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ONYCHOMYCOSIS & LOCERYL NAIL LACQUER

ONYCHOMYCOSIS & LOCERYL NAIL LACQUER. What are MYCOSES?. MYCOSES Definition. They are diseases provoked by fungi, that can be divided among deep or SUPERFICIAL. Where? Skin Hair Nails. Caused by? Dermatophytes Moulds Yeasts . SUPERFICIAL MYCOSES. Pluricelularis, filamentous

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ONYCHOMYCOSIS & LOCERYL NAIL LACQUER

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  1. ONYCHOMYCOSIS&LOCERYL NAIL LACQUER

  2. What are MYCOSES?

  3. MYCOSESDefinition • They are diseases provoked by fungi, that can be divided among deep or SUPERFICIAL

  4. Where? Skin Hair Nails Caused by? Dermatophytes Moulds Yeasts SUPERFICIAL MYCOSES

  5. Pluricelularis, filamentous ANTROPOPHILIC ZOOPHILIC GEOPHILIC Trichophyton (hair, skin, nails) Microsporum (hair, skin) Epidermophyton (skin) DERMATOPHYTES

  6. DERMATOPHYTOSIS Clinical forms Tinea: • Body (corporis) • inguinal area (cruris) • feet (pedis) • hands (manuum) • hairy leather (capitis)

  7. CANDIDIASIS • Yeast • Saprofit PREDISPONENT FACTORS Patogenic (opportunist) skin - eritema, oedema, pruritus nails - paronichia,white spots, striaes

  8. Courtesy dr. Baran

  9. Courtesy dr. Baran

  10. SUPERFICIAL MYCOSIS Clinical Aspects • ALTERATION OF THE COLORATION • ALTERATION OF THE RELIEF • ALTERATION OF THE SENSIBILITY • ALTERATION OF THE CONSISTENCY

  11. Courtesy dr. Baran

  12. Courtesy dr. Baran

  13. Courtesy dr. Baran

  14. SUPERFICIAL MYCOSIS Predisponent/ Trigger Factors • HEAT • HUMIDITY • EXCESSIVE PERSPIRATION • INDIVIDUAL SENSIBILITY • Obesity • Pregnancy • Circulatory problems • Diabetes • Corticoterapy • AIDS

  15. What are ONYCHOMYCOSIS?

  16. Nails fungal infections: DERMATOPHYTES - 85% Yeasts - 14% Non dermatophytes molds - 1% ONYCHOMYCOSISDefinition

  17. ONYCHOMYCOSISEpidemiology • 30-50% of all nail diseases • 30% of the micoses • 2 to 20% of the general population • 48% of older people (70 years) • 80% in toenails - 80% Caused by dermatophytes • 20% in the fingernails - 75% Caused by yeasts

  18. ONYCHOMYCOSISPrevalence (Gupta, 1998)

  19. ONYCHOMYCOSIS Clinical aspects...

  20. ONYCHOMYCOSISClinical Forms(Baran, Hay, Tosti & Haneke,1998) DISTAL SUBUNGUAL ONYCHOMYCOSIS Courtesy dr. Baran

  21. ONYCHOMYCOSISClinical Forms(Baran, Hay, Tosti & Haneke,1998) SUPERFICIAL ONYCHOMYCOSIS Courtesy dr. Baran

  22. ONYCHOMYCOSISClinical Evolution Distal subungueal (DSO ou DLSO) Superficial (SO) TOTAL DYSTROPHIC Endonyx (EO) Proximal subungueal (PSO)

  23. ONYCHOMYCOSISDiagnosis Courtesy dr. Baran • Direct mycologic exam

  24. ONYCHOMYCOSISDiagnosis • Culture

  25. ONYCHOMYCOSISCure criteria • Mycologic cure Direct exam + culture • Clinical cure • OVERALL ASSESMENT

  26. ONYCHOMYCOSISTherapy • General cares • Local cares • Topical medications • Systemic medications

  27. ONYCHOMYCOSISTreatment selection criteria • Causative pathogen • Potencial adverse effects • Dosage schedule • Patient complience • Age and health of patient • Prior antifungal therapy • Allergic history • Cost

  28. Mechanism of action Antimicotic drugs Drugs with capacity of penetrating in the membrane of the fungi, that is quite resistant, and to act: in the nuclear metabolism in the cellular breathing in the cytoplasmic membrane

  29. ONYCHOMYCOSIS Systemic Drugs • New Drugs • Itraconazol • Terbinafine • Fluconazol OLD DRUGS • Griseofulvin • Cetoconazol • Drug interactions • ADVERSE EVENTS • Headache, GI symtoms - diarrhea, dyspepsia • Elevated liver function tests - 0.3 - 5%

  30. SUPERFICIAL MYCOSIS Systemic Drugs • Griseofulvin • IMIDAZOLICS • Cetoconazol • Itraconazol • Fluconazol • ALILAMINES • Terbinafine

  31. Nuclear function GRISEOFULVIN Hepatotoxicity Long term teraphy (6 months fingernails, 18 m toenails) High relapses rates Dermatophites (it doesn't act in yeasts) « Low cost » ONYCHOMYCOSIS Old Systemic Drugs

  32. ONYCHOMYCOSIS Old Systemic Drugs • CETOCONAZOL • fulminant hepatotoxicity (1:10.000) • Low cure rates • Drug interactions • Hipotalamo- hipofise - adrenal

  33. ONYCHOMYCOSIS New Systemic Drugs Itraconazol / Fluconazol / Terbinafina ADVANTAGES • Persistence until 6 months after the interruption of the treatment • Reduction of: • Treatment Duration • Adverse reactions incidence • Failure rates

  34. ONYCHOMYCOSIS New Systemic Drugs Itraconazol Triazole antifungal agent Increased specificity for fungal rather than mammalian cytochrome P450 enzimes Decreases the risk of drug interactions Broad spectrum (dermatophites and yeasts) Drug interactions - terfenadin, astemizol, sinvastatin, lovastatin, midazolan, triazolan, cisapride

  35. ONYCHOMYCOSIS New Systemic Drugs Itraconazol Pharmacokinetics Strong affinity for keratinazed tissue Concentration in nails 90 days after a 7 days course of medication exccds the MIC of common dermatophytes Pulse therapy - 7 days/month 2 - 3 months

  36. ONYCHOMYCOSIS New Systemic Drugs Itraconazol Efficacy Cure rates - 35 - 86% toenails Relapses - 9 - 11% (9 - 12 months) Safety Drug interactions Elevated liver function tests - 0.3 - 5%

  37. ONYCHOMYCOSIS New Systemic Drugs Terbinafine Allylamine antifungal agent Blocks ergosterol synthesis by inhibiting squalene epoxidase - increase squalene, toxic for fungal cells Limitate spectrum (activity against yeasts is variable)

  38. ONYCHOMYCOSIS New Systemic Drugs Terbinafine Pharmacokinetics Concentration in nails 90 days after a 7 days course of medication excceds the MIC of common dermatophytes 250 mg/d - 6 weeks treatment in fingernails 12 weeks treatment in toenails

  39. ONYCHOMYCOSIS New Systemic Drugs Terbinafine Efficacy Cure rates - 90%fingernails / 80% toenails Relapses - 6 - 12%(12 months) Safety Well tolerated Headache (13%), GI symtoms - diarrhea, dyspepsia

  40. ONYCHOMYCOSIS New Systemic Drugs Fluconazol Bis Triazole antifungal agent Increased specificity for fungal rather than mammalian cytochrome P450 enzimes Broad spectrum (dermatophites and yeasts) Drug interactions - terfenadin, astemizol, sinvastatin, lovastatin, midazolan, triazolan, cisapride, antiacids, rifampin, anticoagulants, phenitoin, ciclosporin, theophilin, hypoglicemic agents

  41. ONYCHOMYCOSIS New Systemic Drugs Fluconazol Pharmacokinetics Strong affinity for keratinazed tissue Levels up to 50 times those found in plasma on the stratum corneum of nails Concentration in nails 2 weeks after medication above the MIC of common dermatophytes and nondermatophytes Pulse therapy - 150 - 300mg/ once weekly

  42. CICLOPIROX (loprox*, HMR) celular breath (ATP production) “Fungicida” Nail lacquer Broad Spectrum: Dermatophites Yeasts start 3 times/ week ONYCHOMYCOSIS Topical Drugs

  43. ONYCHOMYCOSIS Topical Drugs AMOROLFINE Solution FILM • Active - 5% • Polimer (metacrílic acid) • Plastificant • Solvent (ethanol) Solvent evaporation • Active - 25% • Polimer • Plastificant

  44. ONYCHOMYCOSIS Topical Drugs - LOCERYL • Adequate vehicle - film • Safety • Efficacy • Once a week - praticity • Broad- spectrum

  45. LOCERYL PHARMACOLOGICAL ASPECTSMode of action • Deprives the membrane of ergosterol and causes accumulation of unusual sterols • Morphological changes in nuclear membranes, mytochondria, vacuoles, cytoplasm, cytoplasmic membrane and the cell wall • Necrosis of the cell

  46. LOCERYL NAIL LACQUERLoceryl Efficacy rates

  47. ONYCHOMYCOSIS Choose of the treatment Combined teraphy TOPICAL TOPICAL + SYSTEMIC Courtesy dr. Baran

  48. ONYCHOMYCOSIS Choose of JUST topical treatment • % of nail plate affected - less than 60% • Distance between the matrix and border involvement more than 6mm (next slide) • Type of onychomycosis - superficial or distal subungeal • Number of affected nails - 1 or 2 • Disease time - less than 5 years

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