Antifungal

Question 1

what are the two types of mycoses and what do antifungal drugs target?

Answer 1

superficial mysoses (skin, hair and nails)
systemic (invasive mycoses, internal organs)

Target cell membrane, DNA synthesis, cell wall chitin

Question 2

What is the use and MOA of amphotericin B

Answer 2

IV only
MOA: binds to sterols in fungal cell membranes, ICF K leaks out, mammals have cholesterol not sterols so no affect

Use: invasive fungal infections (dogs, cats, horses)
- aspergillosis, blastomycosis, cryptococcous, candida

Question 3

Amphotericin B is nephrotoxic to which animal?

Answer 3

Cats
reversible but can become irreversible
- anorexia, vomiting, anemia

Question 4

What are systemic Azole antifungals MOA, PK, and resistance?

Answer 4

bind to cytochrome P450 enzyme complex and inhibits ergosterol (damage fungal membrane)
- can affect humans too..
normal CYP function
- significant drug interactions
PK: concentration dependent, high than MIC, 1x day still

Resistance

• increase efflux or decrease influx
• changes in drug interaction with target enzyme

Question 5

What are 3 common azole drugs?

Answer 5

ketoconazole
itraconazole (sporonox)
fluconazole (human)

Question 6

What us the use and AE for ketoconazole?

Answer 6

oral tablets, suspensions, topical, creams/shampoos

Use: treat mycotic infections: yeasts, systemic fungi
AE: hepatic toxicity, GI, give with food

Question 7

What is the use, PK and AE of intraconazole?

Answer 7

oral solution for cats
Use: feline dermatophyes, blastomycosis (dogs), cryptococcus (cats), guttural pouch mycosis, nasal aspergillosis, fungal keratitis (horses)

PK:
compounded is sketchy
increase F when fasted, high Vd accumulates in skin/hair
- more potent than ketoconazole
similar AE, similar hepatic CYPP45 metabolism and drug interactions

Question 8

What is the PK and use of Fluconazole (human)?

Answer 8

good oral, limited protein binding, penetrates and crosses BBB, limited hepatic metabolism, excreted in urine

narrow spectrum: canidida, cryptococcus, coccidiosis

• limited against others
• none against aspergillus

Question 9

What are 4 topical Azoles?

Answer 9

1. miconazole (surolan)
   - azole + antibiotic + steroid
2. clotrimazole
3. Miconazole + clotrimazole
   - against superficial skin ear mycotic infections in small animal (+antibiotic and steroid)
   - topical only = rapid hepatic enzyme induction, increases clearance and serious adverse events)
4. enilconazole (imaverol)
   - indicated for dermatophyes (dogs and horses)
   - washes (safe)

Question 10

What are two miscellanous antifungals?

Answer 10

terbinfine (osurina)

Griseofulvin

Question 11

What is the use of Terbinafine (osurina)?

Answer 11

topical = skin/ear mycotic dermatophytes in dogs and cats
+ flurfenicol and betamethasone

idophores (betadine)

silver sulfadiazine

Question 12

What is the MOA, PK, Use and AE of Griseofulvin?

Answer 12

depositied in keratin of skin and hair
- long distribution time

MOA: disrupts mitotic spindle division
Use: effective against trichiphytin, epidermophyton and microsporum
- dermatophytes in dogs, cats, horses

PK: hepatic metabolism, absorption highly variable, increase F with high fat

AE: dont use in CATS

• hematologic abnormalities (aplastic anmeia, leukopenia, pancotopenia)
• teratogen
• anorexia, depression, vomiting, diarrhea
• hepatic drug interactions