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Immunology / Micro > Pharmacology of Antimicrobial Agents: Fungi and Antivirals > Flashcards

Pharmacology of Antimicrobial Agents: Fungi and Antivirals Flashcards

1
Q

What are the “endemic fungi”?

A

Histoplasmosis, blastomycosis, coccidiomycosis

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2
Q

Who is cryptococcus neoformans seen in? How is it tested for?

A

HIV patients with CNS infections

Tested for via rapid crpyto tests

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3
Q

What are the azoles?

A 
Flu-conazole
Itra-conazole
Vori-conazole
Posa-conazole
Isuva-conazole
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4
Q

What are the polyenes?

A

Amphotericin B

Nystatin

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5
Q

What are the Echinocandins? How do they differ?

A

Drugs ending in -fungin

They are all the same, just buy whichever is the cheapest

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6
Q

What are the miscellaneous antifungals?

A

Flucytosine
Griseofulvin
Terbinfine

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7
Q

What is one side effect we must always check for when using antifungals?

A

hepatotoxicity

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8
Q

What is the mechanism of action of azole antifungals and why is this clinically important?

A

Inhibits a Cytochrome P450 enzyme, inhibiting production of ergosterol, a component of the cell membrane

Important because it can interact with human CYP450 and cause drug interactions (slower metabolism, opposite of rifampin)

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9
Q

What are two Candida species which fluconazole is not reliable for and what should be used instead?

A

C. glabrata - use echinocandins instead

C. krusei - use voriconazole instead

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10
Q

What is the first line treatment for aspergillus? What azole is not active against it?

A

Voriconazole

Only fluconazole is not active against it

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11
Q

What are two side effects especially associated with voriconazole?

A

Nephrotoxicity and visual disturbances

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12
Q

What heart-related side effect do we worry about with azoles?

A

QT elongation, although isuvaconazole is a QT shortener

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13
Q

Which azole should be used for fungal UTIs and why?

A

Fluconazole, it is the only one renally dosed

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14
Q

Why is fluconazole typically relied on?

A

Only one with predictable absorption, all others require therapeutic drug monitoring

It is the empiric antifungal

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15
Q

What is the clinical application of itraconazole?

A

Non-life threatening cases of endemic mycoses

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16
Q

What are posaconazole / isuvaconazole used for?

A

Mucormycoses, with isuvaconazole’s niche to be determined

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17
Q

What is the mechanism of action of amphotericin B?

A

Binds ergosterol and forms pores in the membrane allowing molecules to leak in and out of the cell, causing cell death

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18
Q

What is amphotericin B the first line therapy for?

A 
Cryptococcus neoforms (serious CNS infection),
Endemic fungi when life-threatening (itraconazole otherwise), and mucormycoses (always serious)
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19
Q

What is amphotericin B’s Candida and aspergillus coverage?

A

Candida - broad coverage, including glabrata, but missing lusitaniae

Aspergillus - second line therapy due to safety (voriconazole is better)

20
Q

What are the side effects of amphotericin / amphoterrible B? How are these dealt with?

A
  1. Nephrotoxicity - causes holes in renal tubules leading to low K+ / Mg - consider Na+ loading to reduce AKI
  2. Infusion reactions - “shake and bake”, chills / rigors and fever. Premedication with tylenol / benadryl / steriods can decrease symptoms
21
Q

How was amphotericin B modified to be more tolerable?

A

Given in lipid formulation to try to clear it more via non-renal mechanisms (liver)

22
Q

How do echinocandins work?

A

Inhibit production of 1,3 beta glucan, a key component of many bacterial cell walls

23
Q

What organisms are echinocandins good against?

A

All candida species, considered first line for all, except maybe C. parapsilosis

Aspergillus - used in combination therapy if patient is intolerant to voriconazole or amphotericin

24
Q

How are echinocandins administered and why are they juicy as fork?

A

IV - juicy because they have little toxicity profile, but not renally cleared (no UTI)

25
When would you know to use echinocandins vs fluconazole for yeast infection?
If patient is not critically ill and this is new, use fluconazole If recent azole exposure, known colonizer with C. glabrata, or critically ill, use echinocandins
26
What is the mechanism of action of flucytosine?
Converted into 5-fluorouracil by fungal cells, inhibiting DNA/RNA synthesis
27
What antibiotics can flucytosine be equated to? When is it used?
Aminoglycosides -> not used as monotherapy outside of UTIs Used with amphotericin B for severe infections, including candida endocarditis and Cryptococcus neoformans infections
28
What are the side effects of flucytosine?
Dose-dependent bone marrow suppression
29
What drugs work for fungal UTIs?
fluconazole, amphotericin, flucytosine
30
What type of virus is CMV?
Betaherpesvirus, causes mononucleosis in myeloid line of cells, more serious in adulthood
31
What is the mechanism of action of acyclovir?
Drug modified by viral thymidine kinase to become monophosphate derivative, then host enzymes convert to triphosphate. This acts as a chain terminator in growing DNA, competitively inhibiting viral DNA polymerase
32
What is acyclovir used for?
HSV | varicella/zoster virus at higher doses
33
Why is acyclovir rarely given orally? What is given instead?
Not well absorbed, requires 5x a day dosing Instead: Valacyclovir, the oral prodrug of acyclovir which is well absorbed
34
When would you want to give IV acyclovir vs oral valacyclovir?
When the infection is very serious
35
What are the side effects of IV acyclovir?
headaches, crystallization in urine at high doses (not fully dissolved) so keep hydrated, neurotoxicity at high doses
36
What is the mechanism of action of ganciclovir?
Same as acyclovir in HSV / VSV | In CMV: Activated by kinase phosphotransferase (Rather than thymidine kinase), then same steps
37
What is ganciclovir used for? How is it given PO?
Used as drug of choice for CMV | Valganciclovir is used for less serious infections and is more orally available
38
What is the major side effect associated with ganciclovir?
Bone marrow suppression -> VERY COMMON, bad since immunosuppressed need this CNS effects -> headache to coma
39
What is the mechanism of action of Cidofovir?
Cytosine nucleotide analog which does not require viral activation
40
What is the spectrum for cidofovir and when is it used?
HSV, VZV, CMV Used for CMV when CMV is resistant to ganciclovir / foscarnet
41
What are the major side effects of cidofovir?
Nephrotoxicity / neutropenia
42
What is the mechanism of action of foscarnet?
inorganic pyrophosphate compound, inhibits DNA polymerase, RNA polymerase, and HIV reverse transcriptase
43
When is foscarnet used and what are its big side effects?
Only for CMV when ganciclovir is not available Side effects: Nephrotoxicity, CNS effects, potential chelator of divalent cations in blood
44
What do neuraminidase inhibitors do and when are they used?
Inhibits viral neuraminidase, in influenza A and B. Only used within 48 hours of symptom onset, otherwise all cells are infected anyway (static).
45
What are the major neuraminidase inhibitors and what is one side effect?
Zanamivir (IV), oseltamivir (PO) Zanamivir can exacerbate COPD if inhaled
46
What are the antifungals for dermatophytes (tinea) and how do they work?
Terbinafine - blocks ergosterol production via inhibition of squalene epoxidase Griseofulvin - blocks infection of new skin structures, eventually old infections get replaced

Immunology / Micro (56 decks)

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