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Pharmacology II > LEC 21 - Antifungal Agents > Flashcards

LEC 21 - Antifungal Agents Flashcards

1
Q

What is the target of the azoles?

A

Lanoesterol to Ergosterol synthesis

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2
Q

What fungi is Griseofulvin used for?

A

Microsporum

Trichophyton

(Dermatophytes)

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3
Q

What drugs are added along with Nystatin in Panalog?

A

Thiostrepton

Polypeptide antibiotic

Triamicinolone

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4
Q

What is the specific mechanism by which Terbinafine works?

A

Inhibits the synthesis of ergosterol

Does so by blocking the enzyme squalene monoxygenase therefore inhibiting the conversion of squalene to sterols

Accumulation of toxic intermediate squalene occurs

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5
Q

How are azoles distributed throughout the body?

A

Tissues with high lipid content

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6
Q

How is clortrimazole or Miconazole given?

A

Topically for treatment of yeast or dermatophyte infections

Nasal infustion for nasal aspergillosis

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7
Q

How is terbinafine used to treat birds?

A

Systemic mycotic infections

(ie. aspergillosis)

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8
Q

What adverse effects are seen with Amphotericin B?

A

Renal toxicity

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9
Q

What is posaconazole used for?

A

Otic + oral preperations

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10
Q

How is Amphotericin B eliminated?

A

Biphasic

65% excreted unchanged

20% urine

45% feces

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11
Q

How is Natamycin used in horses?

A

DOC for fungal keratitis

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12
Q

What are the two anti-fingal drugs that do not target the cell wall/membrane?

A

Griseofulvin

Flucytosine

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13
Q

Polyenes (3)

A

Amphotericin B

Nystatin

Natamyscin

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14
Q

Why is the action of Griseofulvin so slow?

A

Infected cells are shed and replaced with uninfected cells

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15
Q

When is terbinafine fungistatic?

A

yeast infections

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16
Q

Which azole is best at reaching the cerbropinal fluid?

A

Fluconazole

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17
Q

Fungus susceptible to Amphotericin B - (5)

A

Systemic mycoses

Aspergillus

Blastomyces

Coccidioides

Cryptococcus

Histoplasma

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18
Q

What fungi does Azoles work against? (4)

A

Blastomyces

Coccidioides

Cryptococcus

Histoplasma

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19
Q

What is the target of Griseofulvin?

A

Microtubules

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20
Q

What animals is Amphotericin B used in?

A

Dogs

Cats

Horses

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21
Q

How does renal toxicity occur due to Amphotericin B?

A

Causes renal vasoconstriction

Decreased GFR

Damage to tubular epithelium

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22
Q

What are the adverse side effects of flucytosine?

A

Mild GI upset

Rarely - Bone marrow suppression

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23
Q

Where does griseofulvin distribute?

A

Precursor cells of skin, hair shafts, and nails

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24
Q

How is terbinafine adminstered?

A

Oral or Topically

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25
Q

Azoles (6)

A

Ketoconazole

Fluconazole

Clotrimazole

MIconazole

Itraconazole

Posaconazole

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26
Q

What fungi does Terbinafine not reach the appropriate MIC?

A

Sporothrix

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27
Q

How is Nystatin used in poultry?

A

Feed-additive to prevent crop mycosis + mycotic diarrhea

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28
Q

How are azoles absorbed?

A

With food that stimualtes bile flow

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29
Q

Why is fluconazole + itraconazole more likely to be choosen for systemic mycoses infections?

A

longer half lives

Greater activity

Lower toxicity

30
Q

How is terbinafine used in dogs and cats?

A

Dermatophytic infections

31
Q

How is terbinafine metabolized and excreted?

A

Metabolized in the liver (demethylated + deaminated + Dealkylated)

Excreted into the urine

32
Q

Where does terbinafine distribute?

A

Skin and into sebum

33
Q

How is ketoconazole given?

A

Orally, BID

for 3 to 6 months when used for systemic infections

34
Q

How are the azoles metabolized?

A

Microsomal enzymes (CYP450) of the liver

Excreted in the bile

35
Q

How does terbinafine move through the body?

A

99% is attached to albulmin

36
Q

Other anti-fungal agents that do not belong in specific groupings (3)

A

Terbinafine

Griseofulvin

Flucytosine

37
Q

How can you increase the absorption of griseofulvin?

A

High fat foods

38
Q

What are the three groups of anti-fungal drugs?

A

Polyenes

Azoles

Others….

39
Q

How is flucytosine given?

A

Orally

3 to 4 times a day

minimum of 4 weeks

40
Q

How does terbinafine differ from azoles in regards to metabolism?

A

Does not block cytochrome P450 enzymes

41
Q

What is the specific mechanism of action for Griseofulvin?

A

Binds to microtubules of certain fungi and destroys the mitotic spindle structure

42
Q

How is fluconazole and itraconazole administered?

A

Oral or IV to dogs + Cats for systemic mycoses

Given for 1 to 3 months

43
Q

What is the half life of Amphotericin B?

A

24 to 48 hours

1 to 2 weeks

***remember it is biphasic

44
Q

When is terbinafine fungicidal?

A

Dermatophyte infectiosn

45
Q

What is the target of terbinafine?

A

Squalene to Squalene epoxide synthesis

46
Q

What are the adverse effects of the azoles?

A

Vomiting, Diarrhea in cats

47
Q

What is the target of Echinocandins?

A

B-glucan synthase

48
Q

What are the adverse effects of Nystatin + Natamycin?

A

Rare

GI upset

49
Q

What animals is giseofulvin used in?

A

Dogs

Cats

Horses

50
Q

What is the topical treatment of choice for canidia + aspergillus when it comes to the azoles?

A

Clortimazole

Miconazole

Dermatophyte infections as well

51
Q

What fungi do Nystatin + Natamycin work against?

A

Candida

Malassezia

52
Q

How is Nystatin + Natamycin administered?

A

Topically to eye + ear + skin

Orally for mucosal infections of mouth + GI tract

53
Q

What are the adverse effects of griseofulvin?

A

Leukopenia + anemia in kittnes

Teratogenic in pregnant cats

54
Q

What is ketoconazole used for?

A

Dogs + Cats + Horses + Birds

Systemic mycoses + severe yeast infections

55
Q

What situation is flucytosine used alone for treatment?

A

Aspergillosis + Candia infections in some birds

56
Q

What is the exact mechanism of action for polyene agents?

A

Interaction with sterol of fungal membrane (Ergosterol) resulting in the loss of intracellular components

= Pore formation

57
Q

Where is griseofulvin stored?

A

Growing keratin cell producing skin + hair + horn

58
Q

How is griseofulvin adminstered?

A

orally BID in dogs and cats

orally SID for horses

59
Q

How is griseofulvin aborbed?

A

25% to 70%

60
Q

Where is flucytosine distributed?

A

Well distributed, includes the CNS

61
Q

What is flucytosine FUNGICIDAL against?

A

Cryptococcus

Canidida

Aspergillus

62
Q

How is Amphotericin B adminstered?

A

Diluted in 5% dextrose + given IV

63
Q

How is Nystatin absorbed and excreted?

A

Not absorbed well

Excreted in feces

64
Q

What is the specific mechanism of action for flucytosine?

A

Metabolic antagonism of fungal DNA + RNA

Converted to 5-fluorouracil which interferes with fungal DNA/RNA synthesis

65
Q

How is flucytosine metabolized and excreted?

A

Unchanged

Excreted in urine

66
Q

What is Amphotericin B mixed with to reduce toxicity?

A

Ketoconazole

Fluconazole

Itraconazole

67
Q

What specific enzyme does flucytosine inhibit?

A

Thymidylate synthase

68
Q

When is flucytosine combined with amphotericin B?

A

Treatment of cryptococcus in dogs + cats

69
Q

What physiological condition in cats and dogs can be treated with Ketoconazole?

A

Hyperadrenocorticism

70
Q

What is amphotericin B mixed with to get into CNS, bone, or ocular infections?

A

Flucytosine

71
Q

What is the specific mechanism of action when it comes to Azoles?

A

Inhibits synthesis of ergosterol

Leads to depletion of ergosterol in cell membrane + accumulation of toxic intermediates

Increases membrane permeability + inhibition of fungal growth

Pharmacology II (20 decks)

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