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Pharmacology > Lecture 24: Antifungal Agents > Flashcards

Lecture 24: Antifungal Agents Flashcards

1
Q

What are the most commonly used classes of antifungals in vetmed

A
  1. Polyenes
  2. Azoles
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2
Q

What are the therapeutic challenges with anti-fungal treatments

A
  1. Rigid fungal cell wall with chitin and polysaccharides
  2. Cell membrane contains sterols such as ergosterol which influences efficacy and resistance to drugs
  3. Infections located inside host cells
  4. Discontinuing treatment after signs resolved but infection not eradicated
  5. Fungistatic- rely on host immune response to clear
  6. Longer treatment= host toxicity
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3
Q

What is the mechanism of action of polyene antifungals

A

Interaction with sterol of fungal membrane, ergosterol that results in loss of intracellular components—> pore forming

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4
Q

What are the 3 polyene antifungals

A
  1. Amphotericin B
  2. Nystatin
  3. Natamycin
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5
Q

Is amphotericin B broad or narrow spectrum? Fungicidal or fungistatic

A

Broad spectrum, fungicidal

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6
Q

What organisms ins amphotericin B effective against

A

Aspergillus, blastomyces, coccidiosis, cryptococcus, histoplasma

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7
Q

What are the uses for amphotericin B

A
  1. Systemic fungal infections and fungal keratitis in dogs, cats, horses, rabbits, reptiles and birds
  2. Combined therapy with
    - ketoconzole, fluconazole or itraconazole to reduce toxicity
    - flucytosine for CNS, bone or ocular infections
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8
Q

T or F: amphotericin B distributes to CNS, eye and bone

A

False

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9
Q

Amphotericin B is excreted slowly by the ___, therefore ___

A

Kidney, Nephrotoxic

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10
Q

What are some adverse effects of amphotericin B

A
  1. Renal toxicity- produces renal vasoconstriction, decrease GFR
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11
Q

What antifungal should only be considered for progressive or potentially fatal fungal infections due to severe renal toxicity

A

Amphotericin B

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12
Q

Weekly monitoring of renal function is required with what antifungal

A

Amphotericin B

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13
Q

What species has lack of Nephrotoxicity with amphotericin B due to shorter t1/2

A

Birds

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14
Q

What are some therapeutic uses for nystatin and natamycin

A

Fungicidal to yeast infections caused by Candida spp and Malassezia spp

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15
Q

How are nystatin and natamycin administered

A
  1. Topically for yeast infections of eye, ear and skin
  2. Orally for treating mucosal heart infections of mouth and GI tract
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16
Q

What are some therapeutic uses for nystatin

A
  1. Feed additive in poultry to prevent crop mycosis and mycotoxins diarrhea
  2. Administered orally for oral or GI candida infections in dogs, cats, horses, reptiles and birds
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17
Q

T or F: nystatin can be used alone when applied topically

A

False

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18
Q

What are some therapeutic uses for natamycin

A
  1. Ocular mycotoxins infections
  2. Drug of choice for equine fungal keratitis caused by Fusarium
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19
Q

What is the mechanism of action of azoles

A

Inhibits synthesis of ergosterol leads to depletion of ergosterol in the cell membrane and accumulation of toxic intermediate sterols causing increase membrane permeability and inhibition of fungal growth

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20
Q

Are azoles fungistatic or fungicidal and what pathogens do they tx

A

Fungistatic against infections such as Blastomyces, Coccidiodes, cryptococcus and histoplasma

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21
Q

Which azoles have excellent CNS penetration

A

Fluoconazole and voriconazole

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22
Q

What is ketoconazole used for

A
  1. Dogs cats, horses, reptiles and birds for systemic mycoses and severe yeast infections
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23
Q

Is ketoconazole broad or narrow spectrum

A

Broad

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24
Q

What is an adverse effect of ketoconazole

A

Hepatic toxicity

25
Q

How is ketoconazole administered

A

Topical shampoos for dermatophytes
Oral 3-6 months for systemic mycotic infections

26
Q

What is voriconazole used for

A

Used in dogs, cats (with caution), horses and birds for systemic blastomyces

27
Q

How is voriconazole administered

A
  1. Ophthalmic penetrates cornea (equine fungal keratitis)
  2. Oral and IV
28
Q

What is fluconazole used for

A
  1. Systemic mycoses
  2. Penetrates CNS useful for cryptococcal meningitis
  3. Achieves high urinary concentration-useful for fungal UTI’s
  4. Valley fever
29
Q

How is fluconazole and itraconazole administered for systemic mycoses

A

Oral or IV for 1-3 months

30
Q

Itraconazole can be used as an ophthalmic ointment to tx __

A

Fungal keratitis in horses

31
Q

What is clotrimazole and miconazole used for

A

Tx of candida, aspergillus, malassezia and dermatophyte infections

32
Q

How is clotrimazole administered

A

Spay and ointment

33
Q

Topical miconazole is very effective against

A

Malassezia dermatitis

34
Q

What is posaconazole use for

A

Itraconazole or fluconazole resistant infections in cats and small dogs

35
Q

What are some adverse effects of azoles

A

Anorexia, vomiting, diarrhea, drug interactions (potent inhibitor of P450s)

36
Q

Adverse effects of azoles are most prominent in what species

37
Q

What are some side effects of ketoconazole

A
  1. Anorexia, vomiting, diarrhea
  2. Hepatic toxicity (cats), thrombocytopenia
  3. Drug interactions- inhibitor P450
38
Q

What azole is better tolerated and has few drug interactions

A

Fluconazole

39
Q

What are some adverse effects of itraconazole

A

Hepatic toxicity, vasculitis, depression in cats, anorexia in dogs

40
Q

What is the mechanism of action of terbinafine

A

Interferes with sterol biosynthesis, inhibits squalene monoxygenase, build up of squalene is toxic to fungi

41
Q

Terbinafine is fungicidal against

A

Dermatophytes

42
Q

Terbinafine is bacteriostatic against

43
Q

What are some uses for terbinafine

A
  1. Oral or topical administration for tx dermatophytes infections in dogs and cats
  2. Oral tx birds for systemic mycotic infection
44
Q

T or F: terbinafine inhibits P450 enzymes

45
Q

What is the mechanism of action for griseofulvin

A

Binds microtubules of certain fungi and destroys mitosis spindle structure

46
Q

Is griseofulvin fungistatic or fungicidal and for what

A

Fungistatic for dermatophytes

47
Q

What is the only FDA approved systemic antifungal for veterinary use

A

Griseofulvin

48
Q

What are some therapeutic uses for griseofulvin

A

FDA approved for use in dogs and cats to tx dermatophytic fungal infections of the hair, skin, and claws and to tx ringworm in horses

49
Q

How does griseofulvin prevent new structures from being formed

A

Distributed to keratin precursors cells of skin, hair shafts, and nails

50
Q

What are some adverse effects of griseofulvin

A
  1. Leukopenia and anemia in kittens
  2. Photosensitivity, anorexia, neutropenia, hepatotoxicity
  3. Teratrogenic in cats and horses
51
Q

What is the mechanism of action of flucytosine

A

Metabolism antagonism of fungal DNA and RNA. Converted to 5-fluoruracil which interferes with fungal DNA and RNA synthesis

52
Q

What are some therapeutic uses for flucytosine

A
  1. Fungicidal against cryptococcus, candida and aspergillus
  2. Combined with amphotericin by for synergistic effect for tx in cryptococcosis (especially menigeal cryptococcosis) in dogs and cats
53
Q

T or F: flucytosine distributes to CNS

54
Q

What are some adverse effects of flucytosine

A

Mild GI disturbances and bone marrow suppression

55
Q

Select correct answer in photo

A

B- interaction with sterols in the cell membrane

56
Q

Select correct answer in photo

A

E- high urinary concentration

57
Q

select correct answer in photo

A

D- flucytosine penetrates the CNS of infected animals

58
Q

select the correct answer in photo

A

B. Fungistatic

59
Q

select the correct answer from photo

A

B. Griseofulvin

Pharmacology (14 decks)

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