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Pharmacology I Exam 3 > Antifungals > Flashcards

Antifungals Flashcards

1
Q

How is Amphotericin B administered?

A

IV

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2
Q

What is the MOA for Amphotericin B?

A

Interaction with ergosterol of fungal membrane, resulting in loss of intracellular components, depolarization, and pore formation
Fungicidal

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3
Q

What are the uses of Amphotericin B?

A

DOC:

Most systemic antifungal infections

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4
Q

What are the infusion related/immediate toxicities of Amphotericin B?

A
  • Chills, fever, muscle spasms, V, HA (slow infusion rate/decrease dose)
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5
Q

What are the cumulative toxicities of Amphotericin B?

A
  • Nephrotoxicity (excreted slowly; can lead to irreversible damage)
  • Azotemia - BUN/creatinine elevated
  • Jaundice, anorexia, weight loss, hypokalemia
  • Hypersensitivity
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6
Q

What is the MOA of Flucytosine?

A

Converted to 5-fluorouracil which interferes with fungal DNA/RNA synthesis

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7
Q

What are the uses of Flucytosine?

A

Cryptococcus (+ amphotericin B)

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8
Q

What are the toxicities of Flucytosine?

A
  • Bone marrow depression
  • May elevated ALT, AST
  • GI disturbances
  • Renal toxicity if pt has renal impairment due to renal excretion of drug
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9
Q

What is the DOC for most systemic antifungal infections?

A

Amphotericin B

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10
Q

What is the DOC for Cryptococcus infections?

A

Flucytosine + Amphotericin B

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11
Q

How is Ketoconazole administered?

A

Oral, shampoo, cream

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12
Q

What is the MOA for the “azoles”?

A

Inhibits synthesis of ergosterol leading to increased membrane permeability and inhibition of fungal growth

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13
Q

What are the uses for Ketoconazole?

A

Broad spectrum and tried as a substitute for Amphotericin B

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14
Q

What are toxicities of Ketoconazole?

A
  • Potent inhibitor of P450 = drug interactions
  • Gynecomastia and impotence due to inhibition of adrenal/testicular function
  • Prolonged QT
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15
Q

What are contraindications to Ketoconazole?

A

Acute or chronic hepatic disease as extensively metabolized before elimination

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16
Q

How is Fluconazole administered?

A

Oral or IV

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17
Q

What is significant about the penetration of Fluconazole?

A

Has good CNS penetration

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18
Q

What are the uses for Fluconazole?

A

DOC:
Crytococcal meningitis for suppressive and/or prophylactic therapy in HIV+ patients
- Candida

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19
Q

What are the toxicities of Fluconazole?

A
  • Potent inhibitor of CYP2C9
  • Headache
  • Less toxic than amphotericin B or flucytosine and better tolerated than ketoconazole
  • Less drug interactions than other azoles
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20
Q

How is Voriconazole administered?

A

Oral or IV

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21
Q

What is significant about the penetration of Voriconazole?

A

Modest CSF penetration

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22
Q

What are the uses of Voriconazole?

A

DOC:
Aspergillus (+ amphotericin B)

Esophageal candidiasis

23
Q

What are the toxicities of Voriconazole?

A

Drug interactions:

  • Metabolized by P450s
  • Inhibits P450s
  • Genetic polymorphism: CYP2C19
  • Visual impairment (reversible)
24
Q

What is the DOC for Crytococcal meningitis for suppressive and/or prophylactic therapy in HIV+ patients?

A

Fluconazole

25
Q

What is the DOC for Aspergillus?

A

Voriconazole + Amphotericin B

26
Q

How is Itraconazole administered?

A

Oral or IM

27
Q

What are the uses of Itraconazole?

A

Active against many of the same fungi as ketoconazole and fluconazole, but greater against Aspergillus

Dermatophytes
Onychomycosis

28
Q

What are the toxicities of Itraconazole?

A
  • Potent inhibitor of CYP3A4 – drug interactions

- GI effects

29
Q

How is Isavuconazonium administered?

A

Oral and IV

30
Q

What are the uses for Isavuconazonium?

A

Indicated for treatment of mucormycosis and invasive aspergillosis

31
Q

What are the toxicities of Isavuconazonium?

A
  • Nephrotoxicity
  • Short QTc interval (dose dependent)
  • Drug interactions – both substrate and moderate inhibitor of CYP3A4
32
Q

When is Isavuconazonium contraindicated?

A

In patients with familial short QT syndrome

33
Q

How is Posaconazole administered?

A

Oral and IV

34
Q

What are the uses of Posaconazole?

A
  • Aspergillus

- Candida

35
Q

What are the toxicities of Posaconazole?

A
  • Drug interactions – both substrate and moderate inhibitor of CYP3A4
  • GI effects
  • Stomatitis, vaginal bleeding
  • Hypokalemia, thrombocytopenia
36
Q

How is Caspofungin administered?

A

IV, slow infusion

37
Q

What is the MOA for Caspofungin?

A

Inhibits synthesis of major cell wall component, Beta (1,3)-D-glucan, which is not present in mammalian cells

38
Q

What are the uses of Caspofungin?

A

Invasive Aspergillosis in refractory patients (azole or ampho B resistant fungi)

Esophageal candidiasis

39
Q

What are the toxicities of Caspofungin?

A

Increased liver enzymes, histamine release, headache, chills, GI

40
Q

How is Griseofulvin administered?

A

Oral

41
Q

What is the MOA for Griseofulvin?

A

Binds to microtubules of keratin and destroys spindles

Fungistatic – prevents new skin infection

42
Q

What is the DOC for Onychomycosis?

A

Griseofulvin

43
Q

What are the toxicities of Griseofulvin?

A
  • Headache, GI, other CNS effects
  • Disulfiram-like effects
  • Hematological, skin rashes, photosensitivity, albuminuria, hepatotoxicity
44
Q

What are contraindications for Griseofulvin?

A
  • Acute intermittent porphyria
  • Hepatocellular failure
  • Pregnancy
  • Men 6 months prior to fathering child
45
Q

How is Terbinafine administered?

A

Oral or topical

46
Q

What is the MOA for Terbinafine?

A

Interferes with sterol biosynthesis; inhibits squalene which builds up and is toxic to fungi

Fungicidal

47
Q

What are the uses of Terbinafine?

A

Onychomycosis

48
Q

How is Nystatin administered?

A

Oral - GI candida

Topical - other

49
Q

What are the uses for Nystatin?

A

Candidal infection

50
Q

What are the uses for Efinaconzaole (Jublia)?

A

Onychomycosis of toenails caused by Trichophyton rubrum and mentagrophytes

51
Q

What are the uses for Naftifine and Tolnaftate?

A
  • Athlete’s foot

- Jock itch

52
Q

What are the uses for Tioconazole, Clotrimazole, and Miconazole (topical azoles)

A

Skin and vaginal candidiasis

Tinea

53
Q

What is the DOC for Aspergillus in azole or Ampho B resistant fungi?

A

Caspofungin

Pharmacology I Exam 3 (8 decks)

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