Antifungal Agents

Question 1

Amphotericin B

Administration

Answer 1

IV only

Question 2

Amphotericin B

MOA

Answer 2

Binds ergosterol in fungal membrane, forming a pore in the membrane and allowing essential small solutes to efflux.
Fungicidal

Question 3

Amphotericin B

Spectrum

Answer 3

Broadest of all the antifungal agents

Effective against all fungi except Candida lusitaniae and Pseudallescheria boydii

Question 4

Amphotericin B

Clinical Use

Answer 4

Reserved for significant toxicities, life threatening fungal infections (immunosuppres pts, cryptococcal meningitis, invasive Aspergillus)

DOC for Zygomycosis/mucormycosis

Only antifungal agent approved for use in pregnancy or breastfeeding women

Question 5

Amphotericin B

Adverse Effects

Answer 5

Infusion related –> fever, chills, muscle spasm, vomiting, HA, hypotension

Cumulative Tox –>
Nephrotoxicity (vasoconstriction causing low renal perfusion; also causes renal tubule injury)
Hepatotoxicity
Anemia (less EPO)

Question 6

Flucytosine

Spectrum

Answer 6

Very narrow

Very effective against Cryptococcal meningitis

Question 7

Flucytosine

MOA

Answer 7

Enters fungal cell through pores in membrane. Gets converted to 5-fluorouracil intracellularly.

Leads to RNA synthesis inhibition and inhibition of thymidylate synthesis (DNA synthesis inhibition)

Question 8

Flucytosine

Clinical Use

Answer 8

Frequently used with amphotericin B for treatment of Cryptococcal meningitis

Question 9

Flucytosine

Adverse Effects

Answer 9

GI symptoms (nausea, vomiting, diarrhea)

Bone marrow toxicity –> anemia, leukopenia, thrombocytopenia

Teratogen - do NOT use in pregnancy

Question 10

What is the only antifungal agent that may be administered in pregnant women?

Answer 10

Amphotericin B

Question 11

List the drugs in the Azole class of antifungals. Which is the prototype? What are their general spectrums of activity?

Answer 11

Ketoconazole (prototype)

FIVP
Fluconazole (most narrow spectrum)
Itraconazole
Voriconazole
Posaconazole (most broad spectrum)

Question 12

Azoles

MOA

Answer 12

Block 12-alpha-sterol demethylase enzyme involved in ergosterol formation

Less ergosterol synthesis impairs the fungal membrane function and increases permeability
Leads to loss of fungal plasma membrane proteins

Question 13

What are some common adverse effects of all Azole drugs?

Answer 13

GI distress
Hepatotoxicity
Teratogen

Question 14

What are some common drug-drug interactions of Azoles?

Answer 14

They either induce or are substrates of CYP450 enzymes.

NEVER give itraconazole or voriconazole with statins, as they can cause fatal rhabdomyolysis

Question 15

Ketoconazole

Pharmacokinetics

Answer 15

Prototypical azole. 
Poor absorption (requires acidic environment) and poor penetration into CSF and urine

Question 16

Ketoconazole

Adverse Effects

Answer 16

Inhibits CYP450 enzymes in adrenal and gonadal steroid synthesis
Low cortisol and low testosterone

Gynecomastia
Dec. libido
Impoetence

Question 17

Fluconazole

Spectrum and Pharmacokinetics

Answer 17

Very narrow spectrum (used for Cryptococcal meningitis)

Great CSF penetration
Good oral bioavailability

Question 18

Fluconazole

Adverse effects

Answer 18

Nausea
HA
Skin rash
GI upset

Question 19

Itraconazole

Spectrum and Pharmacokinetics

Answer 19

Poor CSF, urine, eye penetration

Strong CYP3A4 inhibitor

Question 20

Itraconazole

Clinical Use

Answer 20

Broader spectrum than fluconazole

Used for oral dermatophytes
Candida

Question 21

Itraconazole

Adverse Effects

Answer 21

GI distress
Hepatotoxicity
Teratogen

Triad: HTN, Hypokalemia, and Peripheral Edema
-Do NOT use in patients with preexisting ventricular dysfunction or CHF

Question 22

Voriconazole

Spectrum

Answer 22

Candida
Endemic fungi
Invasive Aspergillus

Question 23

Voriconazole

Adverse Effects

Answer 23

Hepatotoxicity, GI distress, Teratogen

Periostitis (bone pain)
Transient vision changes
Photosensitivity/rash

Question 24

Posaconazole

Spectrum

Answer 24

Broadest of the azole family

Only azole effective against Mucormycoses/Zygomycosis

Question 25

Posaconazole

Adverse Effects

Answer 25

Hepatotoxicity
GI distress
Teratogen

Question 26

List the Echinocandins

Answer 26

Capsofungin
Micofungin
Anidulafungin

Question 27

Echinocandins

MOA

Answer 27

Inhibit B-1,3-D glucan synthase complex, involved in cell wall formation

Leads to osmotic instability and cell death

Question 28

Echinocandins

Adverse Effects

Answer 28

Histamine-like effect (skin itching)

Embryotoxic

Question 29

Echinocandins

Clinical Uses

Answer 29

Good activity against Candida and Aspergillus

No activity against Cryptococcus or dimorphic fungi

Question 30

Griseofulvin

Clinical Use

Answer 30

Used only for dermatophyte (tinea…) infections

Question 31

Griseofulvin

MOA

Answer 31

Binds fungal microtubules and prevents the mitotic spindle from forming

Question 32

Griseofulvin

Adverse Effects

Answer 32

Inducer of CYP450 enzymes – may have many drug interactions

HA, lethargy, vertigo
Urticaria, photosensitivity
Hepatotoxicity
Leukopenia, neutropenia
Teratogen

Question 33

Terbinafine

Clinical Use

Answer 33

Used for dermatophytes and Candida albicans

High cure rate

Question 34

Terbinafine

MOA

Answer 34

Inhibition of fungal squalene epoxidase.
This prevents the conversion fo fungal squalene to ergosterol, thus causing membrane dysfucntion and squalene buildup in cell, leading to cell death

Question 35

Nystatin

Clinical Use

Answer 35

Similar to amphotericin B, but only used in gels, creams, ointments

Used for oral candidiasis (swish and swallow)