Antifungals: Imidazoles

Question 1

Types of Imidazoles

Answer 1

• Clotrimazole
• Miconazole
• Ketoconazole
• Itraconazole
• Fluconazole

These produce broad spectrum antifungal activity

Question 2

MOA

Answer 2

Azoles inhibit the synthesis of ergosterol, an important component of the fungal cell membrane. Azoles inhibit the fungal cytochrome P450enzyme lanosine 14a - demethylase which catalyses the convertion of lanosterol to ergosterol.

Question 3

Pharmacokinetics

Answer 3

• Ketoconazole: Well absorbed from the gut; food and low gastric pH enhance absorption.
• Fluconazole: water soluble, well-absorbed orally and attains good CSF concentration.

Question 4

Adverse Effects

Answer 4

Ketoconazole: gastric irritation, nausea, vomiting, headache, allergic reaction, and rarely fatal hepatotoxicity.

Fluconazole: Mild gastrointestinal disturbances, headache and rashes.

Question 5

Drug Interactions

Answer 5

Antacids, H2 receptor blockers, and proton pump inhibitors reduce the bioavailability of Ketoconazole.