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x. ID > 5/05 PHARM Antifungals > Flashcards

5/05 PHARM Antifungals Flashcards

* are drugs that weren't mentioned in the SBM, but should know for boards ** are best ones to know of the ones listed

1
Q

difference btwn yeast, mold, and dimorphic fungi in terms of cellularity?

A 
Yeast = Unicellular
Mold = Multicellular 
Dimorphic = Yeast at BT, Mold at RT
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2
Q

examples of Dimorphic fungi?

A

Histoplasma, Blastomyces, Coccidioides (indigenous to specific areas and pt populations - ex: HIV)

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3
Q

How can you tell on a plate if it is growing yeast or mold?

A

yeast: Pasty colonies (resembles bacteria)
mold: Surface texture: Cottony/ woolly/ velvety/ granular…

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4
Q

Are cell membranes present in mammals? fungi?

A

cell wall: present only in fungi

cell membrane: present in both, but comprised of different compositions

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5
Q

What is the basic composition and function of the cell wall? is it antigenic or non-antigenic?

A

polysaccharide, proteins, and glycoproteins

fxn: shape, rigidity, strength and protection from osmotic shock

ANTIGENIC

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6
Q

What is the basic composition and function of the cell membrane? is it antigenic or non-antigenic?

A

phospholipids, sterols

fxn: Protects cytoplasm, Rregulates intake/secretion of solutes, facilitates capsule and cell wall synthesis

didn’t say whether it’s antigenc or not, but personally, I don’t think it’s antigenic??

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7
Q

How does the cell membrane composition differ btwn fungi and mammals?

A

Present – contains ergosterol

Present – contains cholesterol

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8
Q

knowing the compositional differences btwn the cell wall and cell membrane, what drugs can you use to target each one?

A

cell wall: Enchinocandins – glycan synthesis inhibitor

cell membrane: Azoles or polyenes to inhibit cell membrane synthesis

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9
Q
  • Terbinafine MoA? Indications? Side effect?
A

MoA: blocks squalene epoxidase to prevent lansterol synthesis (for cell membrane)

Indication: Onychomycosis

GI upset, HA, hepatotoxicity, taste disturbance

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10
Q

name some ergosterol synthesis inhibitors

A

fluconazole
itraconazole
voriconazole
posconazole*

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11
Q

mechanism of “azoles”?

A

inhibits ergosterol synthesis by inhibiting the cytochrome p450 enzyme (14-a-demethylase) that converts lanosterol -> ergosterol (for cell membrane)

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12
Q

of all the azoles that we learned, which one has the poorest GI absorption/CNS penetration?

A

itraconazole

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13
Q

of all the azoles that we learned, which one has the least drug interactions?

A

fluconazole

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14
Q

indications for fluconazole?

A

suppression of

  • cryptococcal neoforman meningitis in AIDs**
  • candida albicans infections in all drug of choice
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15
Q

indication for itraconazole?

A

histoplasma **
blastomyces
coccidioides

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16
Q

indication for voriconazole?

A

aspergillus**

prophylaxis during neutropenia and gvhd

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17
Q

indication for posconazole?

A 
mainly zygomycosis (mucormycosis)**
but also great activity against: 
-	candida albicans**
-	cryptococcus**
-	aspergillus**
-	fusarium**
18
Q

general side effects of azoles?

A
  • testosterone synthesis inhibitor
  • liver dysfunction/hepatitis (inhibits cytochrome p450)
  • increase drug conc. of drugs metabolized by cyp450
19
Q

which azole is commonly associated with gynecomastia?

A

ketoconazole** and itraconazole (likely due displacement of steroid hormones from serum binding proteins, resulting in a net increasein free E)

20
Q

which azole has a greater likelihood of hepatitis? What ADR also associated with this particular drug?

A

voriconazole; also associated with visual disturbances

21
Q

name 2 drugs that commonly form membrane pores in fungi. What class of drugs do they fall under?

A 
amphotericin b (deoxycolate or lipid formulations)
nystatin

both fall under the polyene class

22
Q

MoA for amphotericin B?

A

binds ergosterol (unique to fungi); forms membrane pores that allows leakage of electrolytes and proteins from the cell

“amphoTEARicin tears holes in the fungal membrane”

23
Q

What must you administer with amphotericin B and why?

A

must give K supplements and Mg supplements because of electrolyte losses that occur as a result of altered renal tubule permeability

24
Q

Why is the liposomal formulation preferred over the deoxycolate formulation of amphotericin B?

A

liposomal formulation decrease toxicity/adrs, but requires higher doses to achieve the same therapeutic effect

25
Q

Indications for amphotericin B?

A 
serious systemic mycoses
-	cryptococcus 
-	blastomyces
-	coccidiodes
-	histoplasma 
-	candida
-	mucormycosis
fungal meningitis (intrathecal)
26
Q

ADRs of amphotericin B? What is cool about these particular symptoms?

A 
ampho“terrible”:
fever, chills/rigors “shake & bake”
hypotension
nephrotoxicity** 
anemia (due to decr. EPO)
iv phlebitis

most of these symptoms can be prevented with prophylactic treatments (ie aspirin, diphenhydramine, hydrocortisone, slow infusion)

27
Q

MoA for nystatin?

A

same mxn as amphotericin b - tears holes in the membrane

28
Q

how is nystatin administered?

A

topic administration - too toxic for systemic use!

29
Q

nystatin indications?

A

“swish and swallow”
oral candidiasis
diaper rash
vaginal candidiasis

30
Q

antifungals that inhibits cell wall synthesis? What class do they fall under?

A

caspofungin
micafungin*
anidulafungin*

all fall under the echinocandins class

31
Q

MoA for caspofungin?

A

inhibit cell wall synthesis by inhibiting synthesis of ß1,3-d-glucan

32
Q

Indications for caspofungin?

A
  • invasive aspergillosis (3rd line rx)

- candida resistant to azoles or azole-allergic patients

33
Q

ADR for caspofungin?

A 
gi upset 
flushing (due to histamine release)
fever, rash, n/v
phlebitis,
hepatits
34
Q

nucleic acid synthesis inhibitors used as a anti-fungal therapy?

A

5-flucytosine*

35
Q

MoA of 5-flucytosine?

A

inhibit DNA/RNA biosynthesis via conversion to 5-FU by cytosine deaminase

36
Q

5-flucytosine is often used in combination with..?

A

amphotericin b

37
Q

Indications of 5-flucytosine?

A

systemic fungal infections (cryptococcus meningitis)

38
Q

ADR of 5-flucytosine

A

bone marrow suppression

39
Q

p450 inhibitors?

A 
"SICKFACES.COM Group"
sodium valproate 
isoniazid 
cimetidine 
ketoconazole 
fluconazole 
alcohol (binge)
chloramphenicol 
erythromycin 
sulfonamides 
ciprofloxacin 
omeprazole 
metronidazole
grapefruit juice
40
Q

p450 inducers?

A 
CRAP GPS induce me to madness
carbemazepines
rifampicin
alcohol (chronic)
phenytoin
griseofulvin
phenobarbitone
sulphonylureas

x. ID (40 decks)

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