ANTIFUNGALS CLASSIFICATION POLYENE ANTIFUNGAL FLUCYTOSINE TONY SCARIA LAST MINUTE REVISION NOTES WITH HIGH YIELD TOPIC

1. Anti fungals
TONY SCARIA 2010 KMC

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6. Griesofulvin
• Used orally
• Ineffective topically
• For dermatophytes
• not useful for systemic infections
• Steptomyces griesofulvum
• Disrupts mitotic spindle
• Never given in empty stomach
• Increased absorption with fat
• Enzyme inducers (azoles are inhibitors)
• S/E
• disulfiram like reaction
TONY SCARIA 2010 KMC

7. Amphotericin B
• Polyene antifungal
• Fungicidal at higher concentration &
fungistatic at lower concentration
• Binds to ergosterol  forms pores in cell
membrane increases permeability
TONY SCARIA 2010 KMC

8. AMB
• Widest antifungal spectrum
• Not absorbed orally used topically
• USED ONLY IV
BROADEST AZOLE  POSACONAZOLE
TONY SCARIA 2010 KMC

9. S/E of AMB
• Nephrotoxicity
• Dose limiting S/E  nephrotoxicity
• Nephrotoxicity can be decreased by
• saline loading of AMB
• Lipid bound IV preparations
• Amphotericin B lipid complex
• Amphotericin B colloidal suspension
• Liposomal AMB
• Nephrotoxicity increased by
• Volume depletion
• Concomitant administration of other nephrotoxic drugs Aminoglycosides
TONY SCARIA 2010 KMC

10. AMB IS INCORPORATED IN TO LIPOSOME
BILAYER
• TARGETED DRUG DELIVERY
• AMB IN LIPOSOME IS BROKEN DOWN IN ANOXIC CONDITIONS ONLY
• Is broken down only in regions with fungal infection
TONY SCARIA 2010 KMC

11. Other S/E of AMB
• Allergic manifestation
• Decreased by intake of steroids + NSAIDS
• Hypokalemia  d/t renal failure
• Hypomagnesemia
• Anemia
TONY SCARIA 2010 KMC

12. S/e of AMB
• Azotemia
• Reduced GFR
• Hypokalemia
• Inability to concentrate urine
• Renal tubular acidosis
• Anemia
• Headache
• Vomiting
• Cranial nerve palsy TONY SCARIA 2010 KMC

13. During AMB monitor
• CBC
• s creatinine
• Serum K+
• Serum Mg2+
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14. • AMB is safe during pregnancy
• Dose is reduced when combined with 5 FC
TONY SCARIA 2010 KMC

15. AMB is also used for
• Kala azar
• Cryptococcus
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16. Other polyene antifungals (like AMB)
• Nystatin
• Hamycin
• Natamycin
Used topically
TONY SCARIA 2010 KMC

17. Flucytosine
• Orally with amphotericin B for
systemic infection
• AMB causes pores in membrane +
flucytosine enters through pores &
inhibit DNA synthesis
• Used in conjuction with AMB in
cryptococcal meningitis
• S/E
• Bonemarrow suppression
TONY SCARIA 2010 KMC

18. Azoles
Imidazole
• Topical
• Clotrimazole
• Econazole
• Miconazole ‘
• Oxiconazole
• Systemic
• Ketoconacole
Triazole
• Fluconazole
• Voriconazole
• Itraconazole
TONY SCARIA 2010 KMC

19. Ketoconazole
• Maintenance drug;
• Given by oral route
• Inhibits lanosterol-danosterol synthesis
• pH dependent absorption; avoided with antacids
• Absorption inhibited by PPI ,H2 blockers, antacids
• Inhibits CYP enzymes
• T_1/2 ^= 24 hours
• Rx-recurrent moniliasis
• Topically, used for dandruff
• Hepatitis-serious side effect
• Antiandrogenic
• Decrease androgen production from testes
• Displaces testosterone from protein binding sites  gynaecomastia/ loss of libido/
TONY SCARIA 2010 KMC

20. Ketoconazole
• Antiglucorticoid with antimineralocorticoid activity
TONY SCARIA 2010 KMC

21. Fluconazole
• Fungistatic
• Long acting
• Half life 24 hours
• Eliminated unchanged in urine
• DOC for UTI d/t candida infection
• Avoided in renal failure
• Use:
• 1. Cryptococcal meningitis
• 2. Coccidia
• 3. Candida (single dose)
• NOT EFFECTIVE MUCOR ASPERGILLOSISTONY SCARIA 2010 KMC

22. Itraconazole
• 1. Fungistatic
• Effect against candida aspergillosis
• 2. Long acting
• 3. Food increases absorption
• 4. pH dependent absorption
• 5. Very weak inhibitor of CYP enzymes*
• S/E  dose dependant sporothrix
• 6. DOC
• 1. Histoplasmosis
• 2. Blastomycosis
• 3. Sporothrix
DOC in sporothrix
TONY SCARIA 2010 KMC

23. VORICONAZOLE
• GOOD ABSORPTION
• Doc AGIANST ASPERGILLOSIS
• VISUAL TOXICITY
• VITREAL INJECTION
• ELEVATED ENZYMES
TONY SCARIA 2010 KMC

24. Posaconazole
• Broadest spectrum azole
• Only azole effective against mucormycosis
TONY SCARIA 2010 KMC

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26. • Terbinafine
• Fungicidal drug
• Long acting
• Blocks synthesis of squalene epoxide
• This causes squalene accumulation-kills fungi
• DOC
• Onycomycosis
• Used orally for onychomycosis
• Topically for dermatophytosisTONY SCARIA 2010 KMC

27. Echinocandins
Echinocandin inhibit
glucan synthase
TONY SCARIA 2010 KMC

28. Echinocandin inhibit glucan synthase
• Capsofungin
• Micafungin
• Anidula fungin
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29. Echinocandins
• Activity against candida & invasive aspergillosis
• Disadv
• No oral form
• Not effective against Cryptococcus mucormycosis histoplasmosis
• Very low CNS penetration
TONY SCARIA 2010 KMC

30. Nikkomycin inhibit chitin synthesis
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32. DOC in pregnancy
• AMB
• All others are C/I
TONY SCARIA 2010 KMC

33. Fungicidal
•AMB
•Terbenafine
•Echinocandins
Fungistatic
•Azoles
•Greisofulvins
•Flucytosine
TONY SCARIA 2010 KMC

34. Coccidomyces Flucoconazole
Aspergillosis Voriconazole
Candida AMB
Cryptococcosis AMB + 5 FC
TONY SCARIA 2010 KMC

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