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Anti Fungal Flashcards

1
Q

What is the mechanism of action of Amphotericin B?

A

Amphotericin B binds to ergosterol in the plasma membranes of sensitive fungal cells to forms pores (channels). The pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death.

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2
Q

What does Amphotericin B cover?

A

It’s a broad spectrum anti fungal. Covers Candida albicans (candidiasis), histoplasmosis, cryptococcus neoformans, aspergillus (aspergillosis).

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3
Q

How is Amphotericin B administered?

A

Parenterally

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4
Q

What formulations of Amphotericin B are there?

A

Amphotericin B is insoluble in water and must be coformulated with either sodium deoxycholate (conventional) or artificial lipids to form liposomes. The liposomal preparations have reduced renal toxicity but are costly.

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5
Q

What are some adverse effects of Amphotericin B?

A
  1. Infusion related toxicity: Fever and chills
  2. Nephrotoxicity: Despite the low levels of the drug excreted in the urine, conventional amphotericin B (ie, not the lipid formulations) causes renal vasoconstriction and can reduce the glomerular filtration rate (GFR) by more than half. Concurrent therapy with other nephrotoxic agents can increase the risk further. Renal function usually returns with discontinuation of the drug. Hydrate patients adequately.
    Can switch to liposomal formulation.
  3. thrombophlebitis
  4. Bone marrow suppression
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6
Q

Can Amphotericin B be used in pregnancy?

A

Yes, cat B, generally safe.

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7
Q

What is the mechanism of action of 5-Flucytosine?

A

5-flucytosine enters fungal cells through cytosine specific permeases and is then converted, by cytosine deaminase, to its metabolically active form 5-fluorouracil (5-FU).

Conversion of 5-FU into 5-fluorouridine triphosphate (FUTP). FUTP
is incorporated into fungal RNA in place of uridylic acid; and inhibits
protein synthesis.

Metabolism of 5-FU into 5-fluorodeoxyuridine monophosphate
(FdUMP), a potent inhibitor of thymidylate synthase, which is a
key enzyme for DNA synthesis.

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8
Q

How is the spectrum of activity like for 5-FC?

A

Narrow spectrum. Need cytosine specific permeates to enter fungal cells and needs cytosine deaminase to form 5-FU.

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9
Q

What combination of 5-FC is used?

A

It is effective in combination with amphotericin B for treating candidiasis and cryptococcosis (meningitis and pulmonary infections).

Gold standard for cryptococcal meningitis.

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10
Q

How is 5-FC given?

A

Oral. It penetrates well into CSF

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11
Q

Is 5-FU used as a single agent?

A

No, leads to resistance

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12
Q

Adverse effects of 5-FC?

A
  1. GI effects
  2. Bone marrow suppression
  3. Hepatotoxicity
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13
Q

What are examples of echinocandin?

A
  1. caspofungin, 2. micafungin 3. anidulafungin
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14
Q

Mechanism of action of echniocandin ?

A

Echinocandins inhibit the activity of the glucan synthase complex, resulting in loss of the structural integrity of the cell wall.

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15
Q

How are echinocandins administered?

A

Parenteral. They cannot penetrate CSF.

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16
Q

Adverse effects of echinocandins

A

Minor. generally safe. Includes GI symptoms, fever, chills, etc.

17
Q

Two types of azoles

A

Triazoles and imidazoles

18
Q

Mechanism of action of azoles

A

They inhibit C-14 α- demethylase (CYP450 enzyme), thereby blocking the demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes. The inhibition of ergosterol biosynthesis disrupts membrane structure and function and inhibits fungal cell growth.

19
Q

What are the 3 triazoles

A

Fluconazole, Itraconazole, Voriconazole

20
Q

How are triazoles administered

A

Oral.

21
Q

What are the uses of fluconazole?

A 
Single dose oral treatment for vulvovaginal candidiasis. 
Cryptococcal meningitis (useful as alternative to Amphotericin B +  5-FC, good CSF penetration)
Candida infections.
22
Q

How is fluconazole cleared

A

Renally.

23
Q

3 adverse effects associated with triazoles

A
  1. GI
  2. Hepatotoxicity
  3. QT prolongation
24
Q

What forms of oral medication is itraconazole used in

A

Oral capsules -> take after full meal and with coke (acidic pH)
Oral solution -> take on empty stomach

25
Q

Is CSF penetration good for itraconazole?

A

Poor.

26
Q

What is voriconazole used for?

A

Invasive aspergillosis

27
Q

CSF penetration for voriconazole?

A

Good

28
Q

Special side effects of itraconazole and voriconazole

A

Itraconazole is associated with cardiotoxicity
Voriconazole is associated with neurotoxicity (visual
disturbances.
hallucinations)

29
Q

Is there DDI for azoles?

A

Yes, azoles INHIBIT CYP450.

30
Q

What are the two imidazoles?

A

Clotrimazole

Miconazole

31
Q

Adverse effects of imidazoles

A

Contact dermatitis
Vulvar irritation
Edema

32
Q

What are imidazoles used for

A

Tinea diseases
Vulvovaginal candidiasis
Oropharyngeal candidiasis

33
Q

Does imidazoles have good oral bio?

A

No, v poor oral bio.

34
Q

What class is nystatin under

A

Polyene

35
Q

How is nystatin administered

A

It can be administered as an oral agent (“swish and swallow” or “swish and spit”) for the treatment of oropharyngeal candidiasis (thrush), intravaginally for vulvovaginal candidiasis, or topically for cutaneous candidiasis.

not used parenterally due to systemic toxicity

36
Q

Mechanism of action of terbinafine

A

These agents act by inhibiting squalene epoxidase, thereby blocking its conversion to lanosterol and biosynthesis of ergosterol, an essential component of the fungal cell membrane. Accumulation of toxic amounts of squalene results in increased membrane permeability and death of the fungal cell.

37
Q

How is terbinafine administered

A

Oral and topical.

Oral terbinafine is used to treat dermatophyte onychomycoses (fungal infections of nails) and tinea capitis (infection of the scalp).

Topical terbinafine (1% cream, gel or solution) is used to treat tinea pedis, tinea corporis (ringworm), and tinea cruris (infection of groin)

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