Micro 28 - Antifungals

Question 1

What does Amphotericin B do?

Answer 1

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

Question 2

What are the side effects of amphotericin B?

Answer 2

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

Question 3

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

Answer 3

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.

Question 4

How is amphotericin B administered?

Answer 4

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

Question 5

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

Answer 5

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.

Question 6

In what pathology do we use Nystatin?

Answer 6

Cutaneous candidiasis: diper rash and vulvovaginitis.

Oropharyngeal candidiasis: “Swich and Swallow”.

Question 7

What are the seven relevant -azoles?

Answer 7

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

Question 8

How do the -azoles work?

Answer 8

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

Question 9

In what organisms do we use Fluconazole?

Answer 9

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

Question 10

In what organisms do we use Ketoconazole?

Answer 10

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

Question 11

In what organisms do we use Itraconazole?

Answer 11

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

Question 12

What is Voriconazole useful for?

Answer 12

Aspergillus.

Question 13

What is Posaconazole useful for?

Answer 13

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

Question 14

What are Clotrimazole and miconazole useful for?

Answer 14

Used for topical fungal infections.

Question 15

What are the side effects of -azoles?

Answer 15

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).

Question 16

What is mechanism of Flucytosine?

Answer 16

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

Question 17

When is Flucytosine used?

Answer 17

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

Question 18

What is the most important toxicity caused by Flucytosine?

Answer 18

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

Question 19

What is the mechanism for Caspofungin?

Answer 19

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

Question 20

In what organism is Caspofungi used for?

Answer 20

Invasive aspergillosis.

Candida infection.

Question 21

What are the toxicities of caspofungin?

Answer 21

GI upset and flushing.

Question 22

What is the mechanism of Terbinafine (Lamisil)?

Answer 22

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

Question 23

In what organisms is Terbinafine used for?

Answer 23

Topically for Tinea pedis and Tinea corporis.

Orally for onychomycosis and Tinea capitis.

Question 24

What are the toxicities of Terbinafine?

Answer 24

GI symptoms and Hepatotoxicity.

Question 25

What is the mechanism of Griseofulvin?

Answer 25

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

Question 26

In what organisms is Griseofulvin useful for?

Answer 26

Tinea corporis and tinea capitis and onychomycosis.

Question 27

What is the side effects of Griseofulvin?

Answer 27

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

Question 28

Which agents blocks the synthesis of Squalene to Lanosterol?

Answer 28

Terbinafine.

Question 29

Which agent interferes with microtubule function?

Answer 29

Griseofulvin.

Question 30

Which agent is used for “swish and swallow” for oral candidiasis?

Answer 30

Nystatin.

Question 31

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

Answer 31

Caspofungin.

Question 32

What is the most common treatments for onychomycosis?

Answer 32

Terbinafine, itraconazole, fluconazole.

Question 33

Which agent binds ergosterol to create membrane pores?

Answer 33

Nystatin and amphotericin B.

Question 34

Which agent inhibits ergosterol synthesis?

Answer 34

Azoles and terbinafine.

Question 35

Which agent has side effect if arrhythmias and nephrotoxicity?

Answer 35

Amphotericin B.

Question 36

Which agent deposits in keratin-containing tissues?

Answer 36

Griseofulvin.

Question 37

Which agent inhibits hormones synthesis and cytochrome P450?

Answer 37

Azoles (esp. ketoconazole).

Question 38

Which agent has side effect of liver dysfuntion?

Answer 38

Azoles, griseofulvin.

Question 39

Which agent has side effect of teratogenic?

Answer 39

Griseofulvin.

Question 40

is used for cryptococcal meningitis in AIDS?

Answer 40

IV amphotericin B + flucytosine.

Question 41

Which agent is drug of choice for sporotrichosis?

Answer 41

Itraconazole.