Antifungals

Question 1

Amphotericin B

Answer 1

• Mech: bind to ergosterol and form ion channels
• effective against most serious systemic fungal infections
• given by IV in hospital setting
• Renal and neurotoxicity
• 1st line therapy for invasive, life-threatening systemic and localized candidemia
• can be effective against aspergillum infection

Question 2

Nystatin

Answer 2

• Mech: bind to ergosterol and form ion channels
• Topical only
• Use: oral and esophageal candidiasis and topical cream for vaginal candida
• disulfiram like reaction

Question 3

Azole antifungals

Answer 3

• Mech: inhibit ergosterol synthesis
• PK: topically systemically
• contraindicated in pregnancy, during lactation, or in patients with hepatic dysfunction
• inhibits human gonadal and steroid synthesis
• hepatotoxic

Question 4

Azole Drugs

Answer 4

1. Fluconazole: most prescribed systemic anti fungal, drug of choice for candidiasis, and treat fungal cryptococcal meningitis in AIDs patients
   - contraindicated with Ampho B
   - does not treat aspergillosis
   - highly teratogenic
2. Ketoconazole: first azole, used for systemic and topical therapy
3. Itraconazole: more toxic than fluconazole
4. clotimazole and miconazole: topical only, yeast infection, oral candida, athlete’s foot, jock rash
5. Vorconizole: 1st line treatment for aspergillosis infections

Question 5

Flucytosine

Answer 5

• Mech: inhibits both DNA and RNA synthesis in fungi
• Spec: systemic
• PK: good for fungal meningitis
• Use: synergistic when given in combination with Amphy B for cryptococcal meningitis
• Adverse effect: bone marrow suppression

Question 6

Caspofungin

Answer 6

• Mech: inhibits cell wall synthesis via b-glucan synthase
• Use: invasive aspergillosis or candida, especially Azole-resistant
• Adverse effects: do used in pregnancy

Question 7

Griseofulvin

Answer 7

• Mech: disrupts microtubule function, inhibiting fungal mitosis
• Use: inhibits growth of dermatophytes
• PK: local effects
• Interactions: induces CYP, metabolizes drugs faster
• Adverse effects: teratogenic, carcinogenic, severe headaches

Question 8

Terbinafine

Answer 8

• Mech: squalene epoxidase to inhibit ergosterol synthesis, disrupts cell membrane permeability
• Use: dermatophytes and onychomycosis
• Adverse effects: hepatoxicty

Question 9

Candidiasis treatment

Answer 9

Normal immune function:
- Topical
- Nystatin and clotrimazole
impaired immune system:
- systemic
- fluconazole and itraconazole