Antifungals

Question 1

Amphitericin B

Answer 1

Binds to ergosterol in cell membrane to form pores and leakage
Used for severe system fungal infections as last resort due to S/E

Binds to cholesterol in human membranes also (lesser extent) in kidneys

S/E nephrotoxicity, hypokalamia, hypomagnesemia, infusion related reaction (prophylactic Tylenol, antiemetic)

Question 2

Nystatin

Answer 2

Binds to ergosterol
More toxic than amphotericin B so not used systemically
Not absorbed from the skin so used for superficial Candida infections of mouth, skin, intestinal tract and vagina

Question 3

Squalene epoxidase

Answer 3

Squalene———acts here— lanosterol - ergosterol

Question 4

Allylamines

Answer 4

Naftifine, terbinafine and butenafine(derivative)

Question 5

14a- demethylase inhibitors

Answer 5

Squalene- lanosterol——acts here—— ergosterol
Azoles- clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole and voriconazole

Cyp450 inhibitors

Question 6

Fungal and human cell difference

Answer 6

1.Fungal cells has cell wall (mannoproteins, B1,3 and B1,6 glucan, chitin)
2. Slight structural difference in cell membrane (has ergosterol instead of cholesterol)

As a result most anti fungal are toxic to human eg azoles cyp inhibition, amphotericin B nephrotoxicity

Question 7

Echinocandins

Answer 7

B-1,3- glucan synthase inhibitors
Osmosis instability and cell lysis

Eg caspofungin, micafungin &
Anidulafungin

Major advantage:-Active against azole resistant Candida strains and aspergillus species.
Also B glucan synthesis absence in humans so low potential for toxicity

Question 8

Griseofulvin

Answer 8

Binds to tubulin, disrupting microtubule function(works like chemotherapeutic agents) so inhibits mitosis

Question 9

Flucytosine

Answer 9

Works at nucleus level and is converted to 5 fluorouracil wc inhibit fungal RNA and DNA synthesis

Question 10

Ketoconazole

Answer 10

Imidazole
Gynecomastia, fetal hepatotoxicity,