B3-046 - Fungal Drugs

Question 1

Membrane-active agents

Answer 1

Amphotericin B
Nystatin

Question 2

Cell wall synthesis inhibitors

Answer 2

Caspofungin

Question 3

Azole derivatives

Answer 3

Ketoconazole
Itraconazole
Fluconazole
Voriconazole

Question 4

Antimetabolite

Answer 4

Flucytosine

Question 5

Microtubule poison

Answer 5

Griseofulvin

Question 6

Allyl amines

Answer 6

Terbinafine

Question 7

Flucytosine mechanism

Answer 7

Activated by fungal cytosine deaminase
converted to 5-fluorouracil (5-FU) which blocks DNA and RNA synthesis by inhibiting thymidylate synthase

Question 8

Flucytosine pharmacokinetics

Answer 8

Orally effective, well distributed, including CNS
Excreted in urine

Question 9

Flucytosine adverse effects

Answer 9

Low tax to patients (not activated in mammalian cells)

Question 10

Flucytosine clinical uses

Answer 10

Narrow spectrum - cryptococcus, some candida
Resistance develops rapidly, use only with amphotericin B or -azoles

Question 11

Fungi use ____ instead of cholesterol

Answer 11

Ergosterol

Question 12

Amphotericin B mechanism

Answer 12

Polyene macrolide anti fungal - binds to ergosterol in fungal membrane - makes plasma mem leaky and cell dies from pore formation and leakage

Question 13

Amphotericin B Pharmacokinetics

Answer 13

Must give IV or direct to CNS
widely distributed (IV doesn’t cover CNS)
very slow excretion (t-1/2 = 2 weeks)

Question 14

Amphotericin B should be administered _____ due to its slow excretion time

Answer 14

Low and slow (infusion, slow IV drip)

Question 15

Liposomal Amphotericin B

Answer 15

Liposomal reservoir of amphotericin. Increases effectiveness, decreases toxicity

Question 16

Affinities of amphotericin B for Fungal membranes, liposome, and human membrane

Answer 16

Fungal mem - 10
Liposome - 1
Human mem - 0.1

Question 17

Amphotericin B clinical uses

Answer 17

Most important drug for mucous - cryptococcus meningitis, blastomyces, candida, coccidoides, more
Broad spectrum antifungal
Use for initial intervention, then switch to other anti-fungals for maintenance/cure

Question 18

Amphotericin B adverse effects

Answer 18

“Ampho-terrible B”
Shake and Banke
- chills, fever, nausea, vomiting, headache
usually medicate to suppress adverse effects
Common irreversible nephrotox

Question 19

Nystatin mechanism

Answer 19

Similar to amphotericin B
too toxic for systemic use

Question 20

Nystatin is given ____ to treat ____

Answer 20

orally - “swish and swallow”.
pseudo-topical treatment for Candidas

Question 21

Nystatin adverse effects

Answer 21

Diarrhea, nausea, sometimes Stevens Johnson rash

Question 22

Terbinafine is administered

Answer 22

Orally (as griseofulvin) or topical

Question 23

Terbinafine has a _____ bioavailability and a half life of __

Answer 23

Low. 2 weeks

Question 24

Terbinafine mechanism

Answer 24

Inhibits squalene epoxidase (ergosterol synthesis)
This causes accumulation of squalene (toxic)

Question 25

Mechanism of -azoles

Answer 25

Inhibit ergosterol synthesis by blocking fungal CYPs This impacts all CYPs so is impacts other drug metabolism

Question 26

Ketoconazole pharmacokinetics

Answer 26

1st effective oral anti fungal for systemic use Absorbed and dist well, except for CNS

Question 27

Ketoconazole adverse effects

Answer 27

Nausea, vomiting, anorexia Hepatotoxicity Blocks adrenal steroidogenesis (gynecomastia) Inhibits drug metabolism - interacts with cyclosporin, and many other drugs

Question 28

Ketoconazole is also used as an adjust therapy for _____

Answer 28

prostate cancer

Question 29

Due to ketoconazole's adverse effects, it is rarely used as _____, however ______ is available.

Answer 29

systemic anti fungal; topical therapy

Question 30

Itraconazole is given

Answer 30

Orally (low bioavailability) and IV

Question 31

Itraconazole has (more or less) effects on mammalian CYPs than ketoconazole

Answer 31

Less

Question 32

Itraconazole clinical uses

Answer 32

histoplasma, blastomyces, sporothrix

Question 33

Fluconazole pharmacokinetics

Answer 33

Most used anti-fungal Oral and IV Water soluble High bioavailability, good CSF delivery More selective for fungal CYPs

Question 34

Fluconazole clinical uses

Answer 34

Cryptococcal meningitis, candidemia, mucocutaneous candidiasis

Question 35

Vorizonazole pharmacokinetics

Answer 35

Newest triazole IV or Oral (90% bioavailability) Metabolism in liver, little mammalian CYP inhibition

Question 36

Vorizonazole is better tolerated and more effective than _____ for treatment against ______

Answer 36

Amphotericin B; invasive aspergillus

Question 37

Voriconazole adverse effects

Answer 37

Visual disturbances (30%) Used for candida and dimorphic fungi

Question 38

Caspofungin mechanism

Answer 38

Inhibits synthesis of B(1-3) gluten fo cell wall Incomplete cell wall synthesis causes cell lysis

Question 39

Caspofungin is given

Answer 39

IV, highly protein bound with slow metabolism

Question 40

Caspofungin adverse effects

Answer 40

GI, flushing

Question 41

Caspofungin clinical uses

Answer 41

Approved for Candida, emperic anti-fungal therapy Salvage therapy for Amphotericin-resistant Aspergillus

Question 42

Caspofungin memory tool

Answer 42

CAspoFunGIN C- Candida A - aspergillus F - glushing G - GI IN - IV

Question 43

Griseofulvin is given ____

Answer 43

orally, concentrates in keratinized tissue

Question 44

Griseofulvin mechanism

Answer 44

Maybe blocks mitosis - still unknown

Question 45

Griseofulvin clinical use

Answer 45

Treatment of ringwork athletes foot

Question 46

Griseofulvin adverse effects

Answer 46

CYP inducer/teratogenic Hepatotoxic