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Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Half life of Amphotericin B

A

15 days

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2
Q

Amphotericin B elimination route

A

urine, slowly

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3
Q

Amphotericin is selective for fungi because it targets this molecule

A

Ergosterol, a fungi cell membrane sterol not found in humans

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4
Q

Amphotericin B MOA

A

Creates larger and larger pores that disrupt membrane potential and ion balance

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5
Q

Describe induction therapy for Amphotericin B

A

Pt is started with a does of Amphotericin to aggressively attack fungal infection, and is then switched to a newer azole drug for chronic treatment or prevention

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6
Q

Flucytosine MOA

A

Taken up by fungal enzyme cytosine permease, converted into metabolites that inhibit DNA and RNA synthesis (it’s a pyrimidine analog)

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7
Q

Describe the toxic effects of flucytosine

A

Conversion to anticancer compound 5-FU can cause bone marrow toxicity with anemia

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8
Q

The two kinds of azoles

A

imidazoles and triazoles

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9
Q

The imidazoles

A

Ketoconazole, miconazole

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10
Q

The triazoles

A

Itraconazole, fluconazole, voriconazole, and posaconazole

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11
Q

Imidazoles or triazoles - which have higher specificity for fungal targets?

A

Triazoles (thus fewer adverse effects)

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12
Q

Imidazole and triazole MOA

A

Targets fungal P450s that synthesize ergosterol

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13
Q

Why are azoles at high risk for interacting with other drug types?

A

SInce they target (fungal) P450s, there is some overlap with human P450 interaction as well

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14
Q

This azole has the highest propensity to inhibit mammalian P450 and isn’t used much anymore

A

ketoconazole

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15
Q

Taking these drugs with itraconazole will result in reduced bioavailability

A

Rifamycins (e.g., rifampin)

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16
Q

Itraconazole is the drug of choice to treat these fungi

A

Dimorphic

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17
Q

Azole of choice to treat Aspergillus

A

vorizonacole

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18
Q

Compare the oral bioavailability of fluconazole, ketoconazole, and itraconazole

A

Fluonazole high others low

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19
Q

This azole has the least effect on human P450 enzymes

A

Fluconazole

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20
Q

Drug of choice to treat fungal meningitis

A

Fluconazole (best CSF penetration)

21
Q

Several azoles inhibit this specific liver enzyme

A

CYP3A4 (does statins, cyclosporine, and tacrolimus)

22
Q

Broadest spectrum of the azoles

A

Posaconazole

23
Q

Echinocandins members

A

Caspofungin, micafungin, anidulafungin

24
Q

Echinocandins available ROA

25
Q

Compare the tolerance of echinocandins and azoles

A

Echinocandins are much better tolerated

26
Q

Griseofulvin has significant interaction with these two drugs

A

Warfarin and phenobarbital

27
Q

Griseofulvin is now only used for this one problem

A

Systemic treatment of dermatophytosis

28
Q

Griseofulvin - fungistatic or fungicidal?

A

Fungistatic

29
Q

Terbinafine - fungistatic or fungicidal?

A

Fungicidal

30
Q

Describe terbinafine MOA

A

Inhibits ergosterol synthesis by inhibiting fungal enzyme squalene monooxygenase, leading to accumulation of the toxic compound squalene

31
Q

Azoles target this enzyme

A

14-alpha-demethylase

32
Q

Amphotericin B is in this drug class

33
Q

Allylamines drugs

A

Terbinafine

34
Q

Terbinafine target

A

squalene monooxygenase

35
Q

Echinocandins enzyme target

A

B-1,3-D-glucan synthesis inhibition

36
Q

Flucytosine target

A

thymidylase synthase

37
Q

Griseofulvin MOA

A

mitosis inhibition

38
Q

Are echinocandins effective against dimorphic fungi?

39
Q

Vorizonacole is a substrate for this P450

40
Q

All azoles have these significant side effects

A

Hepatic - CYP450 interactions; cardiac QT prolongation

41
Q

Amphotericin B side effects

A

Hepatic; renal toxicity; infusion reacitons, anemia from reduced epoetin from BM

42
Q

5-FC side effects

A

hepatic; GI, bone marrow suppression

43
Q

Echinocandins side effects

A

Hepatic, infusion reactions

44
Q

Voriconazole side effects

A

Renal toxicity; CNS toxicity; photopsia; photosensitivity/malignancy

45
Q

Itraconazole side effects

A

GI; cardiac (CHF contraindication); ED; breast pain, gynecomastia; hot flashes, etc.

46
Q

Posaconazole side effects

47
Q

Almost all antifungals have this side effect

48
Q

Most azoles are hepatically eliminated, except for this one

A

Fluconazole (renal)

49
Q

These azoles should never be used in a pregnant patient

A

Fluconazole and Voriconazole (Very Foolish to give!)

Pharmacology (3 decks)

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