydrocarbons in coal tar make the skin more sensitive to UV light<\/li><li>It reduces scaling, itching and inflammation<\/li><li>It&#8217;s messy, stains clothing and bedding, and has a strong odour<\/li><li>Available in over-the-counter shampoos, creams and oils<\/li><\/ul>\n\n\n\n<p><strong>Calcineurin inhibitors<\/strong> \u2014<\/p>\n\n\n\n<p><strong>Topical tacrolimus 0.1%<\/strong> and <strong>pimecrolimus 1%<\/strong> are effective in the treatment of psoriasis in sensitive areas . Facial and intertriginous areas may be well suited to these treatments, which can allow patients to avoid or minimize chronic topical corticosteroid use<\/p>\n\n\n\n<p><strong>PHOTOTHERAPY<\/strong><\/p>\n\n\n\n<p><strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <\/strong>Induces apoptosis&nbsp; &amp; enhanced transcription and expression of IL-10 in keratinocytes<\/p>\n\n\n\n<p>s\/e &#8211; redness, itching and dry skin<\/p>\n\n\n\n<p><strong>Narrow band UVB therapy(311-313 nm)<\/strong> -More effective than broadband UVB treatment<\/p>\n\n\n\n<p>Usually administered 2 to 3 times a week until the skin improves, &nbsp;then maintenance may require only weekly sessions<\/p>\n\n\n\n<p>Narrow band UVB therapy may cause more severe and longer lasting burns<\/p>\n\n\n\n<p><strong>PUVA <\/strong>(2 to 3 sessions a week) \u2013<\/p>\n\n\n\n<ul><li>Light-sensitizing medication psoralen before exposure to UVA makes the skin more responsive to UVA exposure<\/li><\/ul>\n\n\n\n<p><strong>Psoralen<\/strong> sensitizes the skin to UV rays \u00e0 More aggressive therapy<\/p>\n\n\n\n<p>s\/e &#8211; headache, burning and itching, wrinkled skin, freckles &amp; skin cancer<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td>Patients being considered for treatment with biologics should have severe disease defined by a total psoriasis area and severity index (PASI) score of 10 or more (20 for infliximab)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong>Tumor Necrosis Factor Inhibitors<\/strong><\/p>\n\n\n\n<ul><li>Blockade of TNF-\u03b1 <strong>reduces inflammation, decreases keratinocyte proliferation, and decreases vascular adhesion,<\/strong> resulting in improvement in psoriatic lesions.<\/li><li>Because TNF-\u03b1 inhibitors alter immune responses, patients on all anti-TNF-\u03b1 agents are at <strong>increased risk for serious infection and for malignancies.<\/strong><\/li><li>Other adverse events include <strong>exacerbation of congestive heart failure<\/strong> <strong>and demyelinating disease<\/strong> in predisposed patients.<\/li><li>All patients should be screened for <strong>tuberculosis,<\/strong> history of demyelinating disorder, cardiac failure, active infection, or malignancy prior to therapy.<\/li><li>TNF-\u03b1 inhibitors include monoclonal antibodies directed against TNF-\u03b1 <strong>(adalimumab, infliximab)<\/strong> or a soluble TNF receptor that can bind TNF-\u03b1 <strong>(etanercept<\/strong>)<\/li><li>All TNF-\u03b1 inhibitors are able to bind both soluble and membrane-bound TNF, but the monoclonal antibodies against TNF-\u03b1 with an IgG1 Fc portion are also able to activate complement dependent cytotoxicity on binding of membrane-bound TNF-\u03b1.<\/li><li>This may explain the increased efficacy of these agents in comparison to etanercept for treating granulomatous conditions as well as the higher risk of infection with their use.<\/li><li><strong>Etanercept<\/strong> binds both TNF-\u03b1 and TNF-\u03b2. Etanercept is approved for plaque psoriasis and psoriatic arthritis in adults.<\/li><li><strong>Infliximab<\/strong>, a mouse-human chimeric IgG1 monoclonal antibody directed against human TNF-\u03b1, is approved for treatment of chronic severe plaque psoriasis and psoriatic arthritis. Administration\u00e0<strong>intravenous<\/strong>. <strong>Neutralizing antibodies to infliximab may develop<\/strong> and lead to decreased efficacy over time. Concomitant administration of methotrexate or glucocorticoids may suppress this neutralizing antibody formation.<\/li><li><strong>Adalimumab<\/strong> is a human IgG1 monoclonal antibody directed against TNF-\u03b1; thus, the <strong>risk for development of neutralizing antibodies is reduced<\/strong> compared to infliximab.<\/li><li>Adalimumab is approved for treatment of plaque psoriasis and psoriatic arthritis in adults.<\/li><\/ul>\n\n\n\n<p>Because certolizumab pegol lacks the Fc portion, it is not able to activate complement-mediated cytotoxicity.<\/p>\n\n\n\n<p><strong>METHOTREXATE<\/strong><\/p>\n\n\n\n<p>DHFRase inhibitor \u2013 weekly administration<\/p>\n\n\n\n<p>s\/e &#8211; Myelosuppression, mucositis Hepatotoxicity, pulmonary fibrosis, Nephrotoxicity, neurotoxic&nbsp;<\/p>\n\n\n\n<p><strong>IL-12\/23 Inhibitors- Ustekinumab<\/strong><\/p>\n\n\n\n<ul><li>IL-12 promotes Th1 activity and related TNF-\u03b1 and IFN-\u03b3 production, while IL-23 activates Th17 cells that produce IL-17A, which regulates tissue inflammation and autoimmune responses.<\/li><li>Ustekinumab is approved for treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis.<\/li><\/ul>\n\n\n\n<p><strong>IL-17 Inhibitors- <\/strong>Secukinumab (jan <strong>2015<\/strong>), IXEKIZUMAB (march 2016)<\/p>\n\n\n\n<ul><li>with IL-17 stimulation causing increased keratinocyte expression of inflammatory cytokines and other effects that contribute to epidermal hyperproliferation and<\/li><\/ul>\n\n\n\n<p>barrier dysfunction<\/p>\n\n\n\n<ul><li><strong>Secukinumab<\/strong> &#8211; approved for the treatment of moderate-to-severe plaque psoriasis in adults.<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong><u>IL-17 A RECEPTOR INHIBITOR<\/u><\/strong><strong>&nbsp; &#8211; BRODALUMAB \u2013 <\/strong>Feb 2017 FDA approved. <strong><u>Black box warning-<\/u><\/strong><strong> <\/strong>Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with brodalumab. Prior to prescribing brodalumab, weigh the potential risks and benefits in patients with a history of depression and\/or suicidal ideation or behavior. &nbsp;<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong><u>IL-23 INHIBITOR<\/u><\/strong><strong>&nbsp; &#8211; GUSELKUMAB (<\/strong>July 2017<strong>)<\/strong><strong><u>IL-23 INHIBITOR<\/u><\/strong><strong>&nbsp; &#8211; Tildrakizumab (<\/strong>March 2018<strong>)<\/strong>for the treatment of moderate to severe plaque psoriasis<em>selectively blocks interleukin (IL)-23.<\/em><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong><u>Certolizumab pegol \u2014<\/u><\/strong>TNF-alpha inhibitorIn 2018, the FDA approved the drug for the treatment of adults with moderate to severe psoriasis who are candidates for systemic therapy or phototherapy<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong>PDE4 Inhibitors- Apremilast<\/strong><\/p>\n\n\n\n<ul><li>oral PDE4 inhibitor that increases intracellular cyclic AMP levels, thereby decreasing expression of inflammatory cytokines such as TNF-\u03b1 and IL-23 and increasing expression of anti-inflammatory cytokines such as IL-10.<\/li><li>Apremilast is <strong>approved for treatment of moderate to-severe plaque psoriasis<\/strong> and psoriatic arthritis in adults.<\/li><li>The most common side effects are weight loss and depression.<\/li><\/ul>\n\n\n\n<p><strong>Jak Inhibitors<\/strong><\/p>\n\n\n\n<ul><li>Janus kinases are tyrosine kinases involved in cytokine receptor signaling, and Jak inhibition leads to decreased downstream activity of STAT, which modulates transcription of genes involved in cell growth, proliferation, and differentiation.<\/li><li><strong>Tofacitinib &#8211; oral Jak inhibitor approved for use in rheumatoid arthritis<\/strong> in adults. It has demonstrated <strong>efficacy for psoriasis in clinical trials and for atopic dermatitis in a pilot study.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>IL-4 Inhibitors<\/strong><\/p>\n\n\n\n<ul><li><strong>Dupilumab<\/strong> is a fully human monoclonal antibody against the alpha subunit<\/li><\/ul>\n\n\n\n<p>of IL-4R that inhibits both IL-4 and IL-13 signaling as they each exert their action through binding an IL-4R\u03b1\/IL-13R\u03b11 receptor complex<\/p>\n\n\n\n<ul><li>IL-4 and IL-13 are important mediators of the Th2 immune response that is involved <strong>in acute atopic dermatitis<\/strong>.<\/li><\/ul>\n\n\n\n<ul><li><strong>ALEFACEPT &#8211; <\/strong>blocks the interaction between LFA-3 and CD2 and interfering with T-cell activation<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Drugs used in Psoriasis Psoriasis- autoimmune disease&nbsp; five main types of psoriasis: plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. chronic, non-contagious disease of the skin, in[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/754"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=754"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/754\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=754"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=754"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=754"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}