Calcipotriol Used In The Treatment Of Psoriasis
Mr. Sameer Lakade
Calcipotriol (calcipotriene) is a vitamin-D3 analogue Calcipotriol has a well-documented effect in the treatment of psoriasis; Calcipotriol is used to treat plaque psoriasis. Plaque psoriasis is a skin disorder caused by cells in the outer layer of the skin multiplying too quickly. As new skin cells are produced, old ones are shed. If this process is taking place too quickly, old skin cells build up on the skin surface causing red, scaly patches. Calcipotriol helps to control psoriasis by slowing down the production of new skin cells.
Psoriasis is a chronic, recurring skin disease cause discomfort, pain and emotional stress. Its scope can vary considerably from mild out breaks, where the person may not even be aware they have psoriasis, to severe cases, which can be socially disable and in rare instances life-threatening. In principle, people of all ages can get psoriasis, but the early-onset form of the disease is mostly seen in 16 to 22-year-olds and the late-onset form strikes those between the ages of 50 and 60. Psoriasis is derived from the Greek word 'psora', which means itch. Around 2 percent of the populations have psoriasis to a greater or lesser degree.1
Causes of psoriasis
Psoriasis is a condition which runs in families, but the exact way in which the disease moves from generation to generation, although the tendency to contract psoriasis is stored in a person's genes, it is by no means certain that it will ever develop. However, exposure to certain stimuli or damage to the skin may cause an outbreak of psoriasis in persons who have this genetic predisposition. There are two main types of psoriasis: psoriasis vulgaris and psoriasis pustulosa. The different types of psoriasis can be divided into subgroups according to severity, duration, location on the body and appearance of the lesions. Around 6 per cent of the people who have psoriasis also get psoriatic arthritis in the joints. Psoriatic arthritis primarily occurs in fingers and toes, but is also quite common in the back bone.2.
Symptoms of Psoriasis Vulgaris
Psoriasis vulgaris is the most common form. The first signs of an outbreak are:
. Red spots or patches.
· The patches grow bigger and become scaly.
· The upper scales fall off in large quantities, while the lower layers of scales are firmly fixed.
· When the scales are scraped off, a number of small, bleeding points can be seen underneath.
· Psoriasis of the nail often manifests itself as small indentures in the nails. The outbreak can be so severe that the nail thickens and crumbles away.
· Flexural psoriasis occurs in skin folds (flexures). Red, itchy plaques appear in the armpits, under the breasts, on the stomach, in the groin or on the buttocks. The plaques are often infected by the yeast-like fungus candida albicans.
· Guttate psoriasis is a special variant which primarily occurs acutely in children and young people due to a streptococcal infection of the throat. Drop-like, scaly patches appear on the entire body. In many cases, the condition disappears by itself after a few weeks or months.
· Psoriasis of the scalp can be difficult to distinguish from a severe case of cradle cap, and sometimes the two occur simultaneously. An outbreak of psoriasis often leads to lesions on the face. 3
Symptoms of Postural Psoriasis
Postural psoriasis is a rare variant where the inflammation is so severe that, in addition to the usual lesions, blisters or pustules containing fluid appear on the skin. The severity of the condition varies.4
Treatment of Psoriasis:
Psoriasis continues to be one of the more difficult skin conditions to treat. The wide range of treatments available for psoriasis illustrates this; no one treatment will work for everyone. There is no cure for psoriasis but several new medications have recently been introduced and ongoing research looks promising. In general the treatment is chosen on the basis of the pattern of psoriasis and its severity. Sometimes several treatments may need to be tried before the most suitable regime is established. Different medications may need to be used together or in rotation for best effect or to minimize side effects.5
Calcipotriol is belongs to the group of medicines known as vitamin D analogues used to treat plaque psoriasis. Plaque psoriasis is a skin disorder caused by cells in the outer layer of the skin multiplying too quickly. As new skin cells are produced, old ones are shed. If this process is taking place too quickly, old skin cells build up on the skin surface causing red, scaly patches. Calcipotriol helps to control psoriasis by slowing down the production of new skin cells. Approximately 2 percent of adults in the India
are affected by psoriasis. The condition cannot be cured. Although many treatment options are available to control symptoms and minimize the impact of psoriasis on daily activities, effective treatment of patients with psoriasis remains a challenge. Currently, calcipotriol (a synthetic vitamin D3 analog) is one of the most popular topical treatments for this condition.6
Mode of action of Calcipotriol
Calcipotriol binds to be specific intracellular receptors present in the keratinocytes.The receptor- vitamin- D complex binds to a specific gene the DNA that modulates and controls transcription. The receptor is present in human epidermal keratinocytes, dermal fibrinoblasts and lymphocytes. At appropriate concentration, calcipotriol causes a decrease in the proliferation and an increase in the morphologic and biochemical differentiation of keratinocytes, hence regulate their proliferation and differentiation. Calcipotriol competes with calcitriol in binding with these receptors when applied topically over a psoriatic skin. 7
Pharmacokinetics of Calcipotriol
The extents of absorption of calcipotriol are influenced by the site of application. Measurements of radioactivity in blood, urine and faces showed approximately 5.5 percent of a dose of H- radiolabel.Calcipotriol was absorbed after application of 2.5 grams of formulation containing 50 ugs/gm to the backs of healthy volunteers and to lesions in patients with psoriasis for 12 hrs. This increased to 6.1 % treatment for two weeks. The drug is metabolized rapidly after absorption. Studies have shown rapid clearance of calcipotriol and hepatic conversion to metabolites. The metabolites of calcipotriol are less active in cell proliferation and differentiation then calcipotriol. Calcipotriol is 200 times less potent then 1, 25-(OH) 2 D, calcipotriol, in causing hypercalciurea and hypercalcemia; however, its affinity for the vitamin D receptor is equal to it.8
Major regulatory action of calcipotriol on psoriatic skin
It reduces the epidermal cell proliferation and initiate normal cell differentiation these effects of the topically applied calcipotriol on the psoriatic skin are similar to those of calcitriol. Flow cytometric analysis has been used to differentiate epidermal cell type and has shown significant decreases relative to placebo in numbers of proliferating basal keratinocytes psoriatic skin treated with topical calcipotriol.9
Calcipotriol is sometimes also helpful in the following skin conditions:
·Epidermal naevi 10
How does Calcipotriol work
Calcipotriol is a medicine that is a derivative of vitamin D. When applied to the skin it works by reducing the production of skin cells. In psoriasis, the scaling and thickening of the skin and the appearance of raised plaques are the result of excessive skin cell production in this disease. Calcipotriol reduces the excessive skin cell production and therefore helps improve the symptoms of psoriasis.11 Calcipotriol is available as an ointment or cream for psoriasis plaques on the body, and as a scalp solution for easier application to psoriasis on the scalp.12
- If patients are pregnant, trying for a baby or breast-feeding
- If patients suffer from the skin condition called pustular psoriasis
- If patients have any problems with the levels of calcium in your body
- If patients have ever had an allergic reaction to this or any of the ingredients listed on the packaging of this preparation.13
- If patients are using or taking any other preparations, including those available to purchase without a prescription, herbal and complementary medicines
- Calcipotriol should not be applied to the face. If it does come into contact with your face, wash it off straight away.
- Try to avoid applying this preparation to non-affected, healthy skin
- Avoid contact with the eyes, if any of this preparation gets into the eyes rinse thoroughly with warm water.14
Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine.
- Itching (pruritus)
- Abnormal reaction of the skin to light, usually a rash (photosensitivity)
- Flushing of the skin due to widening of the small blood vessels (erythema)
- Worsening of the skin condition psoriasis
- Inflammation of the skin (dermatitis)
- Irritation in area of use.15
Pregnancy and Brest feeding
Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby.16
In this present report, emphasis calcipotriol is an effective treatment in patients with mild to moderate chronic plaque psoriasis and is more effective than many alternative medications, including several forms of steroids. Only highly potent topical corticosteroids provide comparable efficacy after eight weeks of therapy. While calcipotriol therapy avoids the many potential adverse effects of corticosteroids, it is associated with skin irritation in a greater number of patients.
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11.Tham SN, Lun KC & Cheong WK. A comparative study of calcipotriol ointment in chronic plaque psoriasis. Br J Dermatol, 1994, 673-677.
12.Kragballe K & Gjertsen BT,Hoop D, Karlsmark T, Kerkhof PC, Larko O, Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris, Lancet, 1991,337,193-6.
13.Ramsay CA. Management of psoriasis with calcipotriol used as monotherapy. J Am Acad Dermatol, 1997, 37, 53-54.
14.Lyn C., Calcipotriene/betamethasone dipropionate: a new topical ointment for psoriasis Expert Review of Dermatology, December 2006, 6, 791-797
15.Katz HI, Hien NT, Prawer SE, Mastbaum LI, Mooney JJ& Samson CR., Superpotent topical steroid treatment of psoriasis vulgarisclinical efficacy and adrenal function, J Am Acad Dermatol, 1987, 16, 804-811.
Mr. Sameer Lakade Lcturer in Pharmaceutics Modern College of Pharmacy, Yemuna Nagar Nigdi, Pune. E- Mail: Sameer_patil97@rediffmail.com
Mr. Vitthal Chopade, Lcturer in Pharmaceutics Modern College of Pharmacy, Yemuna Nagar Nigdi, Pune. E- Mail: email@example.com.