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Pharm > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Antimicrobial

A

from any source acting against any microorganism

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2
Q

Antibiotic

A

from any microorganism acting against any microorganism

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3
Q

usually in clinics antibiotics mean what ?

A

Antibacterial antimicrobials

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4
Q

Antifungal

A

against fungus (kill or inhibit)

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5
Q

Fungi

A

Eukaryotic cell
Cell wall consist of B- gluten and chitin
Ergosterol

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6
Q

Filamentous fungi: mold
Who are they?

A

Aspergillus

Dermatophytes
-Microsporum
-Trichophyton

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7
Q

Both form: Dimorphic fungi

A

Blastomyces

Coccidioides

Histoplasma

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8
Q

Yeast: Unicellular

A

Candida
Malassezia
Cryptococcus neoformans

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9
Q

If an antifungal targets 100% of the B-glucan
what does this mean for the mammalian cells of our patient?

A

Its means the antifungal won’t be toxic to the mammalian cells because they don’t contain any B-glucan.

The same thing can be said if an antifungal targeted 100% ergosterol

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10
Q

Mechanisms of action of antifungals

A
  • Cell wall
  • Cytoplasmic membrane
  • DNA synthesis
  • Protein synthesis
  • Nuclear division
  • +/- immune system (antifungals that stimulate the immune system, rather than attacking the fungi directly)
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11
Q

Antifungal are more of a target on what?

A

on the pathogen itself than on the host

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12
Q

Routes of administration

A

Topical

Systemic

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13
Q

An antifungal is given topical probably because…

A

it’s too toxic to be given systemically. This could also be said about other drug types.

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14
Q

Cell wall inhibitors

A

Lipopeptides

Lufenuron

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15
Q

Interferenceoncellmembrane

A
  • Polyene antibiotics
  • Azoles
  • Allylamines
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16
Q

Pyrimidine synthesis inhibitors

A
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17
Q

Benzofurancyclohexaneantibiotics

A
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18
Q

Iodides

A
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19
Q

Cell wall inhibitors: Lipopeptides

A

Echinocandins;
- Caspofungi
- Micafungi
- Anidulafungi

20
Q

Cell wall inhibitors: Lipopeptides
MOA

A
  • 1,3-β-D-glucan synthase inhibitors —>

Prevent production of an essential polysaccharide of cell wall

21
Q

Cell wall inhibitors: Lipopeptides
Spectrum

A

very active against:

Aspergillus: mold

candida: yeast

22
Q

Cell wall inhibitors: Lipopeptides

A
  • No reported application in veterinary medicine
    • Suggested for treatment of candidiasis/aspergillosis not responsive to amphotericin B or
      triazole
23
Q

Cell wall inhibitor: Lufenuron
MOA

A

Inhibition of chitin synthesis

24
Q

Cell wall inhibitor: Lufenuron
Spectrum

A
  • Insecticide

-suggested fungicide but there is controversial data on literature

25
Q

Cell wall inhibitor: Lufenuron
work good against ?

A

Dermatophytes: mold
- microsporum

BUT it is no longer recommended for the treatment or prevention of dermatophytosis

26
Q

Since we have better options for treating small animals for dermatophytes than lufenuron. If a question in block ask you to choose an antifungal for treating dermatophytes, which one will you not pick?

A

Lufenuron !

27
Q

Interference on cell membrane

A
  • Polyene antibiotics
  • Azoles
  • Allylamines
28
Q

Polyene antibiotics

A
  • Amphotericin B
  • Nystatin
  • Natamycin
29
Q

Amphotericin B Pharmacokinetics

If given Topically…

A

Irritant

30
Q

Amphotericin B Pharmacokinetics

Oral absorption is…

A

poor

31
Q

Amphotericin B Pharmacokinetics

IV administration

A

Can cause phlebitis

you can still use it, just be aware of what was previously mentioned

32
Q

Amphotericin B Pharmacokinetics

Lipid formulation vs Water soluble formulation

A

Lipid formulation - is less toxic

Water soluble (micellular suspension) - renal toxicity

33
Q

Interference on cell membrane: Polyene antibiotics

Amphotericin B Pharmacokinetics:
Distribution

A

Distribution is variable - explains some treatment failure

High in liver, spleen, kidney, lungs

Do not cross healthy/inflammed meninges, vitreous humor, placenta

Natamycin: water soluble –> topical

34
Q

Interference on cell membrane: Polyene antibiotics: Pharmacodynamics

MOA

A

bind ergosterol –> disturb cell membrane permeability –> fungicide

  • but bind slightly cholesterol of mammalian cells –> MOST TOXIC ANTIFUNGAL
35
Q

Interference on cell membrane: Polyene antibiotics: Pharmacodynamics

Spectrum

A

Broad spectrum

Aspergillus (mold)

Dimorphic fungi:

  • Blastomyces
  • Coccioides
  • Histoplasma

Yeast:

  • Candida
  • Malassezia
  • Cryptococcus neoformans
36
Q

Interference of cell membrane

Polyene antibiotics: Amphotericin B

clinical application

A

Amphotericin B: systemically

  • Filamentous fungal infection (Aspergillus)
  • +/- yeast & dimorphic infection (azoles +/- prioritized)
  • Immunocompromised patient (don’t respond to treatment)
37
Q

Why do immunocompromised patients don’t respond to Amphotericin B ?

A

Amphotericin B is a antifungistat that inhibits growth in order for the immune system of the host to fight the fungal infection.

38
Q

Interference of cell membrane

Polyene antibiotics: Natamycin

clinical application: Topical

A

Dogs:
- Malassezia otitis

Horses:
- Nasal aspergillosis
- Candida metrisits
- Ophthalmological: keratomycosis

Cow: +/- yeast mastitis (don’t need to remember)

39
Q

Interference on cell membrane: azoles

A

Imidazoles

Triazoles

40
Q

Mention imidazoles

A
  • Topical due to hepatic toxicity with systemic administration:
    • Clotrimazole
    • Miconazole
    • Enilconazole
  • Systemic:
    • Ketoconazole
41
Q

Mention Triazoles

A
  • 1st G: Fluconazole, Itraconazole
  • 2nd G: Voriconazole, Posaconazole
42
Q

Imidazole: ketoconazole (lipophilic)

PK/PD

A
  • good oral bioavailability in acidic fluid (after meal)
    • poor in horses( nasogastric tube dissolved in 0.2 N hydrochloric acid HCL)
  • Good distribution in SC and skin
43
Q

Imidazole: ketoconazole (lipophilic)

spectrum

A

Broad spectrum

Mold:

Aspergillus ( may not be as susceptible)
Dermatophytes:
-Microsporum and Trichophyton

All dimorphic fungi

yeast:

Candida and Malassezia

Cryptococcus neoformans is RESISTANT

44
Q

Triazole PK/PD

A
  • Longer t1/2, greater activity
  • Lower toxicity
  • 2nd G: even more improved PK/PD
  • More lipophilic than fluconazole
  • More water soluble than itraconazole & ketoconazole
    èExcellent bioavailability & tissue distribution èGreater spectrum
45
Q

Triazole PK/PD spectrum

A

broad spectrum

works on:

  • All Filamentous fungi except fluconazole for Aspergillus
  • All Dimorphic fungi
  • All yeast
46
Q
A

Pharm (3 decks)

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