LEC 21 - Antifungal Agents Flashcards by Raegan Chambers

What is the target of the azoles?

Lanoesterol to Ergosterol synthesis

How well did you know this?

Not at all

Perfectly

What fungi is Griseofulvin used for?

Microsporum

Trichophyton

(Dermatophytes)

How well did you know this?

Not at all

Perfectly

What drugs are added along with Nystatin in Panalog?

Thiostrepton

Polypeptide antibiotic

Triamicinolone

How well did you know this?

Not at all

Perfectly

What is the specific mechanism by which Terbinafine works?

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

How well did you know this?

Not at all

Perfectly

How are azoles distributed throughout the body?

Tissues with high lipid content

How well did you know this?

Not at all

Perfectly

How is clortrimazole or Miconazole given?

Topically for treatment of yeast or dermatophyte infections

Nasal infustion for nasal aspergillosis

How well did you know this?

Not at all

Perfectly

How is terbinafine used to treat birds?

Systemic mycotic infections

(ie. aspergillosis)

How well did you know this?

Not at all

Perfectly

What adverse effects are seen with Amphotericin B?

Renal toxicity

How well did you know this?

Not at all

Perfectly

What is posaconazole used for?

Otic + oral preperations

How well did you know this?

Not at all

Perfectly

How is Amphotericin B eliminated?

Biphasic

65% excreted unchanged

20% urine

45% feces

How well did you know this?

Not at all

Perfectly

How is Natamycin used in horses?

DOC for fungal keratitis

How well did you know this?

Not at all

Perfectly

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

Griseofulvin

Flucytosine

How well did you know this?

Not at all

Perfectly

Polyenes (3)

Amphotericin B

Nystatin

Natamyscin

How well did you know this?

Not at all

Perfectly

Why is the action of Griseofulvin so slow?

Infected cells are shed and replaced with uninfected cells

How well did you know this?

Not at all

Perfectly

When is terbinafine fungistatic?

yeast infections

How well did you know this?

Not at all

Perfectly

Which azole is best at reaching the cerbropinal fluid?

Fluconazole

How well did you know this?

Not at all

Perfectly

Fungus susceptible to Amphotericin B - (5)

Systemic mycoses

Aspergillus

Blastomyces

Coccidioides

Cryptococcus

Histoplasma

How well did you know this?

Not at all

Perfectly

What fungi does Azoles work against? (4)

Blastomyces

Coccidioides

Cryptococcus

Histoplasma

How well did you know this?

Not at all

Perfectly

What is the target of Griseofulvin?

Microtubules

How well did you know this?

Not at all

Perfectly

What animals is Amphotericin B used in?

Dogs

Cats

Horses

How well did you know this?

Not at all

Perfectly

How does renal toxicity occur due to Amphotericin B?

Causes renal vasoconstriction

Decreased GFR

Damage to tubular epithelium

How well did you know this?

Not at all

Perfectly

What are the adverse side effects of flucytosine?

Mild GI upset

Rarely - Bone marrow suppression

How well did you know this?

Not at all

Perfectly

Where does griseofulvin distribute?

Precursor cells of skin, hair shafts, and nails

How well did you know this?

Not at all

Perfectly

How is terbinafine adminstered?

Oral or Topically

How well did you know this?

Not at all

Perfectly

Azoles (6)

Ketoconazole Fluconazole Clotrimazole MIconazole Itraconazole Posaconazole

What fungi does Terbinafine not reach the appropriate MIC?

Sporothrix

How is Nystatin used in poultry?

Feed-additive to prevent crop mycosis + mycotic diarrhea

How are azoles absorbed?

With food that stimualtes bile flow

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

longer half lives Greater activity Lower toxicity

How is terbinafine used in dogs and cats?

Dermatophytic infections

How is terbinafine metabolized and excreted?

Metabolized in the liver (demethylated + deaminated + Dealkylated) Excreted into the urine

Where does terbinafine distribute?

Skin and into sebum

How is ketoconazole given?

Orally, BID for 3 to 6 months when used for systemic infections

How are the azoles metabolized?

Microsomal enzymes (CYP450) of the liver Excreted in the bile

How does terbinafine move through the body?

99% is attached to albulmin

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

Terbinafine Griseofulvin Flucytosine

How can you increase the absorption of griseofulvin?

High fat foods

What are the three groups of anti-fungal drugs?

Polyenes Azoles Others....

How is flucytosine given?

Orally 3 to 4 times a day minimum of 4 weeks

How does terbinafine differ from azoles in regards to metabolism?

Does not block cytochrome P450 enzymes

What is the specific mechanism of action for Griseofulvin?

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

How is fluconazole and itraconazole administered?

Oral or IV to dogs + Cats for systemic mycoses Given for 1 to 3 months

What is the half life of Amphotericin B?

24 to 48 hours 1 to 2 weeks \*\*\*remember it is biphasic

When is terbinafine fungicidal?

Dermatophyte infectiosn

What is the target of terbinafine?

Squalene to Squalene epoxide synthesis

What are the adverse effects of the azoles?

Vomiting, Diarrhea in cats

What is the target of Echinocandins?

B-glucan synthase

What are the adverse effects of Nystatin + Natamycin?

Rare GI upset

What animals is giseofulvin used in?

Dogs Cats Horses

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

Clortimazole Miconazole Dermatophyte infections as well

What fungi do Nystatin + Natamycin work against?

Candida Malassezia

How is Nystatin + Natamycin administered?

Topically to eye + ear + skin Orally for mucosal infections of mouth + GI tract

What are the adverse effects of griseofulvin?

Leukopenia + anemia in kittnes Teratogenic in pregnant cats

What is ketoconazole used for?

Dogs + Cats + Horses + Birds Systemic mycoses + severe yeast infections

What situation is flucytosine used alone for treatment?

Aspergillosis + Candia infections in some birds

What is the exact mechanism of action for polyene agents?

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

Where is griseofulvin stored?

Growing keratin cell producing skin + hair + horn

How is griseofulvin adminstered?

orally BID in dogs and cats orally SID for horses

How is griseofulvin aborbed?

25% to 70%

Where is flucytosine distributed?

Well distributed, includes the CNS

What is flucytosine FUNGICIDAL against?

Cryptococcus Canidida Aspergillus

How is Amphotericin B adminstered?

Diluted in 5% dextrose + given IV

How is Nystatin absorbed and excreted?

Not absorbed well Excreted in feces

What is the specific mechanism of action for flucytosine?

Metabolic antagonism of fungal DNA + RNA Converted to 5-fluorouracil which interferes with fungal DNA/RNA synthesis

How is flucytosine metabolized and excreted?

Unchanged Excreted in urine

What is Amphotericin B mixed with to reduce toxicity?

Ketoconazole Fluconazole Itraconazole

What specific enzyme does flucytosine inhibit?

Thymidylate synthase

When is flucytosine combined with amphotericin B?

Treatment of cryptococcus in dogs + cats

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

Hyperadrenocorticism

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

Flucytosine

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

Inhibits synthesis of ergosterol Leads to depletion of ergosterol in cell membrane + accumulation of toxic intermediates Increases membrane permeability + inhibition of fungal growth