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Fungal- medical microbiology > antifungals > Flashcards

antifungals Flashcards

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Biology 101 flashcards USMLE® Step 1 flashcards
1
Q

Polyenes

A
  • natural, from streptomyces

- for systemic fungal infection

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2
Q

what do polyenes target

A

the fungal membrane esp Ergosterol (fungal equivalent of cholesterol) , forms pores leading to cell death. hydrophobic and hydrophilic allow it to form pores

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3
Q

membrane sterols

A

stabilise phospholipid layer- without the membrane would be static . Leakage causes lack of cations (Na and sodium loss)

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4
Q

clinical use of polyenes

A

wide spectrum

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5
Q

polyene used to treat systemic infection (serious)

A

Amphotericin B

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6
Q

Nystatin is an

A

polyene used to treat superficial infection

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7
Q

problems with polyenes

A

only available via IV (expensive); nephrotoxicity

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8
Q

when were Azoles found

A

1960

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9
Q

azoles are

A

the largest group of antifungals

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10
Q

examples of azoles

A

imidazole, fluconazole

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11
Q

imidazole

A

2 nitrogen- rarely used due to toxicity and specificity problems

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12
Q

fluconazoles

A

made a lost of money- pobrlems with specificity, doesn’t work again aspergillus

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13
Q

Mode of azole action

A

-inhibit ergosterol synthesis- inhibiting 14 alpha sterol demethylase. Blocks heme iron in enzyme active site. Alters membrane fluidity

mainly FUNGISTATIC- just stop growth

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14
Q

problems with azoles

A

drug interaction (can stop other drugs from metabolizing- causing overdose and resistance

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15
Q

allyamines

A

inhibit ergosterol biosynthesis- fungicidal, due to accumulation of squalene

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16
Q

allyamines are used against

A

dermatophytes

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17
Q

allyamines have a poor activity against

A

candida and aspergillus

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18
Q

5-Flucytosine (5FC)

A

synthetic analogue of cytosine

19
Q

flu cytosine was originally developed as an

A

anti-cancer drug

20
Q

how does Flucytosine work

A

the drug enters the cell via cytosine permeate, where it is converted to 5- fluorouracil and inhibits preotin synthesis and DNA synthesis

21
Q

prodrug of flucytosine

A

fluorouracil

22
Q

flucytosine spectrum of acitvity

A

only works on yeast (candida and C.neoformans)

23
Q

problems with flucytosine

A

resistance is very common

24
Q

echinocandons found

A

in 70s

25
Q

echinocandons

A

semi-synthetics, first new class of antifungals in 20 years

26
Q

which anti-fungal was the first to be found in 20 years

A

echinocandins

27
Q

how do echinocandins work

A

inhibit B1, 3 gluten syntheses - cells lose shape and lyse

28
Q

echinocandins structure

A

very complicated- various layers: structural polysaccharides, chitin and gluten B1,6 and B1,3

29
Q

why do echinocandins not lyse filamentous fungi

A

due to them having other elements in their cell walls

30
Q

clinical use of echinocandins

A

candida, aspergillus

- low toxicity and not problem of cross resistance

31
Q

echinocandins have no activity against

A

Cryptococcus neoformans

32
Q

problems with echinocandins

A

not amiable orally, expensive

33
Q

superficial mycoses: dermatophytes

A

allyamines

34
Q

superficial mycosis: candidiasis

A

azoles

35
Q

systemic mycosis

A

azoles, amphotericin B, echinocandins

36
Q

amphoteicin B is used for

A

serious systemic infection

37
Q

mechanisms of resistance can be

A

natural and acquired

38
Q

acquired is

A

much more worrying

39
Q

acquired resistance is through

A

horizontal gene transfer in fungi

40
Q

main problems with antifungals

A

1) drug- drug interactions
2) toxic
3) new to market
4) IV only
5) expensive

41
Q

market worth

A

10.4 bill $

42
Q

clinically important drug interactions with amphotericin B can cause

A

nephrotoxicity, hypokalaemia and blood dyscrasias

43
Q

allyamines mode of action

A

inhibit the enzyme squalene epoxidase- preventing squalene from being converted to oxide-squalene

Fungal- medical microbiology (11 decks)

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