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09 Review Acitretin in Dermatology Bangladesh Med J. 2016 May; 45 (2) Review Article 5. Other dermatoses, e.g. DLE, Lichen Sclerosus, Discussion 2. Tavakkol A. Griftiths CEM, Keane KM. Cellular 10. Torok L. Kadar L, Geiger J M. Acitretin in treatment of Granuloma anulare Acitretin is highly teratogenic and hence contraindicated in localization of mRNA for cellular retinoic acid-binding severe psoriasis. Acta Dermato Venereologica. 1989; Acitretin in dermatology – A review Women of Childbearing potentials unless pregnancy is protein II and nuclear retinoic receptor-gamma I in 146:104-6. Contraindications of Acitretin reliably prevented 4 weeks before, during and 2 years after retinoic acid-treated human skin. Journal of 1 2 Acitretin is absolutely contraindicated in pregnancy. Bhuiyan ZH , Chowdhury MUK the completion of therapy.12 Clinical evidence has shown Investigative Dermatology. 1992; 99:146-150. 11. Berbis P, Geiger J M, Vaisse C. Benet of progressively Pregnancy is also contraindicated in the two year period that etretinate can be formed with concurrent ingestion of increasing doses during the initial treatment with Introduction Pharmacology after stopping therapy with Acitretin. Relative 3. Blomho HK. Smeland EB, Erikstein B. Vitamin A is acitretin and alcohol. Women of childbearing age must acitretin in psoriasis. Dermatologica. 1989; 178:88-92. Acitretin is a weak acid (pka = 5) and is highly lipophilic, Retinoids by acting upon nuclear receptor aect epidermal contraindications include hepatitis and liver disease a key regulator for cell growth. Cytokine production therefore not consume alcohol (in drink, food or medicine) with a partition coecient (log p) of approximately 6. cell growth and dierentiation as well as sebaceous gland concomitant other diseases e.g. serious retinal disorder, and dierentiation in normal B cells. Journal of 12. Kopan R Fuchs. E 1987 Retinoids as important 1 during treatment with acitretine and for 2 months after Biological Chemistry. 1992; 267:23988-92. Acitretin is normally administered by oral route with food. activity, and also have anti-inammatory properties. diabetes, hyperlipidemia, pancreatits, inammatory bowel regulators of terminal dierentiation: examining cessation of therapy.13 Contraceptive measures and Following administration in this way, the compound is Retinoid X receptor(RXR) and retinoic receptor(RAR) disease. 4. Vane F M, Bugge C J, Rodriguez LC. Identication of keratin expression in individual epidermal cells at pregnancy tests must also be taken for 2 years after relatively rapidly and extensively absorbed from the activate gene transcription by binding to DNA as etretinate metabolites in human bile. Drug various stages of keratinization.Journal of Cell Biology Adverse events during clinical trails completion of acitretin treatment. intestinal tract. e half-life of absorption is 0.2-1.7h. At homodimers or as heterodimers with Vitamin D, thyroid Metabolism and Deposition. 1989,17: 270 - 5. 105:427-440. least 93% of a dose is absorbed over 18 days, the majority hormone or peroxisome- ptoliferator-activated receptors etc. Very common: Over 80% of patients experienced In view of possible eects on Liver function this must be 5. Vahlquist A. Etretinate pharmacokinetics in chronic fairly rapidly. Taking acitretin with food results in increased Skin mainly expresses RAR gama and RXR alpha receptors. hypervitaminosis A e.g. dry lips. 40-80% of patients 13. Bryan PD, HonigbergLL, MellzerNM. Electrochemical monitored regularly during treatment. Hepatic function renal failure. A preliminary study in psoriasis patients. and more consistent absorption. As it is highly lipophilic ere are many consequences including repression of experienced dry mucous membranes of mouth and nose. detection of retinoids using normal phase HPLC. should be checked before starting treatment with Acitretin Dermalogics. 1987; 175:224-8. and penetrates readily into body tissues. Protein binding of Interleukin-2 formation as a result of these nuclear events. 10-40% of patients experienced nose bleed, erythema, every 1-2wks for the rst 2 months after commencement Journal of Liquid Chromatography. 1991; 14: 8-10 6. Brindley CJ. Overview of recent clinical acitretin exceeds 99%. In animal studies, acitretin passed the pruritus, dermatitis, hair loss. and then every 3 months during treatment.14 If abnormal 2287-2295. Clinical Pharmacology pharmacokinetics studies with acitretin, etretinate placentral barrier in quantities sucient to produce fetal results are obtained wkly checks should be monitored. 2-4 Acitretin has been much less studied than its esteried Common: Up to 10% of patients experienced development Dermalogics. 1988;178:79-87. 14. Disdier B, Bun H, Catalin J Durand A. Simultaneous malformation. Due to its lipophilic nature, it can be Serum cholesterol and Serum triglycerides (fasting values) parent compound etretinate but as the latter is rapidly of rhagades, blistering of the skin, and change in hair determination of all trans-13-cis.9-cis-retionic acid and assumed that acitretin passes into breast milk in considerable must be monitored, especially if high risk patients 7. Kingston P, Matt LH, Lowe NZ. Etretinate the therapy hydrolyzed in vivo to acitretin it is highly likely that the data structure. their 4-oxo-metabolites in plasma by high- quantities. (disturbance of lipid metabolism, diabetes mellitus, obesity, for severe psoriasis. Archives of Dermatology. 1987; relating to etretinate are also valid for acitretin. In Psoriasis; performance liquid chromatography. Journal of Rare: Conjunctivitis, ulcer of the Cornea, myalgia , nausea, alcoholism) and during long-term treatment.e eect of 123:55-8. Chemistry Where epidermopoiesis is accelerated and Keratinocyte vomiting, diarrhea, hepatitis and jaundice. UV light is enhanced by retinoid therapy, therefore patients Chromatography B Biomedical Application. 1996; Acitretin is a yellow-to greenish crystalline powder which maturation is down regulated retionoids produce a 8. Lassus A. Geiger J M, Nyblom M. Treatment of severe should avoid excessive exposure to Sunlight and 683:143-4. may have faint odor. It is made by chemical synthesis. It is normalizing eect. e suppression of terminal Investigations psoriasis with etretin. Brirish Journal of Dermatology. unsupervised use of Sun Lamps. 1987; 117:333-341. only very slightly soluble in water but at pH 7.5 (the pH of dierentiation is probably of prime importance in the In addition to a possible increase in liver function values, an 15. Schroder L, Zaun H, Holzmann H. Pustulosis intestinal contents), it is slightly soluble. Chemical name is therapeutic eect of retinoids in psoriasis. Clinical studies elevation of blood lipids has also been observed during Acitretin has moderate inuence on the ability to drive and 9. Paravicini U. On the metabolism and pharmacokinetics palmoplantaris: clinical and histogical changes during (4- Methoxy-2, 3, 6-trimethyl pheny1)-3, 7- dimethyl-2, 4, have conrmed that in psoriasis and dyskeratosis, acitretin treatment with Acitretin.11 use Machines.15 Decreased night vision has been reported of an oral aromatic retinoid. Annals of the New York Retretin (acitretin) therapy. Acta Dermato- 6, 8-nonatetraenoic acid (Figure-1) brings about a normalization of epidermal cell proliferation, with acitretin therapy. e high risk groups of Acitretin Academy of Sciences. 1981;359:54-67. Venereologica. 1989; 146:111-6. e following changes in laboratory values occurred in dierentiation and keratinization in doses at which the side therapy are as: Neonates, Children, pregnant women, patients during clinical trials - elevation of triglycerides, total eects are generally tolerable. e eect of Acitretin is purely elderly. CH3 CH3 CH 3 symptomatic; the mechanism of action is still largely cholesterol, SGPT, creatine phosphokinase, SGOT, alkaline phosphatase, direct bilirubin, lactate dehydrogenase and Retinol (vitamin A) is known to be essential for normal H3C COOH unknown. uric acid; and lowering of HDL cholesterol. epitheliating growrh and dierentiation, through the mode Metabolism of this eect is not yet established. Both retinol and retinoic Drug Interactions Acitretin is extensively metabolized, presumably in the liver. acid are capable if reversing hyperkeratotatic Skin changes. CH3O CH3 No unchanged acitretin or 13-cismetabolite is excreted in Potential hazardous interactions have been found with the urine. e metabolites of acitretin are excreted to following drugs. However, these eects are generally only obtained at dosages Figure-1: Chemical composition of Acitretin approximately equal extents in the urine feces. A small associated with considerable local or systemic toxicity. 1. Oral Contraceptives amount of acitretin is converted by esterication into Acitretin the active ingredient of Acitretin, is a systemic etretinate(the ethyl ester) which is much more lipid soluble 2. Glyburide analogue of retinoic acid and the main metabolite of 1. *Dr Zahid Hossain Bhuiyan, Associate Professor of etretinate, which has been used with success for a number of than the parent compound and persists for much longer in 3. Alcohol Dermatology, MH Samorita Medical College & the body, particularly in fatty tissue.5-7 years in the treatment of Psoriasis and disorders of Hospital, Dhaka 4. Dexamethasone Keratinisation. 2. Professor Dr MU Kobir Chowdhury, Head of the Indications of Acitretine 5. Methotrexate References Department of Dermatology, MH Samorita Medical 1. Psoriasis 6. Tetracyclines College & 2. Disorders of Keratinization
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