Micro 28 - Antifungals Flashcards Preview

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Flashcards in Micro 28 - Antifungals Deck (41):
1

What does Amphotericin B do?

It binds ergosterol in cell membrane of fungi, making pores which causes loss of electrolytes and small molecules, killing the fungi.

2

What are the side effects of amphotericin B?

1. Fever and chills.
2. Hypotension.
3. Hypokalemia.
4. Anemia.
5. Phlebitis.
6. Arrhythmias.
7. Nephrotoxicity.

3

What are some measure one can take to reduce amphotericin B toxicity?

1. Hydrate the patient well to reduce nephrotoxicity.
2. Using the lipid formulation of amphotericin B, like liposomal amphotericin (AmBisome) but its is so much more expensive. This substitute reduces toxicity because amphotericin has a poor specificity for ergosterol and attacks cholesterol of human cells as well.

4

How is amphotericin B administered?

Usually given IV but occasionally infused intratecally since it crosses the blood brain barrier poorly.

5

What are the similarities and difference of Amphotericin B and Nystatin?

They both have the same mechanism: Attach to ergosterol and make pores in fungi membrane. However, Nystatin is only approved to be used topically because it is way more toxic than the amphotericin.

6

In what pathology do we use Nystatin?

Cutaneous candidiasis: diper rash and vulvovaginitis.
Oropharyngeal candidiasis: "Swich and Swallow".

7

What are the seven relevant -azoles?

[FICK MVP]
1. Fluconazole.
2 Ketoconazole.
3. Itraconazole.
4. Voriconazole.
5. Clotrimazole.
6. Miconazole.
7. Posaconazole.

8

How do the -azoles work?

They inhibit the synthesis of ergosterol by inhibiting the P450 enzyme that converts lanosterol to ergosterol.

9

In what organisms do we use Fluconazole?

1. Cryotococcal meningitis, because it can cross the BB barrier.
2. Candidal infections.

10

In what organisms do we use Ketoconazole?

Blastomyces, coccidiodes, Histoplasma, and Candida. Though this drug is not first line.

11

In what organisms do we use Itraconazole?

Blastomyces, Coccidioides, Paracoccidiodes, Histoplasma, Sporothrix. This drug is useful for dimorphic fungi.

12

What is Voriconazole useful for?

Aspergillus.

13

What is Posaconazole useful for?

Active against many fungi refractory to other treatments such as Mucor.

14

What are Clotrimazole and miconazole useful for?

Used for topical fungal infections.

15

What are the side effects of -azoles?

1. Reduces production of cortisol and testosterone.
2. Gynecomastia.
3. Impotence.
4. Drug-drug interactions (inhibits the P450 of humans as well).
5. Hepatotoxicity (increased hepatic enzyme).

16

What is mechanism of Flucytosine?

It is converted into 5-fluorouracil that converts to a false nucleotide that disrupts DNA and RNA synthesis.

17

When is Flucytosine used?

Used in combination w/ amphotericin B to treat systemic candidal and cryptococcal infections.

18

What is the most important toxicity caused by Flucytosine?

Bone marrow toxicity, GI symptoms (nausea, vomiting and diarrhea).

19

What is the mechanism for Caspofungin?

Inhibitis cell wall synthesis by inhibiting synthesis of beta-1,3-D glucan that leads to cell lysis and cell death.

20

In what organism is Caspofungi used for?

Invasive aspergillosis.
Candida infection.

21

What are the toxicities of caspofungin?

GI upset and flushing.

22

What is the mechanism of Terbinafine (Lamisil)?

Inihibits fungal enzyme squalene epoxidase which leads to decrease in ergosterol synthesis.

23

In what organisms is Terbinafine used for?

Topically for Tinea pedis and Tinea corporis.
Orally for onychomycosis and Tinea capitis.

24

What are the toxicities of Terbinafine?

GI symptoms and Hepatotoxicity.

25

What is the mechanism of Griseofulvin?

Targets microtubule function which inhibits mitosis. It deposits in keratin-containing tissues.

26

In what organisms is Griseofulvin useful for?

Tinea corporis and tinea capitis and onychomycosis.

27

What is the side effects of Griseofulvin?

1. Teratogenic.
2. Headche.
3. GI symptoms.
4. Confusion.
5. Cytochrome P450 inducer.

28

Which agents blocks the synthesis of Squalene to Lanosterol?

Terbinafine.

29

Which agent interferes with microtubule function?

Griseofulvin.

30

Which agent is used for "swish and swallow" for oral candidiasis?

Nystatin.

31

Which agent is a cell wall synthesis inhibitor used in invasive aspergillosis?

Caspofungin.

32

What is the most common treatments for onychomycosis?

Terbinafine, itraconazole, fluconazole.

33

Which agent binds ergosterol to create membrane pores?

Nystatin and amphotericin B.

34

Which agent inhibits ergosterol synthesis?

Azoles and terbinafine.

35

Which agent has side effect if arrhythmias and nephrotoxicity?

Amphotericin B.

36

Which agent deposits in keratin-containing tissues?

Griseofulvin.

37

Which agent inhibits hormones synthesis and cytochrome P450?

Azoles (esp. ketoconazole).

38

Which agent has side effect of liver dysfuntion?

Azoles, griseofulvin.

39

Which agent has side effect of teratogenic?

Griseofulvin.

40

is used for cryptococcal meningitis in AIDS?

IV amphotericin B + flucytosine.

41

Which agent is drug of choice for sporotrichosis?

Itraconazole.