INTRODUCTION
• Fungi are eukaryotic, heterotrophic organisms
• Have rigid cell wall composed of chitin(bacterial cell wall is composed of peptidoglycan).
• Fungal cell membrane contains ergosterol(human cell membrane is composed of cholesterol).
• Superficial fungal infections respond well to topical agents
• Systemic management when :
-infection is extensive
-recalcitrant
-involves hair and nails
Ideal antifungal agent• Broad spectrum of action
• Fungicidal at therapeutic concentrations
• Absence of resistance within targeted fungi
• Keratophilic with penetration of cornified envelop
• Anti inflammatory properties
• Short duration of therapy for cure
• Once per day application for cure
• Available in multiple formulations
• Inexpensive and well tolerated
History
• World war II marked da pivotal transition in the development of antifungals
• Prior to 1940 antifungals used were:
- castellini’s paint ( basic fuchsin 0.3, ethyl alcohol 95%, boric acid 1.0, acetone 5.0,resorcinol, phenol)
- whitfield ointment ( benzoic acid 6%, SA 3%)
-gentian violet
CLASSIFICATION
• POLYENES
• IMIDAZOLES
• ALLYLAMINES AND BENZYLAMINES
• OTHERS : ciclopirox
selenium sulphide
Polyenes
• One of the First agents discovered to possess antifungal properties
• Produced by streptomyces
• Major topical polyenes are :
nystatin
amphotericin B
• Indications : cutaneous and mucocutaneous
candidiasis
POLYENES
• They bind selectively to ergosterol in fungus but not in mammalian cell wall.
Binding to sterol in cell membrane.
Deformity in plasma membrane occurs
Interferes with permeability and with transport functions
This allows leakage of intracellular ions and enzymes especially loss of intracellular k+
cell death.
Side effects
• Normally well tolerated
• Common adverse effects : burning , pruritus, pain, eczema, and rash
• Very rarely hypersensitivity reactions are reported
• Possess anti inflammatory and anti-bacterial properties
• Indications : dermatophytes , M.furfur, candida
• Cotrimazole : cream, lotion, solution, oral troches, intravaginal tablets
• Ketoconazole : cream, shampoo
• Miconazole : cream, powder, spray, gel
ALLYAMINES/BENZYLAMINES
• ALLYAMINES : terbinafine
naftifine
• BENZYLAMINES : butenafine
Indications : dermatophytes, candida(terbinafine)
Acetyl CoA
Squalene
Lanosterol
(ergosterol)
Allylamine
Drugs (Terbinafine)
Azoles
Squalene-2,3 oxide
Squalene
epoxide
14-α-demethylase
Pharmacokinetics
• Highly lipophlic
• Attain high concentration in stratum corneum, hair follicles and sebum; thus reducing probability of reinfection
• Persistant concentrations observed after 7 days of therapy
• Also has anti inflammatory and anti bacterial properties
• Butenafine has been detected within stratum corneum at minimum inhibitory concentration for 72hrs after application ( so can be applied once daily, whereas terbinafine is to be adviced twice daily)
Ciclopirox olamine
• Does not affect sterol biosynthesis
• Interfers with active membrane transport of essential macromolecules, disrupting cell membrane integrity
• Inhibits enzymes essential for respiration
• Available – cream, gel, nail lacquer, shampoo
• Inhibits PGs and Leukotreines synthesis in leukocytes ; anti inflammatory property
• Has anti bacterial property also – against g–veand g+ve bacteria
• Indications – t.pedis, t.corporis, t.versicolor, cutaneous candidiasis
Selenium sulphide
• Indications – t.versicolor, seb dermatitis
• Available – lotion 2.5%
• Possess cytostatic effect on cells of epidermis and follicular epithelium, which allows shedding of fungi via reduction of corneocyteadhesions