Topical calcipotriol

Vitamin D3( cholecalciferol) is produced naturally by epidermal keratinocytes and metabolized to the to the biologically active form 1,25(OH)2D3.The therapeutic effect of 1,25(OH)2D3 is limited by its hypercalcimic action . The synthetic analogue of vitamine D3 produced by the modification of the side chain is Calcipotriol which is about 200 times less potent in hypercacemia and hypercalciuria than 1,25(OH)2D3. The calcipotriol is most important synthetic analog of vitamin D3, as it quickly transformed into the inactive metabolites there by reducing the side effects like hypercalcemia and hypercalciuria. which act through antiproliferative and anti-inflammatory effects and stimulates terminal differentiation of keratinocytes by acting through immunologic mechanism and regulating intracellular calcium concentration. In India its available as 50 µg/g ointment.
Mechanism of action
It acts on vitamin D receptor (VDR) which belong to the group of steroid receptor. The biologic actions of the ligands-receptor complex are mediated by binding to DNA sequence within the vitamin D responsive genes. It has inhibitory action on cell proliferation and normalizes cell differentiation in the epidermal layer of skin. It also exerts immunologic effect by acting on the monocytes , macrophages, B & T lymphocytes that expresses the VDR. It also inhibits the thymocyte proliferation induced by IL-1 and the release of IL-6 and interferon-y from activated mononuclear cells. In the psoriatic lesion when its applied it causes progressive reduction in the dermal cellular infiltrate with change in the cell type CD4+ helper cells to CD8+ suppressor cells in the lesion and reducing infiltration of neutrophils.
Indications
It is currently used in psoriasis, vitiligo, morphoea, pityriasis rubra pilaris, ichthyoses and palmoplantar keratodermas
Contraindications
Calcipotriol is contraindicated in hypercalcemia, hypercalciuria, urolithiasis, parathyroid disease, disorders of calcium metabolism, photosensitivity, pregnancy, lactation and concomitant use of vitamin D or calcium or any other drug that affect calcium homeostasis.
Combination of calcipotriol with psoralen UVA
The combination therapy in vitiligo is found to be more effective than PUVA alone. It is advised to apply calcipotriol after UVA exposure because there is a significant decrease in the calcipotriol concentration ranging from 2% to 75% with a mean reduction of 28% if applied before hand.

Mode of application
The Calcipotriol ointment is applied twice daily and application amount should not exceed 100g in adult and 50g in children in a week.
Side effects
Commonly noted side effects noted during the topical application are skin irritation, burning sensation, erythema ,scaling, & stinging sensation. In systemic side effects are hypercalcimia, which is observed, when its application exceeds 100g/week, however the serum level of calcium comes down to normal after discontinuing the drug for a week.

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