Antifungal Drugs Flashcards
What are the antifungals
Amphoteracin B Flucytosine Ketoconazole Miconazole Clotrimazole Fluconazole Itraconazole Voriconazole Posaconazole Caspofungin Griseofulvin Terbinafine Nystatin
What is Amphoteracin B
Polyene ABX
How does Amphoteracin work
Binds ergosterol
Pores in cell membrane
What does Amphoteracin B work on
Yeast and Molds
When do you give Amphoteracin B
Life-threatening infections
Initial therapy to reduce viral load
Continue on azole
What is the preferred antifungal for deep fungal infection during pregnancy
Amphoteracin B
Amphoteracin B administration
IV
Intrathecal if meningeal disease
Amphoteracin B AE
Renal toxicity
Anemia - Decreased EPO
Seizures in intrathecal
Fever, chills, muscle spasms, HA, hypotension
How do you reduce nehphrotoxicity with Amphoteracin B
Lipid colloid
How does Flucytosine work
Enters cell via cytosine permease Converted to 5-FU then 5-FdUMP/5-FUMP Inhibits Thymidylate Synthase Incorporates into protein DNA and Protein synthesis inhibition
What is Flucytosine used for
Candida
Cryptococcal
How does Flucytosine cause BM toxicity
Formation of 5-FU from gut flora
Synergistic with Flucytosine
Amphoteracin B
Imidazoles
Ketoconazole
Miconazole
Clotrimazole
How do the azoles work
Inhibit 14-alpha sterol demethylase
Blocking conversion of lanosterol to ergosterol
Membrane disruption
What are the triazoles
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Which azoles are less specific for fungal CYP
Imidazoles
DOC candida and most coccidioides
Fluconazole
Inhibitor of 3A4
Azoles
Fluco - moderate but strong 2C9
Voriconazole - also 2C9, 2C19
What do imidazoles potentiate the toxicity of
Warfarin
Cyclosporine
Since it has a narrow spectrum what should imidazoles be used for
Superficial mycoses
Why can PPIs and H2 blockers interfere with Ketoconazole absorption
Best absorbed at low pH
Imidazole AE
Gynecomastia
Menstrual irregularities
Decreased plasma cortisol (inhibition of adrenal steroid synthesis)
Which imidazoles are available as topical OTC
Clotrimazole
Miconazole
Maintenance therapy or prophylaxis for cryptococcal meningitis
Fluconazole (after Amphoteracin B initial)
Which azoles can penetrate CSF
Fluconazole
What is the only azole that has renal excretion
Fluconazole
What can Fluconazole increase the plasma levels of
Phenytoin
Zidovudine
Warfarin
What is Fluconazole not good for
Aspergillus and other filamentous fungi
What is the absorption of Itraconazole reduced by
H2 blockers and PPIs
What is Itra/Vori/Posaconazole given for
Aspergillus Blastomycoses Sporothrix Histoplasma Dermatophytosis Onychomycosis
When can Itraconazole cause fatal arrhythmias
When given with Cisapride or Quinidine
DOC invasive aspergillosis
Voriconazole
Voriconazole AE
Transient visual disturbance
Good for Mucor
Posaconazole
How does Caspofungin act
Inhibits beta (1.3) glucan synthesis in cell wall
What does Caspofungin act on
Candida
Aspergillus
What is Caspofungin ineffective against
C. neoformans
Structure of Caspofungin
Large cyclic peptide linked to long chain FA
How does Griseofulvin work
Disrupt mitotic spindle
What is Griseofulvin for
Dermatophysis (skin, hair, nails)
How do you improve Griseofulvin absorption
Give with fatty food
Induces P450
Griseofulvin
Action of Terbinafine
Inhibitis Squalene Epoxidase
No ergosterol and toxic levels of squalene
Most effective against Onychomycosis
Terbinafine
Is an Allylamine
Terbinafine
Accumulates in keratin
Terbinafine
No effect on P450
Terbinafine
Terbinafine AE
GI upset
Rash, HA, taste disturbance
Topical cream use of Terbinafine
Tinea cruris, corporis
What is Nystatin
Polyene macrolide
What is Nystatin similar to
Amphoteracin B (structure and action)
What is the only use of Nystatin
Candidiasis
Cutaneous oral/vaginal administration
Why isn’t Nystatin given IV
Too toxic
What else can you give for cutaneous candidiasis
Topical Amphoteracin B
