Antifungal medications Flashcards
What is the MoA of Amphotericin B?
Binds to ergosterol of fungal PM and alters membrane permeability, causing cell lysis
Can be fungistatic or fungicidal
How is Amphotericin B distributed?
Has poor CSF penetration
What are the ADRs of amphotericin B?
Nephrotoxicity
Anemia
Systemic: shaking, chills, fever, myalgias
What is the potential benefit of Amphotericin Lipid formulations?
Lower incidence of nephrotoxicity
What is the MoA of 5-Fluocytosine?
Penetrates fungal cell where it is deaminated by a fungus specifi enzyme
Inhibits pyrimidine metabolism an ultimately RNA and protein synthesis
How does FLuorocytosine distribute?
60-100% CSF penetration
What are the ADRs of 5-Fluocytosine?
Bone marrow hypoplasia
More common in prolonged therapy
What is the MoA of Azole products?
Interfere with fungal cytochrome P450 enzymes responsible for ergosterol production
Fungistatic or fungicidal
What are the ADRs of azole antifungals?
N/V
Hepatitis
Increases aminotransferases
What ADR is specific to Ketoconazole?
Dose dependent depression of serum testosterone and ACH
What are the drug interactions for azole antifungals?
Antacids, PPIs and H2 antagonists
Cyclosporin
Warfarin
Describe the absorption of Ketoconazole.
Rapidly absorbed from GI tract
pH dependent bioavailability (increased pH, decreased absorption)
Describe the absorption and distribution of Fluconazole.
Rapidly absorbed from GI tract
Widely distributed, readily into CSF
How is Fluconazole eliminated?
Renal, 60-80% unchanged in urine
How is Itraconazole distributed?
Widely distributed
Poorly into CSF
How is Itraconazole used in therapy?
Effective for oral therapy of histo/blasto
Useful for aspergillosis
How is Voriconazole absorbed and distributed?
GI, decreased by high fat meals
40-70% in CSF
How is voriconazole eliminated?
Metabolized in liver
Interacts with CYP3A4
How is voriconazole used in therapy?
Invasive aspergillosis and Fusarium spp.
Candidiasis
What is the use of Posaconazole?
Candida and Aspergillus infection in immunocompromised patients
Inhibits CYP3A4
What is the MoA of Caspofungin acetate?
Echinocandin - blockes fungal cell wall synthesis
Glucan synthesis inhibitor
What is Caspofungin acetate used for?
Candidiasis
Invasive aspergillosis
What are the ADRs of Caspofungin acetate?
Phlebitis, headache, fever
Increased LFTs, SrCr
What is the MoA of Griseofulvin?
Disrupts the cells mitotic spindle structure
What is the use of Griseofulvin?
Dermatophytosis
What are the ADRs of Griseofulvin?
NVD
Hypersensitivity
Hepato/Nephrotoxicity
Headace
CYP3A4 inducer
What is the MoA of Terbinafine?
Synthetic allylamine derivative
Inhibits squalene epoxidase
What are the ADRs of Terbinafine?
Hypersensitivity/Rash - erythema multiforme, toxic epidermal necrolysis
Liver enzyme abnormalities
Headache
What are the drug interactions with Terbinafine?
Cimetidine - T clearance decreased
Rifampin - T clearance increased
Cyclosporin - increased clearance
Warfarin
What is Terbinafine used for?
Onychomycosis
Consider ADRs
What are the treatments of oral candidiasis?
Nystatin - oral suspension
Clotrimazole troches
Amphotericin B
