ONYCHOMYCOSIS
&
LOCERYL NAIL
LACQUER
What are MYCOSES?
MYCOSES
Definition
 They
are diseases provoked by fungi,
that can be divided among deep or
SUPERFICIAL
SUPERFICIAL MYCOSES
Where?
 Skin
 Hair


Nails
Caused by?
 Dermatophytes
 Moulds
 Yeasts

DERMATOPHYTES
 Pluricelularis,
filamentous
 ANTROPOPHILIC
 ZOOPHILIC
 GEOPHILIC
 Trichophyton
(hair, skin, nails)
 Microsporum
(hair, skin)
 Epidermophyton
(skin)
DERMATOPHYTOSIS
Clinical forms
Tinea:
 Body (corporis)
 inguinal area (cruris)
 feet (pedis)
 hands (manuum)
 hairy leather (capitis)
CANDIDIASIS
Yeast
 Saprofit

PREDISPONENT FACTORS
Patogenic (opportunist)
skin - eritema, oedema, pruritus
nails - paronichia,white spots, striaes
Courtesy dr. Baran
Courtesy dr. Baran
SUPERFICIAL MYCOSIS
Clinical Aspects
ALTERATION OF THE COLORATION
 ALTERATION OF THE RELIEF
 ALTERATION OF THE SENSIBILITY
 ALTERATION OF THE CONSISTENCY

Courtesy dr. Baran
Courtesy dr. Baran
Courtesy dr. Baran
SUPERFICIAL MYCOSIS
Predisponent/ Trigger Factors




•
HEAT
•
HUMIDITY
•
EXCESSIVE PERSPIRATION•
•
INDIVIDUAL SENSIBILITY
•
Obesity
Pregnancy
Circulatory problems
Diabetes
Corticoterapy
AIDS
What are
ONYCHOMYCOSIS?
ONYCHOMYCOSIS
Definition
Nails fungal infections:
 DERMATOPHYTES 85%
 Yeasts - 14%
 Non dermatophytes
molds - 1%
ONYCHOMYCOSIS
Epidemiology
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

ONYCHOMYCOSIS
Prevalence (Gupta, 1998)
20
18
16
14
12
10
8
6
4
2
0
20
13,7
14,1
9,8
6,5
1,6
Onychomycosis prevalence in different ages
children
ADULTS
40-50
50-60
60-70
70 & older
ONYCHOMYCOSIS
Clinical aspects...
ONYCHOMYCOSIS
Clinical Forms
(Baran, Hay, Tosti & Haneke,1998)
DISTAL SUBUNGUAL
ONYCHOMYCOSIS
Courtesy dr. Baran
ONYCHOMYCOSIS
Clinical Forms
(Baran, Hay, Tosti & Haneke,1998)
SUPERFICIAL
ONYCHOMYCOSIS
Courtesy dr. Baran
ONYCHOMYCOSIS
Clinical Evolution
Distal subungueal
Superficial
(DSO ou DLSO)
(SO)
TOTAL
DYSTROPHIC
Proximal subungueal
(PSO)
Endonyx
(EO)
ONYCHOMYCOSIS
Diagnosis
Courtesy dr. Baran
•Direct mycologic exam
ONYCHOMYCOSIS
Diagnosis
•Culture
ONYCHOMYCOSIS
Cure criteria
 Mycologic
cure
Direct exam + culture
 Clinical cure
 OVERALL ASSESMENT
ONYCHOMYCOSIS
Therapy
 General
cares
 Local cares
 Topical medications
 Systemic medications
ONYCHOMYCOSIS
Treatment selection criteria
Causative pathogen
 Potencial adverse effects
 Dosage schedule
 Patient complience
 Age and health of patient
 Prior antifungal therapy
 Allergic history
 Cost

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
ONYCHOMYCOSIS
Systemic Drugs
OLD DRUGS
 Griseofulvin
 Cetoconazol
New Drugs
• Itraconazol
• Terbinafine
• Fluconazol
•Drug interactions
•ADVERSE EVENTS
Headache, GI symtoms - diarrhea, dyspepsia
Elevated liver function tests - 0.3 - 5%
SUPERFICIAL MYCOSIS
Systemic Drugs

Griseofulvin
ALILAMINES
• Terbinafine
IMIDAZOLICS
• Cetoconazol
• Itraconazol
• Fluconazol
ONYCHOMYCOSIS
Old Systemic Drugs
 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
CETOCONAZOL
• fulminant hepatotoxicity (1:10.000)
• Low cure rates
• Drug interactions
• Hipotalamo- hipofise - adrenal
ONYCHOMYCOSIS
New Systemic Drugs
Itraconazol / Fluconazol / Terbinafina
Reduction of:
ADVANTAGES
 Persistence until 6
months after the
interruption of the
treatment
• Treatment Duration
• Adverse reactions
incidence
• Failure rates
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
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
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%
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)
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
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
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
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
ONYCHOMYCOSIS
Topical Drugs
CICLOPIROX
(loprox*, HMR)
 celular breath
(ATP production)
“Fungicida”
Nail lacquer
Broad Spectrum:
 Dermatophites
 Yeasts
 start 3 times/ week
ONYCHOMYCOSIS
Topical Drugs
AMOROLFINE
Solution
Solvent evaporation
FILM
• Active - 5%
• Polimer (metacrílic
acid)
• Plastificant
• Solvent (ethanol)
• Active - 25%
• Polimer
• Plastificant
ONYCHOMYCOSIS
Topical Drugs - LOCERYL
Adequate vehicle - film
 Safety
 Efficacy
 Once a week - praticity
 Broad- spectrum

LOCERYL PHARMACOLOGICAL ASPECTS
Mode 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

LOCERYL NAIL LACQUER
Loceryl Efficacy rates
80
70
60
50
40
30
20
10
0
71
47
CLINICAL CURE MYCOLOGICAL
CURE
ONYCHOMYCOSIS
Choose of the treatment
Combined teraphy
TOPICAL
TOPICAL + SYSTEMIC
Courtesy dr. Baran
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

6 mm
Courtesy dr. Baran
ONYCHOMYCOSIS
Choose of the treatment
COMBINATE THERAPY (topical + systemic)
 ANY TYPE AND INVOLVEMENT
 IMPROVE CURE RATES
 REDUCE THE TIME OF TREATMENT
 REDUCE THE RELAPSE RATES