Flashcards in Antifungals Deck (27):
How are pathogenic fungals classified
Moulds/filamentous - hyphae, mycelium, septa
What disease does candida albicans cause?
What disease does cryptococcus neoformans
Meningitis in immunosuppressed
Targets of anti-fungals
What makes up fungal cell membranes?
What makes up fungal cell walls
Beta- 1,3 - glucan
How is ergosterol synthesised (name the components of synthesis)
Squalene --squalene epoxidase -> lanosterol --lanosterol 14 alpha demthylase --> ergosterol
(enzymes squalene epoxidase and lanosterol 14 a demthylase = potential targets)
What enzyme makes Beta 1,3 glucan
Beta 1,3 glucan synthase (potential targets)
Anti fungal classes - name all 5...
Name 2 examples of polyenes
Nystatin (very toxic) - only for superficial infection (oral/vaginal thrush) - not absorbed orally but very toxic
Amphotericin B (serious systemic infections) - given by IV (parentally), not orally
Polyenes - mode of action
associates with ergosterol, resulting in the formation of pores. This results in cell leakage and loss of membrane integrity, resulting in cell death
Remember 'P' = plasma membrane
What does Amphotericin B effect and name its adverse effects
- Kills most fungi of clinical important
-allergic reactions and nephrotoxicity
Example of allylamine (only one!) and adverse effect
Terbinafine - athletes foot - liver toxicity (RARE!)
Mode of action of allylamines
Inhibits ergosterol synthesis - blocks squalene epoxidase
What are allylamines used for?
superficial fungal infections (dermatophyte)
- topical - athletes foot (tinea pedis)
- oral - scale ringworm (tine cupids)
Name the 2 types of azoles
Imidazole's - 2 N atoms - v toxic
Triazoles - 3 N atoms - less toxic, systemic use common
What is the mode of action of Azoles
Block ergosterol synthesis - block lanosterol 14a demethylase
Give example of an Imidazole
(CLOT - RIM - AZOLE)
Give examples of Triazoles
Fluconazoles (Flu-CON-azole) - does not kill aspergillis
Voriconazoles (vori- CON-azole)
Adverse effects of azoles
- hepatotoxicity (hepatitis)
- Interact with Cytochrome P450 enzymes (increases conc of all drugs metabolised by Cy P-450)
What fungal infections are the following used for..
Fluconazoles - yeasts ONLY
Intraconazoles/Voriconazoles - Yeasts and aspergillis
Posconazole/isavuconazole - all!!
What is clotrimazole used for?
What is the mode of action of echinocandins?
Blocks beta 1,3 gluten synthase (prevents construction of fungal cell wall)
What does/does not Echinocandins effect?
- effects aspergillus and candida
- misses some moulds and cryptococcus
Adverse effects of echinocandins?
minimal - because there are no things similar to beta 1,3 glucan synthase - very selective toxicity
Why do we do therapeutic drug monitoring?
Minimise toxicity while ensuring efficacy