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Retinoids in dermatology seminar

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Retinoids in dermatology seminar

  1. 1. DR.AARYA.S MODERATOR-DR .JAYASHREE NAYAK RETINOIDS IN DERMATOLOGY
  2. 2. DISCUSSIONS • HISTORY • STRUCTURE • NATURAL RETINOIDS AND CAROTENOIDS • MECHANISM OF ACTION • CLASSIFICATION • EFFECT OF RETINOIDS ON HUMAN BODY • INDIVIDUAL DRUGS • SIDE EFFECTS,DRUG INTERACTION • NEWER RETINOIDS
  3. 3. RETINOIDS • All synthetic and natural compounds that have biological activity similar to Vitamin A.
  4. 4. HISTORY • First dermatological use 1943 by Straumford for acne vulgaris • 1962Stuttgen –Therapeutic effectiveness of topical tretinoin for keratinisation disorders. • 1969Kligman and colleguestopical tretinoin for Acne vulgaris. • 1955Isotretinoin first synthesised in Europefirst used for disorder of keratinisationacne vulgaris. • 1982FDA approved isotretinoin for severe nodulocystic acne
  5. 5. • 1972Bollag discovered etretinate and Acitretin • 1986 Etretinate used for PSORIASIS • 1988Etretinate phased out ,replaced by ACITRTETIN. • 1999Bexarotene approved for CTCL • 1999Alitretinoin approved for KAPOSI SARCOMA
  6. 6. STRUCTURE Cyclohex enyl Ring Conjugat ed Side Chain Polar Terminal Group
  7. 7.  All classes of Retinoids : basic sructure of Vit A with modifications 1st gen. Retinoids 2nd gen. Retinoids 3rd gen Retinoids Change of Polar end group & polyene side chain Replacing cyclic end group of Vit A with subsituted & non subsituted ring systems. Cyclization of polyene side chain.
  8. 8. NATURAL RETINOIDS  Daily requirement: 0.8-1mg/ 2400-3000IU  FUNCTIONS : Retinal(as 11-cis &11-trans isomer) : in Visual function Retinol : in Reproduction Retinoic acid : in Epithelial differentiation & normal growth
  9. 9. VITAMIN A
  10. 10. CAROTENOIDS  Organic pigments : Naturally occurring in chlorophyll & chromoplast of plants .  They are not biologically active until converted to one of the retinoids in the body .  1 mol. Of β carotenes = 2 mol. of retinal.  Found in vegetables and fruits.  Ex : Carotene α, Carotene β, Lutein, Lycopene, Zeaxanthin
  11. 11. VITAMIN A RICH FOODS
  12. 12. ABSORBTION AND DISTRIBUTION • BA fatty foodmax Acitretin and Bexarotene • Serum transporter albumin . • Storge ito cells hepatocytes • Cytosolic transporter CRABP1Modulates level of RA in tissues. • CRABP 2 Human epidermisepidermal differentiation. • RA predominantly all trans RA (ATRA)
  13. 13. ISOTRTINOIN and ACITRETIN water soluble,less deposition ETRETINATE -LIPOPHILIC
  14. 14. Retinol
  15. 15. • 1. Isotretinoin • oxidation 4 oxo isotretinoin 2. Etretinate Hydrolysis Acitretin Isomerization Cis isomer • β-glucoronide derivatives (13 trans and 13 cis acitretin) Demethoxylation
  16. 16. RETINOID RECEPTORS  Belongs to Steroid thyroid hormone receptor superfamily  Exists as α, β, γ types  Human skin mainly contains RXRγ & RARα
  17. 17. BASIC PRINCIPLES: RETINOID RECEPTORS RARs and RXRs are ligand-dependent transcription factors that regulate gene expression in two ways:  Upregulate expression of genes by binding to RARE located in the promoter region of target genes  Downregulate expression of transcription factors such as AP1.
  18. 18. CLASSIFICATION OF RETINOIDS
  19. 19.  Non-Aromatic Retinoids Tretinoin (all-trans retinoic acid) Isotretinoin (13-cis retinoic acid) Alitretinoin (9-cis retinoic acid) All-trans Retinoyl B-glucornide Fenretinide Ist GENERATION
  20. 20.  Monoaromatic Retinoids Etretinate Acitretin Motretinide 2nd GENERATION
  21. 21. • POLYAROMATIC RETINOIDS BEXAROTENE TAZOROTENE TAMIBAROTENE(Am-80) AROTINOID SULFONES Adapalene:- naphtoic acid derivative have properties of retinoids,not in 3 generations 3rd GENERATIONS
  22. 22. Newer retinoids • Seletinoid –G :-4th generation • Arotinoids The effects of a novel synthetic retinoid, seletinoid G, on the expression of extracellular matrix proteins in aged human skin in vivo,2005
  23. 23. 1.Epithelial differentiation 2.Sebolytic 3.Synthesis of dermal matrix 4.Anti inflammatory 5.Angiogenesis 6.Immunomodulation 7.Melanotrophism 8.Morphogenesis
  24. 24. EFFECTS ON EPIDERMAL GROWTH AND DIFFERENTIATION • Modulate the growth and differentiation. • Have actions on cultured keratinocytes and invivo human skin. • Promote cell proliferation in normal epidermis • Normalisation of hyperkeratotic skin. • TGF –α,EGF,c AMP mediated cell growth,TGF-β2 mediated cell growth.
  25. 25. • Reduction of tonofilaments, corneocyte cohesiveness,impaired function of the permeability barrier, TEWL NORMALISE HYPERPROLIFERATIVE EPIDERMIS,DESQUAMATION AND PEELING
  26. 26. EFFECTS ON SEBACEOUS GLANDS • ISO>>ACI>ETRETINATE • Reduce gland size by 90% decr proliferation of sebocytes and suppressing sebum production. • Oral isodecr TAG , free sterols and ceramide in sebum. • 80% in local DHT pdn and 2x androgen binding capacity • Mechanism unknown-not receptor mediated.
  27. 27. IMMUNOMODULATORY AND ANTI INFLAMMATORY • Inhibits Proinflammatory cytokines and enzymes of Phagocytosis • ↑ cell surface antigens of T cells and NK cells • Inhibition of Transcription factor AP-1 • ↓ Neutrophil migration, leukotriene B4 mediated chemotaxis, NO, TNFα levels • Psoriasis : ↑ IL6, IL8, ICAM1
  28. 28. ANTI PSORIATIC ACTION • Reduce the proliferation rate by downregulating the no of cycling cells • Promote terminal differentiation and filaggrin synthesis • Regulate desquamation of corneocytenormalise TG Levels. • Modulation of lymphocyte functions and inhibition of neutrophilic migration. • Effects seen over 6-12 weeks
  29. 29. ANTI TUMOR EFFECTS • Retinoid induced apoptosis : • Regulation of expression of apoptosis linked gene products: BCL-2, tissue transglutaminase • Activation of tumour suppressor genes, viz. p21, p38, p53 • ↑ Caspase proteolytic activity • Inhibition of AP-1 • SPHINGOMYELINcontrol proli n differentiation • intracellular ceramideinhibit proliferation,induction of differentiation and apoptosis
  30. 30. EFFECTS ON INTERCELLULAR MATRIX COMPONENTS • Physiological conc : promote wound healing • ↑ MPS, collagen, fibronectin & GAG, ↓ collagenase • Supraphysiologic conc: inhibit wound healing • ↓ fibroblast prolif, ↓ collagen 1 & 3, ↓ GAG
  31. 31. EFFECTS ON EMBRYONIC DEVELOPMENT • Vit A & retinoids needed for formation of face, heart, eye, limb & nervous system • All RAR agonists – strong teratogens • All RXR agonists – low to absent teratogenic response • Retinoids not binding to RAR/RXR – likely non teratogenic
  32. 32. CLINICAL USES –TOPICAL FDA APPROVED TOPICAL RETINOIDS ALL TRANS RETINOIC ACIDAcne vulgaris,fine rytids,mottled pigmentation,tactile roughness of facial skin ADAPALENEAcne vulgaris TAZOROTENEAcne vulgaris,Psoriasis (<20%) ALITRETINOINAIDS related kaposi sarcoma BEXAROTENECTCL (Stage 1A & 1B)
  33. 33. CLINICAL USES –ORAL RETINOIDS
  34. 34. OTHER USES-NON FDA FOLLICULAR DISORDERS 1.Acne related conditionGram neg follicuitis,HIV associated eosinophilic folliculitis,Acne with solid facial edema 2.rosacea papulopustular,granulomatous 3.HIDRADENITIS SUPPURATIVA 4.DISSECTING CELLULITIS OF SCALP
  35. 35. CHEMOPREVENTION OF MALIGNANCY 1. Organ transplantation 2. Syn with risk of cutaneous malignancy a) Bazex syndrome b) Nevoid BCC c) Kaposi sarcoma d) Frequent BCC/SCC
  36. 36. DISORDERS OF KERATINISATION 1. DARIER’S DISEASE 2.ICHTHYOSIS SPECTRUM 3.PRP 4.KERATODERMA INFLAMMATORY DERMATOSIS 1. SLE 2.LP-ORAL EROSIVE,PALMOPLANTAR 3.LSEA
  37. 37. CONTRAINDICATIONS
  38. 38. TRETINOIN • ALL TRANS RETINOIC ACID • 1st retinoid introduced in clinical use. • MOA:-Gene transcription affects growth and differentiation of cells • Decreasing cohesiveness of follicular corneocyte. • Effects :-Comedolysis • Palliative effects on fine wrinkling,Mottled hyperpigmentation
  39. 39. • Available topically as 0.01% to 0.1% cream,gel,solutn • New microsphere formation in 0.1% and 0.04% • 4*more potent,less irritation,better tolerated • Enhance efficacy by target delivery system • Preg C
  40. 40. ACTIONS IN ACNE SKIN
  41. 41. ACNE SKIN • ACTIONS-> 1. Inhibit abn proli of keratinocyte 2. Decr infl lesions 3. Improve differentiation 4. Inhibit TLR-2anti infl 5. No direct role on sebum /P.acne Aerobic environmentnon compatable to P.acne First line non-infl acne Not used in severe nodular acne vulgaris
  42. 42. Photodamaged skin • Inc Basal and granular layer thickness • melanocytic activity, dispersion of melanin • glycosaminoglycan secretion into intracellular space. • synthesis of collagen and elastin • comedolysis
  43. 43. 1. Smoothness of skin(4-6 weeks) 2. Lightening of hyperpigmentation(8-16 wk) 3. Diminished fine wrinkle(16 wk)
  44. 44. • FDA approved 2 topical retinoidtretinoin 0.05% &0.02%, tazorotene 0.1% cream • Photolabile, bedtime • S/Eskin irritation,erythema and peeling,RETINOID DERMATITIS • Avoid astringents,harsh soaps,irritating agents traumatise epidermis • Antiaging creamfine wrinkles • +hyaluronic acid+GA Rx wrinkles &scarring
  45. 45. Sunscreen use is
  46. 46. ISOTRETINOIN • 13-cis-retinoic acid • No affinity for RAR/RXR • First retinoid for systemic use • Initially evaluated for ichthyotic disorder,later very effective in nodulocystic acne.
  47. 47.  Best agent for acne vulgaris : targets all pathogenic factors of acne  Rapid and early improvement in the inflammatory lesions (pustules)  Closed comedonal acne & microcystic acne are less responsive
  48. 48. IMPORTANT INDICATIONS 1. Nodulocystic acne 2. Inflammatory acne with scarring 3. Acne with psychological distress 4. Gram negative folliculitis 5. Pyoderma faciale 6. Severe rosacea 7. Hidradenitis suppurativa and dissecting cellulitis of the scalp 8. Darier’s disease 9. PRP,LE,LP
  49. 49. STANDARD DOSING • 1mg/kg/day for 4-5 months. • Start with 0.5mg/kg/day gradually to 1mg/kg for 4-5 months. • Total cumulative dose120mg-150mg/kg • Acne fulminans0.5-1mg/kg/day with prednisolone. • Rosacea10mg/dayRx telengiectasia,erythema,papules and pustules • Hidradenitis suppurativa1-2mg/kg/day • DSOSIso+rifamp more effective
  50. 50. • Lichen planuswidespread,hypertrophic or oral erosive LPIso+low dose CS
  51. 51. High dose Isotretinoin in acne vulgaris:Improved treatment outcomes and quality of life  80 participants  Three year study period
  52. 52. Isotretinoin therapy for acne: Results of a multicentre dose response study John S,Ronald P JAAD 10:490-496,1984 • 150 patients nodulocystic acne • Double blinded study with 0.1,0.5,1mg/kg/day • Comparing clinical response,s/e,lab abnormalities and duration of induced remission. • Results no significant difference in the clinical response between dosages. • 42% patients with 0.1mg/kg/dayrelapse. • 10% relapsed in 1mg/kg/day
  53. 53. • Minor effects in s/e and lab abnormalities • CONCLUSIONHIGHER DOSES ARE INDICATED
  54. 54.  To compare the efficacy and tolerability  Daily,alternate,pulse,low dose regime  120 patients  30 group each  1mg/kg/day,A/D,1mg/kg/day*1week/4week,20 mg A/D 16 weeks and follow up 8 weeks.  Conventional dose for 8 weeks and maintain with low dose-nodulocystic acne
  55. 55. Key points • Max sebosuppression • Alter VEGF incidence of pyogenic granuloma • Failure on microcystic acne and closed comedones • Total cumulative dose 120mg/kg150mg/kg with no better benefit
  56. 56. ACITRETIN • Acid metabolite of etretinate. • Retinoids as monotherapy in psoriasis • Effects thickness,scaling,itching • Initial effects4-6 weeks • Full effects3-4 months • Maintenance dose z needed • Re –esterification • Contraception 2 years in Europe and 3 years in USA
  57. 57. ACITRETIN VS ETRETINATE
  58. 58. STANDARD DOSING • PSORIASIS CHRONIC PLAQUE POSORIASIS 0.3-1 mg/kg/day for 4-12 weeks Combination with PUVA/NBUVB 25mg stat 2 weeks prior to the therapy. 0.3-0.5mg/kg/day for 6 weeks. If pt on stable dose of UV,reduce by 30-70% 7days after acitretin therapy Erythrodermic psoriasis Start with 0.3mg/kg/day ,inc to 0.5- 0.6mg/kg/day for 3 months.maintenance to 6 months Pustular psoriasis Start with 1mg/kg/day,dec to 0.5- 0.6mg/kg/day for 3-6 months,maintenance to 6-12 months
  59. 59. • Not combined with MTX/Ciclosporin • Sequential therapy z preferred • Combination therapytopical/PUVA/NBUVB Preferred
  60. 60. PRECAUTIONS ON ACITRETIN • NOT donate blood for 1 year after stoppage • Not recommed in childrenbone changes • Effects of UV radiation enhanced,avoid excessive exposure to sunlight • Refrain from waxingskin fragility • Greater insulin sensitivityinduce hypoglycaemia on OHA.Serum BS should check • Avoid excess intake of vit A
  61. 61. Keratinisation disorders • Lamellar ichthyosisgood • BCIE,CIEModerate • Rapid response,long term treatment • Low dose in BCIE,Darier’s prevent relapses • <1mg/kg/day preferrable OthersPRP,chemoprevention of non-melanoma skin cancer in solid organ transplant receipients
  62. 62. BEXAROTENE • Modulation of RXR receptors • apoptosis through redn of anti-apoptotic protein,activates capsase 3 • effects;induces tumor regression by PPAR Incre cellular differentiation and decreased cellular growth • Inhibit G1,G2,M phase of cell cycle • 99%plasma bound,mets by CYP450. • Central hypothyroidism
  63. 63. • Sun protection ,preg X • FDAEarly stage I A&I B persistant or refractory CTCL. • Dose300mg/m2 • Application A/D *1wkOD*1wkbd*1wktidqid*1wk • Response early as 4 week • Relapse rate 28% • Effective in lymphamatoid papulosis,chronic severe hand dermatitis,psoriasis,Alopecia • S/Esite reaction,rash,pruritis,icd,pain • fre of appl /+steroid. • Unlike other retinoids, very little renal elimination – extreme caution in liver insuff.
  64. 64. TAZOROTENE • Prodrugtazorotenic acid • High affinity RAR gammaregulate cell pro n diff • inflammation and proliferation throu AP-1 in psoriasis • Highest cutaneous conc,rapidly metabolised • T1/2 <20 min • Preg X • USES1st topical approved in C/C Psoriasis • Photo damaged skinclinical and histological improvement
  65. 65. • USES1st topical approved in C/C Psoriasis as mono/combination therapy1st line. • Photo damaged skinclinical and histological improvement • Early stage of CTCL • Genodermatosis (LI,EKV) • Doses 0.05% and 0.1%
  66. 66. ALITRETINOIN • Naturally occuring • Binds to all retinoid receptor • Down regulate IL-6,alter the expression of oncogen • Dose0.1% gel. • FDAAIDS related kaposi sarcoma • Other usesnon AIDS Kaposi sarcoma,photoaging,hand dermatitis. • Preg D • Expensive,long term Rx
  67. 67. ADAPALENE • Derivative of napthoic acid • Affinity to RAR • More stable,less photoliable,more lipophilic • Not binding to CRABP I and II • Less systemic exposure • Anti inflammatory action LT,PG,Anti AP-1 action • Immunomodulatory action TLR-2,Cytokine inhibition
  68. 68. • Comedolysis, microcomedone formation • Not carcinogenic,mutagenic • Not teratogenic,genotoxic • More photostable • Used for acne,hyperpigmentation,AK,Photoaging • S/Eerythema, scaling • Available in 0.1%gel,cream
  69. 69. SIDE EFFECTS
  70. 70. SERIOUS ADVERSE EFFECTS I)TERATOGENICITY • Retinoic acid embryopathy • Spontaneous abortion • IPLEDGE • PREGNANCY CAT X
  71. 71. EXTERNAL
  72. 72. CRANIOFACIAL ABNORMALITIES
  73. 73. EXTERNAL ABNORMALITIES • AUDITORY ABNORMALITIES Microtia Absent auditory canals Conductive hearing loss Sensorineural hearing loss Vestibular dysfunction • OCULAR ABNORMALITIES Micropthalmia Optic nerve atrophy
  74. 74. Agenesis of Cerebellar Vermis Abnormal Cortical Tracts CNS ABNORMALI TIES
  75. 75. INTERNAL ABNORMALITIES • CVS Abnormalities • CNS abnormalities • Parathyroid hypoplasia • Thymic hypoplasia • BONE abnormalities
  76. 76.  CARDIOVASCULAR ABNORMALITIES ASD VSD Hypoplastic or Interrupted Aortic Arch Septum
  77. 77. • BONE ABNORMALITIES Absent clavicle and scapula Aplasia/hypoplasia of long bones Short sternum Sternoumbilical raphe Absent thumb • OTHER ABNORMALITIES Thymic aplasia or hypoplasia Anal and vaginal atresia
  78. 78. • Lipids Hypercholestrelemia hyperTAG GIT
  79. 79. • OCCULAR Persistent dry eyes  night vision Staph aureus infection • Endocrine effects Hypothyroidism DM • HEMATOLOGIC Leukopenia,agranulocytosis • Neurologic Pseudotumor cerebri depression
  80. 80. • hepatic Transaminases,toxic hepatitis
  81. 81. Bone changes DISH Osteophyte formation Premature epiphyseal closure Osteoporotic changes osteophyte
  82. 82. MC MINOR SIDE EFFECTS • CUTANEOUS
  83. 83. • NASAL Nasal mucosa dryness, dec mucus secretion,epistaxis • Msk Myalgia Tendinitis Arthralgia and fatigue
  84. 84. Uses and complications of Isotretinoin therapy. Charles N Ellis,Kent J krach J Am Acad Dermatol 2001 • Mucocutaneous side effects • Cheilitis90-100% • Hair fall20% • Dry eyes33% • Spontaneous abortion15% • Teratogenicity 25% • Myalgia15% • transaminases15%(normal within 2-4 wks) • Photosensitivity 1-5%
  85. 85. VITAMIN E(alpha –tocopherol),800IU daily,may reduce retinoid toxicity. Lebowohl M,J Am Acad Dermatol 1999;41:260
  86. 86. Concomitant administration of vitamen E does not change the side effects of isotretinoin as used in acne vulgaris: a random- ized trial. Strauss JS, Gottlieb AB, Jones T et al J Am Acad Dermatol 2000;43:777-84 • Strauss et al, however, found that vitamin E at dose 800 IU/d provided no significant improvement when used in acne patients on isotretinoin.
  87. 87. Isotretinoin & Depression : A controversy
  88. 88. Jacobs DG, Deutsch NL, Brewer M. Suicide, depression and isotretinoin is there a causal link? J Am Acad Dermatol 2001;45:S168-75. • Systematic review article 19 articles • found no biologic basis for depression and isotretinoin usage. • further stated that no evidence for a causal connection existed between isotretinoin and depression or suicide. • the authors do recommend the physician monitor for signs of these symptoms.
  89. 89. Jick SS, Kremers HM, Vasilakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol 2000;136:1231-6 • Cohort study • found no significant difference in depression or suicide rates between patients that took oral antibiotics and patients that took isotretinoin for acne
  90. 90. An analysis of reports of depression and suicide in patients treated with isotretinoin. Wysowski DK, Pitts M, Beitz J. J Am Acad Dermatol 2001;45:515-9 • found in an analysis of depression,suicide or suicidal thoughts a temporal association between depression by positive de-challenges (improvement upon medication stoppage), and positive re-challenges (recurrence of symptoms on re-starting) with isotretinoin. • The study called for further research to establish a causal relationship and to elucidate a possible synergistic interaction between individuals predisposed to depression and isotretinoin usage.
  91. 91. Isotretinointreatment for acne and risk of depression: A systematic reviewandmeta- analysis Yu-Chen Huang, MD, Ying-Chih Cheng, MD,J Am Acad Dermatol july 2017,volume 76 • A systematic review and meta-analysis of the literature published from inception to September 30, 2016, was conducted. • change in depression scores from baseline was not significantly different between patients receiving isotretinoin treatment and those receiving an alternative treatment (95% confidence interval [CI] −0.680 to 0.011). •
  92. 92. • The prevalence of depression after isotretinoin treatment significantly declined (relative risk [RR] 0.588, 95% CI 0.382–0.904). • The mean depression scores significantly decreased from baseline (SMD −0.335, 95% CI −0.498 to −0.172). • Conclusions: Isotretinoin treatment for acne does not appear to be associated with an increased risk for depression. The treatment of acne appears to ameliorate depressive symptoms.
  93. 93. MONITORING GUIDELINESS
  94. 94. BAD GUIDELINES 2010 FOR ISO & ACITRETIN Clinical LAB  SERUM PREGNANCY TEST  CBC  LFT  RFT  FLP  URE  RBS Before the treatment and every 2-4 weeks for 2 months,then every 3months
  95. 95. BAD GUIDELINES 2010 FOR ISO & ACITRETIN • Special tests X-ray of wrist,ankles,thoracic spine(long term therapy) All symptomatic joint should be evaluated Ophthal examination
  96. 96. BEXAROTENE • Free T3,T4 and TSH and FLP • Highest TAGStatin or fenofibrate prior Rx. • >300-500mg/dllife style n diet • >500-800mg/dl dose/add a LLA,freq monitoring • >800-1000mgdldrug discontinue(pancreatitis) • Ophthal • Follow up • Every 2 weeks*1-2 months • Monthly *next 3 months • Every 2-3 months
  97. 97. GUIDELINESS FOR PREGNANCY MONITORING • 2 Urine/serum preg test • One 2 weeks before of initiation of isotretinoin • 2nd during first 5 days of the menstruation/11 days after the last act of unprotected sexual intercourse. • Each month –ve UPT • Therapy start on 2nd or 3rd day of next cycle • 2 forms of contraception for atleast 1 month prior,during and 3 years after discontinuation. • Written consent
  98. 98. DRUG INTERACTION • Drug Increase the level(toxicity)  VIT A  Tetracyclin,doxycyclin,mi nocyclin  Gemfibrozil  Macrolides,Azoles Decrease the retinoid  ATT  Anticonvulsantph enytoin,pheno,carb amazepine
  99. 99. • RETINOIDS INCRESES THE DRUG CICLOSPORIN CORTICOSTEROID DECREASES ANTI OVULATORY EFFECTS OF MINI PILLS ACITRETINMTx hepatotoxicity. ALCOHOLRE -ESTERIFICATION
  100. 100. INVESTIGATIONAL RETINOIDS  LGD -1069 RXR panagonist,in clinical trial  TAMIBAROTENE Topical antipsoriatic agent  CD 437 Induction of apoptosiscutaneous carcinoma  MOFAROTENE Used in chemotherapy Augment activity of Doxorubicin,5FU,IL
  101. 101. • AROTINOID SULPHONES • Used in AK • Do not bind RAR. LESS SIDE EFFECTS ,MORE EFFICACY
  102. 102. TAKE HOME MESSAGE • Retinoids are biologically and structurally related to VIT A • TretinoinMultifunctional from acne to pigmentation to photodamaging. • Adapalenesimilar efficacy with less side effects and photostable. • Isotretinoinhighly effective in nodulocystic acne ;max sebosuppression.long term for severe and resistant acne
  103. 103. • Acitretinbest in keratinisation disorder. long term use recurrence after discontinuation contraception from 2-3 years. • Etretinate best for psoriasis • phased out due to side effects. • Bexaroteneeffective for early stages of CTCL. Max s/ecareful monitoring hypothyroidism • Investigational retinoidslesser side effects
  104. 104. THANK YOU

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