Antifungal Agents

Question 1

What do the “fungins” or eichinocandin drugs target? MOA?

Answer 1

Beta glucan which is component of the cell wall of

Question 2

What is the MOA of azole drugs?

Answer 2

14-a- demethylase

Lanosterol cannot be converted into ergosterol which is needed to maintain cell membrane integrity of the fungus

Question 3

What is the purpose of 14-a-demethylase?

Answer 3

to convert lanosterol into ergosterol

Question 4

MOA of terbinafine?

Answer 4

inhibits squalene epoxidase

Question 5

What is the purpose of squalene epoxidase?

Answer 5

to convert squalene to squalene epoxide and ultimately forming ergosterol to become a part of the fungal cell membrane

Question 6

MOA Amphotericin B?

Answer 6

binds ergosterol and interacts to form artificial pores which disrupt the membrane permeability?

Question 7

What are the polyene drugs for antifungals?

Answer 7

amphotericin B, Nystatin

Question 8

What does amphotericin B remain the DOC for?

Answer 8

severe infection caused by cryptococcus and Mucor

Question 9

What other drug does amphotericin B have synergistic action with?

Answer 9

flucytosine

Question 10

Can Nystatin be used systemically?

Answer 10

no too toxic for systemic use

Question 11

How is Nystatin used?

Answer 11

used topically for localized infections (e.g. candidiasis)

Question 12

How is Amp B given to a patient?

Answer 12

given by slow IV infusion: poor penetration into the CNS (intrathecal possible)

Question 13

What are the S/E of Amp B use?

Answer 13

fever chills, muscle rigor, hypotension (histamine release) occur during IV infusion (test dose advisable)

nephrotoxic

Question 14

How can the S/E of administering Amp B be alleviated?

Answer 14

partly by pretreatment with NSAIDs antihistamines, meperidine, and adrenal steroids

Question 15

Amphotericin nephrotoxicity can be diminished with what other methods?

Answer 15

protect by Na+ loading, use of liposomal amp B, or by drug combinations (e.g flucytosine) permitting a dec in the amp B dose

Question 16

Ketoconazole indications.

Answer 16

DOC for paracoccidioides and backup for blastomyces and Histoplasma

Question 17

Indications for fluconazole?

Answer 17

DOC for esophageal and invasive candidiasis and coccidioidomycosis

Prophylaxis and supression in cryptococcal meningitis

Question 18

Indications for itraconazole and voriconazole?

Answer 18

DOC in blastomycoses, sporotrichoses, aspergillosis

Question 19

Indication for clotrimazole and miconazole?

Answer 19

used topically for candidal and dermatophytic infection

Question 20

Which “azole” is the only one that can penetrate the CSF?

Answer 20

fluconazole

Question 21

S/E of some azole drugs?

Answer 21

• ketoconazole is a P450 inhibitor can decrease synthesis of steroids because P450 is needed in their production including cortisol > dec. libido, gynecomastia, menstrual irregularities; inc.
• LFTs and rare heptotoxicity

Question 22

MOA flucytosine?

Answer 22

activated by fungal cytosine deaminase to 5-fluorouracil (5-FU) which after triphosphorylation is incorporated into fungal RNA

5-FU then form 5 fluorodeoxyuridine monophosphate (5-Fd-UMP) which inhibits thymidylate synthase > dec thymine

Question 23

Toxicity associated with flucytosine associated with what?

Answer 23

toxic to bone marrow

Question 24

MOA griseofulvin? Indications?

Answer 24

active only against dermatophytes (orally, not topically) by depositing newly formed keratin and disrupting microbtuble structure

Question 25

Terbinafine MOA? What are the indications?

Answer 25

active only against dermatophytes by inhibiting squalene epoxidase > dec ergosterol

Question 26

Eichinocandins MOA?

Answer 26

inhibit synthesis of beta-1, 2 glucan, a critical component of fungal cell walls

Question 27

Indication for echinocandins?

Answer 27

back-up drugs give IV for disseminated and mucocutaneous Candida infection or invasive aspergillosis