Antifungals

Question 1

Describe the steps to get to Ergosterol

Answer 1

Squalen —-> Use Squalen epoxidase –> Lanosterol —-> Lanosterol 14alpha demethylase (CYP450) —> Ergosterol

Question 2

Polyenes (AMPHOTERICIN B)

1. Admin route?
2. MOA : Interacts with ___ in fungal membranes to form ____
3. Clinical use? DOC for?
4. AE’s (4) H,F,M,C,N,H,H

Answer 2

1. IV
2. Ergosterol , artificial pores (pokes holes in fungi)
3. Broad spectrum. Severe infections caused by aspergillus, candida, cryptococcus, histoplasma
4. Infusion related rxns (HA,Fever, Myalgia, chills)
   Nephrotoxic (Admin with saline)
   Hypokalemia, Hypomagnesemia (direct damage to distal tubules)

Question 3

5-FC or 5 Flucytosine

1. MOA? Penetrates ____ ; ___ by cytosine deaminase to 5FU which inhibits ____
2. AEs : Hematologic such as ? (3)

Answer 3

1. Cell wall
   -deaminated , RNA and DNA synthesis
2. anemia, leukopenia, thrombocytopenia

Question 4

Azoles : State the admin route + AE for each

1. Fluconazole
2. Voriconazole
3. Posaconazole
4. Isavucomazole
5. What’s the MOA of Azoles?
6. What are the class AE’s?
7. Drug interactions? (Many ____ interactions)

Answer 4

1. PO and IV
   - GI AE and chapped lips
2. PO and IV
   -Visual disturbances
3. PO and IV
   -GI AE’s
4. PO and IV
   -GI AE’s
5. They inhibit lanosterol 14a demethylase which converts lanosterol to ergosterol
6. N,V, Hepatotoxic
7. CYP. Azoles are CYP inhibs

Question 5

Echinocandins (Micafungin, Caspofungin, Anidulafungin)

1. Admin route?
2. MOA?
3. AE’s ? Minor , some histamine release –> (4)

Answer 5

1. IV
2. Inhibit beta glucan synthase enzyme
3. Flushing, HA, Urticaria, pruritus

Question 6

Terbinafine

1. MOA?
2. Used for?
3. AE’s ? (4)

Answer 6

1. inhibs squalen epoxidase
2. Dermatophyte skin infections (tinea), especially on the fingernails and or toenails
3. Taste disturbances, GI upset, hepatotoxicity, HA

Question 7

For the following drugs , State their coverage ranges –> For yeast, Candida + Cryptococcus , For Mold, Aspergillus + Mucorales

1. Fluconazole
2. Voriconazole
3. Posaconazole
4. Micafungin
5. 5FC + Amphotericin
6. Amphotericin solo agent

Answer 7

1. Candida + Cryptococcus
2. Candida + Cryptococcus + Aspergillus
3. Everything (All four)
4. Candida + Aspergillus
5. Cryptococcus only
6. Everything (All four)