Antifungals

Question 1

Mechanism: Terbinafine

Answer 1

Inhibits the fungal enzyme squalene epoxidase → inhibiting ergosterol synthesis

Question 2

Administration of amphotericin B requires supplementation of what electrolytes due to altered renal tubule permeability?

Answer 2

K⁺

Mg²⁺

Question 3

Mechanism: Flucytosine

Answer 3

Inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase

Question 4

Benefits to liposomal amphotericin

Answer 4

Decreased toxicity

Question 5

Mechanism: Amphotericin B

Answer 5

Binds ergosterol (unique to fungi) → forms membrane pores that allow leakage of electrolytes

Question 6

Mecahnism: Echinocandins

(end in -fungin)

Anidulafungin

Caspofungin

Micafungin

Answer 6

Inhibit CELL WALL (not cell membrane) synthesis by inhibiting synthesis of beta-glucan (major polysaccharide to fungal cell wall)

Question 7

Adverse effects: Griseofulvin

Answer 7

1. Teratogenic
2. Carcinogenic
3. P-450 INDUCER
4. Disulfiram-like reaction
5. Confusion
6. Headaches

Question 8

Adverse effects: Amphotericin B

Answer 8

1. Initial infusions: Fever/chills, hypotension
   
   • Can give antipyretics, antihistamines to prevent
2. Nephrotoxicity (binds cholesterol)
   
   • Hydration decreases nephrotoxicity
3. Arrythmias (electrolyte abnormalities)
4. Anemia (decreased renal EPO synthesis)
5. IV phebitis

Question 9

Adverse effects: Terbinafine

Answer 9

1. GI upset
2. Headache
3. Hepatotoxicity
4. Taste disturbance

Question 10

Adverse effects: Flucytosine

Answer 10

Bone marrow suppression

Question 11

Mechanism: Azoles

Answer 11

Inhibit fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol (14-alpha-demethylase)

Question 12

Mechanism: Nystatin

Answer 12

Binds ergosterol (unique to fungi) → forms membrane pores that allow leakage of electrolytes

Same as amphotericin B, but topical use only as it is too toxic for systemic use

Question 13

Adverse effects: Azoles

Answer 13

1. Testosterone synthesis inhibition → gynecomastia (especially with ketoconazole)
2. Liver dysfunction (inhibits cytochrome P-450)

Question 14

Mechanism: Griseofulvin

Answer 14

Interferes with microtubule function → disrupts mitosis

Deposits in keratin-containing tissues (e.g., nails)

Question 15

Adverse effects: Echinocandins

(end in -fungin)

Anidulafungin

Caspofungin

Micafungin

Answer 15

1. GI upset
2. Flushing (by histamine release)