Antifungals

Front 1

What is the target of antifungal agents? (What are the 2 exceptions?)

Back 1

Cell membrane or cell wall
*Exceptions = flucytosine (targets DNA/RNA syn) & griseofulvin (targets microtubules)

Front 2

What serious side effect do all antifungals carry?

Back 2

Teratogens!! - exception = amphortericin B

Front 3

What are the only 2 antifungals that can cross the BBB?

Back 3

Flucytosine
Fluconazole

Front 4

Amphortericin B

Back 4

Class – Polyene
MOA – Binds ergosterol to form pores in membrane and allow K+ and Mg2+ to leak out. Amphoteric molecule (can be + or – depending on pH) best at neutral pH
USE – Broad: All fungal ifxns (except dermatophytes, leishmeniasis (protozoa) - *Good empiric*
SE – interactions w/ mammalian cell membranes that cause infusion rxns and renal toxicity – renal toxicity ↓ by Na+ loading or using lipid formation (↑affintiy for ergosterol to ↓ attraction to mammalian cholesterol). Safe for pregnancy

Front 5

Nystatin

Back 5

Class – polyene
MOA – same as amphor. B but only given orally (too toxic for IV)
USE – Intestinal or oral Candidasis

Front 6

Flucytosine

Back 6

Class – antimetabolite/ pyrimidine analog
MOA – metabolized to 5-flurouracil which inhibits Thymidylate synthase to inhibit DNA/RNA synthesis (static)
USE – Cryptococcal chronic meningitis in combo w/ Amphor. B (switch to fluncazole later in therapy)
SE – Cancer chemo-like side effects (due to 5-fluro metabolite)

Front 7

What is the shared MOA of Azoles?

Back 7

Inhibit fungal CYP p450 to inhibit demethylation of lanosterol to block synthesis of ergosterol (and thus cell membrane)

Front 8

What is the shared side effect of azoles?

Back 8

Inhibit human Cyp enzymes and thus cause many drug-drug interactions

Front 9

Keto-conazole

Back 9

Class – azole
USE – topical use only (very toxic)
SE – If orally administered: hormone imbalances, inhib P450 to cause Rx-interactions, decreased GI absorption if acidic stomach

Front 10

Itra-conazole

Back 10

Class – azole
USE – All fungal except mucormycosis (zygomyco) and Candidia
SE – Pharmacokinetics make it difficult to predict its bioavailability, contraindicated in ventricular dysfxn

Front 11

Flu-conazole

Back 11

Class – Azole – able to cross BBB
USE – Blasto, histo, candidias (except Cadidia krusei), Crypto meningitis (after trx w/ ampho B + flucytosine)
SE – Less Rx-Rx-interactions, prolonged QT intervals

Front 12

Vori-conazole

Back 12

Class – Azole
USE – Invasive aspergillosis and candidiasis
SE – Transient visual disturbances, prolonged QT interval

Front 13

Posa-conazole

Back 13

Class – Azole
USE – same as irtra + mucormycosis (zygomyco)
SE – Prolonged QT interval

Front 14

What side effect is seen with topical azoles?

Back 14

Still see Rx-Rx-Interactions!

Front 15

What are the 3 Echinocandins? How are they administered?

Back 15

Caspo-fungin, Anidula-fungin, Mica-fungin
*IV administration*

Front 16

What is the MOA of Echinocandins?

Back 16

Inhibit synthesis of β-1,3-D-glucan to disrupt cell wall

Front 17

What is the clinical use of Echinocandins?

Back 17

. Deep invasive Candidia and Aspergillus,
. Ampho B/Fluco/Vorico resistant strains,
. Combo therapy w/ Ampho B against Murcomyco (Zygomyco),
. Empiric fungal ifxns

Front 18

What kind of drug interactions do Echinocandins display?

Back 18

Not metabolized by CYP enzymes thus little interactions, but metabolized by anti-rejection meds (cyclosporine, sirolimus, tacrolimus) and thus interact w/ them

Front 19

What is the MOA of Allylamines?

Back 19

Target squalene 2-3 epoxides to inhibit erogsterol synthesis (cause pores to form in membranes)

Front 20

What is the only allylamine drug and what is its main use?

Back 20

Terbinafine – dermatophytes – nail/toenail infxns (onychomycosis) and ringworm

Front 21

What is the MOA of Grisefulvin and is main use?

Back 21

MOA = Inhibit microtubule polymerization
USE = dermatophytes – ringworm

Front 22

What is the 1st line drug for Mucuromycoses (Zygomycoses)?

Back 22

Amphortericin B