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Pharmacology Exam 3 (Lauren) > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Why do you have to be careful giving aminoglycosides with amphotericin B?

A

Both are nephrotoxic

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2
Q

What is the route of administration for terbinafine

A

Oral or topical

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3
Q

Why do we think amphotericin B is SO toxic?

A

Human cholesterol looks a lot like ergosterol, so it probably binds to human cholesterol

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4
Q

Is griseofulvin static or cidal?

A

Static ***

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5
Q

How long is treatment with griseofulvin?

A

6-12 months. You have to replace all of the infected keratin

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6
Q

What is the administration of fluconazole?

A

Oral and IV

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7
Q

What is the MOA of nystatin?

A

Just like amphotericin B- forms pores

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8
Q

What makes micafungin and anidulafungin different from caspofungin?

A

They are all very similar, just a few altered pharmacokinetic properties

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9
Q

Why is caspofungin an attractive treatment option?

A

Doesn’t kill kidneys

Few drug interactions

(Why don’t we use them more?! They are cidal Penicillins of antifungals)

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10
Q

What are the 2 types of toxicities that are caused by amphotericin B?

A

Due to either:
1. Infusion of drug

  1. Reactions occurring over time (much more of a problem)
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11
Q

How is amphotericin B administered?

A

IV only

This will be given in hospital setting

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12
Q

What is the main complaint with fluconazole?

A

Headache

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13
Q

If you’re getting bored with your itraconazole capsules, can you mix it up with some oral solution?

A

No, do not use the two dosage forms interchangeably

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14
Q

Would fluconazole be a good choice for fungal meningitis?

A

Yes**

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15
Q

What organisms can cause onychomycosis?

A

Dermatophytes

Candida

Nondermatophytic molds

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16
Q

What is the DOC for almost all systemic fungal infections?

A

Amphotericin B

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17
Q

How is caspofungin administered?

A

IV

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18
Q

What is the DOC for cryptococcus infections?

A

a COMBO of flucytosine+amphotericin B

synergistic effect on crypto*

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19
Q

What drugs are in the echinocandins class?

A

Caspofungin

Micafungin

Anidulafungin

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20
Q

What is the DOC for candida infections?

A

Nystatin

Oral for GI candidiasis

Topically for other infections

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21
Q

What are the main toxicities of ketoconazole?

A

POTENT inhibitor of P450-many many many drug interactions

Gynecomastia and impotence- inhibits adrenal and testicular function

Prolonged QT

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22
Q

What is the DOC for onychomycosis?

A

Griseofulvin

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23
Q

Is amphotericin kidney damaging?

A

Extraordinary so

Kills their kidneys but worth it to save their life

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24
Q

What are the azoles?

A

Ketoconazole

Fluconazole

Voriconazole

Itraconazole

Isavuconazonium

Posaconazole

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25
Q

Is amphotericin B broad spectrum?

A

Yes

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26
Q

What is the MOA of amphotericin B?

A

It binds to ergosterol (in membrane) that causes a depolarization of the membrane and formation of pores that causes everything to leak out.

fungicidal

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27
Q

What are the cumulative toxicities of amphotericin B?

A

NEPHROTOXICITY!!***

Dose dependent, irreversible kidney damage

Azotemia- increased nitrogen in blood (BUN and creatinine will be increased)

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28
Q

Is fluconazole a good choice for suppressive or prophylactic therapy in HIV patients?

A

Yes

For example when their CD4 levels drop and they’re open to infection, this would be good prophylactic therapy

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29
Q

What are the main toxicities of voriconazole?

A

Drug interactions (it even inhibits the same enzyme that it’s metabolized by)

Visual impairment (reversible if taken off)

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30
Q

Is oral terbinafine good for onychomycosis?

A

Yes but it is not the DOC

31
Q

How does the oral bioavailability of itraconazole change depending on whether you took capsules vs an oral solution?

A

Capsules have better availability if taken with food or soda

Oral solution has better availability on an empty stomach

DO NOT TAKE TWO DIFFERENT TYPES

32
Q

What is the target of most antifungals?

A

Cell membrane or cell wall

Griseofulvin and flucytosine are exceptions

33
Q

How is voriconzaole administered?

A

IV and oral

34
Q

What is the food source for dermatophytes?

A

Keratin in skin hair and nails

35
Q

If your patient is on voriconazole + ampho B for their aspergillosis infection and they start to have photophobia and changes in their vision, what do you think is causing it and what should you do?

A

Voriconazole is causing it

Take them off of it while vision changes are still reversible

36
Q

What are the contraindications to ketoconazole?

A

Liver disease

QT prolonged

37
Q

Is amphotericin B a good choice for fungal meningitis?

A

No, it has poor CNS penetration

38
Q

How is griseofulvin administered?

A

Orally only!

Yes, it treats Dermatophytosis and onychomycosis but it is oral

39
Q

What is the main side effect of itraconazole?

A

Potent inhibitor of CYP 3A4 - drug interactions

40
Q

What is the MOA of the azoles?

A

Inhibits synthesis of ergosterol

which inhibits fungal growth- static***

41
Q

What are the antifungals that are used for dermatophytes?

A

Griseofulvin

Terbinafine

Nystatin

42
Q

What is meant by systemic mycoses due to opportunistic pathogens?

A

Infections of patients with immunodeficiency who would otherwise not be infected

Ex: candidiasis, aspergillosis, cryptococcosis

43
Q

What drug would you use for invasive aspergillosis if voriconazole didn’t work? (aka refractory patient)

A

Caspofungin** must know

44
Q

What is the MOA of griseofulvin?

A

Binds to microtubules and destroys spindle structure

Fungistatic

45
Q

Is amphotericin B fungicidal or static?

A

Cidal

Causes depolarization of the membrane and pores that allows everything to leak out

46
Q

Of all the azoles, which 2 have the most drugs interactions and which 2 have the least?

A

Most: ketoconazole and itraconazole

Least: fluconazole and voriconazole

47
Q

How is terbinafine administered?

A

Orally or topically

48
Q

What is the spectrum of ketoconazole?

A

Very broad spectrum.

It has even been tried as a substitute for amphotericin B

49
Q

What is the fluid penetration like for fluconazole?

A

Very good penetration into body fluids, especially CSF

50
Q

Why is griseofulvin effective against dermatophytosis infections of the skin hair and nails?

A

It binds to keratin. Dermatophytes EAT keratin.

This prevents infection in new skin.

51
Q

Is terbinafine fungicidal or fungistatic?

52
Q

What is the MOA of echinocandins?

The fungins

A

Inhibit synthesis of B(1,3)-D-glucan, a major fungal cell wall component

CIDAL

53
Q

If an antifungal agent has “flu” in the name, what kind of infection is it good for?

54
Q

What is the DOC for aspergillus infection?

A

Voriconazole + Amphotericin B***

55
Q

Who should NOT take griseofulvin?***

A

Pregnant women 🤰

Men 6 months prior to fathering a child! 👨‍👦

Acute intermittent porphyria

Hepatocellular failure

56
Q

How is nystatin administered?

A

Oral or topical

57
Q

What is used for the primary treatment of invasive aspergillosis?

A

Voriconazole (plus amphotericin)

58
Q

What are the toxicities of flucytosine?

A

Depression of bone marrow- anemia, leukopenia, thrombocytopenia

Elevated AST or ALT

GI- it is converted to 5-FU bu bacteria too and then kills your flora

(All worth it because crypto is life-threatening)

59
Q

What is the MOA of flucytosine?

A

Gets converted to 5-fluorauracil which messes with DNA and RNA synthesis

60
Q

What is known as “ringworm of the nail”

A

Dermatophytic onychomycosis

61
Q

What is the MOA of terbinafine?

A

Interferes with sterol biosynthesis

62
Q

What are the main toxicities of griseofulvin?

A

Headache

Disulfiram-like reaction- no alcohol for 6-12 months to treat your toenail infection!!!!!???! 😟

Photosensitivity- I CAN’T EVEN TAN? 👙

63
Q

Does fluconazole have any drug interactions?

A

It does, but way less than the other azoles.

It inhibits CYP2C9, but way less drugs are metabolized by 2C9

64
Q

What are the 2 polyene antibiotics?

A

Nystatin

Amphotericin B

65
Q

Are echinocandins static or cidal?

A

Cidal**

They are the “penicillins of antifungals”

Inhibit synthesis of cell wall component!

66
Q

When would we ever use ketoconazole?

A

Only when NO other antifungal therapy can be used

67
Q

What is the MOA for terbinafine

A

Interferes with sterol biosynthesis.

67
Q

Does terbinafine have a lot of side effects?

67
Q

What are the 2 drugs on this exam that have visual side effects?

A

Ethambutol

Voriconazole

67
Q

If someone is immunocompromised and develops a systemic fungal infection, can you give them amphotericin B to reduce the load until their kidneys cant take it anymore, and then maintain it with a static drug like an azole?

A

Yes this is a good plan

67
Q

What is a a symptom of nephrotoxicity you need to look out for when your patient is on amphotericin B?

A

Azotemia (BUN and creatinine are increased)

67
Q

Ketoconazole and Rifampin both affect the CYP450 system, but not in the same way. Which is which?

A

Keto inhibits P450

Rifampin induces

(So Keto would cause toxicity of the drugs it interacted with and rifampin would cause them to be less effective)

67
Q

What drug would be the second line for aspergillus if voriconazole didn’t work?

A

Caspofungin

Pharmacology Exam 3 (Lauren) (8 decks)

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