PHD - Overview of Fungi and Anti-fungal Agents (Steed) Flashcards
Why does griseofulvin tend to produce many side effects?
It induces cytochrome P450 enzymes
What specific fungus is flucytosine typically used to treat?
Cryptococcus
Which of the following antifungal agents acts by inhibiting Beta-glucan synthesis in the fungal cell wall?
A. Amphotericin B
B. Capsofungin
C. Fluconazole
D. Griseofulvin
E. Terbinafine
B. Capsofungin
Incorrect choices:
Amphotericin B binds ergosterol and pokes holes in cell membranes
Fluconazole and terbinafine prevent synthesis of ergosterol
Griseofulvin inhibits mitotic spindle formation
What are hyphae?
Hyphae are filamtous structures with intercommunicating tubular cells
Hyphae appear like branches on a tree
What is beta-D-glucan and which anti-fungal drugs inhibit its production?
Beta-D-glucan is a polysaccharide that is present in the cell walls of fungi.
Echinocandin drugs (micofungin, capsofungin, andulifungin) inhibit the synthesis of beta-D-glucan, which prevents the fungal cells from being able to fix their cell membranes and to divide to produce daughter cells.
What are the 4 types of conidia and how are they different from each other?
- Blastoconidia - formed by budding along a hyphae or by yeast
- Chlamydoconidia - enlarged, thick-walled, round conidia
- Arthroconidia - breaking up of a hyphae at the point of septation
- Macroconidia - multicellular
How do nucleoside analogs, such as 5-flucytosine, act as anti-fungal agents?
5-flucytosine inhibits DNA and RNA synthesis in fungi, preventing them from being able to replicate.
In the slide below showing Candida albicans, a common yeast, what is the name of the structure that the yellow arrow is pointing to?
Chlamydoconidia
Remember that chlamodyconidia are large, round spores with thick walls
What is the difference between a septate and non-septate hyphae on visual examination?
Septate hyphae have cross-walls within the hyphae, making them appear to be made up of separate units
Non-septate hyphae appear as one continuous structure
What is the term used to describe a cluster of many hyphae?
Mycelium
What is the primary mechanism of action of azole drugs such as ketoconazole, voriconazile, and miconazole?
Azole drugs inhibit ergosterol biosynthesis by inhibiting the enzyme 14-alpha-demethylase.
Without ergosterol, the component that makes up fungal cell membranes, the cells cannot divide.
What are dimorphic fungi and what factor is involved in their transition?
Dimorphic fungi are fungi that change between mold and yeast.
When at body temperatures (37C) - yeast form
When at environmental temperatures (25C) - mold form
Truly pathogenic fungi are yeast in the body, but mold in the environment
What is the route of administration of Amphotericin B?
IV
Which anti-fungal agents function by indirectly inhibiting cell replication and what is their mechanism of action?
- Nucleoside analogs (5-flucytosine) - DNA/RNA synthesis inhibitors
- Grisans (griseofulvin) - inhibits microtubule function during mitosis
What is one main advantage of using capsofungin over ketoconazole?
Capsofungin has few drug interactions and does not inhibit any cytochrome P450 enzymes.
What is the most commonly prescribed azole drug for non-life threatening fungal infections?
Itraconazole
Which anti-fungal agents are responsible for inhibiting squalene epoxidase?
Allylamines (eg terbinafine) and thiocarbamates (eg tolnaftate)
What is the route of administration of nystatin?
Topical ointment
Nystatin is not readily absorbed if taken orally, and has significant toxicity if given via IV.
Why is amphotericin B typically used as a last resort anti-fungal agent?
Amphotericin B is very effective at killing fungi, but it can also react with human cell membrane cholesterol. This makes it a very toxic drug, and is only used when all else fails.
What is one of the reasons that azole drugs (ketoconazole, miconazole, etc.) have many interactions with other drugs?
Azole drugs inhibit Cytochrome P450 3A4
Fluconazole is the least toxic of the azole drugs, which is why it is given more often than the others
What is the mechanism of action of capsofungin, an echinocandin drug?
Capsofungin inhibits the synthesis of beta-D-glucan.
Beta-D-glucans make up a part of the fungal cell wall of certain fungi. Inhibition of its synthesis will prevent cell division and replication.
What are the major differentiating characteristics between fungal cells and mammalian cells?
- Fungi have cell walls
- Fungal cell membranes are made up of ergosterol; mammalian cell membranes have cholesterol
What is the primary difference between dematiaceous hyphae and hyaline hyphae?
Hyaline hyphae are typically smooth and clear on a slide.
Dematiaceous hyphae appear brown because they have melanin in their cell walls
What is one significant side effect of amphotericin B toxicity in patients being treated for fungal infections?
Nephrotoxicity
What is a sporangiospore?
Asexual reproductive cells enclosed in a saclike structure.
Which anti-fungal agent is used almost exclusively to treat tinea capitis?
Griseofulvin
Why is flucytosine rarely used on its own to treat fungal infections? What drug is usually given in conjunction with flucytosine to combat this?
Fungi rapidly develop drug resistance to flucytosine.
Typically given with amphotericin B or fluconazole
Your patient is a 27-year-old male who is HIV+ and severely immunocompromised. During rounds, you discover the patient has a dark black lesion on the roof of his mouth (seen below). You decide to culture this lesion thinking that it could be a bacterial or fungal infection. Lab analysis reveals a fungi with non-septate hyaline hyphae. What fungal disease process does this patient have and what 2 types of fungi could be causing it?
Zygomycosis (mucormycosis)
Caused by: Rhizopus or Mucor fungi
Zygomycosis typically affects patients with immunosupression and uncontrolled diabetes. Lesions tend to start in the respiratory tract or through cuts of the skin, but can travel through the body and produce lesions of the skin and mucosa.
Which anti-fungal agent inhibits microtubule function during mitosis, thus preventing fungal cells from dividing?
Griseofulvin (grisans)
Which anti-fungal drug has been proven to work, but the mechanism of action is unknown?
Potassium Iodide (SSKI)
The main problem with this drug is that it does not taste good, which makes patients less likely to comply with taking their medication.
What is the route of administration of an echinocandin drug, such as micofungin or capsofungin?
IV
What are the 3 types of selective media agar used for fungal culture?
- Inhibitory mold agar - contains antibiotics in agar to prevent growth of bacteria; ensures only mold grows
- Dermatophyte test medium - contains phenol red, which turns red in presence of basic pH
- Dermatophytes use nitrogen compounds –> alkaline environment
- Chromogenic agar for yeasts - makes candida turn blue and other yeasts turn pink
- Good for isolating and IDing different yeasts in a sample
Outline the steps of fungal invasion from a spore to a vegetative hyphae.
- Spore lands and extends a germ tube
- The germ tube grows into a hypha
- Multiple hyphae form
- Hyphae extend above the surface
- Hyphae produce conidia or sporangiospores that spread to other areas
True or False: All human pathogenic forms of dematiaceous molds contain septated hyphae.
True
When collecting a fungal sample, what are two important things to remember?
- Disinfect the skin before collecting
- Collect a lot more specimen than you would for a bacterial culture
In the slide below showing Candida albicans, what structure is the blue arrow pointing to?
Blastoconidia
Remember that blastoconidia are small, round spores that tend to bud along the hyphae
Which drugs bind to ergosterol in fungal cell membranes?
Polyenes such as amphotericin B and nystatin
These agents bind to ergosterol and disrupt the cell membrane, causing cell contents to leak out.
Which anti-fungal agent is most commonly used in the treatment of infections with dermatophytes and chromomycosis fungal agents?
Terbinafine
Terbinafine is an allylamine that inhibits ergosterol synthesis
What is unique about where fungal cells grow in comparison to bacterial cells?
Fungal cells grow in nutritionally poor/adverse environments
Bacterial cells need nutrients
Which of the following antifungal agents has the most toxicity?
A. Amphotericin B
B. Capsofungin
C. Fluconazole
D. Griseofulvin
E. Terbinafine
A. Amphotericin B
What are conidia and what is their purpose?
Conidia are spores that are not enclosed in a saclike structure that allow for asexual reproduction of fungi
Appear as little spherical structures on a histological slide
Which anti-fungal agents interfere with fungal cell membranes?
- Polyenes - amphotericin B and nystatin
- Azoles - miconazole, ketoconazole, etc.
- Allylamines - terbinafine
- Thiocarbamides - tolnaftate
- Echinocandins - capsofungin
Flucytosine is converted to which chemical within fungal cells and what enzyme does this chemical inhibit?
Flucytosine is converted into 5-fluorouracil in fungal cells.
Remember that 5-fluorouracil inhibits the enzyme thymidylate synthase, preventing the conversion of dUMP into TMP. This halts DNA synthesis.
