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POD III > Anti-fungals > Flashcards

Anti-fungals Flashcards

1
Q

What is considered the “gold standard” in antifungal therapy?

A

Amphotericin B Deoxycholate

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2
Q

What is the mechanism of action for Amphotericin B?

A

Binds to sterols (ergosterol) and alters the membrane permeability leading to leakage of essential cell contents and eventually cell lysis and death.

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3
Q

What is the major ADR for Amphotericin B?

A

Nephrotoxicity.

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4
Q

What is the mechanism of action of 5-fIuocytosine?

A

Penetrates fungal cell where it is deaminated by a fungal enzyme (cytosine deaminase). Competes with uracil inhibiting DNA, RNA and protein synthesis.

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5
Q

Does fIuocytosine distribute to CSF?

A

Yes, 60-100%

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6
Q

What are the Imidazoles?

A
  1. Ketoconazole (PO/Topical)

2. Miconazole (IV/Topical)

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7
Q

What are the Triazoles?

A
  1. Fluconazole (PO/IV)
  2. Itraconazole (PO)
  3. Voriconazole (PO/IV)
  4. Posaconazole (PO)
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8
Q

What is the mechanism of action for Azole anti-fungals?

A

Interfere with the fungal cytochrome P-450-dependent enzymes responsible for the demethylation of lanosterol and conversion to ergosterol.

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9
Q

What is the drug of choice for coccidioidomycosis?

A

Fluconazole.

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10
Q

What is the mechanism of action for caspofungin acetate?

A

Blocks fungal cell wall synthesis. Glucan synthesis inhibitor.

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11
Q

What is the spectrum of activity for Amphotericin B?

A
  • Aspergillosis
  • histoplasmosis
  • Blastomycosis
  • Coccidioidomycosis
  • Paracoccidioidomycosis
  • Cryptococcus
  • Candida (topical only)
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12
Q

What is the benefit to Amphotericin B Lipid formulations?

A
  • Lower incidence of nephrotoxicity

- Equal efficacy to parent compound

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13
Q

What ADRs occur with 5 Fluocytosine and when are they most common?

A
  • Bone marrow hypoplasia

- More common in prolonged therapy or when in combination with Ampho B

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14
Q

What are the indications for 5-Fluocytosine?

A
  • Serious infections of candida and cryptococcus
    • Possible synergistic effect with Ampho B
  • Cryptococcal meningitis (combo with Ampho B)
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15
Q

What are the ADRs for Azole antifungals?

A
  • Nausea/vomiting
  • Ketoconazole: dose dependent depression of serum testosterone and adrenocorticotropic hormon
  • Hepatitis (rare)
    • Most in first 3 months
  • Increased aminotransferases
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16
Q

What are drugs do azole antifungals interact with?

A
  • Antacids, PPIs and H2 antagonists
    • Not seen with fluconazole or voriconazole
  • Cyclosporin
  • Warfarin
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17
Q

What is the drug interaction between azoles and antacids, PPIs and H2 antagonists?

A

Decreased absorption due to decreased acidic environment.

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18
Q

What are the drug interactions between azoles and cyclosporin?

A

Increased cyclosporin concentrations.

19
Q

What are the drug interactions between azoles and warfarin?

A

Increased anticoagulation effect.

20
Q

What is the spectrum of activity for Ketoconazle?

A
  • Histoplasmosis
  • Blastomycosis
  • Coccidioidomycosis
  • Candidiasis
  • Tinea
  • Vulvovaginal candidiasis
21
Q

What is the bioavailability of Fluconazole taken orally?

A

F > 90%

22
Q

How is Fluconazole eliminated?

A
  • Renal excretion

- 60-80% unchanged in urine

23
Q

What is the spectrum of activity for Fluconazole?

A
  • Cryptococcal infections
  • Coccidioidomycosis (drug of choice)
  • Candidiasis
  • Prophylaxis of candidiasis
24
Q

How well does itraconazole distribute into the CSF?

A

Poorly.

25
Q

What is the spectrum of activity for Itraconazole?

A
  • Aspergillosis
  • Cryptococcal infections
  • Coccidioidomycosis
  • Histoplasmosis
  • Blastomycosis
  • Tinea unguium (onychomycosis)
26
Q

What can decrease the absorption of voriconazole?

A

High fat meals

27
Q

What is the bioavailability of voriconazole?

A

96%

28
Q

Where is voriconazole eliminated?

A

Metabolized in the liver.

29
Q

What are the ADRs for voriconazole?

A
  • Visual disturbances
  • Rash
  • Increased LFTs
30
Q

What drug contraindications exist with voriconazole?

A
  • Rifampin
  • Carbamazepine/phenobarbitol
  • Quinidine
  • Sirolimus
  • Ergot alkaloids
31
Q

What are the uses for voriconazole?

A
  • Invasive aspergillosis

- Candidiasis

32
Q

What are the uses for posaconazole?

A
  • In severely immunocompromised pts:
    • Candida
    • Aspergillus
  • Oropharyngeal candidiasis
33
Q

What are the indications for capsofungin acetate?

A
  • Candidiasis

- Invasive aspergillosis (pts are refractory to to other drugs)

34
Q

What are the ADRs of capsofungin acetate?

A

Phlebitis, headache, fever, increased LFTs and SrCr

35
Q

What is the mechanism of action of Griseofulvin?

A

Disrupts the cells mitotic spindle structure thus arresting the metaphase of cell division.

36
Q

What is the spectrum of activity for griseofulvin?

A

-Dermatophytosis

37
Q

When is griseofulvin used?

A

When topical agents fail/are not effective.

38
Q

What is the most common ADR for griseofulvin?

A

Headache/dizziness

39
Q

What is the mechanism of action for terbinafine?

A

Inhibits squalene epoxidase (enzyme in sterol biosynthesis in fungi).

40
Q

What are the most common ADRs for terbinafine?

A
  • Hypersensitivity/rash

- Erythema multiforme, toxic epidermal necrolysis

41
Q

What drugs interact with terbinafine?

A
  • Cimetidine
  • Rifampin
  • Cyclosporin
  • Warfarin
42
Q

What are the indications for terbinafine?

A

-Onychomycosis

43
Q

What are the contraindications for terbinafine?

A
  • Liver/renal dysfunction

- Pregnancy

44
Q

What are the treatments for oral candidiasis (thrush)?

A
  • Nystatin: swish and swallow TID
  • Clotrimazole troches: 5 x day
  • Amphotericin B suspension

POD III (12 decks)

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