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Pharm Final antibiotics/fungals > Antifungals > Flashcards

Flashcards in Antifungals Deck (56):
1

What are the benefits of fungi

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

2

What are the levels of fungal treatment

prophylaxis
Empiric
Targeted

3

what is prophylaxis treatment of fungal infections

preventive treatment of a specific pathogen in an at risk pt

4

what is empiric treatment for fungal infections

treatment as soon as possible or probable fungal infection
based on presence of symptoms consistent with a fungal infection, but no positive culture data

5

what is targeted treatment of fungal infections

definitive positive culture data exists allowing for targeted treatment

6

Who is at risk for getting fungal infections

Immunosuppressed patients

7

What are big challenges of fungal infections

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

8

What drugs make up the Azoles

fluconazole
Itraconazole
Voriconazole
Posaconazole

9

what drugs make up the polyenes

Nystatin
Amphotericins

10

what is the definition of a fungistatic drug

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

11

What is the definition of fungicidal drugs

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

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?

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

13

what is the mechanism of action for amphotericin?

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

14

What organism are resistant to Amphotericin

Candida lusitainae
Pseudallescheria boydii
Candida krusei (somtimes)

15

what are some adverse effects of amphotericin that are infusion related

fever, chills, rigors, hypotension

16

what should you premedicate patients with before getting amphotericin

acetaminophen
diphenhydramine
merepridine
hydrocortisone

17

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

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

18

what are adverse effects of amphotericin due to chronic use

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

19

what is the purpose of creating lipid formulations of amphotericin?

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

20

what are the clinical uses of amphotericin

reserved for life threatening or refractory conditions
Given IV over 2-6 hours

21

what is the mechanism of action for flucytosine

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

22

what are the adverse effects of flucytosine

myelosupression (bonemarrow)
hepatotoxicity

23

what re the clinical uses of flucytosine

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

24

what makes up the imidazoles (3)

ketoconazole
miconazole
clotrimazole

25

what makes up the triazoles
(4)

itraconazole
fluconazole
voriconazole
posaconazole

26

what is the MOA for the azoles

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

27

what are the adverse effects of the azoles

Gi upset
increased LFTs

28

what are potential drug interactions for the azoles

inhibit the human CYP450 enzyme
Major target is CYP450 3A4

29

which has less enzyme selectivity imidazole or the triazoles

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

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?

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

31

what species for Itraconazole cover?

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

32

What is Itraconazole used to treat

onychomycosis
can also be used in histoplasmosis and blastomycosis

33

What are is fluconazole used for

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

34

what species does fluconazole have no effectiveness against?

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

35

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

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

36

How is voriconazoles coverage?

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

37

what organism does posaconazole cover

candida, aspergillus, other molds

38

what is posaconazole approved for?

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

39

What dosage forms is posaconazole available in

oral solution, IV, and tablets

40

What increased the bioavailability of posaconazole?

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

41

What class of fungi do echinocandins treat

candida and apergillus

42

what dose form are echinocandins available in?

IV only

43

what is the MOA of echinocandins

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

44

Echinocandins are fungistatic against which of the two fungi

aspergillus

45

echinocandins are fungicidal against which fungi

candida

46

what are the adverse effects of echinocandins

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

47

what is echinocandins used for

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

48

what drugs are part of the echinocandins class

caspofungin
micafungin
anidulafungin

49

what is caspofungin used to treat

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

50

what is micafungin used to treat

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

51

what is andifulafungin used to treat

esophageal candidiasis and invasive candidiasis

52

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

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

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

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

54

what is tolnaftate used to treat

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

55

what is nystatin used to treat
what is its dose form

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

56

how do you select antifungal treatment

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