Antifungal agents Flashcards
What are dermatophytes?
Fungal infections of the epidermis and integuments (hair and nails)
Treatment for dermatophytes?
Topical antifungals such as clotrimazole or terbinafine
Do onychomycoses require topical or systemic treatment?
systemic
What systemic antifungals can treat onychomychosis?
Itraconazole, terbinafine
Treatment for candida infections?
Clotrimazole or nystatin topical
Fluconazole PO if no response
What are the common systemic fungal infections?
Blastomycosis, Coccidioidomycosis, Cryptococcosis, Histoplasmosis
General treatment of systemic fungal infections?
Amphotericin B infusions
Who is at risk for opportunistic infections?
Anyone after use of broad spectrum antibiotics
Immunosuppressed patients
Patients with systemic disease
What are 3 pathogens of opportunistic infections and first line treatments?
Candidiasis - fluconazole
Aspergillosis - amphotericin B
Pneumocystis pneumonia - TMP-SMX
Mechanism of action of amphotericin B?
Binds ergosterol in fungal membrane, which opens pores and leads to leakage of cell constituents.
T/F? Amphotericin B is highly selectively toxic.
False - it also binds to cholesterol components in mammalian cells
What is the major limiting factor of amphotericin B infusions?
Nephrotoxicity.
Most common adverse reaction to amphotericin B?
Anemia - 75%
Mechanism of action of nystatin?
Same as amphotericin B.
Is nystatin topical or IV?
Topical only
What are the echinocandins?
Micafungin and anidulafungin
Mechanism of action of echinocandins?
Inhibits essential component (Beta (1,3)-D-glucan) of fungal cell walls
Echinocandins more or less toxic than amphotericin B?
Less, because mammalian cells do not have that component
Uses of echinocandins?
Treatment of aspergillosis in patients refractory to amphotericin B or itraconazole.
Adverse effects of echinocandins?
Histamine mediated symptoms
fever, N/V, headache
What are the triazoles and their mechanism of action?
Fluconazole, itraconazole
Selective inhibition of fungal cytochrome P450
Clinical uses of fluconazole?
Vaginal candidiasis if topical treatment fails, oropharyngeal and esophageal candidiasis
Also initial treatment for cryptococcal meningitis
Clinical uses for itraconazole?
Systemic therapy for dermatophytoses, 2nd line for onychomycosis
Excretion of triazoles?
Fluconazole - renal
Itraconazole - hepatic
Adverse reactions of triazoles?
Generally well tolerated
Can cause DDIs due to inhibition of CYP450
What are the imidazoles?
ketoconazole, clotrimazole, miconazole
Mechanism of action for imadazoles?
Inhibits P450 dependent enzyme 14 alpha demethylase
Clinical uses of imidazoles?
Oral and vaginal candidiasis
Mechanism of terbinafine?
Inhibits squalene oxidase.
Terbinafine fungicidal or fungistatic?
fungicidal
Clinical uses of terbinafine?
Onychomycosis
Adverse reactions to terbinafine?
Inhibition of CYP450 drug metabolism
