Antifungal agents are those drugs used for superficial and systemic fungal infection

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