Psoriasis vitamin

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can he treated adequately with use of topical therapy.1 Topical therapies include corticosteroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pime-crolimus.18 Vitamin D3 analogues and topical retinoids all affect keratinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations. 

Vitamin D analogues (calcipotriol, calcitriol, and tacalcitol) are also frequently selected as initial pharmacotherapy in the management of mild to moderate psoriasis.2 These inhibit keratinocyte differentiation and proliferation and maybe antiinflammatory.2 Unlike corticosteroids, tachyphylaxis does not occur with prolonged use. Clearance of lesions should occur after 4 to 6 weeks of treatment.2 Lack of response by 8 weeks... 

The title compound 188, currently under development for the treatment of acne, psoriasis and photoaging via a topical application, has been synthesized161 in two steps by reacting carboxyl-[14C]vitamin A, 189, with ethyl chloroformate and subsequent treatment of the mixed anhydride 190 with acetamidophenol in the presence of a catalytic amount of 4-dimethylaminopyridine (equation 68), Carbon- 14-labelled compound was needed to investigate its metabolism and the extent of systematic adsorption of 188 after dermal application. 

Calcipotriene (Dovonex) is a synthetic vitamin D analog used for mild to moderate plaque psoriasis. Improvement is usually seen within 2 weeks of treatment, and approximately 70% of patients demonstrate marked improvement after 8 weeks. Adverse effects occur in about 10% of patients and include lesional and perilesional burning and stinging. Calcipotriene 0.005% cream, ointment, or solution is applied one or two times a day (no more than 100 g/wk). 

Calcitriol and tacalcitol are other vitamin D derivatives that have been studied for treatment of psoriasis. 

Calcipotriol is a vitamin D derivative used topically for psoriasis. It does not cause skin discoloration and does not stain clothes. 

Phototherapy is the generic term covering therapies which use light either with or without a sensitiser. Those that do not require a sensitiser use the natural chromophores within the tissue to perform this function e.g. treatment of vitamin D deficiency in rickets, and neonatal jaundice). Those that do use an added sensitiser include photochemotherapy (largely psoriasis and skin disorders) and photodynamic therapy (currently mainly cancer). Photodynamic therapy is differentiated from photochemotherapy by its additional requirement for the presence of oxygen at molecular or ambient levels.In this text we will deal only with photodynamic therapy since, at the present time, this is the main driving force in phototherapy. ° ... 

Posner and coworkers have prepared a series of semi-synthetic and synthetic ether and ester-linked dimers that were found to have potent anti-proliferative and antitumour activities in vitro. Some of these trioxane dimers were found to be as antiproliferative as calcitriol, the hormonally active form of vitamin D, which is used to treat psoriasis, a skin disorder characterized by uncontrolled cell prohferation. Of the semi synthetic dimers, a polyethylene glycol-linked dimer 107, with S-stereochemistry at both of the lactol acetal positions, was found to be very anti-proliferative and showed activity against leukaemia and colon cancer cell hues in the National Cancer Institute (NCI), USA 60-cell line assay. 

Calcipotriol, a vitamin D derivative without vitamin D activity is used to treat psoriasis. 

There are many retinol containing preparations to treat vitamin deficiency states. Retinoids are also used to treat dermatological diseases like acne, psoriasis, Darier s disease, and ichthyosis. Tretinoin, all-trans-retinoic acid, is a topical preparation while isotretinoin or 13-cis-retinoic acid, and etretinate are available for oral administration. 

Calcipotriol is a vitamin D3 derivative which is used as a topical agent in the treatment of psoriasis. Although not completely elucidated its mechanism of action seems to be based on inhibition of the proliferation and stimulation of the differentiation of epidermal keratinocytes. Adverse effects include irritation of the skin but also urticarial reactions. Calcipotriol has 100 fold less vitamin D activity as its active vitamin D3 metabolite calcitriol. However, calcipotriol in overdose can cause symptoms of hypercalcemia. 

Calcipotriene (Dovonex), a synthetic vitamin D3 derivative, is indicated for the treatment of moderate plaque psoriasis. Its mechanism of action is unknown, although it competes for calcitriol receptors on keratinocytes and normalizes differentiation. It also has a variety of immunomodulatory effects in the skin. Although the drug can cause local irritation, the most serious toxicities are hypercalciuria and hypercalcemia, which are usually reversible. 

Mechanism of Action A synthetic vitamin Dj analog that regulates skin cell (kerat-inocyte) production and development. Therapeutic Effect Preventing abnormal growth and production of psoriasis (abnormal kerafinocyte growth). Pharmacokinetics Minimal absorption through intact skin. Metabolized in liver. 

The past twenty years have witnessed considerable progress in the synthesis and use of other retinoid-like molecules related to vitamin A. The aromatic retinoid etretin (8.54) and its ester etretinate (8.55) had some effectiveness in the treatment of psoriasis, a disorder of skin. 13-cA-Retinoic acid (isotretinoin) produces sebaceous gland atrophy and could prove useful in the treatment of severe acne vulgaris. Although these compounds have toxic side effects and are not in regular use, they have opened up new therapeutic possibilities. Retinoic acid (tretinoin, 8.56) has been employed in the treatment of acne. 

It is indicated in night blindness, vitamin A deficiency (in infants, in pregnancy, lactation, malabsorption syndrome), for prophylaxis of vitamin A deficiency, acne, ichthyosis, psoriasis, xerophthalmia, Bitot s spots (especially children). 

It is a synthetic vitamin derivative effective in the treatment of plaque type psoriasis vulgaris. Adverse effects include itching and mild irritation. 

Kawaguchi M, Mitsuhashi Y, Kondo S. Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24 OH2D3) combined with thiazide diuretics in a case of psoriasis. J Dermatol 2(X)3 30 801 —4. 

Two vitamin D derivatives, calcipotriol and tacalcitol (Figure 5.107) are widely used in the topical treatment of psoriasis, to inhibit the cell proliferation characteristic of this condition. 

Vitamin A may be helpful in certain diseases of the skin, such as acne, psoriasis, Darier s disease, and ichthyosis. 

The stratum corneum consists of denucleated corneocytes filled with cross-linked proteins, while the intercellular space is occupied by lipids synthesized prior to and during cornification [24], Formation of this barrier relies on the cornification of epidermal keratinocytes, which undergo growth arrest, terminal differentiation, and an epidermal-specific cell death, referred to as planned cell death [25], Abnormalities in any of these programmed events may lead to epidermal disorders such as psoriasis, atopic dermatitis, and cancer. Flowever, biological events that enable basal cells (stem cells) to proliferate, differentiate, and commit planned cell death are still poorly understood [10]. The keratinocyte differentiation process can be stimulated by prodifferentiation agents such as extracellular calcium and 1,25-dihydroxy cholecalciferol (referred to as vitamin D3 hereafter) [23], Aberrant or absent differentiation can be found in other skin disorders such as atopic keratosis, seborrheic keratosis, and rosacea. 

For dermatological treatment the main focus has been on vitamins A and D. Retinoids have been used systemically and topically for the treatment of acne and a variety of hyperkeratotic disorders including psoriasis, ichthyoses, and lichenoid dermatoses as well as skin cancer.1 Vitamin D-analogs are of great importance for the topical treatment in psoriasis. 

In reconstructed human epidermis the presence of vitamin C was required to normalize stratum corneum lipids, which was accompanied by an improvement of skin barrier formation.36 Interestingly the ascorbic acid concentration in the skin of atopic dermatitis37 and psoriatic patients38 measured in vivo by microdialysis was significantly lower than in healthy subjects. In psoriasis there was no significant difference in lesional versus nonlesional skin. There has also been demonstrated a decrease of ascorbic acid concentration in skin with increasing age.39... 

Topical vitamin D analogs as calcipotriol, and tacalcitol are well established, effective and safe preparations for the treatment of psoriasis vulgaris due to their antiproliferative and prodifferentiating effects on keratinocytes.110 They can be used either as monotherapy or in combination with other treatment modalities.111 The main side effect is the increasing risk ofhypercalcaemia with increasing amounts of vitamin D analogs applied to the skin. 

Vitamin D analogs seem to be limited in dermatology to the topical treatment of psoriasis vulgaris, which is not least because of their overall effects on calcium and phosphorus homoostasis. 

Fischer, M., The topical application of vitamin D3-analogues in psoriasis vulgaris, i n Trends inDerma-topharmacy, Trends Clin. Exp. Dermatol., vol. 1, Wohlrab, J., Neubert, R., and Marsch, W., Eds.,... 

Stucker, M. etal., Vitamin B( 12) cream containing avocado oil in the therapy of plaque psoriasis, Dermatology, 203, 141, 2001. 

Vitamin A and its analogues, in particular retinoic acid, are involved in the proliferation and differentiation of epithelial tissues and have continued to be used in the treatment of dermatological disorders such as acne, psoriasis and hyperkeratosis [133, 134]. Currently, much effort is being focused on... 

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