Antifungals

Question 1

Amphotercin B

Answer 1

• Forms pores in fungal cell membrane
• binds ergosterol
• parental administration
• insoluble (has modified forms, but $ and not much better)
• Renal Toxicity* => anemia, abnormal liver function, seziures

Question 2

Nystatin

Answer 2

• Forms pores in fungal cell membrane
• binds ergosterol
• Topically administered

Question 3

Terbinafine

Answer 3

• Inhibits ergosterol synthesis & creates squalene toxicity
• blocks conversion of squalene to squalene epoxide

Question 4

Fluconazole

Answer 4

• Azole (inhibits ergosterol synthesis via CYP3A4 inhibition)
• lanosterol–x—> Ergosterol (where x = CYP3A4)
• Best tolerated (renal elim.) (widest therapeutic window)
• Good oral bioavailability, good CSF penetration
• SE: pro-arrythmogenic

Question 5

Voriconazole

Answer 5

• Azole (inhibits ergosterol synthesis via CYP3A4 inhibition)
• lanosterol–x—> Ergosterol (where x = CYP3A4)
• Good oral bioavailability
• Drug-drug interactions via CYP (cyclosporine & tacrolimus)
• SE: neurologic, visual, and pro-arrythmogenic

Question 6

Ketoconazole

Answer 6

• Azole (inhibits ergosterol synthesis via CYP3A4 inhibition)
• lanosterol–x—> Ergosterol (where x = CYP3A4)
• DISCOURAGED by FDA
• poor oral solubility
• SE: Severe hepatic damage and adrenal insufficiency

Question 7

Posaconazole

Answer 7

• Azole (inhibits ergosterol synthesis via CYP3A4 inhibition)
• lanosterol–x—> Ergosterol (where x = CYP3A4)
• Poor oral solubility
• SE: GI discomfort

Question 8

Itraconazole

Answer 8

• Azole (inhibits ergosterol synthesis via CYP3A4 inhibition)
• lanosterol–x—> Ergosterol (where x = CYP3A4)
• Poor oral solubility & poor CSF penetration
• SE: GI discomfort

Question 9

Caspofungin

Answer 9

• Echocandin, Inhibits Beta-1,3-glucan synthesis
• Cell wall disruptor
• parental administration

Question 10

Flucytosine

Answer 10

• pyrimadine analog (DNA & RNA synthesis inhibitor)
• MOA: uses cytosine permease in enter fungal nucleus; gets converted to 5-flurouracil which gets incorporated
• Mammals do not have conversion enzyme but intestinal flora does => SE
• SE: Anemia, Leukocytosis, Thromocytopenia, elevated hepatic enzymes
• Oral administration

Question 11

Griseofulvin

Answer 11

• Microtubule disruptor (inhibits mitotic spindle formation)
• inhibits cell cycle
• Drug-drug interactions (cyp3a4 inducer): Warfarin, cyclosporine, and oral contraceptives
• used for severe skin infections (Tinea & other dermatophytosis)