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Small Animal Medicine > Antifungal Therapy > Flashcards

Antifungal Therapy Flashcards

1
Q

Mechanism of action of amphotericin B?

A
  1. Binds ergosterols in cell membrane of fungal organisms
  2. Increases cell permeability
  3. Leakage of nutrients and electrolytes
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2
Q

What is the route by which Amphotericin B is administered?

A

IV occ. SQ (not absorbed well orally)

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3
Q

What are the acute side effects of Amphotericin B when giving the infusion? How can these side effects be decreased?

A

fever, vomit, myalgia, muscle tremors, phlebitis, anaphylaxis

Give the infusion slowly

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4
Q

What are the chronic side effects of Amphotericin B?

A

NEPHROTOXICITY

weight loss

Non-regen anemia

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5
Q

What is the spectrum of action of Amphotericin B?

A

Most systemic antifungals (blasto, histo, crypto, coccidiosis, asper)

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6
Q

In which species of fungal organisms is resistance being reported to Amphotericin B?

A

Aspergillosis

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7
Q

What are the four formulations of Amphotericin B?

A

Amphotericin deoxycholate (Fungizone®)
Amphotericin cholesteryl sulfate (Amphocil®)
Liposome encapsulated amphotericin (AmBisome®)
Lipid complexed amphotericin (Abelcet ®)

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8
Q

Which Lipid complexed amphotericin formulation has the best CSF penetration?

A

Liposome encapsulated amphotericin (AmBisome®)

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9
Q

Which amphotericin formulation is predominantly protein bound and NOT lipid complexed?

A

Amphotericin deoxycholate (Fungizone®)

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10
Q

What is the MOA for flucytosine?

A

Fluorinated pyrimidine–> Converted to fluorouracil w/in fungal organism (yeasts)–> Interferes w/DNA synthesis

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11
Q

How is amphotericin administered?

A

IV

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12
Q

What drug/s is/are synergistic with amphotericin B?

A

flucytosine

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13
Q

In which fungal oraganisms is flucytosine effective & ineffective?

A

Effective:

Crypto

Candida

Ineffective:

aspergillus

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14
Q

What are the side effects of flucytosine?

A

nephrotoxicity

Drug eruptions (dogs)

TCP (cats)

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15
Q

What is the MOA for azole derivatives?

A

Inhibit sterol synthesis

Also inhibit synthesis of nucleic acid, triglycerides and fatty acids

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16
Q

With the concentrations that can be achieved systemically with Azole derivatives, are they fungistatic or fungicidal?

A

fungistatic

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17
Q

How are azole derivatives metabolized? Why is this important?

A

CP450 in liver

affects metabolism of other drugs

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18
Q

When administering ketoconazole to a dog, what two things can help increase its absorption?

A

small fatty meal

avoid antacids (better absorbed in acidic env.)

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19
Q

What are the side effects of ketonazole?

A

Nausea/Vomiting

Decr. appetite

Hepatotox (incr. ALT, AST, SAP, usually reversible*)

TCP, anemia

Teratogenic

Suppress cortisol production

20
Q

Spectrum of action of ketoconazole?

A

candida

malassezia

histo

blasto

coccidiosis

21
Q

Because relapse of fungal dz is common with ketoconazole, what can be done to try to prevent this relapse?

A

TX 4 weeks past resolution of clinical disease

22
Q

What are the side effects of itraconazole?

A

Less toxic than ketoconazole

Nausea, vomiting

Inappetence

Hepatotoxicity

Ulcerative dermatitis*

Does NOT suppress cortisol production*

23
Q

What is the spectrum of action of itraconazole?

A

Histo

Blasto

Crypto

Coccidio

Aspergillus

24
Q

Compar CNS penetration for ketoconazole, itraconazole, & fluconazole?

A

ketoconazole & itraconazole= poor penetration

fluconazole= good penetration in CNS, CSF, and eye

25
Q

How is fluconazole metabolize?

A

Renal excretion of ACTIVE drug

26
Q

What are the side effects of fluconazole?

A

V/D

27
Q

Spectrum of action for fluconazole?

A

crypto (TX of choice is in CNS/eye)

Candida

Blast & histo (less effective than itraconazole)*

Min effective against asper

28
Q

If a canine is DX with systemic blasto or histo, which antifungal is a better choice fluconazole or itraconazole?

A

itraconazole

29
Q

How long do you typically TX with keto, itra, and fluconazole?

A

Keto: 1-9 mo

Itra: 60 days

Fluconazole: 8 mo (TX until Ag test neg), 2 mo past clinical resolution

30
Q

Newer azoles (ex: voriconazole) are most effective against which fungal organisms?

A

Candida

crypto

Histo

Blasto

Asper

Some activity against zygomycetes

31
Q

What is Posaconazole a derivative of? How does it’s spectrum of action differ?

A

Itraconazole

Both: Histo, blasto, Crypto, asper

POSA only: Candida, malassezia

32
Q

What is voriconazole a derivative of? How does it’s metabolism differ?

A

fluconazole

metabolized by the liver (rather than excreted in active form by kidneys)

33
Q

What is the benefit of using clotrimazole? What are the side effects?

A

TOPICAL

Irritating

Erythema

Airway obstruction secondary to inflammation caused by carrier

May prolong barbiturate anesthesia

34
Q

what are the two methods of administering clotrimazole for nasal apsergillosis?

A

nasal infusion

trephination of frontal sinus and administration of cream into sinus

35
Q

What are the two topical azole derivatives that treat fungal diseases?

A

clotrimazole

enilconazole

36
Q

What is the MOA for terbinafine?

Where does the drug accumulate in the highest concentrations?

A

Allylamine–> Inhibits ergosterol synthesis (different enzyme than azoles)
High concentrations in skin and nails

37
Q

What are the side effects of terbinafine?

A

V/D

hepatotox (hepatic metabolism)

neutropenia, pancytopenia

38
Q

What is the spectrum of action of terbinafine?

A

Hyphal organisms (asper, sporothrix, dermatophytes)

39
Q

Which fungal organisms is terbinafine ineffective against?

A

yeast or dimorphic organisms (blasto, histo)

40
Q

What is the MOA of Echinocandins?

A

inhibit cell wall synthesis (glucan synthesis–> Caspofungin, Micafungin, Anidulafungin)

41
Q

What is the spectrum of action of Echinocandins?

A

Effective against invasive candidiasis and aspergillus (esp if resistant to AMB and/or triazoles)

Some efficacy against pythium

42
Q

What are the side effects of Echinocandins?

A

Fever, urticaria, pruritis

Vomiting, diarrhea

Increased liver enzymes (hepatic metab)

43
Q

What is often the limiting factor in being able to use Echinocandins?

A

VERY $$$$

44
Q

What is the MOA for Mefenoxam? What is it proposed to be effective against?

A

Agricultural fungicide–> Inhibits RNA polymerase
o Plant pathogen oomycetes (pythium)

45
Q
A

Small Animal Medicine (7 decks)

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