What is the main challenge in treating fungal infections?
As eukaryotes, fungi and humans share several metabolic pathways and cell functions. This leads to problems identifying good trug targets without severe human toxicity.
What are the three populations of concern for increased risk of mycoses?
The immunocompromised
ICU patients
patients with prostheses.
What is the main problem with diagnosing fungal infections? How has technology overcome this?
Fungi grow exceptionally slow in culture.
PCR, Western Blots, and antigen detection can help recognize and diagnose infections.
Fungi use __________ as a structural component in their cell membranes.
Ergosterol
Ergosterol is synthesized in __________, similar to those found in human livers.
Microsomes
T/F Inhibitors of the ergosterol synthesis pathway are fungicidal.
False, they are fungistatic
Conversion from squalene to lanosterol requires activity of which enzyme?
Squalene Epoxidase
__________ & __________ are inhibitors of squalene epoxidase (general classes).
Allylamines
Benzylamines
What catalyzes the reaction of lanosterol to ergosterol?
14alpha-sterol demethylase
Fungi cell wall is made up of what four components?
Chitin
Beta-(1,3)-D-Glucan
Beta-(1,6)-D-Glucan
Mannoproteins
What are the five general types of mycoses?
Superficial
Cutaneous
Subcutaneous
Systemic (primary)
Opportunistic
Athletes foot and jock itch are caused by __________ & __________, respectively.
Tinea pedis
Tinea cruris
The combination of antineoplastic administration and an immunocompromised host can lead to what particular fungal infection? What are the symptoms?
Candidiasis (thrush)
Painful erosions of the tongue.
A deep-seeded lung infection can be caused by which fungi?
Aspergillus
All of the following are targets for anti-mycotic agents except:
A) Endoplasmic Reticulum
B) Mitochondria
C) DNA
D) Plasma membrane
E) Mitotic spindle
Amphotericin B is __________ water soluble.
Poorly
Amphotericin B is commonly formulated with __________ , within a _________, or in a __________.
Deoxycholate
Unilamellar vesicle,
Colloidal dispersions
Amphotericin B binds to __________ within the fungal plasma membrane.
Erosterol moieties
Bound amphotericin forms a __________ through the membrane allowing for disruption of __________.
pore/channel, transmembrane potential or flow of nutrients across it.
T/F Amphotericin is readily absorbed in the GI tract.
False, it is only given IV
What does amphotericin have such a long half-life?
90% protein bound, and it readily binds fungi and human plasma membranes.
Amphotericin B may be administered __________ for meningitis due to __________.
Intrathecally
Coccidioides
T/F Amphotericin B is used for a wide array of systemic fungal infections.
TRUE
The major acute reaction to IV amphotericin is __________ & __________.
Fever
Chills
How can hypochromic and normocytic anemia occur from amphotericin use?
It damages the interstitial cells of the kidney leading to decreased ___________ production.
Flucytosine inhibits fungi replication and DNA synthesis by inhibiting which enzyme?
Thymidylate synthetase
Why won't flucytosine inhibit DNA synthesis in mammalian cells?
They don't possess the permease transporter that allows for cellular uptake.
What is the active metabolite of flucytosine that inhibits thymidylate synthetase?