Antifungals

Question 1

What are the benefits of fungi

Answer 1

source of many medications
penicillin and other beta-lactams
Food-edible mushroom
Insect control-process of competitive exclusion to actively compete for nutrients
Biotech-yeast species used to produce peptide drugs

Question 2

What are the levels of fungal treatment

Answer 2

prophylaxis
Empiric
Targeted

Question 3

what is prophylaxis treatment of fungal infections

Answer 3

preventive treatment of a specific pathogen in an at risk pt

Question 4

what is empiric treatment for fungal infections

Answer 4

treatment as soon as possible or probable fungal infection

based on presence of symptoms consistent with a fungal infection, but no positive culture data

Question 5

what is targeted treatment of fungal infections

Answer 5

definitive positive culture data exists allowing for targeted treatment

Question 6

Who is at risk for getting fungal infections

Answer 6

Immunosuppressed patients

Question 7

What are big challenges of fungal infections

Answer 7

hard to diagnose
potential toxicity
need for targeted therapy
development of resistance to available agents
limited formulations
aggressiveness of pathogen

Question 8

What drugs make up the Azoles

Answer 8

fluconazole
Itraconazole
Voriconazole
Posaconazole

Question 9

what drugs make up the polyenes

Answer 9

Nystatin

Amphotericins

Question 10

what is the definition of a fungistatic drug

Answer 10

inhibit growth then the immune system can then complete eradication of pathogenic fungi

Question 11

What is the definition of fungicidal drugs

Answer 11

kill fungal pathogens. dependent on mechanism of drug and ability to reach adequate concentration at the site of action
preferred treatment in immunocompromised patients

Question 12

Amphotericin
what class does it belong to?
when was it first made?
how is it administered?
how long is its half-life?
what is the dose adjustment in renal or hepatic impairment?

Answer 12

polyene macrolide antifungal
1950's
only IV form can make oral rinse
15days
no dose adjustment for renal or hepatic impairment

Question 13

what is the mechanism of action for amphotericin?

Answer 13

binds to and disrupts ergosterol in fungal cell membrane.
Disrupts membranes integrity leading to creation of pores in cell membrane
alteres membrane permeability
This leads to leakage of intracellular components out of the cell and fungal cell death ensues

Question 14

What organism are resistant to Amphotericin

Answer 14

Candida lusitainae
Pseudallescheria boydii
Candida krusei (somtimes)

Question 15

what are some adverse effects of amphotericin that are infusion related

Answer 15

fever, chills, rigors, hypotension

Question 16

what should you premedicate patients with before getting amphotericin

Answer 16

acetaminophen
diphenhydramine
merepridine
hydrocortisone

Question 17

What should you do to test a patients risk/tolerance of ampotericin

Answer 17

administer 1mg test dose to asses risk. need to monitor for 15-30min

Question 18

what are adverse effects of amphotericin due to chronic use

Answer 18

Renal toxicity
increased Scr
increased nitrogen comp. like BUN
renal tubular acidosis
K&Mg wasting
hepatic toxicity
increased LFT

Question 19

what is the purpose of creating lipid formulations of amphotericin?

Answer 19

created to improve tolerability
helps deliver amphotericin to affected tissue
reduce toxicity, but don’t eliminate it
high expense limits use

Question 20

what are the clinical uses of amphotericin

Answer 20

reserved for life threatening or refractory conditions

Given IV over 2-6 hours

Question 21

what is the mechanism of action for flucytosine

Answer 21

taken up by fungal cells and converted to 5-Fu and then 5-FdUMP and 5-FdUTP
these molecules inhibit fungal DNA and RNA synthesis
has synergistic action with amphotericin

Question 22

what are the adverse effects of flucytosine

Answer 22

myelosupression (bonemarrow)

hepatotoxicity

Question 23

what re the clinical uses of flucytosine

Answer 23

mostly used to treat crytococcal meningitis
almost always used with other antifungal
rapid development of resistance

Question 24

what makes up the imidazoles (3)

Answer 24

ketoconazole
miconazole
clotrimazole

Question 25

what makes up the triazoles | 4

Answer 25

itraconazole fluconazole voriconazole posaconazole

Question 26

what is the MOA for the azoles

Answer 26

inhibit fungal cytochrome p-450 dependent enzyme lanosterol 14 alpha demethylase reduces formation of ergosterol considered fungistatic

Question 27

what are the adverse effects of the azoles

Answer 27

Gi upset | increased LFTs

Question 28

what are potential drug interactions for the azoles

Answer 28

inhibit the human CYP450 enzyme | Major target is CYP450 3A4

Question 29

which has less enzyme selectivity imidazole or the triazoles

Answer 29

the imidazoles which is why they have more of an effect on the CYP450 enzymes. So they have more drug interactions

Question 30

What how selective is ketoconazole for the CYP450 enzymes how is its potentcy compared to new azoles? what type of infection is it used for?

Answer 30

less selective for the fungal CYP450 enzymes not as potent as the newer azoles used in topical fungal infection

Question 31

what species for Itraconazole cover?

Answer 31

candida and apergillus but have been replaced by voriconazole due to better bioavalibility and penetration of CNS

Question 32

What is Itraconazole used to treat

Answer 32

onychomycosis | can also be used in histoplasmosis and blastomycosis

Question 33

What are is fluconazole used for

Answer 33

for tx and prophylaxis of coccidiodal and cryptococcal meningitis. Effective in treatment of canddida used in pts as prophylaxis in neutropenic patients

Question 34

what species does fluconazole have no effectiveness against?

Answer 34

aspergillus | with resistance seen in C. krusei and C. glabrata

Question 35

``` Voriconazole what is it available in? how is its bioavialbility? what are the adverse effects? what do you need to does adjust for? ```

Answer 35

oral tabs, solution, IV form. excellent bioavail hepatic tox, rash, visual changes just need hepatic impairment adjustment

Question 36

How is voriconazoles coverage?

Answer 36

broad range of activity candida, aspergillus, fusarium, scedosporium used in prophylaxis and invasive fungal infections

Question 37

what organism does posaconazole cover

Answer 37

candida, aspergillus, other molds

Question 38

what is posaconazole approved for?

Answer 38

prophylaxis of fungal infections in immunosuppressed pts | can also be used for salvage therapy in systemic fungal infections

Question 39

What dosage forms is posaconazole available in

Answer 39

oral solution, IV, and tablets

Question 40

What increased the bioavailability of posaconazole?

Answer 40

when taken after a full meal or with an acidic carbonate beverage

Question 41

What class of fungi do echinocandins treat

Answer 41

candida and apergillus

Question 42

what dose form are echinocandins available in?

Answer 42

IV only

Question 43

what is the MOA of echinocandins

Answer 43

inhibit beta-1,3-glucan synthase inhibits creation of component of fungal cell walls disrupts fungal cell integrity and leads to cell death

Question 44

Echinocandins are fungistatic against which of the two fungi

Answer 44

aspergillus

Question 45

echinocandins are fungicidal against which fungi

Answer 45

candida

Question 46

what are the adverse effects of echinocandins

Answer 46

typically well tolerated GI effects flushing reaction if unfused too fast increased LFT

Question 47

what is echinocandins used for

Answer 47

limited to IV | often used in refractory cases or in patients with renal or hepatic impairment

Question 48

what drugs are part of the echinocandins class

Answer 48

caspofungin micafungin anidulafungin

Question 49

what is caspofungin used to treat

Answer 49

disseminated candidiasis, salvage treatment of apergillosis or empiric treatment of possible fungal infection

Question 50

what is micafungin used to treat

Answer 50

esophageal candidiasis, candidemia and prophylaxis of candida infections in SCT patients

Question 51

what is andifulafungin used to treat

Answer 51

esophageal candidiasis and invasive candidiasis

Question 52

what is griseofulvin used to treat how is it absorbed what is its MOA what is the risk associated with it

Answer 52

used to treat fungal skin and nail infection very poor oral absorption is increased with a high fat meal Works by binding to keratin in skin and prevents spreading of fungal infection take weeks to be effective risk of liver toxicity

Question 53

``` what is terbinafine used to treat what is its MOA how is it dosed what is its dose form what are the risks with this medication ```

Answer 53

``` treats dematophytoses and onychomycosis interferes with ergosterol synthesis by inhibiting squalene epoxidase dosed over several months topical cream or tablets hepatic tox. with oral tablets ```

Question 54

what is tolnaftate used to treat

Answer 54

used in topical creams and sprays treats athletes foot and other superficial infections works by interfering ergosterol synthesis risk of skin irritation

Question 55

what is nystatin used to treat | what is its dose form

Answer 55

active candidiasis well tolerated topically powders, cream, vaginal suppositories, oral suspension

Question 56

how do you select antifungal treatment

Answer 56

identify patient with or at risk for fungal infection consider level of treatment (prophylaxis vs empiric vs targeted treatment) consider fungi involved and severity select therapy from available agents based on route, spectrum of activity, availability cost and tolerability