Fungal Rx

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)