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Owenpharm Block 3 > Anti-fungals > Flashcards

Anti-fungals Flashcards

1
Q

There are two major classification of mycoses. What are they? What are some examples of each?

A

Systemic:
Opportunistic - Aspergillus, Candida, Phycomyces, Cyptococcus, Histoplasma
Geographically localized - Blastomyces, Histoplasma, Coccidioides, Sporothrix

Superficial:
Mucous membranes - Candida
Dermatophytic - Trichophyton, Microsporum, Epidermophyton

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2
Q

What are some potential antifungal targets?

A
  1. Membranes - Ergosterol
  2. Nucleic acids (limited)
  3. Cell wall (1 drug class)
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3
Q

What drugs are used for systemic fungal infections?

A
  1. Amphotericin B
  2. Flucytosine
  3. Fluconazole/Itraconazole/Voriconazole
  4. Caspofungin
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4
Q

What is the spectrum of action for Amphotericin B?

A

Effective for most serious systemic mycoses: especially those that are immediately life threatening.

It is the gold standard for anti-fungal effectiveness by which other drugs are judged.

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5
Q

Why should Amphotericin B only be used for proven or highly suspected systemic infections?

A

The side effects are particularly intense

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6
Q

What is the mechanism of action of Amphotericin B?

A

Binds to ergosterol in fungal membrane after inserting itself into membrane. This causes leaks in the fungal membrane.

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7
Q
  1. What is the most serious side effect of Amphotericin B?
  2. What are some other serious side effects?
A
  1. Permanent renal toxicity - total cumulative dose is major determinant.
  2. Hypotension, Hypokalemia, Tachypnea
    90% show temporary nephrotoxicity
    Reversible hypochromic, normocytic anemia
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8
Q
  1. What fungi are treated effectively with Flucytosine (5-FC)?
  2. Is it used alone or in combination therapy?
A
    1. **Candida, Cryptococcus*
      1. Used in conjunction with Amphotericin B
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9
Q

What is the mechanism for Flucytosine?

A

Converted to 5-FU by fungal cytosine deaminase
Inhibits thymidylate synthetase and thus DNA synthesis and is also incorporated in RNA in place of uracil.

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10
Q

What are the major side effects of Flucytosine?

A
  1. Leukopenia, Thrombocytopenia
  2. Reversible elevated hepatic enzymes
  3. Extreme caution needed with patients who have renal insufficiency and bone marrow depression.
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11
Q

What are the three Triazole drugs used for serious fungal infections?

A

Fluconazole
Voriconazole
Itraconazole

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12
Q

What is the mechanism for imidAZOLES and triAZOLES?

A

Inhibits 14-alpha-sterol demethylase, a fungal P450 that converts lanosterol to ergosterol.

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13
Q
  1. What are the two fungal species that are treated well with Fluconazole?
  2. Which *Candida *species does Fluconazole not cover?
A
  1. Cryptococcus (meningitis), Candida.
  2. C. krusei
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14
Q
  1. What non-candida species does itraconazole cover?
  2. What is itraconazole’s relative candida coverage?
A
  1. Blastomyces, Histoplasma
  2. It has moderate coverage but does not penetrate CNS or urinary.
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15
Q
  1. What non-candida species does voriconazole cover?
  2. What is the relative candida coverage for voriconazole?
A
  1. Aspergillus
  2. Extensive coverage but does not treat urinary infection
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16
Q

If fluconazole covers the fewest types of candida, why is it the most effective for treating urinary infections?

A

It is the only drug that is eliminated into urine in the active form. It also has the best CNS penetration.

17
Q

What are the side effects for Triazoles?

A

GI effects

Mild hepatotoxicity - should be discontinued with onset of liver dysfunction.

Potent P450 inhibitor - CYP3A (itraconazole) and CYP2C (fluconazole)

18
Q

Why is it so important not to give itraconazole with other drugs that are metabolized by CYP3A4?

A

There is potential for serious cardiovascular events including death.

19
Q

What is are some side effects that is specific to Voriconazole?

A
  • Visual disturbances in 30%
  • Photosensitive component to rash
20
Q
  1. What is Caspofungin primarily used to treat?
  2. What is the mechanism for Caspofungin?
A
  1. Invasive Aspergillus, Candida - esophageal and systemic
  2. Inhibits fungal cell wall synthesis by noncompetitively blocking synthesis of B(1,3)-D-glucan in filamentous fungi

There is no cross resistance with imidazoles and triazoles

21
Q

What are the side effects of Caspofungin?

A
  1. fever
  2. nausea/vomiting
  3. flushing
  4. phlebitis at injection site
22
Q

What are the drugs for treatment of superficial mycoses? (3 items)

A
  1. Nystatin
  2. Imidazoles (i.e. Fluconazole, ketoconazole, clotrimazole)
  3. Natamycin (for Ophthalmic infections)
23
Q

What is the major indication for Fluconazole?

A

Candida infections of vagina, urinary tract, oropharynx

24
Q
  1. What form is Miconazole (Monistat) primarily administered and for what condition?
  2. What are side effects with topical use?
A
  1. As a cream/suppository for vaginal Candida
  2. Burning, itching, irritation
25
Q
  1. How is Clotrimazole primary administered?
  2. What is a major side effect of oral troche form?
A
  1. Topical
  2. Abnormal liver function tests
26
Q

What is Itraconazole primarily used to treat?

A

Oropharyngeal and esophageal Candida

27
Q
  1. When would Nystatin be a good choice for Candida infection?
  2. What is a major side effect of Nystatin?
A
  1. In the presence of -azole resistant strains
  2. Gastrointestinal distress
28
Q
  1. What drug with a mechanism similar to amphotericin B is good for treatment of ophthalmic fungal infections?
  2. What would toxicity look like?
A
  1. Natamycin
  2. Conjunctival chemosis and hyperemia
29
Q
  1. What are three different types of drugs used to treat dermatophyte infection?
  2. What is the only FDA approved topical Rx for mild to moderate fungal nail infections?
A
  1. Miconazole, Tolnaftate, Terbinafine
  2. Ciclopirox
30
Q

What is an oral preparation for dermatophyte infection? How long is treatment?

A

Terbinafine - for 12 week therapy

31
Q

What is the MOA of Terbinafine?

A

Inhibits squalene epoxidase which causes an accumulation of squalene lipid droplets which disrupt the fungal cell membrane and are fungicidal

32
Q

What are the most common side effects of Terbinafine?

A

Diarrhea, Dyspepsia, Abdominal pain

33
Q
  1. What is an oral preparation other than Terbinafine for dermatophyte infection?
  2. What condition is this safe for use with children?
A
  1. Griseofulvin
  2. Tinea capitis
34
Q

What is the MOA of Griseofulvin?

A

Interference with microtubule function/mitotic spindle/mitosis

35
Q

What are some major side effects of Griseofulvin? (3 items)

A
  1. Worsens condition for those with porphyria and advanced liver disease
  2. Increases metabolism of other drugs through CYP induction
  3. Should be used with caution in those with penicillin allergies.
36
Q

What is an oral therapy for fungal toenail infections?

A

Itraconazole

Owenpharm Block 3 (8 decks)

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