EXAM #4: ANTIFUNGALS

Question 1

List the systemic fungi.

Answer 1

• Histoplasma capsulatum
• Blastomyces dermatiditis
• Coccidioides immitis
• Sporothrix schenckii

Question 2

List the opportunistic fungi.

Answer 2

• Candida
• Aspergillus
• Cryptococcus neoformans

Question 3

What are the common cutaneous and subcutaneous fungal infections?

Answer 3

Sporothrix schenckii 
Dermatophytes 
- Ringworm
- Athlete's Foot 
- Onychomycosis

Question 4

What are the unique targets used in antifungal therapy?

Answer 4

• Fungal cell membrane i.e. ERGOSTEROL

- Fungal cell wall i.e. GLUCANS

Question 5

List the drugs that inhibit Ergosterol synthesis.

Answer 5

Azoles
Naftidfine
Terbnafine

Question 6

What drug inhibits fungal membrane function?

Answer 6

Amphotericin B

Question 7

What drug inhibits fungal cell wall synthesis?

Answer 7

Caspofungin

Question 8

What drug inhibits fungal nuclei acid synthesis?

Answer 8

5-fluorocytosine

Question 9

What drugs can be used to treat systemic fungal infections?

Answer 9

1) Polyenes- amphotericin B
2) Azoles
3) Flucytosine
4) Echinocandins

Question 10

What drug has the broadest spectrum of all the antifungals?

Answer 10

Amphotericin B

Question 11

Why has Amphotericin B been replaced for newer compounds?

Answer 11

High degree of toxicity

Question 12

What is the MOA of Amphotericin B

Answer 12

• Binds ergosterol in fungal cell membrane

- Forms Amp B pores in fungal membrane

Question 13

Why is there high toxicity associated with Amphotericin B?

Answer 13

Not only binds ergosterol, but can also bind cholesterol

Question 14

What is Amphotericin B the treatment of choice for?

Answer 14

1) Disseminated candidasis
2) Cryptococcal (neoformans) meningitis

Note that it is a second line treatment for systemic disease caused by molds

Question 15

What is the mechanism of resistance of Amphotericin B?

Answer 15

Decreased membrane ergosterol concentration

Question 16

How is Amphotericin B administered?

Answer 16

• Note that it is INSOLUBLE in water*
• Complex-ed to a bile salt
• Given IV

Question 17

How is Amphotericin B administered for Cryptococcal meningitis?

Answer 17

Intrathecal

Question 18

What are the adverse reactions seen with Amphotericin B?

Answer 18

1) Infusion reaction seen in nearly all patients

2) NEPHROTOXICITY

Question 19

How is the toxicity of Amphotericin B being combated?

Answer 19

Packaging the drug in lipid micelle i.e. “liposomal packaging”

Question 20

What are the two groups of Azoles?

Answer 20

1) Imidazoles (2x nitrogens)

2) Triazoles (3x nitrogens)

Question 21

List the imidazoles.

Answer 21

Ketoconazole
Miconazole
Clotrimazole

Question 22

List the triazoles.

Answer 22

Fluconazole
Itraconazole
Voriconazole
Posaconazole

Question 23

What is the MOA of the azoles?

Answer 23

Inhibit the enzyme the produces ergosterol

- Makes the cell membrane leaky

Question 24

What are the mechanisms of resistance to the azoles?

Answer 24

1) Drug efflux pumps
2) Mutation in target enzyme
3) Decreased ergosterol synthesis

Question 25

Why is Ketoconazole rarely used clinically today?

Answer 25

Toxicity

Question 26

What is the typical first line drug for systemic fungal infections?

Answer 26

Fluconazole

Question 27

Why is Fluconazole highly utilized in the treatment of systemic fungal infections?

Answer 27

- Highest TI - Distributed to the CNS - Few drug-drug interactions

Question 28

What is Fluconazole a first ling agent for?

Answer 28

1) Systemic Candidiasis 2) Cryptococcosis 3) Coccidiomycosis

Question 29

How does Itraconazole compared to Fluconazole?

Answer 29

Broader spectrum of activity BUT lower TI

Question 30

What does Itraconazole require for absorption?

Answer 30

Low GI pH

Question 31

Can Itraconazole penetrate the CNS?

Answer 31

NO

Question 32

What is Itraconazole the drug of choice for?

Answer 32

adf

Question 33

What is Voriconazole?

Answer 33

Derivative of Fluconazole

Question 34

What is Voriconazole commonly used to treat?

Answer 34

Aspergillosis Note that it has replaced Amphotericin B as the first line drug b/c of lower toxicity.

Question 35

What is the major adverse reaction associated with Voriconazole?

Answer 35

Visual disturbances

Question 36

What drug has the broadest spectrum of all the azoles?

Answer 36

Posaconazole

Question 37

What is Posaconazole used to treat?

Answer 37

Mucromycoses | Aspergillus

Question 38

What is the MOA of Flucytosine?

Answer 38

This is a fluorinated pyrimidine analog that inhibits DNA synthesis

Question 39

What is Flucytosine used to treat?

Answer 39

Used as a combination therapy for severe Cryptococcal infections

Question 40

What are the adverse reactions seen with Flucytosine?

Answer 40

Bone marrow supression i.e. - Anemia - Leukopenia - Thrombocytopenia

Question 41

What is the MOA of the Echinocandins?

Answer 41

Inhibit the synthesis of Beta-glucan i.e. inhibit the CELL WALL *We don't have Beta-glucan; thus, very low toxicity*

Question 42

List the Echinocandins.

Answer 42

Caspofungin Micafungin Andidulafungin

Question 43

What are the Echinocandins primarily used to treat?

Answer 43

Aspergillus Candida *Note that both have a high degree of Beta-glucan in their cell wall*

Question 44

What is Griseofulvin used to treat?

Answer 44

This is an oral agent used to treat Dermatophyte infections

Question 45

What is unique about Griseofulvin?

Answer 45

Concentrates in Keratin precursor cells - Skin - Hair - Nails

Question 46

What are Allylamines?

Answer 46

Class of antifungal that inhibits ergosterol synthesis

Question 47

What is the MOA of Allylamines?

Answer 47

Inhibit the enzyme squalene epoxidase

Question 48

What is the hallmark Allylamine?

Answer 48

Terbinafine

Question 49

What is Terbinafine used to treat?

Answer 49

First line for Onychomycosis i.e. nail infections

Question 50

What are the topical antifungal agents?

Answer 50

``` Nystatin- polyene Clotrimazole- azole Miconazole- azole Terbinafine- Allylamine Naftifine- Allylamine ```

Question 51

What is the MOA of Nystatin?

Answer 51

Polyene that binds ergosterol and forms pores | - Only used topically

Question 52

What is Nystatin used to treat?

Answer 52

Candida - Oral - Vagial i.e. yeast infections

Question 53

What are the topical azoles, Clotrimazole and Miconazole used to treat?

Answer 53

1) Vulvovaginal candidiasis 2) Dermatophyte infections 3) Oral thrush

Question 54

What infections are the topical Allylamines used to treat?

Answer 54

``` Tinea curis (jock-itch) Tinea corporis (ringworm) ```