Antifungal Drugs (Azoles)

Question 1

Drugs & Spectrum of Imidazoles

Answer 1

Ketoconazole (Narrow Spectrum)

Question 2

Drugs & Spectrum of Triazoles

Answer 2

Fluconazole
Itraconazole
Posaconazole
Voriconazole
(Wide Spectrum)

Question 3

RoA of Azoles

Answer 3

• Oral, either:
  → Pills, given with food
  → Suspension, on empty stomach

❖ Taking these drugs with acidic beverage (low pH) is recommended

Question 4

MoA of Azoles

Answer 4

Azoles inhibit Ergosterol by inhibiting the enzyme that transforms Lanosterol to Ergosterol (Cytochrome P450-C14-alpha-demethylase)

Question 5

Resistance of Azoles

Answer 5

1: Mutation of Cytochrome P450-C14-alpha-demethylase

#2: reduction of ergosterol
content in cell membrane
#3: Efflux pumps

❖ Resistance is common in immunocompromised patients

Question 6

Drug-Drug Interactions of Azoles

Answer 6

Azole & AmB antagonism Since AmB requires ergosterol to bind to fungal membrane, Azole, which inhibit ergosterol synthesis, are contraindicated with AmB

Question 7

Indications of Ketoconazole

Answer 7

Cutaneous mycoses (Skin fungal infection)

Question 8

Indications of Fluconazole

Answer 8

1. Prophylaxis before BM transplant
2. Cryptococcosis (DoC)

Question 9

Indications of Voriconazole

Answer 9

Aspergillosis (DoC)

Question 10

Adverse Effects of Azoles

Answer 10

• Endocrinologic discomfort
  → these drugs affect endocrine glands, including sex hormones
• Teratogenicity (Category D)
• CYT P450 inhibition
  → due to similarities between fungal and human CYT P450
  → this includes CYT P450 (3A4, 2C9, 2C19) in human

Question 11

Properties of Fluconazole

Answer 11

the least effective azole

Question 12

Properties of Itraconazole

Answer 12

• the only azole that can’t cross BBB
• associated with Negative inotropy; decreasing HR

Question 13

Properties of Posaconazole

Answer 13

• the most effective azole
• metabolized by Glucuronidation process, not CYT P450

Question 14

Properties of Voriconazole

Answer 14

causes Visual toxicity & Ototoxicity