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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 is synthesized in __________, similar to those found in human livers.
T/F Inhibitors of the ergosterol synthesis pathway are fungicidal.
False, they are fungistatic
Conversion from squalene to lanosterol requires activity of which enzyme?
__________ & __________ are inhibitors of squalene epoxidase (general classes).
What catalyzes the reaction of lanosterol to ergosterol?
Fungi cell wall is made up of what four components?
What are the five general types of mycoses?
- Systemic (primary)
Athletes foot and jock itch are caused by __________ & __________, respectively.
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?
All of the following are targets for anti-mycotic agents except:
A) Endoplasmic Reticulum
D) Plasma membrane
E) Mitotic spindle
Amphotericin B is __________ water soluble.
Amphotericin B is commonly formulated with __________ , within a _________, or in a __________.
- Unilamellar vesicle,
- Colloidal dispersions
Amphotericin B binds to __________ within the fungal plasma membrane.
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 __________.
T/F Amphotericin B is used for a wide array of systemic fungal infections.
The major acute reaction to IV amphotericin is __________ & __________.
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?
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?
5-FdUMP (5-flourodeoxyuridylic acid monophosphate)
Flucytosine is useful for infections of the __________.
Flucytosine can be used in conjunction with __________ to treat cryptococcosis in AIDS patients.
Flucytosine is used in conjunction with __________ to treat cryptococcal meningitis.
What is itraconazole's MOA?
It inhibits 14alpha-sterol demethylase
The imidazoles and triazoles inhibit _________, causing several drug interactions.
Does itraconazole cause renal toxicity?
- Not by itself.
- Hydroxypropyl-B-cyclodextrin, an exipient, can accumulate and cause toxicity.
__________ is particularly effective against oropharyngeal and esophageal candidiasis.
Profound __________ can occur at 600mg/day of itraconazole.
T/F Fluconazole has poor GI absorption.
False, it is nearly completely absorbed in the GI tract.
Fluconazole is effective at treating which of the following?
A) Vaginal candidiasis
B) Deep candidiasis of bone marrow transplants
C) Coccidiodal meningitis
D) All of the above
D) All of the above
Fluconazole is used for maitenance therapy of __________.
All of the following are side effects of fluconazole except:
C) Reversible allopecia
E) None of the above
(this multiple choice question has been scrambled)
What is the MOA of Griseofulvin?
It inhibits fungal mitosis by binding tubulin and disruptingmitotic spindle formation.
__________ is a fungistatic drug used to treat many species of dermatophytes.
How does griseofulvin prevent recolonization of the skin?
It binds keratin in keratinocyte precursor cells
Griseofulvin treats fungal infections of the skin but is ineffective at treating __________ or __________ infections.
All of the following are ADR's of Griseofulvin except:
__________ inhibits ergosterol synthesis by inhibiting squalene epoxidase.
Terbinafine is used for __________.
Topical antifungals can't be used to treat __________ or __________
- Nail oncomychosis
- Tinea capitis
What formulations do topical antifungals come in?
Naftifine is a topical antifungal that inhibits __________.
Nystatin has a similar MOA of __________.