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Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

1
Q

What are the benefits of fungi

A

source of many medicationspenicillin and other beta-lactamsFood-edible mushroomInsect control-process of competitive exclusion to actively compete for nutrientsBiotech-yeast species used to produce peptide drugs

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2
Q

What are the levels of fungal treatment

A

prophylaxisEmpiricTargeted

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3
Q

what is prophylaxis treatment of fungal infections

A

preventive treatment of a specific pathogen in an at risk pt

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4
Q

what is empiric treatment for fungal infections

A

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

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5
Q

what is targeted treatment of fungal infections

A

definitive positive culture data exists allowing for targeted treatment

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6
Q

Who is at risk for getting fungal infections

A

Immunosuppressed patients

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7
Q

What are big challenges of fungal infections

A

hard to diagnosepotential toxicityneed for targeted therapydevelopment of resistance to available agentslimited formulationsaggressiveness of pathogen

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8
Q

What drugs make up the Azoles

A

fluconazoleItraconazoleVoriconazolePosaconazole

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9
Q

what drugs make up the polyenes

A

NystatinAmphotericins

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10
Q

what is the definition of a fungistatic drug

A

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

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11
Q

What is the definition of fungicidal drugs

A

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

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12
Q

Amphotericinwhat 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?

A

polyene macrolide antifungal1950’sonly IV form can make oral rinse15daysno dose adjustment for renal or hepatic impairment

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13
Q

what is the mechanism of action for amphotericin?

A

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

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14
Q

What organism are resistant to Amphotericin

A

Candida lusitainaePseudallescheria boydiiCandida krusei (somtimes)

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15
Q

what are some adverse effects of amphotericin that are infusion related

A

fever, chills, rigors, hypotension

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16
Q

what should you premedicate patients with before getting amphotericin

A

acetaminophendiphenhydraminemerepridinehydrocortisone

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17
Q

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

A

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

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18
Q

what are adverse effects of amphotericin due to chronic use

A

Renal toxicityincreased Scrincreased nitrogen comp. like BUNrenal tubular acidosisK&Mg wastinghepatic toxicityincreased LFT

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19
Q

what is the purpose of creating lipid formulations of amphotericin?

A

created to improve tolerabilityhelps deliver amphotericin to affected tissuereduce toxicity, but don’t eliminate ithigh expense limits use

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20
Q

what are the clinical uses of amphotericin

A

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

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21
Q

what is the mechanism of action for flucytosine

A

taken up by fungal cells and converted to 5-Fu and then 5-FdUMP and 5-FdUTPthese molecules inhibit fungal DNA and RNA synthesishas synergistic action with amphotericin

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22
Q

what are the adverse effects of flucytosine

A

myelosupression (bonemarrow)hepatotoxicity

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23
Q

what re the clinical uses of flucytosine

A

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

24
Q

what makes up the imidazoles (3)

A

ketoconazolemiconazoleclotrimazole

25
Q

what makes up the triazoles(4)

A

itraconazolefluconazolevoriconazoleposaconazole

26
Q

what is the MOA for the azoles

A

inhibit fungal cytochrome p-450 dependent enzyme lanosterol 14 alpha demethylasereduces formation of ergosterolconsidered fungistatic

27
Q

what are the adverse effects of the azoles

A

Gi upsetincreased LFTs

28
Q

what are potential drug interactions for the azoles

A

inhibit the human CYP450 enzymeMajor target is CYP450 3A4

29
Q

which has less enzyme selectivity imidazole or the triazoles

A

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

30
Q

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

A

less selective for the fungal CYP450 enzymesnot as potent as the newer azolesused in topical fungal infection

31
Q

what species for Itraconazole cover?

A

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

32
Q

What is Itraconazole used to treat

A

onychomycosiscan also be used in histoplasmosis and blastomycosis

33
Q

What are is fluconazole used for

A

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

34
Q

what species does fluconazole have no effectiveness against?

A

aspergilluswith resistance seen in C. krusei and C. glabrata

35
Q

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

A

oral tabs, solution, IV form.excellent bioavailhepatic tox, rash, visual changesjust need hepatic impairment adjustment

36
Q

How is voriconazoles coverage?

A

broad range of activitycandida, aspergillus, fusarium, scedosporiumused in prophylaxis and invasive fungal infections

37
Q

what organism does posaconazole cover

A

candida, aspergillus, other molds

38
Q

what is posaconazole approved for?

A

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

39
Q

What dosage forms is posaconazole available in

A

oral solution, IV, and tablets

40
Q

What increased the bioavailability of posaconazole?

A

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

41
Q

What class of fungi do echinocandins treat

A

candida and apergillus

42
Q

what dose form are echinocandins available in?

A

IV only

43
Q

what is the MOA of echinocandins

A

inhibit beta-1,3-glucan synthaseinhibits creation of component of fungal cell wallsdisrupts fungal cell integrity and leads to cell death

44
Q

Echinocandins are fungistatic against which of the two fungi

A

aspergillus

45
Q

echinocandins are fungicidal against which fungi

A

candida

46
Q

what are the adverse effects of echinocandins

A

typically well toleratedGI effectsflushing reaction if unfused too fastincreased LFT

47
Q

what is echinocandins used for

A

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

48
Q

what drugs are part of the echinocandins class

A

caspofunginmicafunginanidulafungin

49
Q

what is caspofungin used to treat

A

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

50
Q

what is micafungin used to treat

A

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

51
Q

what is andifulafungin used to treat

A

esophageal candidiasis and invasive candidiasis

52
Q

what is griseofulvin used to treathow is it absorbedwhat is its MOAwhat is the risk associated with it

A

used to treat fungal skin and nail infectionvery poor oral absorption is increased with a high fat mealWorks by binding to keratin in skin and prevents spreading of fungal infectiontake weeks to be effectiverisk of liver toxicity

53
Q

what is terbinafine used to treatwhat is its MOAhow is it dosedwhat is its dose formwhat are the risks with this medication

A

treats dematophytoses and onychomycosis interferes with ergosterol synthesis by inhibiting squalene epoxidasedosed over several monthstopical cream or tabletshepatic tox. with oral tablets

54
Q

what is tolnaftate used to treat

A

used in topical creams and spraystreats athletes foot and other superficial infectionsworks by interfering ergosterol synthesis risk of skin irritation

55
Q

what is nystatin used to treatwhat is its dose form

A

active candidiasis well tolerated topicallypowders, cream, vaginal suppositories, oral suspension

56
Q

how do you select antifungal treatment

A

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

Pharmacology (14 decks)

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