C H A P T E R 1 1
Antifungal agents
153
Ketoconazole, fluconazole and itraconazole work by
blocking the activity of a sterol in the fungal wall. In
addition, they may block the activity of human steroids,
including testosterone and cortisol (see usual indications
in Table 11.1).
Posaconazole is one of the newest antifungals (see
Table 11.1 for uses). This drug and voriconazole inhibit
the synthesis of ergosterol, which leads to the inability
of the fungus to form a cell wall, which results in cell
death. Terbinafine is a similar drug that blocks the for-
mation of ergosterol. It inhibits a cytochrome P450 2D6
(CYP2D6) enzyme system, so it may be a better choice
for people who need to take drugs metabolised by the
cytochrome P450 (CYP450) system. It is available in a
sprinkle formulation for children.
Pharmacokinetics
Ketoconazole, itraconazole, posaconazole and terbi-
nafine are administered orally. Ketoconazole is also
available as a shampoo and a cream.
Fluconazole and voriconazole are available in oral
and intravenous (IV) preparations, making it possible to
start the drug intravenously for a serious infection and
TABLE 11.1
DRUGS IN FOCUS Systemic antifungals continued
Drug name
Dosage/route
Usual indications
griseofulvin (Grisovin)
Tinea corporis, tinea cruris and tinea capitis:
Adult: 500 mg/day
Tinea pedis and tinea unguium:
Adult: 500 mg/day
Paediatric: 10 mg/kg/day in divided doses
Treatment of variety of ringworm or
tinea infections caused by susceptible
Trichophyton species, including tinea
corporis, tinea pedis, tinea cruris, tinea
barbae, tinea capitis and tinea unguium
nystatin (Kenacomb,
Mycostatin, Nilstat)
500,000–1,000,000 units t.d.s. PO; continue
for 48 hours after resolution to prevent
relapse; also used topically
Treatment of candidiasis (oral form);
treatment of local candidiasis, vaginal
candidiasis, and cutaneous and
mucocutaneous infections caused
by Candida species
Rough
endoplasmic
reticulum
Smooth
endoplasmic reticulum
Polyribosomes
Golgi
apparatus
Cilia with
microtubules
Peroxisomes
Lysosomes
Nucleus:
Nuclear
membrane
Nuclear pore
Nucleolus
Cell membrane
Microtubules
Mitochondria
Centrioles
Topical
antifungals
Systemic
antifungals
FIGURE 11.1
Sites of action of antifungal agents.
Both systemic and topical antifungals alter
fungal cell permeability, leading to prevention
of replication and cell death.
