Anti-Fungal Agents Flashcards
Name 2 polyenes antifungal
- Amphotericin B
- Nystatin
Name the 2 categories of azole antifungals
- Triazole
- Imidazole
What is the mechanism of action polyene antifungals?
They bind to ergosterol in the plasma membranes of sensitive fungal cells to forms pores (channels). These pores disrupt membrane function, allowing electrolytes and other small molecules to leak from the cell, resulting in cell death.
How is amphotericin B commonly administered?
IV (poor oral bioavailability)
What advantage does the liposomal formulation of amphotericin B has over the conventional deoxycholate formulation?
- Liposomal formulation has reduced renal toxicity
State 2 adverse effects associated with amphotericin B deoxycholate formulation
- Fever and chills
- Nephrotoxicity
Name 2 clinical indications for amphotericin B
- Candidiasis
- Aspergilliosis
- Cryptococcal meningitis
Name an anti-fungal, which is relatively safe for use in pregnancy despite systemic exposure.
Amphotericin B
What is the mechanism of action for 5-Flucytosine?
5-flucytosine is converted, by cytosine deaminase, to its metabolically active form 5-fluorouracil (5-FU), which inhibits protein synthesis and inhibits thymidylate synthase hence inhibiting DNA synthesis.
FYI: How is 5-Flucytosine commonly administered?
Oral (good oral bioavailability)
FYI: State at least 2 adverse effects associated with the use of 5 flucytosine
- Bone marrow suppression
- Hepatotoxicity
- GI related effects
FYI: State one clinical indication for 5-flucytosine
- Cryptococcal meningitis (usually in combination with amphotericin B, rarely used as single agent due to resistance)
Name 3 echinocandins
- Caspofungin
- Micafungin
- Anidulafungin
State the mechanism of action of the echinocandins
Echinocandins inhibit the activity of the glucan synthase complex, resulting in loss of the structural integrity of the cell wall
How are echinocandins commonly administered?
Intravenously
Name 2 fungal species against which Echinocandins have potent activity
- Candida
- Aspergillus
What is the mechanism of action of azoles?
They inhibit C-14 α-demethylase (CYP450 enzyme), thereby blocking the demethylation of lanosterol to ergosterol. This inhibition of ergosterol biosynthesis disrupts membrane structure and function and inhibits fungal cell growth.
Do the triazoles have good oral bioavailability?
Yes
State 3 adverse effects common to the triazoles
- QT prolongation
- Hepatotoxicity
- GI side effects
Name a triazole which is associated with the adverse effect of cardiotoxicity
Itraconazole
Name a triazole which is associated with the adverse effect of neurotoxicity
Voriconazole
Name one class of anti-fungals, which is significantly associated with CYP450 enzymes related drug-drug interactions?
Azoles
Which azole should not be taken with antacids?
Itraconazole (low pH improves absorption)
Which azole is the treatment of choice for the management of aspergillosis?
Voriconazole
How are the imidazoles commonly administered?
Topical (minimally absorbed)
Name 2 anti-fungal drugs that can be used in the management of vuvlovaginal candidiasis and describe how it is administered
- clotrimazole (cream)
- fluconazole (oral)
- miconazole (vaginal suppository)
- nystatin (vaginal suppository)
Is nystatin administered parenterally?
No
State a clinical indication for nystatin, and how it is administered.
- oropharyngeal candidiasis (oral agent; swish and swallow or swish and spit)
- vulvovaginal candidiasis (vaginal suppository)
What is terbinafine’s mechanism of action?
It inhibits squalene epoxidase, thereby blocking its conversion to lanosterol and biosynthesis of ergosterol, an essential component of the fungal cell membrane.
How is terbinafine administered for the management of tinea capitis?
Oral (Topical application cannot be used for the management of tinea capitis)
