Anti-Fungal Flashcards
What are the common primary care fungi?
Which two are resistant to fluconazole?
C. albicans
resistant:
- C. krusei
- C. glabrata
Who gets griseofulvin and why?
Peds - tinea capitis
What is the main echinocandin? What’s the MOA?
Micafungin
MOA: cell wall
- inhibit synthesis of b-D-glucan
Echinocandins are not excreted in urine. What should you not use these meds for?
UTI
- active drug is broken down before getting to kidneys
What are echinocandins indicated for?
“deep seeded systemic blood stream infections and abscesses”
- invasive candida infection (including most non-albicans Candida)
- Aspergillus infections
What are the three classes that work on the cell membrane?
- Polyenes
- Azoles
- Allylamines
What is the go-to Polyene to be aware of?
Liposomal amphotericin B (IV)
Nystatin is a topical polyene used for these two things?
- OP candidiasis
2. “Intertrigo”
What is the MOA of amphotericin B?
Binds ergosterol –> alters CELL MEMBRANE permeability –> leakage of cell components and death
How is amphotericin B excreted from the body?
Preceptor trick Q!!
No one knows!!
What are the drug interactions of amphotericin B?
Drug interaction: nephrotoxic drugs**
Monocytes/macrophages are stimulated and release proinflammatory cytokines = F/C/rigors during infusion
There are plenty of jibberish clinical indications for amphotericin B. What’s the bolded one?
Aspergillosis
Ampho B common ADRs?
- F/C/rigors (common)
- HA, NV, dec BP, tachypnea
Occur 1-3hr into infusion and last 1hr
Pre hydrate + slow infusion to minimize these ADRs
Ampho B dose-limiting ADRs?
Most concerned about electrolyte abnormalities (DEC K & Mg)
Monitor SCr - nephrotoxicity
Azoles can be used topically for what 3 “areas”? Name the bolded drug for each as well.
Oral - clotrimazole
Skin - clotrimazole
Vaginal - clotrimazole, miconazole
What are the 3 “old” systemic azoles?
- Ketoconazole
- Fluconazole
- Itraconazole
“New” systemic azoles - essentially supercharged fluconazole and will be “distractors” on the exam
Ketoconazole is rarely used systemically, except for what condition?
Metastatic prostate cancer
Itraconazole has minimal use except for which two fungi?
Histoplasmosis
Blastomycosis
What is the azole MOA?
CELL MEMBRANE
Inhibits fungal CYP450 which converts lanosterol –> ergosterol
No ergosterol = damaged cell wall, increased permeability, cell lysis
Tell me about fluconazole CYP?
Strong inhibitor of 2C9, 2C19, 3A4
What are 3 other pearls about the pharmacology of azoles (fluconazole)?
- Renal excretion (80% as unchanged drug)
- only antifungal that develops appropriate active urinary concentration** - > 90% bioavailability
- 30hr half life - single dose will be in your system for a week
Due to CYP interactions, what is one medication Paxton specified to have careful monitoring of if the patient is on fluconazole? (2C9)
Warfarin
What are fluconazole clinical indications?
Candida infections: thrush, vaginitis, cutaneous, “invasive”
Fluconazole ADRs?
Fairly well-tolerated
Teratogen
High dose - start getting concerned about QT prolongation
What should you use in a pregnant patient for vaginal candidiasis? What should you avoid?
Use: vaginal azoles (e.g. clotrimazole) - 1st line**
Avoid: Fluconazole (teratogen)
- do not use for vaginitis
- do not use in women TRYING to become pregnant, either**
What is the allylamine to know? What’s the MOA?
Terbinafine
MOA: CELL MEMBRANE
- inhibits ergosterol synthesis earlier in the pathway (similar concept as ACL inhibitor)
(inhibits squalene epoxidate which prevents ergosterol synthesis)
What two things should you be aware of regarding terbinafine and pharmacology?
- Strong 2D6 inhibitor
2. Concentrates in skin and nail beds and has relatively low bloodstream concentration
What are the two common clinical indications for allylamines (terbinafine)?
- Cutaneous dermatophyte infections (topical)
2. Onychomycosis (PO)
What are the main ADRs for allylamines (terbinafine)?
- Dysgeusia (like metformin, etc, etc)
- HTX - get baseline LFTs. If normal, you don’t really need to monitor
- more concern for older person with liver disease
