antifungals

Question 1

Polyenes: amphotericin (IV) and nystatin (suspension powder) MOA

Answer 1

bind to ergosterol in the cell membrane leading to pore formation and efflux of K leading to cell death

Question 2

which is has the broader spectrum: mphotericin (IV) and nystatin MOA

Answer 2

amphotericin B

Question 3

the 2 majot toxicities for Amph-B

Answer 3

1. infusion-related- cytokine release

2. nephrotoxicity- approx. 30% of pt. will have this

Question 4

Nystatin is used for

Answer 4

mucocutaneous candidiasis only topical infections

Question 5

inhibits squalene epoxidase activity early in ergosterol synthesis pathway; deficiency of ergosterol in fungal cell membrane leading to fungal cell death

Answer 5

terbinafine (allylamines)

Question 6

terbinafine (allylamines) spectrum of activity

Answer 6

dermatophyte (skin and nail) infections

Question 7

terbinafine (allylamines) side effects

Answer 7

change in tastes perception and decreased appetite

Question 8

Azoles MOA

Answer 8

inhibit ergosterol synthesis in cell membrane
inhibition of cytochrome P450-dependent 14α-lanosterol demethylase activity

***all are metabolized via hepatic cytochrome P450 system and thus are associated with drug interactions
interactions differ with each agent

Question 9

zoles: Toxicities (2 major)

Answer 9

1. hepatitis

2. QTc prolongation

Question 10

Fluconazole is not active against

Answer 10

Aspergillus spp

Question 11

First line therapy for Invasive Pulmonary Aspergillosis

Answer 11

voriconazole

Question 12

voriconazole polymorphisms in CYP2C19 can lead to_________ metabolism

________ CYP43A4 – anticipate drug interactions

Answer 12

voriconazole polymorphisms in CYP2C19 can lead to slow or rapid metabolism

Inhibits CYP43A4 – anticipate drug interactions

Question 13

voriconazole adverse effects

Answer 13

vision changes

Question 14

Clinical uses: mucosal candidiasis, systemic candidiasis, Cryptococcosis

**Penetrates most body tissues including CNS, eye, and urine

Answer 14

fluconazole

Question 15

Commonly used for prophylaxis of invasive fungal infection in stem cell transplant patients and patients with prolonged neutropenia

Answer 15

posaconazole

Question 16

Mechanism of action
Disrupt fungal cell wall
inhibit Beta-(1,3)-D-glucan synthase
Beta-(1,3)-D-glucan is a fungal cell wall polysaccharide essential for Candida and Aspergillus species

Answer 16

Echinocandins

Question 17

Echinocandins fungicidal against

Answer 17

candida spp

Question 18

Echinocandins side effect

Answer 18

minimal!!!!! it is a selective fungal cell wall target

Question 19

Flucytosine

MOA

Answer 19

Interrupts fungal DNA and protein synthesis by inhibiting pyrimidine inhibitors

Question 20

Flucytosine resistance and tox

Answer 20

Resistance rapidly develops with monotherapy

and bone marrow suppression

Question 21

Echinocandins (Caspofungin

) have minimal toxicity because

Answer 21

mammalian cells do not have cell walls