Antifungal Drugs

Question 1

Relate the mechanism of action to selective toxicity

Answer 1

Flucytosine is most selective, gets activated by cytosine deaminase (which humans lack)

Triazoles come next. They target fungal CYP450

Amphotericin is probably last. It targets ergosterol, but also binds cholesterol components in human cells

Question 2

Amphotericin B

Answer 2

MOA: Membrane disruption: binds ergosterol –> creates pores –> cell death.

FungiCIDAL

ROA: IV, Topical

Excretion: Renal AND Hepatic

Treatment: broad spectrum, use for life-threatening systemic infections

ADR: NEPHROTOXICITY, shake & bake, anemia

less selective toxicity, also binds cholesterol

Suuuuper long half life (like 2 weeks)

Question 3

Nystatin

Answer 3

MOA: Same as Ampho

ROA: Topical (can’t be used IV b/c its soooo lethal)

Treatment: superficial Candida

ADR: mild GI upset if swallowed

Question 4

Imidazoles (KCM)

Answer 4

MOA: inhibit P450 ergosterol synthesis, altering membrane permeability (specifically 14a-demethylase)

ROA: Keto = IV, PO, Topical / Clotrim, Micon = topical

Elimination: HEPATIC

Treatment: systemic infections (e.g., candidiasis). Clotrim, Micon are good for oral & vaginal candiasis

ADR: testosterone synthesis, anorexia, n/v, hepatotoxicity. inhibits CYP450 drug metabolism and androgen-GC biosynthesis

CIDAL (mostly) or STATIC

Came out first. Semi-selective. More cross-over

Question 5

Triazole (FI)

Answer 5

MOA: inhibit P450 ergosterol synthesis, MORE SELECTIVE FOR FUNGAL P450!!!!

ROA: PO (and IV?)

Excretion: Flu = renal, Itra = hepatic

Flu Treatment: mucosal candidiasis, cryptococcal meningitis
Itra Treatment: superficial dermatophytosis, onychomycosis, aspergillus, histoplasmosis

ADR: GI upset in both. Itra inhibits CYP450 drug metabolism, Flu less so

FungiSTATIC

Question 6

Terbafine

Answer 6

MOA: Inhibits ergosterol synthesis (squalene oxidase)

ROA: PO, Topical

Excretion: Hepatic

Treatment: onychomycosis of finger/toe nails (po), athletes foot

ADR: headache, diarrhea, rash, inhibition of CYP450

FungiCIDAL

Question 7

Flucytosine

Answer 7

MOA: converted to 5-FU, inhibit DNA synthesis

ROA: PO

Elimination: renal

Treatment: serious cryptococcosis and candidiasis

ADR: n/v, skin rash, myelosuppression

Resistance in fungi that lack cytosine deaminase

Question 8

Griseofluvin

Answer 8

MOA: Inhibits mitotic function: binds to fungal microtubules

ROA: PO

Elimination: Poop? Hepatic

Treatment: pediatric scalp infections, severe dermatophytosis

ADR: hypersensitivity, GI distress, HA, confusion,

FungiSTATIC

Takes sooooo long to work, sucks =\

Question 9

Caspofungin

Answer 9

MOA: B-glycan synthesis inhibition

Question 10

Both flus are PO, Renal, CNS penetration (pretty much the only renal)

Answer 10

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