Antifungals

Question 1

What antifungals target membrane function?

Answer 1

amphotericin B

Question 2

What drugs target ergosterol synthesis?

Answer 2

• Fluconazole
• Itraconazole
• Voriconazole
• Naftifine
• Terbinafine

Question 3

What drugs target nucleic acid synthesis?

Answer 3

5-fluorocytosine

Question 4

What drugs target cell wall synthesis?

Answer 4

Caspofungin

Question 5

What are the options to treat superficial dermatophyte infections?

Answer 5

• Azoles - Either Triazoles or imidazoles
• Allylamines

Question 6

What are the options to treat superficial Candida infections?

Answer 6

• Azoles - Triazoles or Imidazoles
• Polyenes

Question 7

What are the options to treat deep fungal infections?

Answer 7

Triazoles or Amphotericin B

Question 8

What are the two drugs that are generally used to treat Candida? Dermatophytes?

Answer 8

• Candida - Polyenes, Azoles
• Dermatophytes - Allylamines, Azoles

Question 9

MOA of imidazoles and allylamines?

Answer 9

• Inhibit ergosterol synthesis by blocking lanosterol demethylase

Question 10

Spectrum of imidazoles and allylamines?

Answer 10

• imidazoles - broad - candida and dermatophytes
• Allylamines - narrow - eradicate only dermatophytes

Question 11

What are the topically applied cell wall synthesis inhibitors?

Answer 11

• imidazoles - clotrimazole
• Allylamines - tolnaftate

Question 12

What are the systemically administered cell wall synthesis inhbitors?

Answer 12

• Triazoles - fluconazole
• Allylamines - Terbinafine

Question 13

Spectrum of triazoles as systemically administered drugs?

Answer 13

Broad spectrum - eradicate fungi causing deep mycoses and dermatophytes

Question 14

Spectrum of allylamines as systemically administered drugs?

Answer 14

Used systemically for nail infections (fungi causing onchomycosis)

Question 15

Why is clotrimazole limited to topical application?

Answer 15

Due to toxicity

Question 16

What are the adverse effects of both triazoles and allylamines when used systemically?

Answer 16

• Rarely hepatotoxicity
• Drug interactions thru inhibition of CYP isoforms

Question 17

What drug is used for azole-resistant candida and aspergillus?

Answer 17

Caspofungin

Question 18

What is the MOA of caspofunginin?

Answer 18

It inhibits the glucan synthase complex which is responsible for fungal cell wall synth in the plasma membrane

Question 19

What is caspofungin reserved for?

Answer 19

Life-threatening fungal infections unresponsive to older agents (candida/aspergillus)

Question 20

What is the mechanism of the polyenes?

Answer 20

Pores formed in the fungal cell membrane allowing leakage of K+ and Mg++

Question 21

What are the polyenes and their particular route of administration?

Answer 21

• Nystatin - limited to topical use
• Amphotericin B - systemically

Question 22

For what infectious agent is nystatin used?

Answer 22

Only efficacious against candidiasis. Not dermatophytes

Question 23

For what type of infection is amphotericin B used? Tx strategy of deep mycoses in IC patients?

Answer 23

Life-threatening deep mycoses

• Amphotericin B
• Flucytosine

Question 24

Acute and chronic toxicities of amphotericin B

Answer 24

• Acute - (During IV infusion) -> Fever/chills, potential for hypotension
• Chronic - fall in Cr clearance, Mg and K wasting, renal tubular acidosis, bone marrow: normocytic anemia

Question 25

Patient in DKA with elevated blood sugar. Likely Dx? Tx?

Answer 25

Mucormycosis (bad mammajamma); Amphotericin B

Question 26

What is the MOA of flucytosine?

Answer 26

Cytosine deaminase (in fungi) eventually gets converted into 5-FdUMP which inhibits fungal thymidylate synthase

Question 27

SEs of flucytosine?

Answer 27

Sloughing of GI mucosa, centrolobular hepatitis and BM cytopenia