TOPICAL ANTIFUNGALS

Preethi chekuriDermatology

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.

Mechanism of action of

polyenes

Nystatin(polyene)

Pharmacokinetics

• Insoluble in water

• Not absorbed from intact skin or vagina

Side effects

• Normally well tolerated

• Common adverse effects : burning , pruritus, pain, eczema, and rash

• Very rarely hypersensitivity reactions are reported

AZOLES

TOPICAL : Ketoconazole

AZOLES Clotrimazole

Econazole

Miconazole

Oxiconazole

Sertaconazole

Mechanism of action

• 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

Side effects

• Irritation

• Burning

• Stinging

• Contact dermatitis

• Pruritus

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

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