Antifungals Systemic & Topical Level III lectures Dr Keli Some are fungistatic, while others are fungicidal

Fungal Infection in Humans = Mycosis

Major Types of Mycoses
superficial cutaneous subcutaneous systemic opportunistic

Symptoms vary from cosmetic to life threatening

Nystatin
It was isolated from Streptomyces noursei MOA; binds to ergosterol, a major component of the fungal cell membrane causing K+ leakage and death of the fungus No injectable formulations May be safely given orally as well as applied topically due to its minimal absorption through mucocutaneous membranes such as the gut and the skin

Uses
Cutaneous, vaginal, mucosal and esophagea l Candida infections responce good Oral candiasis child 2ml adult 5ml suspension QID or vaginal tablet QID Adult 0.5-1 milli units or 100,000 units in a child Vulvovaginal candidiasis vaginal tablet

Amphoterecin B
MOA; binds to ergosterol, a component of fungal cell membranes, forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl) leakage and fungal death Uses ; for paronychal and intertriginous candidiasis applied 3-4 times may stain the skin yellow

Imidazole and triazole

MOA; They interfere with conversion of lanosterol to ergosterol, required in fungal cell membrane synthesis Imidazoles have activity against dermatophytes, and yeasts fugi that cause s ptyriasis vesicolor These drugs also block steroid synthesis in humans.

Imidazoles:
Miconazole Ketoconazole Clotrimazole Mebendazole Isoconazole Sertaconazole Thiabendazole Bifonazole Butoconazole Econazole Fenticonazole Oxiconazole Sulconazole Tiaconazole

Imidazoles
Miconazole clotrimazole available for treatment of vaginal candiasis Ketokonazole Rx serborrheic dermatitis, dermatophytosis, vaginal candidiasis Topical antifungals are available in combination with steroids for rapid resolve of symptoms May cause erythema, local irritation, pruritus, stinging

Antifungal Agents
The triazoles are newer, and are less toxic and more effective:
Fluconazole Itraconazole Ravuconazole Posaconazole Voriconazole

Antifungal Agents
Allylamines
Allylamines inhibit the enzyme squalene epoxidase, another enzyme required for ergosterol synthesis:
Terbinafine - marketed as Lamisil Amorolfine Naftifine

Butenafine

 Naftifine ; effective against dermatophytes but not yeasts A/E erythema, burning sensation, irritation Terbinafine should be used for a minimum of 1 week not > 4 weeks clinical improvement may continue 2-4 weeks after cessation of therapy Butenafine; For Rx of superficial dermatophytes

 Tolnaftate; synthetic antifungal, effective against microsporum, trichophyton, epidermophyton and P orbiculare Rx tinea Ciclopixon; synthetic effective against dermatophytes, candida, P, orbiculare, MOA interferes with cell wall synthesis Effective against dermatomycosis, candidiasis, tinea vescicolor,

Antifungal Agents
Echinocandin
Echinocandins inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3- glucan synthase:
Anidulafungin Caspofungin Micafungin

Antifungal Agents
Others:
Flucytosine is an antimetabolite. Griseofulvin Fluocinonide Salicylic Acid (topical) Potassium Iodide

Griseofulvin
It binds to polymerized microtubules and inhibits

fungal mitosis Can be detected in the stratum corneum 4-8 hrs after oral adm Reducing its particle sizes increases its absorption Dosage adult 500mg 1g child 10mg/kg/d Indications Tinea, finger nail infection for 6 months Cross sensitivity with penicillin may occur its derived from penicillin C/I porphyria, hepatic failure May affect coumarin activity

Oral azoles
Ketoconazole Rx of chronic mucocutaneous mycosis 200mg/d Effctive against epidermophyton, micrposporum, trichophyton A/E N pruritus, significant is gynaecomast ia, hepatis liver enzymes

 Fluconazole and itraconazole are newer azoles Fluconazole T1/2 30 hrs, 100mg for mucocutaneous mycosis, Dermatomatophyt e infections alternate day Rx Itraconazole therapeutic levels may be detected a month after oral adminstration A/E May cause HF, Requires evaluation of the liver Azoles potentiate and prolong the hypnotic and sedative effects of midazolum and triazolam With HMDA CoA reductase inhibitors causes rhabdomyolysis Terbinafine 250 mg OD for 6/52 for finger nail infections, 12 weeks for toe nail infections A/E, liver failure, and deathserious hepatotoxicity