Antifungal drugs II

Question 1

Triazoles (Fluconazole – Itraconazole): MOA

Answer 1

selective inhibition of fungal CYP450 -> fungistatic-cidal

Question 2

Triazoles (Fluconazole – Itraconazole): PK props

Answer 2

oral

• F: renal excretion, can enter CSF
• I: elim by hepatic metabolism

Question 3

Triazoles (Fluconazole – Itraconazole): adverse drug rxns

Answer 3

overall well tolerated

• no inhibition of mammalian steroid biosynthesis
• DDI: inhib CYP450

Question 4

Triazoles (Fluconazole – Itraconazole): pharmacotherapy

Answer 4

• F: vaginal candidiasis, oropharyngeal and esophageal candidiasis, cryptococcal meningitis in AIDS patients
• I: broader spectrum than F, tx in dermatophytoses and onychomycosis

Question 5

Imidazoles (Ketoconazole - Clotrimazole - Miconazole): MOA

Answer 5

inhib P450-dependent enzyme -> decreased levels of ergosterol -> alterations in memb permability
-fingistatic/fungicidal depending on concentration

Question 6

Imidazoles (Ketoconazole - Clotrimazole - Miconazole): PK props

Answer 6

• systemic: oral and IV
• elim by hepatic metab (CYP450 oxidation)
• excreted in breast milk

Question 7

Imidazoles (Ketoconazole - Clotrimazole - Miconazole): adverse rxns

Answer 7

• GI (improves with food or at bedtime!)
• can inhib mammaliam testosterone synthesis
• DDI: strong inhib or CYP3A4 metab

Question 8

Imidazoles (Ketoconazole - Clotrimazole - Miconazole): pharmacotherapy

Answer 8

• chronic mucocutaneous candidiasis and other systemic fungal infections (keto- oral)
• clotrimazole: topically as creams and troches for oral and vaginal candidiasis

Question 9

Terbinafine: MOA

Answer 9

inhib squalene oxidase -> dec ergosterol synth -> fingicidal

Question 10

Terbinafine: PK props

Answer 10

• oral

- topical

Question 11

Terbinafine: adverse rxns

Answer 11

• GI upset, rash, taste disturbances

- inhib CYP450

Question 12

Terbinafine: pharmacotherapy

Answer 12

• oral for toe/finger infections (onychomycosis)

- topical for athlete’s foot