Anti-Fungals

Question 1

Ergosterol

Answer 1

Used instead of cholesterol to maintain the cell membrane structure and function

Question 2

Allylamines

Answer 2

Target squalene epoxidase

Prevent formation of lanosterol (precursor for ergosterol)

Question 3

Azoles

Answer 3

Target 14-alpha-sterol demethylase

Prevent formation of ergosterol for lanosterol

Question 4

Amphotericin B & Nystatin

Answer 4

HOUSE episodes
large molecule with H2O side and lipid soluble side
IV (older, cheap); lipid solution (new, safe, expensive)
Form pores in membrane, affinity for ergosterol side chain
RESISTANCE IS RARE
Broad spectrum, serious life threatening infx

Question 5

Nystatin

Answer 5

oral/topical/cutaneous - vaginal, mucosal and esophageal candidasis
“swish and swallow” tx

Question 6

Amphotericin B

Answer 6

Used initially for serious fungal infx empirically to reduce fungal burden then replaced to safer azole

Question 7

Adverse effects of Amphotericin B and Nystatin

Answer 7

CYTOKINE STORM - fever, chills, rigor, hypotension
Renal toxicity (vasoconstriction, PT cell injury)
Hematologic toxcidity (anemia, erythropoietin)
Lipid solutions are less toxic

Question 8

Flucystosine

Answer 8

DNA and RNA synthesis inhibitor
*Actively transported by cytosine permease
only in fungus
Converted to 5-FU to inhibit thymidylate synthase = cannot make thymine
Narrow spectrum, need to give with amphotericin B

Question 9

Griseofulvin

Answer 9

Binds to tubulin - disrupt mitotic spindle action
Fungistatic
Accumulate in keratin precursor cells, prevent infection of new cells
*DOESN’T WORK FOR CANDIDA
Take a long time 2-6 weeks - tinea capitis
Adverse: pyphoria

Question 10

Terbinafine (Lamisil)

Answer 10

inhibits squalene epoxidase
prevent formation of precursor lanosterol
accumulation of squalene is toxic
Topical: ringworm (all types)
Oral: onychomycosis - toes and nals 
Hepatotoxicity is rare, but serious

Question 11

Fluconazole (Diflucan)

Answer 11

inhibit 14-alpha-sterol demethylase (fungal CYP450) prevent formation of ergosterol from lanosterol
Fungistatic
Triazloles - more selective for fungal CYP
Superficial - single 150mg dose fluconazole (yeast infection)

Question 12

Fluconazole adverse reactions

Answer 12

GI upset
Drug interactions - inhibition of human CYPs (34A, 2C9, 2C19)
Avoid during pregnancy

Question 13

Caspofungin

Answer 13

Inhibit B(1,3)-D-glucan synthesis
Disrupts cell wall integrity resulting in osmotic stress and cell lysis (similar to B lactam)
Fungicidal
Tx: IV - Asperillosis, empiric - Febrile neuotropenia, severe systemic candidiasis