Antifungals

Question 1

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

Answer 1

Both are nephrotoxic

Question 2

What is the route of administration for terbinafine

Answer 2

Oral or topical

Question 3

Why do we think amphotericin B is SO toxic?

Answer 3

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

Question 4

Is griseofulvin static or cidal?

Answer 4

Static ***

Question 5

How long is treatment with griseofulvin?

Answer 5

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

Question 6

What is the administration of fluconazole?

Answer 6

Oral and IV

Question 7

What is the MOA of nystatin?

Answer 7

Just like amphotericin B- forms pores

Question 8

What makes micafungin and anidulafungin different from caspofungin?

Answer 8

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

Question 9

Why is caspofungin an attractive treatment option?

Answer 9

Doesn’t kill kidneys

Few drug interactions

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

Question 10

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

Answer 10

Due to either:
1. Infusion of drug

2. Reactions occurring over time (much more of a problem)

Question 11

How is amphotericin B administered?

Answer 11

IV only

This will be given in hospital setting

Question 12

What is the main complaint with fluconazole?

Answer 12

Headache

Question 13

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

Answer 13

No, do not use the two dosage forms interchangeably

Question 14

Would fluconazole be a good choice for fungal meningitis?

Answer 14

Yes**

Question 15

What organisms can cause onychomycosis?

Answer 15

Dermatophytes

Candida

Nondermatophytic molds

Question 16

What is the DOC for almost all systemic fungal infections?

Answer 16

Amphotericin B

Question 17

How is caspofungin administered?

Answer 17

IV

Question 18

What is the DOC for cryptococcus infections?

Answer 18

a COMBO of flucytosine+amphotericin B

synergistic effect on crypto*

Question 19

What drugs are in the echinocandins class?

Answer 19

Caspofungin

Micafungin

Anidulafungin

Question 20

What is the DOC for candida infections?

Answer 20

Nystatin

Oral for GI candidiasis

Topically for other infections

Question 21

What are the main toxicities of ketoconazole?

Answer 21

POTENT inhibitor of P450-many many many drug interactions

Gynecomastia and impotence- inhibits adrenal and testicular function

Prolonged QT

Question 22

What is the DOC for onychomycosis?

Answer 22

Griseofulvin

Question 23

Is amphotericin kidney damaging?

Answer 23

Extraordinary so

Kills their kidneys but worth it to save their life

Question 24

What are the azoles?

Answer 24

Ketoconazole

Fluconazole

Voriconazole

Itraconazole

Isavuconazonium

Posaconazole

Question 25

Is amphotericin B broad spectrum?

Answer 25

Yes

Question 26

What is the MOA of amphotericin B?

Answer 26

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

Question 27

What are the cumulative toxicities of amphotericin B?

Answer 27

NEPHROTOXICITY!!*** Dose dependent, irreversible kidney damage Azotemia- increased nitrogen in blood (BUN and creatinine will be increased)

Question 28

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

Answer 28

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

Question 29

What are the main toxicities of voriconazole?

Answer 29

Drug interactions (it even inhibits the same enzyme that it’s metabolized by) Visual impairment (reversible if taken off)

Question 30

Is oral terbinafine good for onychomycosis?

Answer 30

Yes but it is not the DOC

Question 31

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

Answer 31

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

Question 32

What is the target of most antifungals?

Answer 32

Cell membrane or cell wall | Griseofulvin and flucytosine are exceptions

Question 33

How is voriconzaole administered?

Answer 33

IV and oral

Question 34

What is the food source for dermatophytes?

Answer 34

Keratin in skin hair and nails

Question 35

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?

Answer 35

Voriconazole is causing it Take them off of it while vision changes are still reversible

Question 36

What are the contraindications to ketoconazole?

Answer 36

Liver disease QT prolonged

Question 37

Is amphotericin B a good choice for fungal meningitis?

Answer 37

No, it has poor CNS penetration

Question 38

How is griseofulvin administered?

Answer 38

Orally only! | Yes, it treats Dermatophytosis and onychomycosis but it is oral

Question 39

What is the main side effect of itraconazole?

Answer 39

Potent inhibitor of CYP 3A4 - drug interactions

Question 40

What is the MOA of the azoles?

Answer 40

Inhibits synthesis of ergosterol which inhibits fungal growth- static***

Question 41

What are the antifungals that are used for dermatophytes?

Answer 41

Griseofulvin Terbinafine Nystatin

Question 42

What is meant by systemic mycoses due to opportunistic pathogens?

Answer 42

Infections of patients with immunodeficiency who would otherwise not be infected Ex: candidiasis, aspergillosis, cryptococcosis

Question 43

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

Answer 43

Caspofungin**** must know

Question 44

What is the MOA of griseofulvin?

Answer 44

Binds to microtubules and destroys spindle structure ***Fungistatic***

Question 45

Is amphotericin B fungicidal or static?

Answer 45

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

Question 46

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

Answer 46

Most: ketoconazole and itraconazole Least: fluconazole and voriconazole

Question 47

How is terbinafine administered?

Answer 47

Orally or topically

Question 48

What is the spectrum of ketoconazole?

Answer 48

Very broad spectrum. It has even been tried as a substitute for amphotericin B

Question 49

What is the fluid penetration like for fluconazole?

Answer 49

Very good penetration into body fluids, especially CSF

Question 50

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

Answer 50

It binds to keratin. Dermatophytes EAT keratin. This prevents infection in new skin.

Question 51

Is terbinafine fungicidal or fungistatic?

Answer 51

Cidal

Question 52

What is the MOA of echinocandins? | The fungins

Answer 52

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

Question 53

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

Answer 53

CNS

Question 54

What is the DOC for aspergillus infection?

Answer 54

Voriconazole + Amphotericin B***

Question 55

Who should NOT take griseofulvin?***

Answer 55

Pregnant women 🤰 Men 6 months prior to fathering a child! 👨‍👦 Acute intermittent porphyria Hepatocellular failure ***********

Question 56

How is nystatin administered?

Answer 56

Oral or topical

Question 57

What is used for the primary treatment of invasive aspergillosis?

Answer 57

Voriconazole (plus amphotericin)

Question 58

What are the toxicities of flucytosine?

Answer 58

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)

Question 59

What is the MOA of flucytosine?

Answer 59

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

Question 60

What is known as “ringworm of the nail”

Answer 60

Dermatophytic onychomycosis

Question 61

What is the MOA of terbinafine?

Answer 61

Interferes with sterol biosynthesis

Question 62

What are the main toxicities of griseofulvin?

Answer 62

Headache Disulfiram-like reaction- no alcohol for 6-12 months to treat your toenail infection!!!!!???! 😟 Photosensitivity- I CAN’T EVEN TAN? 👙

Question 63

Does fluconazole have any drug interactions?

Answer 63

It does, but way less than the other azoles. It inhibits CYP2C9, but way less drugs are metabolized by 2C9

Question 64

What are the 2 polyene antibiotics?

Answer 64

Nystatin Amphotericin B

Question 65

Are echinocandins static or cidal?

Answer 65

Cidal** They are the “penicillins of antifungals” Inhibit synthesis of cell wall component!

Question 66

When would we ever use ketoconazole?

Answer 66

Only when NO other antifungal therapy can be used

Question 67

What is the MOA for terbinafine

Answer 67

Interferes with sterol biosynthesis.

Question 67

Does terbinafine have a lot of side effects?

Answer 67

No

Question 67

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

Answer 67

Ethambutol Voriconazole

Question 67

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?

Answer 67

Yes this is a good plan

Question 67

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

Answer 67

Azotemia (BUN and creatinine are increased)

Question 67

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

Answer 67

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)

Question 67

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

Answer 67

Caspofungin