Antifungal agents for the treatment of systemic fungal infections in children Flashcards

1
Q

What major toxicities are associated with amphotericin B?

A
  1. Nephrotoxicity

2. Infusion related events i.e. fever, chills, rigors

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2
Q

What is the spectrum of activity for amphotericin B?

A
Asperigillus fumigatus ++
Aspergillus flavus ++
Candida albicans +++
Candida glabrata ++
Candida lustinaiae +/-
Candida tropicalis +++
Candida krusei ++
Candida parapsilosis +++
Candida gulliermondii ++
Cryptococcus neoformans +++
Fusarium species ++ (lipid products)
Scedosporium apiospermum +/-
Scedosporium prolificans +/-
Zygomycetes +++ (lipid products)
Dermatiaceous moulds +
Dimorphic fungi +++
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3
Q

What does amphotericin B not cover?

A

Aspergillus terreus

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4
Q

What is the most common indications for use of amphotericin B?

A
  1. Invasive fungal infections caused by susceptible organisms. 2. Empirical therapy of presumed febrile neutropenic patients
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5
Q

What are the major benefits of the lipid preparation of amphotericin B?

A

Fewer infusion related reactions and nephrotoxicity and broader spectrum of action

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6
Q

What are the major side effects of fluconazole?

A
  1. Rare but serious hepatotoxicity

2. Drug interactions as it induces cytochrome p450 isoenzymes

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7
Q

What is the action of fluconazole?

A

Candida more active against albicans then other strains. Can treat cryptococcal agents. No activity against aspergillus or other moulds.

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8
Q

What are the indications for fluconazole?

A
  1. Candida infections
  2. Cryptococcal infections
  3. Antifungal prophylaxis for HSCT patients and neonates
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9
Q

What are common adverse effects of itraconazole?

A
  1. abdominal pain
  2. vomiting
  3. diarrhea
  4. elevated liver enzymes
  5. drug interactions due to inhibition of cytochrome p450 3A4 enzyme
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10
Q

What are the indications for itraconazole?

A
  1. Invasive and non-invasive aspergillosis, oropharyngeal and esophageal candidiasis
  2. blastomycosis
  3. chronic pulmonary histoplasmosis
  4. antifungal prophylaxis in HSCT and lung transplant patients
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11
Q

What are the major side effects or voriconazole?

A
  1. Liver function abnormalities
  2. Skin rash
  3. Visual disturbances
  4. Cytochrome P450 isoenzyme drug interactions
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12
Q

What are the indications for voriconazole?

A
  1. invasive aspergillosis
  2. esophageal candidiasis
  3. refractory infections due to scedosporium, angiospermum, and fusarium species
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13
Q

What are the major side effects of posaconazole?

A
  1. GI symptoms
  2. headaches
  3. elevated liver enzymes
  4. cytochrome P450 3A4 enzyme drug interactions
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14
Q

What are the indications for posaconazole?

A
  1. Aspergillosis in patients intolerant/refractory to other agents
  2. Fusariosis in patients intolerant/refractory to other agents
  3. Zygomycosis in patients intolerant/refractory to other agents
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15
Q

What is the activity of ravuconazole?

A
Candida species
Aspergillus species
Cryptococcus neoformans
Histoplasma capsulatum
Coccidioides immitis
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16
Q

What are the major adverse effects of ravuconazole?

A

Unclear, appears to be similar to flucoanzole

17
Q

What would be a benefit of ravuconazole?

A

Long half life of approx. 100h so ideal for step-down therapy and ambulatory treatment

18
Q

How do echinocandins work?

A

Glucan synthesis inhibitors that specifically inhibit beta-(1-3)-D glucan synthesis, thereby compromising the integrity of the fungal cell wall

19
Q

What are examples of echinocandins?

A

Caspofungin
Micafungin
Anidulafungin

20
Q

What are the main indications for caspofungin?

A
  1. Candida infections
  2. Invasive aspergillosis in patients refractory/intolerant to other therapy
  3. Empirical therapy in febrile neutropenic patients
21
Q

What are the main adverse effects for caspofungin?

A
  1. Liver function abnormalities
  2. Fever
  3. Headache
  4. Rash
  5. GI symptoms
  6. Anemia
22
Q

What are the main indications for micafungin?

A

Similar to caspofungin prophylaxis of Candida infections in HSCT patients

23
Q

What are the main adverse effects for micafungin?

A
  1. liver function abnormalities
  2. nausea
  3. vomiting
24
Q

What are the main indications for anidulafungin?

A

being evaluated for esophageal candidiasis

25
Q

What are the main adverse effects for anidulafungin?

A
  1. Phlebitis/thrombophlebitis
  2. Fever
  3. Headache
  4. Nausea
  5. Vomiting
  6. Rash
26
Q

What are the main indications for flucytosine?

A

combination therapy with amphotericin B for Candida and cryptococal infections

27
Q

What are the main adverse effects for flucytosine?

A
  1. GI intolerance
  2. bone marrow suppression
  3. Rash
  4. Hepatotoxicity
  5. Headache
  6. Confusion
  7. Hallucinations
  8. Sedation
  9. Euphoria