Basic Pharmacology of Topical Imiquimod, 5-Fluorouracil, and Diclofenac for the Dermatologic Surgeon

Heights Dermatology, Houston, Texas 77008, USA.
Dermatologic Surgery (Impact Factor: 2.11). 10/2011; 38(1):97-103. DOI: 10.1111/j.1524-4725.2011.02194.x
Source: PubMed


Ultraviolet radiation (UVR) contributes to the vast majority of nonmelanoma skin cancer (NMSC). As the incidence of NMSC continues to rise, topical therapies will be used with increasing frequency. Topical therapies may benefit high-risk surgical candidates as an alternative treatment modality and may improve overall cosmesis. The most commonly employed topical therapies are imiquimod, 5-fluorouracil (5-FU), and diclofenac.
To review the detailed mechanism of action and side-effect profiles of each topical therapy used to treat NMSC and to explore newly discovered actions. Uncommon adverse events are also presented.
An extensive literature search was performed to describe the pharmacologic actions of imiquimod, 5-FU, and diclofenac.
A keen understanding of the pharmacologic concepts of these topical therapies may aid the dermatologic surgeon in making sound choices before, during, and after surgery.

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    • "The mechanism of the action of this combined treatment of vitiligo patients may be better understood by briefly summarizing the previous pharmacological, clinical, and experimental studies related to 5-FU. Pharmacologically, 5-FU is an antimetabolite analogue of the naturally occurring pyrimidine uracil which is ISRN Dermatology metabolised via the same metabolic pathways as uracil [9]. Due to its antimitotic activity, it is easy to understand that topical 5-FU is a useful therapy for the treatment of many dermatological disorders characterized by a high mitotic rate (e.g., nonmelanoma skin cancers, actinic keratosis, benign tumours, nail psoriasis, and porokeratosis) [10] [11] [12]. "
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    ABSTRACT: The combination of skin ablation and 5-Fluorouracil (5-FU) ointment was previously tried in the treatment of vitiligo, and good results were specifically reported in glabrous skin without follicular melanocyte reservoirs. Methods. This study was carried out on the skins of seven guinea pigs: three were treated with mechanical dermabrasion plus topical 5-FU in an achromic area contiguous to a pigmented area; two were treated by only dermabrasion in a similar area; and two were treated by topical 5-FU alone. Clinical, histological, and ultrastructural studies were performed over two months. Results. In guinea pigs treated with dermabrasion plus 5-FU, we observed firstly a delay of wound healing with an obvious inflammatory reaction, and, after two months, evident pigment spread from the pigmented into the achromic area. After six months, we noticed black hair regrowing in the achromic area. Pigment spread was not seen in the guinea pigs skin treated by either dermabrasion or topical 5-FU. We suggest that the inflammatory mediators and enzymes (metalloproteinases), which are locally released over a long time, could stimulate and facilitate melanocyte proliferation and migration through the enlarged intercellular spaces of the epidermis. This sequence of events may be applied to vitiligo patients treated with 5-FU on ablated lesions.
    Full-text · Article · Apr 2013
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    ABSTRACT: Skin cancer is the most frequent malignant neoplasm in Caucasians, presenting a constantly increasing incidence and morbidity. The incidence typically depends on ultraviolet radiation levels, however, the increasing number of cases among immunosuppressed patients is a relatively new clinical phenomenon. Surgical excision remains the gold standard in the treatment of non-melanoma skin cancers (NMSC). The aim of the study is to present the procedures, both surgical and nonsurgical, in the therapy of skin cancers. The concept of "fields of cancerisation", as well as non-surgical chemopreventive methods are considered to be relatively new therapeutic approaches. Molecularly guided treatment strategies are developing and will probably be clinically effective in the management of advanced skin cancers.
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    ABSTRACT: Abstract Signal transducer and activator of transcription 3 (Stat3) assumes central functions in the regulation of apoptosis, proliferation, angiogenesis, and immune responses in normal cells. It also plays crucial roles in inflammatory and malignant diseases and in the cellular communication in the tissue microenvironment. Signaling interactions among normal endothelial cells, immune cells, and tumor cells, mediated by the release of cytokines, chemokines, and growth factors, often result in the activation of Stat3 and promotion of cancer cell proliferation, invasion, angiogenesis, and immune evasion. Stat3 also causes the differentiation and activation of T helper 17 (Th17) cells, which is involved, e.g., in psoriasis, an inflammatory autoimmune disease of the skin. Here, we describe molecular characteristics of a mouse model triggered by the treatment of mouse skin with the immune modulator imiquimod. The application of this compound causes the local release of proinflammatory cytokines and symptoms that resemble human psoriasis. We show that this process is accompanied by strong Stat3 activation. We also investigated the effects of a membrane-permeable, peptide-based Stat3 inhibitor, recombinant Stat3-specific peptide aptamer (rS3-PA). This molecule specifically interacts with Stat3 and prevents its transactivation potential in cultured cells. rS3-PA is able to penetrate the skin, enter cells, and reduce the level of activated Stat3. The topical applications of rS3-PA to the skin could thus possibly become useful in the treatment of inflammatory skin diseases and skin cancer.
    Full-text · Article · Jun 2012 · Hormone molecular biology and clinical investigation
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