David's Antifungals

Front 1

Amphotericin B MOA? 2) absorption 3) plasma protein binding?

Back 1

binds to ergosterol in the membrane (some binding to humans occurs -> toxicity). 2) poorly absorbed in the GI tract and CNS (but used for meningitides) 3) 90%, mostly to beta-lipoprotein

Front 2

Amphotericin B is complexed with what for IV? Excretion?

Back 2

To bile salt dexoycholate. Metabolized and excreted in kidneys but hepatic/renal impairment does not alter blood levels much.

Front 3

Amphotericin B adverse effects (4)

Back 3

1) renal impairment seen in almost all (dec. renal perfusion, possibly ATN). 2) abnormal liver function. 3) anemia from reduced erythropoietin. 4) Infusion related toxicity with all sorts of stuff. Pre-medicate with meperidine and acetaminophen or corticosteroids

Front 4

Amphotericin B has broad spectrum but less sensitive to what? Resistant?

Back 4

Candida lusitaniae (works for albicans though). Fusarium resistant

Front 5

Nystatin structure? Administration? Use?

Back 5

forms pores like Amphotericin B. 2) Too toxic for internal -> topical. 3) Candida for oropharyngeal thrush and vaginal candidiasis

Front 6

Azoles, name the two and what was written in the syllabus about them. Yeah I know.

Back 6

1) Imidazoles have the greater effect on human sterol synthesis so more side effects. 2) Triazoles are more slowly metabolized.

Front 7

Azoles MOA? Fungi-?

Back 7

Reduce ergosterol synthesis and inhibit P450 enzyme C-14 demthylase. Fungiostatic

Front 8

Azoles absorption (3 specific drugs mentioned). Distribution? Metabolism?

Back 8

Variable absorption. Ketoconazole and Itraconazole depend on the pH of stomach. Fluconazole is well absorbed. 2) Fluconazole penetrates even into the eyes, joints, CNS. 3) All in the liver

Front 9

Ketoconazole absorption? Effects (3)?

Back 9

Requires low stomach pH. 2) teratogenic, inhibits adrenal and gonadal steroid synthesis so reverses hirsutims in women, and alters metabolism of other drugs leading to toxicity (cyclosporine)

Front 10

Ketoconazole drug interactions (3)

Back 10

1) Antacids and H2 blockers block absorption. 2) Rifamycins increase metab of ketoconazole. 3) inhibition of P450s increases other drugs like cyclosporine

Front 11

Ketonconazole uses (4) and replaced by what?

Back 11

Remember that this is for mild stuff. 1) oral thrush. 2) mild histo (non-CNS). 3)mild blasto. 4) Onychomycosis. Replaced by itraconazole

Front 12

Itraconazole similar to what? Different how? Clinical uses (3)

Back 12

Similar to ketoconazole but NO interaction with mammalian P450s. 1) Dermatophytoses and oncyomycoses. 2) activity against aspergillus. 3) preferred against histo, blasto, and sporotrichosis

Front 13

Fluconizole solubility? Distribution? DOC for? Prophylactic for?

Back 13

1) water soluble. 2) Good CNS penetration. 3) DOC for cryptococcal meningitis. 4) prophylactic for fungal disease in bone marrow

Front 14

Voriconazole similar to? Excellent activity against? More effective than ampho for?

Back 14

Itraconazole. Excellent activity against Candida. More effective than ampho against aspergillus

Front 15

Clotrimazole use? 2 uses?

Back 15

topical use. Lozenges taste better than Nystatin or OTC for vaginal yeast

Front 16

Miconazole use? OTC for?

Back 16

1) topical. 2) athlete's foot

Front 17

Flucytosine MOA? Fungi-?

Back 17

Transported by permease. Deamidated into 5-fluorouracil (anti-metabolite) by cytosine deaminase (which host cells lack). 5-FU blocks DNA/RNA synthesis. Fungistatic

Front 18

Flucytosine adverse effects (7)?

Back 18

Metabolism into 5-FU by gut flora causes: 1) antineoplastic effects. 2) bone marrow toxicity. 3) anemia. 4) leucopenia. 5) thrombocytopenia. 6) nausea. 7) skin rash

Front 19

Flucytosine Clinical use?

Back 19

Only in combination therapy b/c resistance develops quickly. Effective synergy with amphoB for cryptococcal meningitis in AIDS

Front 20

Griseofulvin MOA?

Back 20

Inhibits fungal mitosis by disrupting the mitotic spindle by interacting with polymerized microtubles and intermediate filaments.

Front 21

Griseofulvin solubility? Excretion? Toxicity?

Back 21

Water insoluble. 2) excreted in urine. 3) low toxicity

Front 22

Terbinafine MOA? Administration? Effect?

Back 22

1) interferes with ergosterol synthesis by inhibiting squalene epoxide -> toxic. 2) topical or oral use with large first pass effect. 3) accumulates in nails, skin, and fat

Front 23

Terbinafine clinical use? Duration of Tx?

Back 23

more effective than itraconazole for nail fungus. 3 months

Front 24

Echinocandins (caspofungin) MOA? Protein binding?

Back 24

Inhibits formation of cell wall by binding beta1, 3-D-glucan synthesis. 2) Highly bound to albumin

Front 25

Echinocandins (caspofungin) Degradation? Elimination? Solubility?

Back 25

1) Spontaneously degraded and conjugation. 2) Kidneys. 3) water-soluble, semi-synthetic lipoprotein

Front 26

Echinocandins (caspofungin) clinical use (2)? Adverse effects (3 main groups, 1 minor)

Back 26

Deep candidiases and aspergillosis. 1) phlebitis/thrombophlebitis. 2) HA. 3) fever/chills. 4) N/V, diarrhea, rash

Front 27

Drug for immunocompromised Aspergillosis

Back 27

ampho B

Front 28

Drug for competant aspergillosis

Back 28

ampho B or itraconazole

Front 29

Drug for rapid or CNS blastomycosis

Back 29

amphoB

Front 30

Drug for slow or non-CNS blastomycosis

Back 30

itraconazole or ketoconazole

Front 31

Drug for Coccidioidomycosis rapid

Back 31

amphoB

Front 32

Drug for Coccidioidomycosis indolent

Back 32

Azole

Front 33

Drug for Coccidioidomycosis Meningeal

Back 33

Fluconazole, intrathecal AmphoB

Front 34

Drug for crypto

Back 34

AmphoB +/- flucytosine

Front 35

drug for crypto maintenance

Back 35

Fluconazole, intrathecal AmphoB

Front 36

drug for chronic pulmonary histoplasmosis

Back 36

Itraconazole

Front 37

Drug for rapid or CNS histoplasmosis

Back 37

AmphoB

Front 38

drug for indolent or maintenance histoplasmosis

Back 38

Itraconazole

Front 39

Drug for mucormycosis

Back 39

AmphoB

Front 40

Drug for Pseudallescheriasis

Back 40

Itraconazole

Front 41

Drug for cutaneous sporotrichosis

Back 41

Iodide or Itraconazole

Front 42

Drug for extracutaneous sporotrichosis

Back 42

AmphoB or itraconazole