Antifungal Agents Flashcards
Amphotericin B
Administration
IV only
Amphotericin B
MOA
Binds ergosterol in fungal membrane, forming a pore in the membrane and allowing essential small solutes to efflux.
Fungicidal
Amphotericin B
Spectrum
Broadest of all the antifungal agents
Effective against all fungi except Candida lusitaniae and Pseudallescheria boydii
Amphotericin B
Clinical Use
Reserved for significant toxicities, life threatening fungal infections (immunosuppres pts, cryptococcal meningitis, invasive Aspergillus)
DOC for Zygomycosis/mucormycosis
Only antifungal agent approved for use in pregnancy or breastfeeding women
Amphotericin B
Adverse Effects
Infusion related –> fever, chills, muscle spasm, vomiting, HA, hypotension
Cumulative Tox –>
Nephrotoxicity (vasoconstriction causing low renal perfusion; also causes renal tubule injury)
Hepatotoxicity
Anemia (less EPO)
Flucytosine
Spectrum
Very narrow
Very effective against Cryptococcal meningitis
Flucytosine
MOA
Enters fungal cell through pores in membrane. Gets converted to 5-fluorouracil intracellularly.
Leads to RNA synthesis inhibition and inhibition of thymidylate synthesis (DNA synthesis inhibition)
Flucytosine
Clinical Use
Frequently used with amphotericin B for treatment of Cryptococcal meningitis
Flucytosine
Adverse Effects
GI symptoms (nausea, vomiting, diarrhea)
Bone marrow toxicity –> anemia, leukopenia, thrombocytopenia
Teratogen - do NOT use in pregnancy
What is the only antifungal agent that may be administered in pregnant women?
Amphotericin B
List the drugs in the Azole class of antifungals. Which is the prototype? What are their general spectrums of activity?
Ketoconazole (prototype)
FIVP Fluconazole (most narrow spectrum) Itraconazole Voriconazole Posaconazole (most broad spectrum)
Azoles
MOA
Block 12-alpha-sterol demethylase enzyme involved in ergosterol formation
Less ergosterol synthesis impairs the fungal membrane function and increases permeability
Leads to loss of fungal plasma membrane proteins
What are some common adverse effects of all Azole drugs?
GI distress
Hepatotoxicity
Teratogen
What are some common drug-drug interactions of Azoles?
They either induce or are substrates of CYP450 enzymes.
NEVER give itraconazole or voriconazole with statins, as they can cause fatal rhabdomyolysis
Ketoconazole
Pharmacokinetics
Prototypical azole. Poor absorption (requires acidic environment) and poor penetration into CSF and urine
Ketoconazole
Adverse Effects
Inhibits CYP450 enzymes in adrenal and gonadal steroid synthesis
Low cortisol and low testosterone
Gynecomastia
Dec. libido
Impoetence
Fluconazole
Spectrum and Pharmacokinetics
Very narrow spectrum (used for Cryptococcal meningitis)
Great CSF penetration
Good oral bioavailability
Fluconazole
Adverse effects
Nausea
HA
Skin rash
GI upset
Itraconazole
Spectrum and Pharmacokinetics
Poor CSF, urine, eye penetration
Strong CYP3A4 inhibitor
Itraconazole
Clinical Use
Broader spectrum than fluconazole
Used for oral dermatophytes
Candida
Itraconazole
Adverse Effects
GI distress
Hepatotoxicity
Teratogen
Triad: HTN, Hypokalemia, and Peripheral Edema
-Do NOT use in patients with preexisting ventricular dysfunction or CHF
Voriconazole
Spectrum
Candida
Endemic fungi
Invasive Aspergillus
Voriconazole
Adverse Effects
Hepatotoxicity, GI distress, Teratogen
Periostitis (bone pain)
Transient vision changes
Photosensitivity/rash
Posaconazole
Spectrum
Broadest of the azole family
Only azole effective against Mucormycoses/Zygomycosis
Posaconazole
Adverse Effects
Hepatotoxicity
GI distress
Teratogen
List the Echinocandins
Capsofungin
Micofungin
Anidulafungin
Echinocandins
MOA
Inhibit B-1,3-D glucan synthase complex, involved in cell wall formation
Leads to osmotic instability and cell death
Echinocandins
Adverse Effects
Histamine-like effect (skin itching)
Embryotoxic
Echinocandins
Clinical Uses
Good activity against Candida and Aspergillus
No activity against Cryptococcus or dimorphic fungi
Griseofulvin
Clinical Use
Used only for dermatophyte (tinea…) infections
Griseofulvin
MOA
Binds fungal microtubules and prevents the mitotic spindle from forming
Griseofulvin
Adverse Effects
Inducer of CYP450 enzymes – may have many drug interactions
HA, lethargy, vertigo Urticaria, photosensitivity Hepatotoxicity Leukopenia, neutropenia Teratogen
Terbinafine
Clinical Use
Used for dermatophytes and Candida albicans
High cure rate
Terbinafine
MOA
Inhibition of fungal squalene epoxidase.
This prevents the conversion fo fungal squalene to ergosterol, thus causing membrane dysfucntion and squalene buildup in cell, leading to cell death
Nystatin
Clinical Use
Similar to amphotericin B, but only used in gels, creams, ointments
Used for oral candidiasis (swish and swallow)
