This document provides an overview of antifungal agents, including their classification, mechanisms of action, pharmacokinetics, indications, contraindications, adverse effects and dosing. It discusses major classes such as azoles, polyenes, echinocandins, allylamines and others. Key antifungal drugs summarized include amphotericin B, fluconazole, terbinafine, griseofulvin and clotrimazole. It describes their uses in treating superficial and systemic fungal infections.

1. ANTIFUNGAL AGENTS
ARATHY R NATH
5th year pharmD

3. INTRODUCTION
Antifungal agents are those drugs used for
superficial and systemic fungal infection.
Fungal infection can be of two types:
superficial infection
systemic infection
 Superficial infection –occur on the surface or just below
the skin or nail.
 Systemic infection –occur inside the body such as in
lungs and other body organs.

4. • Fungal infections are common ,not only
as primary disease but also secondary to
therapy with oral antibiotics.
• Individuals suffering from malignancy
,DM those on corticosteroids and
immunocompromised subjects are more
prone to develop fungal infection.

5. CLASSIFICATION OF ANTI FUNGAL AGENTS

6. 1. ANTIBIOTICS
Polyenes : Amphotericin B,
Nystatin,
Hamycin
Echinocandin : Caspofungin,
micafungin
Anidulafungin
Heterocyclic benzofuran : Griseofulvin
2 . ANTIMETABOLITE : Flucytosine
3.AZOLES
2types : Imidazoles and triazoles

7.  Imidazoles
a)Topical : clotrimazole,
Econazole,
Miconazole,
Oxiconazole
b) Systemic : ketoconazole
Triazoles : Fluconazole,
Itraconazole,
Voriconazole

8. 4. ALLYLAMINE : Terbinafine
5. OTHER TOPICAL AGENT : Tolnaftate,
undecylenic acid
Benzoic acid,
Sod.thiosulphate,
Butenafine

9.  POLYENES
• Amphotericin B
o MOA : -They bind to fungal membrane,
- act as a false membrane component,
- bind closely to ergosterol and produce a
change in cell permeabiity
-This leaks out the ctyoplasmic content and
cause cell lysis
o DOSE : 100 to 200mg tablet/ suspension 4 times
daliy

10. o Pharmacokinetics: - Not absorbed orally
- t ½ : 15 days
- Metabolised in liver
- Excreted slowly both in
urine and bile
o Indication : used topically for oral,vaginal
and cutaneous candidiasis and otomycosis. It
is the most effective drug for various types of
systemic mycoses.
o Contraindications : hypersensitivity

11. oAdverse effect: kidney toxicity
hypokalemia
Hypotension
fever
chills
nausea
vomiting.
oSpecial precautions:
- Do not use for noninvasive fungal disease such as
oral thrush,vaginal candidiasis in pt with normal
neutrophil count.

12. -Do not use injectable dose >1.5mg/kg should be
Cautious in pt with kidney problem
- .
oMonitoring : - Monitor renal function frequently,
-liver function
- serum electrolytes( calcium
magnesium, potassium)
-blood counts, hb.

13.  Echinocandins
These are a new class of antifungal antibiotics
with a complex cyclic lipopeptide structure
and have a low toxicity compared to AMB.
o MOA: interfere with cell wall boisynthesis through
inhibition of enzyme beta-1,3-glucansynthase;
which is very imp component of many fungal
cell wall.

14. oCaspofungin
Pharmacokinetics :
- not absorbed orally; has to be infused iv.
- metabolism is extensive and metabolite is excreted in
urine.
- Plasma t ½ : 10 hrs
 Indication : to treat oesophageal candidiasis and
invasive aspergillosis
DOSE : 50mg daily

15. Contraindication : hypersensitivity
Adr : fever ,
nausea,
vomiting,
anaphylaxis ,
rash
 Precautions:
- Discontinue treatment if patient shows
anaphylaxtic reaction
- Monitor for LFTs.

16. o Griseofulvin
o MOA: Inhibit fungal mitosis by disrupting the mitotic
spindle through interaction with polymerised
microtubules. Thus interfere with transport of
secretory material which inhibit cell wall
synthesis.
oPharmacokinetics:
- Absorption is increased by taking it with fatty
meals.
- Plasma t ½ : 24 hrs but it persist for weeks in skin
and keratin

17. o Indication : infection caused by ringworm in body,
hair, nail (tinea infection)
o Contraindication: hypersensitivity,
porphyria
pregnancy,
hepatocellular failure.
o Adr : rash,
urticaria,
oral thrush,
headache,
gynaecomastia

18. oPrecautions:
- If severe skin reactions ( stevens johnsons syndrom) are
reported ,discontinue the therapy.
- Elevation in AST,ALT bilirubin if reported, discontinue
therapy
oMonitoring:
Monitor renal ,hepatic system and also blood
counts.
oDose: 0.5 – 1g daily in single or divided dose

19.  ANTIMETABOLITE
oFlucytosine
- MOA : it inhibit fungal protien synthesis by replacing
the uracil with 5-flurouracil in fungal RNA and
also inhibit thymidine synthetase by interfering
with fungal DNA synthesis.
- Indication: candidiasis ,
Cryptococcus infection
- Contraindication : hypersensitivity reaction

20. -Adr: bone marrow suppression,
rash,
photosensitivity
-Monitor: hematology, renal,hepatic function.
Use extreme caution in patients
with renal impairment.
- Dose : 50 – 150mg/kg/day administered
in divided doses at 6hrs interval

21.  ALLYLAMINE
o TERBINAFINE
- MOA: Inhibit squalene epoxidase of
the fungi,which lead to decreasing of
ergosterol synthesis.
- Pharmacokinetic
75% of oral terbinafine is absorbed
t ½ : after single dose is 11- 16 hrs
-

22. -Indication: tinea pedis,
tinea corporis
tinea cruris
- Contraindication: hypersensitivity,
liver disease
- Adr: headache,
rash,
pruritis,
elevated liver enzymes,
taste disturbances
-

23. -precautions: discontinue if following develop;
Liver disease, neutropenia, skin rashes.
- monitor: monitor LFTS
- Dose : 250mg once daily. Duration 2 to 4 weeks (Tinea cruris )
4 weeks ( Tinea corporis )
6 weeks ( Tinea pedis )
6 – 12 weeks ( Nail infections)

24.  AZOLES
-MOA: Act by inhibiting ergosterol
biosynthesis through the inhibition
of 14a-demethylase.

25. oClotrimazole
-Well tolerated by most of the patients
- Indication: tinea pedis,
tinea cruris.
tinea capitis,
tinea vesicular,
cutaneous candidiasis,
vaginal candidiasis.
-dose : 100mg daily for 6 days

26. - Contraindication: hypersensitivity
- Adr: abnormal LfTs
GI irritation
- Monitor: monitor LFT periodically
Should be cautious in case of pt
with hepatic impairment.

27. oFluconazole
• Cross BBB
• Pharmacokinetics
oral bioavailability is not affected by food
or
gastric pH T ½ : 25-30 hr
• Indication: esophageal and oropharyngeal
candidiasis,cryptococcal
meningitis
• Contraindication : hypersensitivity,
pregnancy,

28. • Adr: nausea
vomiting,
abd pain
• Caution:
Use with caution in pt with hepatic impairment,
renal impairment, proarrhythmic cond.
• Dose : 50 – 200 mg daily

29. oTolnaftate
- MOA : Inhibit squalene epoxidase in a similar way
to allylamines.
- Indication: dermatophytes,
ring worm,athletes foot
- Contraindication : hypersensitivity
- Adr : pruritis,
irritation