Page 875 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 48 Antifungal Agents 861

Topical and shampoo forms of ketoconazole are also available TOPICAL ALLYLAMINES
and useful in the treatment of seborrheic dermatitis and pityriasis
versicolor. Several other azoles are available for topical use (see Terbinafine and naftifine are allylamines available as topical
Preparations Available). creams (see Chapter 61). Both are effective for treatment of tinea
cruris and tinea corporis. These are prescription drugs in the USA.

SUMMARY Antifungal Drugs

Pharmacokinetics, Toxicities,
Subclass, Drug Mechanism of Action Effects Clinical Applications Interactions
POLYENE MACROLIDE
• Amphotericin B Forms pores in fungal Loss of intracellular contents Localized and systemic Oral form is not absorbed • IV for
membranes (which contain through pores is fungicidal candidemia • Cryptococcus systemic use • intrathecal for fungal
ergosterol) but not in • broad spectrum of action • Histoplasma • Blastomyces meningitis • topical for ocular and
mammalian (cholesterol- • Coccidioides • Aspergillus bladder infections • duration, days •
containing) membranes Toxicity: Infusion reactions • renal
impairment • Interactions: Additive with
other renal toxic drugs
• Lipid formulations: Lower toxicity, higher doses can be used

PYRIMIDINE ANALOG
• Flucytosine Interferes with DNA and RNA Synergistic with Cryptococcus and Oral • duration, hours • renal excretion
synthesis selectively in fungi amphotericin • systemic chromoblastomycosis • Toxicity: Myelosuppression
toxicity in host due to DNA infections
and RNA effects
AZOLES
• Ketoconazole Blocks fungal P450 enzymes Poorly selective • also Broad spectrum but toxicity Oral, topical • Toxicity and interactions:
and interferes with interferes with mammalian restricts use to topical Interferes with steroid hormone
ergosterol synthesis P450 function therapy synthesis and phase I drug metabolism
• Itraconazole Same as for ketoconazole Much more selective than Broad spectrum: Candida, Oral and IV • duration, 1–2 d • poor entry
ketoconazole Cryptococcus, blastomycosis, into central nervous system (CNS)
coccidioidomycosis, • Toxicity and interactions: Low toxicity
histoplasmosis

• Fluconazole, voriconazole, posaconazole, isavuconazole: Fluconazole has excellent CNS penetration, used in fungal meningitis
ECHINOCANDINS
• Caspofungin Blocks β-glucan synthase Prevents synthesis of fungal Fungicidal Candida sp • also IV only • duration, 11–15 h • Toxicity:
cell wall used in aspergillosis Minor gastrointestinal effects, flushing
• Interactions: Increases cyclosporine
levels (avoid combination)
• Micafungin, anidulafungin: Micafungin increases levels of nifedipine, cyclosporine, sirolimus; anidulafungin is relatively free of this interaction

ALLYLAMINE
• Terbinafine Inhibits epoxidation of Reduces ergosterol Mucocutaneous fungal Oral • duration, days • Toxicity:
squalene in fungi • increased • prevents synthesis of infections Gastrointestinal upset, headache,
levels are toxic to fungi fungal cell membrane hepatotoxicity • Interactions: None
reported