A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

CHAPTER 45
FUNGAL AND NON-HIV VIRAL
INFECTIONS
● Antifungal drug therapy 340
● Antiviral drug therapy (excluding anti-HIV drugs) 344
● Interferons and antiviral hepatitis therapy 348
ANTIFUNGAL DRUG THERAPY
INTRODUCTION
Glucan in
cell wall
Fungal cell
Amphotericin B and
nystatin bind with
ergosterol and
disrupt cell membrane
Fungi, like mammalian cells but unlike bacteria, are eukaryotic
and possess nuclei, mitochondria and cell membranes.
However, their membranes contain distinctive sterols, ergosterol
and lanesterol. The very success of antibacterial therapy
has created ecological situations in which opportunistic fungal
infections can flourish. In addition, potent immunosuppressive
and cytotoxic therapies produce patients with seriously
impaired immune defences, in whom fungi that are nonpathogenic
to healthy individuals become pathogenic and
cause disease. Table 45.1 summarizes an approach to antifungal
therapy in immunocompromised patients. Sites of action
of antifungal drugs are summarized in Figure 45.1.
Ergosterol in
cell membrane
DNA and RNA
in nucleus
Griseofulvin inhibits
cell division and
reproduction of
fungal cells
Flucytosine inhibits
synthesis of fungal
DNA and RNA
Figure 45.1: Sites of action of antifungal drugs.
Fluconazole, other
azoles, and terbinafine
inhibit synthesis of
ergosterol and disrupt
cell membrane
Caspofungin inhibits
synthesis of glucan
and disrupts cell wall
Table 45.1: An approach to antifungal drug therapy in the immunocompromised host
Fungal infection Drug therapy for superficial infection Drug therapy for deep-seated infection
Candida Nystatin – topical Amphotericin B with or without flucytosine
Clotrimazole – topical
Miconazole – topical
Fluconazole – oral or i.v.
Fluconazole – oral
Itraconazole or voriconazole oral
Caspofungin if failing azole therapy
Aspergillus
Amphotericin B i.v. (liposomal)
Voriconazole or caspofungin if failing azole
therapy
Cryptococcus
Amphotericin B plus flucytosine or fluconazole
i.v. (oral continuation therapy)
Disseminated histoplasmosis
Itraconazole or amphotericin B i.v. (or
fluconazole)
Disseminated coccidiomycosis
Fluconazole or amphotericin B i.v. (plus
flucytosine) or itraconazole
Blastomycosis
Amphotericin B i.v. or itraconazole