(7) Antimicrobials: Antifungals (5.1-5.3) Flashcards
MOA: Amphotericin B
Binds ergosterol
⇒ Pores in membrane
⇒ Osmotic lysis
(Same MOA for Nystatin)
What serves the role of cholesterol in a fungus’ cell membrane?
Ergosterol
ROA: Amphotericin B
(1) IV
(2) Intrathecal
* (Intrathecal only for severe fungal CNS infections)*
Name 2 methods used to reduce the toxicity of Amphotericin B
(1) Liposomal formulation
(2) Volume expansion with saline prior to administration
* (Liposomal formulation ⇒ Reduced affinity for human cholesterol)*
Why is Amphotericin B so toxic to humans?
AmphoB is poorly selective for ergosterol over cholesterol
(∴ It significantly damages human cell membranes)
Adverse Effects - Unrelated to kidneys (4) : Amphotericin B
(1) Infusion reaction ⇒ Hypotension
(2) “Shake and bake” chills
(3) Seizures
(4) Thrombophlebitis
* (Note: Seizures usually due to intrathecal administration)*
Under what scenario does Amphotericin B most commonly cause seizures and CNS side effects?
Intrathecal administration
Adverse Effects - Related to kidney (4) : Amphotericin B
(1) Type I renal tubular acidosis
(2) ⇒ Hypokalemia
(3) & ⇒ Mg2+ wasting
(4) ↓ EPO ⇒ Anemia
* (Type I RTA ⇒ More (-) luminal voltage ⇒ ↓ Driving force for Mg2+ reabsorption || ↑ Driving force for K+ secretion)*
MOA: Flucytosine
Incorporates into DNA/RNA ⇒ Halts DNA and protein synthesis
(Not completely specific for fungal DNA ∴ ⇒ bone marrow suppression as a side effect)
What is the active form of Flucytosine?
5-Fluorouracil
(Activated by cytosine deaminase)
What combo regimen is used to treat Cryptococcus?
(1) Flucytosine
(2) Amphotericin
What drug has the exact same MOA as Amphotericin B?
Nystatin
Name 3 topical agents used for vaginal/mucocutaneous candidiasis?
(1) Nystatin
(2) Clotrimazole
(3) Miconazole
What is the topical treatment for oropharyngeal candidiasis?
MOUTH RINSE of Nystatin
MOA: Azoles
Inhibits conversion of Lanosterol → Ergosterol
(Via inhibition of 14α-demethylase)
What effect do azoles have on the CYP450 system?
Inhibit the CYP450 system
Which azole is the strongest inhibitor of the CYP450 system?
Voriconazole
(Strong enough to throw house onto car)
Adverse Effects (2) : Voriconazole
(1) Blurry vision with flashes of light
(2) Changes in color vision
Name 2 antibiotics which may cause changes in color vision
(1) Voriconazole
(2) Ethambutol
* (Not an antibiotic, but Digoxin also causes this side effect)*
Name 2 first-line treatments for invasive aspergillosis
(1) Echinocandins
(2) Voriconazole
* (Amphotericin B is used for angioinvasive aspergillosis)*
Name 4 systemic antifungals which can be used to treat esophageal candidiasis
(1) Voraconazole
(2) Fluconazole
(3) Amphotericin B
(4) Capsofungin
Which systemic antifungal is used to treat mucocutaneous candidiasis?
Fluconazole
(Whereas Nystatin is the TOPICAL antifungal which is used)
What is the azole of choice for the treatment of Cryptococcal meningitis?
Fluconazole
(Combined with Flucytosine)
Which azole has a particularly high level of CNS penetration?
Fluconazole
Which azole is used to treat infections by dimorphic fungi?
Itraconazole
(“ITTTraconazole for fungi with two ITTTerations”)
Which azole is used to treat onychomycosis and dermatophytosis?
Itraconazole
Name 2 azoles used to treat tinea infections
(1) Clotrimazole
(2) Miconazole
Other than Itraconazole, which azole can be used to treat dermatophytosis?
Ketoconazole
(However, it’s not used due to extensive side effects)
What anabolic mammalian enzyme does Ketoconazole strongly inhibit?
Desmolase
(Thus inhibiting the conversion of Cholesterol → Pregnenolone and ∴ synthesis of androgens, aldosterone, and cortisol)
Name a (1) diuretic and (2) antimicrobial which can cause gynecomastia
(1) Diuretic: Spironolactone
(2) Antimicrobial: Ketoconazole
MOA: Griseofulvin
Binds microtubules ⇒ Halts mitosis
Name an antifungal which activates the CYP450 system
Griseofulvin
(Note: Griseofulvin is also associated with a disulfiram-like reaction similar to Metronidazole)
Treatment (2) : Tinea capitis
(1) Griseofulvin
(2) Terbinafine
* (Note: Griseofulvin is fungistatic whereas Terbinafine is fungicidal**)*
Treatment (2) : Onychomycosis
(1) Griseofulvin
(2) Terbinafine
* (∵ it accumulates in keratin)*
MOA: Terbinafine
Inhibits squalene epoxidase
What type of infections is Griseofulvin used to treat?
Dermatophytic
Other than tinea capitis in children, what is Terbinafine used to treat?
Dermatophytosis
Adverse Effects (2) : Terbinafine
(1) GI distress
(2) Hepatotoxicity
MOA: Echinocandins
Inhibit synthesis of β-1,3-glucan
(At the fungal cell wall, NOT cell membrane)
Where in the fungal cell are echinocandins active?
Cell wall
ROA: Echinocandins
IV
