Treatment of Fungal Infections Flashcards
See CMOD cards for all other fungal information
See CMOD cards for all other fungal information
An increase in resistance of aspergillus towards azoles has been seen. What mutation is most often implicated in resistance?
Resistance to Azole:
• Mutation in promotor region of CYP51A, which encodes lanosterol-14-alpha-sterol demethylase activity
Why is there a move away from the use of itraconazole towards the use of other newer azoles?
• which of these azoles can cross the BBB?
Newer Azoles:
• Fluconazole - ONLY one that can cross the BBB
• Voriconazole
• Posaconazole
What CYPs are inhibited by AZOLES.
CYP2C9, 2C19, 3A4
Why would it be a bad idea to use amphotericin with a high dose of corticosteroids?
Kidney damage may cause hypokalemia resulting in Cardiac Problems
Remember corticosteroids cause hypokalemia by up-regulating Na+/K+ pumps which leads to intracellular sequestration of K+
What are the only two antifungals that don’t undergo major hepatic metabolism?
Flucytosine
Amphotericin B
What are some strange adverse effects of flucytosine?
• May produce anemia, blood dyscrasias, including agranulocytosis (NO NEUTROPHILS, eos, or basos)
In what 4 cases where Amphotericin B is not the first line treatment?
All the time: Aspergillus and Bastomyces
• start with -azole
Mild to moderate Histo or Coccidio:
• use voriconazole or posaconazole
**Amphotericin remains second line treatment in case of failure with these treatments
By what mechanism has Aspergillus become more resistant to azoles?
Mutation in the promoter region of CYP51A which encodes lanosterol-14-alpha demethylase (azole drug target)
What are some adverse effects of Flucytosine?
- Anemia
- Blood Dyscrasias
- AGRANULOCYTOSIS
What drug types should be monitored with given with Amphotericin?
• Other nephrotoxic drugs and drugs that produce hypokalemia
