Introduction to Antifungals Flashcards
What are fungi classified into?
> Filamentous
Yeast
Mould
What is the most common filamentous fungi?
Athlete’s foot.
What does Pneumocystic Jiroveci cause?
Pneumonia in the immunosuppressed.
What does the fungal cell wall contain?
B-1,3-glucan
What does the fungal cell membrane contain?
Ergosterol
Why is it hard to target fungi?
They have similar processes to humans.
What is the function of Ergosterol?
Main cell membrane constituent, regulates membrane PERMEABILITY.
What is the synthesis pathways of Ergosterol?
Squalene -1-> Lanosterol -2-> Ergosterol.
1) Squalene Epoxidase
2) Lanosterol 14a demethylase
What is B-1,3-Glucan made up of?
Polymers of UDP Glucose, made from B-1,3-glucan synthase.
What does B-1,3-glucan do?
Makes up 50% fungal wall dry weight, fibrous network on inner surface.
How do Polyenes (Anti-fungal drugs work)?
> Work w/ Ergosterol.
Make pore-like aggregates
Lose membrane integrity
K+ leakage –> Cell Death
Specifically what does Amphotericin B do (Polyene)?
Stabs Ergosterol.
Nystatin problems?
> Not orally absorbed
Too toxic for systemic use
Only superficial infections
Amphotericin B problems?
> Allergic reactions
> Nephrotoxicity
Why is some Amphotericin B lipid associated?
Minimize delivery to kidney cells –> more target to fungal cells or reticulo-endothelial system (liver,spleen)
What do Allylamines do?
Inhibit Squalene Epoxidase - Ergosterol Synthesis.
What are Allylamines used for?
> Superficial fungal infections > Tinea Corporis/Cruris > Athletes foot > Scalp ringworm > Onchyomycosis
What type of Antifungal drug is Terbafine?
Allylamine
What is Terbafines spectrum?
Broad
What are the negative side effects of Terbafine?
Liver toxicity - Hepatitis, Jaundice.
What do Azoles do?
Block lanosterol 14a-demethylase - Ergosterol synthesis.
What are Azoles?
Synthetic compound with a 5M azole ring.
What builds up as a result of using Azoles?
Non-ergosterol 14a-sterols in cell membrane.
What type of spectrum do Azoles have?
Broad
What can Fluconazole not be used to treat?
Aspergillus spp.
What adverse effect do Azoles have?
Cause hepatotoxicity
What do Azoles inhibit apart from lanosterol 14a-demethylase?
Cytochrome P450 enzymes.
How many N atoms in Imidazoles?
2
How many N atoms in Triazoles?
3
Why arent Imidazoles used?
Toxic
What are Triazoles used for?
Aspergillosis and candidiasis.
How do Echnocandins work? (End in FUNGIN)
Inhibit B-1,3-glucan synthase –> abnormal cell wall.
What do Echnocandins treat?
Aspergillus and candida.
What do Echnocandins not treat?
Some moulds and cryptococcus.
What type of analogue is 5 -FlouroCysteine?
Pyrimidine
What does 5-FC do?
Inhibit DNA/RNA synthesis
What does 5-FC need to get into a fungal cell?
Cysteine Permease
What is 5-FC converted to inside the cell?
> 5- Flourouracil
> 5- Flourodeoxyuridine monophosphate
What can 5-FC only be used for?
Yeasts
Adverse effect of 5-FC?
Bone marrow depression
What is the clinical use of 5-FC?
Cryptococcal meningitis ( use w/ Amphotericin B)
What does Grisofulvin do?
Inhibit fungal mitosis in dermatophyte infections
