Flashcards in EXAM #4: ANTIFUNGALS Deck (54):
List the systemic fungi.
- Histoplasma capsulatum
- Blastomyces dermatiditis
- Coccidioides immitis
- Sporothrix schenckii
List the opportunistic fungi.
- Cryptococcus neoformans
What are the common cutaneous and subcutaneous fungal infections?
- Athlete's Foot
What are the unique targets used in antifungal therapy?
- Fungal cell membrane i.e. ERGOSTEROL
- Fungal cell wall i.e. GLUCANS
List the drugs that inhibit Ergosterol synthesis.
What drug inhibits fungal membrane function?
What drug inhibits fungal cell wall synthesis?
What drug inhibits fungal nuclei acid synthesis?
What drugs can be used to treat systemic fungal infections?
1) Polyenes- amphotericin B
What drug has the broadest spectrum of all the antifungals?
Why has Amphotericin B been replaced for newer compounds?
High degree of toxicity
What is the MOA of Amphotericin B
- Binds ergosterol in fungal cell membrane
- Forms Amp B pores in fungal membrane
Why is there high toxicity associated with Amphotericin B?
Not only binds ergosterol, but can also bind cholesterol
What is Amphotericin B the treatment of choice for?
1) Disseminated candidasis
2) Cryptococcal (neoformans) meningitis
*Note that it is a second line treatment for systemic disease caused by molds*
What is the mechanism of resistance of Amphotericin B?
Decreased membrane ergosterol concentration
How is Amphotericin B administered?
*Note that it is INSOLUBLE in water*
- Complex-ed to a bile salt
- Given IV
How is Amphotericin B administered for Cryptococcal meningitis?
What are the adverse reactions seen with Amphotericin B?
1) Infusion reaction seen in nearly all patients
How is the toxicity of Amphotericin B being combated?
Packaging the drug in lipid micelle i.e. "liposomal packaging"
What are the two groups of Azoles?
1) Imidazoles (2x nitrogens)
2) Triazoles (3x nitrogens)
List the imidazoles.
List the triazoles.
What is the MOA of the azoles?
Inhibit the enzyme the produces ergosterol
- Makes the cell membrane leaky
What are the mechanisms of resistance to the azoles?
1) Drug efflux pumps
2) Mutation in target enzyme
3) Decreased ergosterol synthesis
Why is Ketoconazole rarely used clinically today?
What is the typical first line drug for systemic fungal infections?
Why is Fluconazole highly utilized in the treatment of systemic fungal infections?
- Highest TI
- Distributed to the CNS
- Few drug-drug interactions
What is Fluconazole a first ling agent for?
1) Systemic Candidiasis
How does Itraconazole compared to Fluconazole?
Broader spectrum of activity BUT lower TI
What does Itraconazole require for absorption?
Low GI pH
Can Itraconazole penetrate the CNS?
What is Itraconazole the drug of choice for?
What is Voriconazole?
Derivative of Fluconazole
What is Voriconazole commonly used to treat?
Note that it has replaced Amphotericin B as the first line drug b/c of lower toxicity.
What is the major adverse reaction associated with Voriconazole?
What drug has the broadest spectrum of all the azoles?
What is Posaconazole used to treat?
What is the MOA of Flucytosine?
This is a fluorinated pyrimidine analog that inhibits DNA synthesis
What is Flucytosine used to treat?
Used as a combination therapy for severe Cryptococcal infections
What are the adverse reactions seen with Flucytosine?
Bone marrow supression i.e.
What is the MOA of the Echinocandins?
Inhibit the synthesis of Beta-glucan i.e. inhibit the CELL WALL
*We don't have Beta-glucan; thus, very low toxicity*
List the Echinocandins.
What are the Echinocandins primarily used to treat?
*Note that both have a high degree of Beta-glucan in their cell wall*
What is Griseofulvin used to treat?
This is an oral agent used to treat Dermatophyte infections
What is unique about Griseofulvin?
Concentrates in Keratin precursor cells
What are Allylamines?
Class of antifungal that inhibits ergosterol synthesis
What is the MOA of Allylamines?
Inhibit the enzyme squalene epoxidase
What is the hallmark Allylamine?
What is Terbinafine used to treat?
First line for Onychomycosis i.e. nail infections
What are the topical antifungal agents?
What is the MOA of Nystatin?
Polyene that binds ergosterol and forms pores
- Only used topically
What is Nystatin used to treat?
- Vagial i.e. yeast infections
What are the topical azoles, Clotrimazole and Miconazole used to treat?
1) Vulvovaginal candidiasis
2) Dermatophyte infections
3) Oral thrush