antifungals

Question 1

Amphotericin B

Answer 1

IV injection only, broad spectrum standard treatment for life threatening mycoses. associated with significant adverse effects. Only anti fungal for pregnant women

Question 2

MOA amphotericin

Answer 2

Ampho B binds to ergosterol in fungal membrane, forming pore

Question 3

What is ampho B not active against?

Answer 3

Pseudallescheria boydii and C lusitaniae

Question 4

Flucytosine

Answer 4

Treats cryptococcal meningitis, good oral absorption, used with other drugs

Question 5

MOA flucytosine

Answer 5

Inhibits thymidylate synthase (dna synthesis) and 5-FUTP (RNA synthesis)

Question 6

What is the spectrum of activity for the azoles?

Answer 6

Fluconazole &laquo_space;itraconazole < voriconazole< posaconazole

Question 7

How do azoles work?

Answer 7

inhibit 14a sterol demthylase involved int he biosynthesis of ergosterol, increasing membrane permeability and decreasing membrane function

Question 8

Azole drug interactions

Answer 8

CYP450. most drug interactions with itraconazole and voriconazole. NEVER give itraconazole and voriconazole with statins due to rhabdo. inducers of cyp450 reduce levels of drug

Question 9

Ketonazole

Answer 9

Not used frequently. issues with cortisol and testoerone. requires acidic environment for absoprtion

Question 10

fluconazole

Answer 10

narrowest spectrum of activity, but good oral bioavailability and excellent CSF penetrasion. used for cyrptococcal meningitis and against mucocutaneous candida. associated with alopecia and mild ae

Question 11

Itraconazole

Answer 11

used for oral treatment of dermatophyte infections, preferred for non meningeal endemic dimophroic infections

Question 12

Itraconazole AE

Answer 12

hypertension, hypokalemia, and peripheral edema. Should not be used with ventricular dysfunction or CHF

Question 13

Voriconazole

Answer 13

good absorption into CSF but inhibited by fatty meals. Non linear metabolism. good activity against everything, treatment of choice for invasive aspergillus

Question 14

Voriconazole AE

Answer 14

Periostitis, transient vision changes, photosensititvyt and stevens johnson

Question 15

Posaconazole

Answer 15

poor penetration of CSF and urine, broadest spectrum, good safety profile. Used for invasive fungal infections and antifungal prophylazis in patients with prolonged neutropenia and severe graft vs host disease

Question 16

Echinocandins

Answer 16

Caspofungin, micafungin, anidulafungin. Directly target the fungal cell wall, not significant interactions with CYP45 no significant activity. good activity against aspergillus. towards Crypto or dimorphic fungihistimaine like effect. must be administered IV

Question 17

Echinocandin MOA

Answer 17

inhibits B(1-3)-D glucan synthase complex. impair structural integrity of fungal cell well and increases osmotic instability leading to cell death

Question 18

What drugs are used for cutaneous fungal infections?

Answer 18

Griseofulvin and terbinafine

Question 19

Griseofulvin

Answer 19

only effective against dermatophytes-microsporum, epidermophyton, and trichophyton. Many adverse effects and drug interactions.

Question 20

MOA griseofulvin

Answer 20

binds to fungal microtubules, preventing the formation of the mitotic spindle and inhibiting fungal mitosis. Infected cells are exfoliated and replaced by new uninfected cells because it accumulates in newly differentied keratin producing precursor cells.

Question 21

Terbinafine

Answer 21

activity limited to dermatophytes and candida albicans. Much more effective than other meds for these. well tolerated

Question 22

Terbafine MOA

Answer 22

inhibiton of fungal squalene epoxidase leading to impaired membrane function and increased toxic products

Question 23

Topical antifungals for cutaneous fungal infections

Answer 23

nyastatin, clotrimazole, miconazole, terconazole, terbinafine, naftifine, butenafine

Question 24

Nyastatin

Answer 24

binds to ergosterol and forms pores, but too toxic for IV administration and not active against dermatophytes. used for oral candidiasis (swish and swallow)

Question 25

Topical azoles

Answer 25

Used for oral and vulvovaginal candidiasis and dermatophyte infections

Question 26

Where does each group of drug work on the cell?

Answer 26

1) Plasma membrane: polyenes like amphotericin B and nystatin
2) Nucleus (DNA?RNA synthesis): flucytosine
3) ER (inhibition of ergosterol synthesis): azoles and terbinafine
4) Cell wall: B glucan synthesis : echinocandins
5) mitotic spindle: griseofulvin