Antifungal Agents Flashcards
Amphotericin
1) Mechanism of Action: binds to ergosterol, forming pores in membranes with loss of vital intracellular constituents (fungicidal)
2) Pharmacokinetics: IV or topical only; Slow excretion by kidney plus hepato-biliary (t1/2 15d)
3) Spectrum / Uses: broad spectrum, choice for life threatening systemic infections
4) Adverse Reactions: very toxis: fever/chills on infusion; nephrotoxicity (80%), anemia
Nystatin
1) Mechanism of Action: binds to ergosterol, forming pores in membranes with loss of vital intracellular constituents
2) Pharmacokinetics: topical only; (not absorbed orally)
3) Spectrum / Uses: superficial Candidal infections
4) Adverse Reactions: well tolerated given topically; mild GI upset (if swallowed)
Caspofungin (Echinocandin)
1) Mechanism of Action: inhibits synthesis of cell wall component, disrupting assembly (high selective toxicity)
2) Pharmacokinetics: IV infusion only; levels ↓ by P450 inducers
3) Spectrum / Uses: aspergillosis (if refractory to ampho B)
4) Adverse Reactions: infusion related symptoms (via histamine > rash, pruritus, n/v)
Triazole: Fluconazole
1) Mechanism of Action: like imidazoles, but more selective inhibition of fungal P450 reducing normal sterol
synthesis (fungistatic)
2) Pharmacokinetics: IV/po, renal excretion; enters CNS
3) Spectrum / Uses: oropharyngeal/esophageal candidiasis; vulvovaginal candidiasis (single dose); cryptococcal meningitis
4) Adverse Reactions: well tolerated (GI upset); lesser effect on CYP450 metabolism
Triazole: Itraconazole
1) Mechanism of Action: like imidazoles, but more selective inhibition of fungal P450 reducing normal sterol synthesis (fungistatic) 2) Pharmacokinetics: hepatic excretion 3) Spectrum / Uses: aspergillosis 4) Adverse Reactions:
Triazole: Terconazole
1) Mechanism of Action: like imidazoles, but more selective inhibition of fungal P450 reducing normal sterol
synthesis (fungistatic)
2) Pharmacokinetics: topical only
3) Spectrum / Uses: vulvovaginal candidiasis
4) Adverse Reactions:
Imidazole: Ketoconazole
1) Mechanism of Action: inhibit P450 ergosterol synthesis, altering membrane permeability
2) Pharmacokinetics: IV / po / topical; hepatic metabolism; excreted in breast milk
3) Spectrum / Uses: systemic infections (e.g., candidiasis); (declining systemic use due to toxicity); wide use in dermatologic indications
4) Adverse Reactions: anorexia, n/v, hepatotoxicity; inhibits CYP450 drug metabolism, and androgen-GC biosynthesis, teratogenic
Imidazole: Clotrimazole / Miconazole
1) Mechanism of Action: inhibit P450 ergosterol synthesis, altering membrane permeability
2) Pharmacokinetics: topical only
3) Spectrum / Uses: oral and vaginal candidiasis
4) Adverse Reactions:
Terbinafine
1) Mechanism of Action: inhibits squalene oxidase reducing ergosterol synthesis (Fungicidal)
2) Pharmacokinetics: po and topical; metabolized by hepatic P450
3) Spectrum / Uses: onychomycosis of finger/toe nails (po); athlete’s foot (topical)
4) Adverse Reactions: headache, diarrhea, rash; inhibition of CYP450
Flucytosine
1) Mechanism of Action: converted to 5FU in fungi > inhibits thymidylate synthetase and DNA synthesis
2) Pharmacokinetics: well-absorbed and distributed; renally eliminated (decreased dose if renal impairment)
3) Spectrum / Uses: serious infections of cryptococcosis, and candidiasis
4) Adverse Reactions: n/v, skin rashes (prolonged use > bone marrow depression)
Griseofulvin
1) Mechanism of Action: binds to fungal microtubules inhibiting mitosis (fungistatic)
2) Pharmacokinetics: poor po absorption, improved by microsizing particle, fatty meal
3) Spectrum / Uses: severe dermatophytosis of skin, hair, finger / toenails
4) Adverse Reactions: hypersensitivity reactions, GI distress, headache, confusion
Pentamidine
1) Mechanism of Action: Inhibits protein and nucleic acid synthesis
2) Pharmacokinetics: IV/IM, inh
3) Spectrum / Uses: protozoa, P. jirovici pneumonia in AIDS pts
4) Adverse Reactions: Nephrotoxicity / hepatotoxicity, hypoglycemia
Superficial Fungal Infections
topical azole-antifungal agents: ketoconazole, miconazole, clotrimazole
Cutaneous-Mucocutaneous Fungal Infections:
Dermatophytes (ringworm, Athlete’s Foot, Jock Itch, scalp, nails)
- topical antifungal agents: clotrimazole, miconazole, terbinafine
- hair infections: griseofulvin po
- nail infections: itraconazole, terbinafine (systemic)
Cutaneous-Mucocutaneous Fungal Infections:
Candida
Topical nystatin, clotrimazole, terconazole for mucocandidiasis
Subcutaneous Fungal Infections (rare)
oral itraconazole and parenteral amphotericin B (severe systemic infection)
Systemic Fungal Infections
amphotericin B infusions
Opportunistic Fungal Infections
eg in someone with AIDS
Candidiasis: disseminated: fluconazole
Aspergillosis: amphotericin B, caspofungin
