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IBI Test 2 > B3-046 - Fungal Drugs > Flashcards

B3-046 - Fungal Drugs Flashcards

1
Q

Membrane-active agents

A

Amphotericin B
Nystatin

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2
Q

Cell wall synthesis inhibitors

A

Caspofungin

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3
Q

Azole derivatives

A

Ketoconazole
Itraconazole
Fluconazole
Voriconazole

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4
Q

Antimetabolite

A

Flucytosine

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5
Q

Microtubule poison

A

Griseofulvin

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6
Q

Allyl amines

A

Terbinafine

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7
Q

Flucytosine mechanism

A

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

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8
Q

Flucytosine pharmacokinetics

A

Orally effective, well distributed, including CNS
Excreted in urine

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9
Q

Flucytosine adverse effects

A

Low tax to patients (not activated in mammalian cells)

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10
Q

Flucytosine clinical uses

A

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

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11
Q

Fungi use ____ instead of cholesterol

A

Ergosterol

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12
Q

Amphotericin B mechanism

A

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

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13
Q

Amphotericin B Pharmacokinetics

A

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

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14
Q

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

A

Low and slow (infusion, slow IV drip)

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15
Q

Liposomal Amphotericin B

A

Liposomal reservoir of amphotericin. Increases effectiveness, decreases toxicity

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16
Q

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

A

Fungal mem - 10
Liposome - 1
Human mem - 0.1

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17
Q

Amphotericin B clinical uses

A

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

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18
Q

Amphotericin B adverse effects

A

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

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19
Q

Nystatin mechanism

A

Similar to amphotericin B
too toxic for systemic use

20
Q

Nystatin is given ____ to treat ____

A

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

21
Q

Nystatin adverse effects

A

Diarrhea, nausea, sometimes Stevens Johnson rash

22
Q

Terbinafine is administered

A

Orally (as griseofulvin) or topical

23
Q

Terbinafine has a _____ bioavailability and a half life of __

A

Low. 2 weeks

24
Q

Terbinafine mechanism

A

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

25
Q

Mechanism of -azoles

A

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

26
Q

Ketoconazole pharmacokinetics

A

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

27
Q

Ketoconazole adverse effects

A

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

28
Q

Ketoconazole is also used as an adjust therapy for _____

A

prostate cancer

29
Q

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

A

systemic anti fungal; topical therapy

30
Q

Itraconazole is given

A

Orally (low bioavailability) and IV

31
Q

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

32
Q

Itraconazole clinical uses

A

histoplasma, blastomyces, sporothrix

33
Q

Fluconazole pharmacokinetics

A

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

34
Q

Fluconazole clinical uses

A

Cryptococcal meningitis, candidemia, mucocutaneous candidiasis

35
Q

Vorizonazole pharmacokinetics

A

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

36
Q

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

A

Amphotericin B; invasive aspergillus

37
Q

Voriconazole adverse effects

A

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

38
Q

Caspofungin mechanism

A

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

39
Q

Caspofungin is given

A

IV, highly protein bound with slow metabolism

40
Q

Caspofungin adverse effects

A

GI, flushing

41
Q

Caspofungin clinical uses

A

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

42
Q

Caspofungin memory tool

A

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

43
Q

Griseofulvin is given ____

A

orally, concentrates in keratinized tissue

44
Q

Griseofulvin mechanism

A

Maybe blocks mitosis - still unknown

45
Q

Griseofulvin clinical use

A

Treatment of ringwork athletes foot

46
Q

Griseofulvin adverse effects

A

CYP inducer/teratogenic
Hepatotoxic

IBI Test 2 (5 decks)

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