This document discusses various classes of antifungal drugs, including their mechanisms of action and toxicities. The main classes covered are polyenes, flucytosine, azoles, echinocandins, griseofulvin, terbinafine, and tolnaftate. Polyenes like amphotericin B and nystatin bind to ergosterol in the fungal cell membrane to create pores. Flucytosine is converted to 5-fluorouracil which inhibits fungal DNA and RNA synthesis. Azoles like ketoconazole and itraconazole inhibit ergosterol synthesis. Echinocandins are the newest class and inhibit beta-

2. Drug Classes
 Polyenes: Amphotericin B & Nystatin
 Flucytosine
 Azoles
 Echinocandins
 Griseofulvin
 Terbinafine
 Tolnaftate

3. Polyenes
 Amphotericin B & Nystatin
 MoA: binds ergosterol on fungal cell membrane 
creates pores  fungicidal/fungistatic
 Amphotericin B is insoluble in water so complexed
with bile salt or lipids; it is for general use (affects
many spp) in SYSTEMIC infections
 Nystatin has poor absorption from mucous
membranes; use for Candida spp  good for obese
and diabetic pts

4. Polyene Toxicity
 Amphotericin B
 TI is narrow
 Acute:
HA, arthralgia, nausea/vomiting, fever, hypotension, Th
rombophlebitis, delirium, seizures
 Chronic: Malaise, weight
loss, NEPHROTOXICITY, anemia

5. Flucytosine (5 – FC)
 Distributes in all body tissues
 Almost entirely excreted by kidneys
 Converted to 5 – FU (fluorouracil – chemotherapeutic
agent)
 Fungal resistance develops fast during flucytosine
monotherapy  use in combination with other
antifungals

6. Flucytosine MoA
 5-FC is taken up into fungal cells  converted to 5-FU
 5-FU is phosphorylated to produce
5fluorouridine monophosphate (5 – FUMP) – this
metabolite can be used in 2 pathways
 First pathway: 5-FUMP is converted to 5-FdUMP 
acts as an irreversible inhibitor of Thymidylate
Synthetase (aids in making molecules for new DNA) –
thus, inhibits fungal DNA synthesis
 Second pathway: 5-FUMP converted to 5-FUDP 
inhibits RNA synthesis
 Ultimate effect: Fungicidal/Fungistatic

8. Flucytosine Toxicity
 Adverse effects due to 5 – FU
 Reversible MYELOSUPPRESSION (13%)
 LIVER DYSFUNCTION (10%)

9. Azoles
 Ketoconazole, Itraconazole
 Structure contains 5 membered azole ring
 MoA: Inhibition of fungal ergosterol synthesis 
inhibits Lanosterol 14 – α – Demethylase 
fungicidal/fungistatic
 Cross resistance is common
 Ketoconazole can inhibit human sterol synthesis
& Cyp P450 enzymes
 Seborrheic Dermatitis – ketoconazole shampoo

10. Azole Toxicity
 Gynecomastia (ketoconazole)
 Liver toxicity
 Hypokalemia, hypertension
 Itraconazole

11. Echinocandins
 Newest class of antifungals; large cyclic
 Caspofungin, Micafungin, Anidulafungin
 MoA: noncomp inhibitors of Beta-D-Glucan Synthase
(makes components of fungal cell wall)  disrupts
integrity of fungal cell wall (not cell membrane!) 
Fungicidal
 Targets: Aspergillus & Candida
 Resistance develops via FSK1 mutations
 No major toxicities

12. Griseofulvin






Absorption ~ 50%  improved by fatty foods
Ineffective topically
Induces liver enzymes
Distributes only in keratinized tissues
MoA: inhibits fungal mitosis  Fungistatic
Use: Dermatophytes – tx is continued until tissue is
replaced with normal healthy tissue
 Hair: 1 month; Skin/Finger nails: 6 – 9 months; Toe
nails: 12 months
 Toxicity: induces CYP enzymes, Photosensitivity
 Itraconazole is more effective for toe nail infections
(Onychomycosis)

13. Terbinafine
 Distribution almost only in keratinized tissue and fat
 MoA: inhibits fungal enzyme Squalene Epoxidase
(inhibits ergosterol biosynthesis)  accumulation
of squalene is toxic to fungi  fungicidal
 Effective for onychomycosis
 Contraindicated in use with CYP inducers/inhibitors

14. Summary

15. RELATED PRODUCTS
If you enjoyed this presentation, please take a look at the rest of our
products. Our website has many more FREE excellent presentations and
tons of other FREE information.
HIGHSCORE: Must Know
Pharmacology
Description: This is a book of 400+
flashcards covering 20 highly
tested, and high-yield topics in
pharmacology. It is designed so
that you can use it anywhere on any
device or print it out and use as
flashcards.
Get the eBook: HERE!
Our site: Exam Masters Tutoring Service

16. RELATED PRODUCTS
HIGHSCORE: Comparisons of High Yield Topics for
the Medical Boards
Description: This book contains over 100
comparisons of some of the most highly tested
diseases and topics on the USMLE Step 2 CK. The
questions on the exam are much more vague than
what you see in the practice question banks and it is
very difficult to differentiate between two diseases
with similar symptoms. So this book is designed to
help students improve their score by targeting these
types of difficult questions.
Get the Free Sample: HERE!
Get the whole eBook: HERE!

17. RELATED PRODUCTS
USMLE STEP 2 CK TIDBITS & TIPS
MONTHLY SUBSCRIPTION
Join hundreds of other students
preparing for the USMLE Step 2 CK on
our USMLE Step 2 CK Tidbits & Tips
newsletter! It is an amazing
newsletter with tons of great info. The
monthly subscription entails a weekly
newsletter with info such as high
yield disease comparisons, most
commonly tested facts, treatments &
management, and much more!
View a sample Newsletter: HERE!
Subscribe to this awesome Newsletter: HERE!