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Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

1
Q

what is the component of fungal cell walls that humans don’t have, making it a good drug target

A

ergosterol

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2
Q

what are the 3 classes of antifungals

A

antibiotics (amphotericin B)
antimetabolite (pyrimidine analog)
azoles

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3
Q

is amphotericin B fungicidal or fungistatic

A

fungicidal

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4
Q

what is the mechanism of action for amphotericin B

A

it binds to ergosterol and forms pores, allowing for the leakage of cell content and death of the fungal cell

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5
Q

is amphotericin B able to cross the BBB

A

no

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6
Q

is amphotericin B polar or nonpolar

A

polar so it is water soluble and can’t cross the cell membrane, given IV

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7
Q

amphotericin B is used for topical actions for __ infections

A

GI

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8
Q

amphotericin B can lead to __ toxicty

A

renal

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9
Q

how is amphotericin B prepared to decrease its toxicity

A

bound to liposomes which have low affinity to human tissue and therefore bind poorly

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10
Q

amphotericin B is the drug of choice for what fungal infections

A

serious and life threatening

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11
Q

what is the acute/immediate reaction of amphotericin B due to IV infusion

A

release of histamine leads to fever, chills, vomiting, HA, etc.

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12
Q

how can the acute/immediate reaction due to amphotericin B be reduced

A

by slowing the rate of IV infusion and using a test dose of 1mg

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13
Q

what is the adverse effect of amphotericin B that occurs in most people

A

nephrotoxicity–>tubular acidosis, hypokalemia and hypomagnesaemia

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14
Q

flucytosine is a pyrimidine antimetabolite which is an analog of __

A

5-fluorouracil

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15
Q

is flucytosine fungistatic or fungicidal

A

fungistatic

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16
Q

is flucytosine able to cross the BBB

A

yes

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17
Q

what is the mechanism of action of flucytosine

A

it inhibits fungal thymidylate synthetase, inhibiting RNA and DNA synthesis

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18
Q

amphotericin B is used synergistically with flucytosine. why

A

amphotericin B produces pores and increases the penetration of 5-fluorouracil into the fungal cell

19
Q

what does it mean to say that flucytosine has a narrow therapeutic window

A

at high concentration it produces more toxic effects and at low concentration it develops resistance

20
Q

what is the mechanism of action of azole drugs

A

inhibition of 14-alpha demethylase leads to inhibition of demethylation and leakage of cell contents

21
Q

mutation in what gene can lead to azole drug resistance

A

ERG11

22
Q

what are 2 adverse reactions of ketaconazole azole drugs

A

blockage of androgen receptors–> impotence, decreased libido, gynecomastia, and menstrual irregularities

disulfiram like reactions

23
Q

amphotericin B should not be combined with what other drug

A

azoles

24
Q

fluconazole is useful for meningitis due to the fact that it has __

A

good CSF permeability

25
Q

fluconazole is as efficacious as amphotericin B at preventing __

A

candidemia in ICU patients

26
Q

what is the drug of choice for cryptococcal meningitis

A

fluconazole

27
Q

itraconazole has poor __ and __

A

absorption (enhance with food)

CSF penetration

28
Q

what is the broadest spectrum of azole

A

itraconazole

29
Q

itraconazole is the drug of choice for what 3 fungal infections

A

histoplasmosis
blastomycosis
sporothrichosis

30
Q

what are 2 adverse effects of itraconazole

A

hepatotoxicity
should be avoided in pregnancy

31
Q

what drug is effective in fluconazole resistant candidiasis

A

vorconazole

32
Q

what is an adverse effect of posaconazole

A

hyperaldosteronism

33
Q

what is the mechanism of action of echinocandin drugs

A

inhibits beta 1,3 D-glucan synthase leading to inhibition of 1,3 beta-glucan synthesis, preventing integrity of fungal cell wall and leading to lysis of the fungal cells

34
Q

what is the mechanism of action of echinocandin drugs

A

inhibits beta 1,3 D-glucan synthase leading to inhibition of 1,3 beta-glucan synthesis, preventing integrity of fungal cell wall and leading to lysis of the fungal cell

35
Q

what is the mechanism of resistance to echinocandins

A

amino acid changes in fks subunits of glucan synthase

36
Q

are echinocandins fungicidal or fungistatic

A

fungicidal

37
Q

capsofungin, an echinocandin, is used in what 3 cases

A

disseminated and mucocutaneous candida infections
empirical and stem cell transplants
salvage therapy in invasive aspergillosis

38
Q

griseofulvin is used for what type of mycotic infections

A

superficial

39
Q

what is the mechanism of action of griseofulvin

A

it binds to microtubules and prevents spindle formation, inhibiting fungal mitosis

*it prevents infection of new tissue, not the tissue that is already infected

40
Q

how can the absorption of griseofulvin be increased

A

give with fatty food

41
Q

why is prolonged therapy required with griseofulvin

A

it is required until the infected tissue is replaced by new healthy skin or nail

42
Q

what is the main adverse effect of griseofulvin

A

disulfiram like reaction

43
Q

what is the mechanism of action of allylamine

A

it inhibits squalene epoxidase and ergosterol synthesis, leading to the accumulation of squalene which is toxic to fungus

44
Q

what is the drug of choice for dermatophytosis (especially for onychomycosis)

A

terbinafine

Pharmacology (16 decks)

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