This document discusses various antifungal drugs used to treat oral mycotic infections. It begins by introducing mycology and the importance of treating fungal diseases. It then describes 8 classes of antifungal drugs in detail, including their mechanisms of action, spectra of activity, uses, and adverse effects. The major classes discussed are polyenes like amphotericin B and nystatin, azoles like fluconazole and itraconazole, fluorinated pyrimidines like flucytosine, allylamines like terbinafine, echinocandins like caspofungin, and others.

1. ANTIFUNGAL THERAPY FOR ORAL
MYCOTIC INFECTIONS
BY
K V SAI SHANMUKH
4 BDS
ROLL NO-030
KAMINENI INSTITUTE OF DENTAL SCIENCES
DEPARTMENT OF ORAL MEDICINE AND
RADIOLOGY

2. INRODUCTION
ANTIFUNGAL DRUGS
FUNGAL INFECTIONS OF THE ORAL
CAVITY
ANTIFUNGAL THERAPY FOR ORAL
MYCOTIC INFECTIONS
BIBLIOGRAPHY AND SOURCE
CONTENTS

3. Mycology ,the study of fungal infection has gained
importance in the past few years, owing to the fact
that fungal diseases are more common than was
suspected previously.
INTRODUCTION

4. ANTIFUNGAL DRUGS

6. 1. Polyene antibiotics
MODE OF ACTION:
Amphotericin B and Nystatin bind to the fungal cell membrane
component ergosterol, leading to increased fungal cell membrane
permeability and the loss of intracellular constituents.
SPECTRUM:
Amphotericin B has activity against Candida spp.,
Cryptococcus neoformans, Blastomyces dermatitidis,
Histoplasma capsulatum, Sporothrix schenckii,
Coccidioides immitis, Paracoccidioides braziliensis,
Aspergillus spp., Penicillium marneffei, etc.
AMPHOTERICIN B

7. Amphotericin uses:
i.v. for treatment of Candida esopha-gitis, rapidly progressive
mucormycosis or invasive aspergillosis. Intrathecal infusion of
amphotericin B is useful in patients with meningitis caused by
Coccidioides.
Intravenous administration of amphotericin B is the treatment of
choice for mucormycosis and is used for the initial treatment of
cryptococcal meningitis, severe or rapidly progressing
histoplasmosis, blastomycosis, and coccidioidomycosis.
Intraocular injection has been used successfully for fungal
endophthalmitis.

8. ADVERSE EFFECTS:
The major acute reaction to i.v. amphotericin B is fever and chills.
Tachypnea and respiratory stridor or modest hypotension also may
occur.
 Patients with preexisting cardiac or pulmonary disease may tolerate
the metabolic demands of the reaction poorly and develop hypoxia or
hypotension.
Although the reaction ends spontaneously in 30 to 45 minutes,
pethidine may shorten it.
Pretreatment with oral paracetamol or use of i.v. hydrocortisone
hemisuccinate, at the start of the infusion decreases reactions.
Azotemia occurs in 80% of patients who receive amphotericin
in deep mycoses.

9. NEW FORMULATIONS:
Several lipid formulations of amphotericin B – colloidal
dispersion and liposomal amphotericin B, have been developed in
an attempt to reduce the toxicity profile of this drug and to increase
its efficacy.
Formulating amphotericin with lipids alters drug distribution,
with lower levels of drug in the kidneys, reducing the incidence of
nephrotoxicity.
While less toxic, thelipid formulations are significantly more
expensive than conventional amphotericin B.

10. Nystatin is a polyene antifungal drug with a ring structure
Mechanism of action- similar to that of amphotericin B.
Adverse effects- Too toxic for systemic use, nystatin is limited to
the
topical treatment of superficial infections caused by C.albicans.
Uses:Infections commonly treated by this drug include oral
candidiasis(thrush), mild esophageal candidiasis, and vaginitis.
NYSTATIN

11. 2. Antifungal Azoles are synthetic drugs
with broad-spectrum fungistatic activity.
Azoles can be divided into two groups:-
imidazole agents (clotrimazole, ketoconazole, miconazole)
in which the five-member azole nucleus contains two nitrogens.
the newer triazole compounds (fluconazole, itraconazole,
and voriconazole), in which the azole nucleus contains three
nitrogens.
ANTIFUNGAL AZOLES

12. Mechanism of action:
All azoles exert antifungal activity by inhibiting cytochrome P450
enzymes responsible for the demethylation of lanosterol to ergosterol.
Reduced fungal membrane ergosterol concentrations result in
damaged, leaky cell membranes.
Adverse effects:
The toxicity of these drugs depends on their relative affinities for
mammalian and fungal cytochrome P450 enzymes.
The triazoles tend to have fewer side effects, better absorption, better
drug distribution in body tissues, and fewer drug interactions.

13. Fluconazole does not require an acidic environment, as does ketoconazole,
for GI absorption.
About 80 to 90% of an orally administered dose is absorbed, yielding high
serum drug levels.
The t1/2 of the drug is 27 to 37 h, permitting once-daily
dosing in patients with normal renal function.
The drug penetrates widely into most body tissues.
Cerebrospinal fluid levels are 60 to 80% of serum levels,
permitting effective treatment for fungal meningitis.
About 80% of the drug is excreted unchanged in the
urine.
FLUCONAZOLE

14. Uses:
It is very effective in the treatment of infections with most
Candida spp.
Thrush in the end-stage AIDS patient, often refractory to
nystatin, clotrimazole,and ketoconazole, can usually be
suppressed with oral fluconazole.

15. Adverse effects:
 Asymptomatic liver enzyme elevation has been described, and
several cases of drug associated hepatic necrosis have been
reported.
Alopecia has been reported as a common adverse event in
patients receiving prolonged high-dose therapy.
Coadministration of enzyme inhibitor fluconazole with
phenytoin results in increased serum phenytoin levels.

16. Itraconazole is lipophilic and water insoluble and requires a
low gastric pH for absorption.
Oral bioavailability is variable (20 to 60%). It is highly protein
bound (99%) and is metabolized in the liver and excreted into the
bile.
Uses:
Itraconazole is most useful in the long-term suppressive
treatment of disseminated histoplasmosis in AIDS and in the oral
treatment of nonmeningeal blastomycosis.
It is the drug of choice for all forms of sporotrichosis xcept
meningitis.
Itraconazole has replaced ketoconazole as the drug of choice in
the treatment of paracoccidioidomycosis and chromomycosis.
ITRACONAZOLE

17. Ketoconazole (Nizoral®) can be absorbed orally, but it requires an
acidic gastric environment.
Uses:
It remains useful in the treatment of cutaneous andmucous
membrane dermatophyte and yeast infections, but it has been replaced
by the newer triazoles in the treatment of most serious Candida
infections and disseminated mycoses.
Ketoconazole is usually effective in the treatment of thrush, but
fluconazole is superior to ketoconazole for refractory thrush.
Widespread dermatophyte infections on skin surfacescan be treated
easilywith oral ketoconazole.
KETOCONAZOLE

18. Adverse effects:
Nausea, vomiting, and anorexia occur commonly with ketoconazole when high doses are
prescribed.
Epigastric distress can be reduced by taking ketoconazole with food. Pruritis and/or
allergic dermatitis occurs in 10% of patients.
Liver enzyme elevations during therapy are usually reversible. Severe ketoconazole-
associated hepatitis is rare.
At high doses,ketoconazole causes a clinically significant reduction in testosterone
synthesis and blocks the adrenal response to corticotrophin.
Gynecomastia, impotence, reduced sperm counts, and diminished libido can occur in men,
and prolonged drug use can result in irregular menses in women.
These hormonal effects have led to the use of ketoconazole as a potential adjunctive
treatment for prostatic carcinoma.

19. Clotrimazole is a broad-spectrum fungistatic imidazole drug
used in the topical treatment of oral, skin, and vaginal infections
with C. albicans.
It is also employed in the treatment of infections with
cutaneous dermatophytes.
Topical use results in therapeutic drug concentrations in the
epidermis and mucous membranes; less than 10% of the drug is
systemically absorbed.
CLOTRIMAZOLE

20. 3. Fluorinated pyrimidines
Flucytosine (5-flucytosine, 5-FC) is an analogue of cytosine that was
originally synthesized for possible use as an antineoplastic
agent.
Mechanism of action:
5-FC is converted to 5-fluorouracil inside the cell by the fungal enzyme
cytosine deaminase.
The active metabolite 5-fluorouracil interferes with fungal DNA
synthesis by inhibiting thymidylate synthetase.
Incorporation of these metabolites into fungal RNA inhibits protein
synthesis.
Uses: Flucytosine has a significant antifungal activity against Candida
spp. and the fungal organisms responsible for chromomycosis.
FLUCYTOSINE

21. 4. Allylamines – reversible noncompetitive
inhibitors of the fungal enzyme squalenemonooxygenase, which converts squalene
to lanosterol.
Mechanism of action:
With a decrease in lanosterol production, ergosterol production is also diminished,
affecting fungal cell membrane synthesis and function.
Spectrum:These agents exhibit fungicidal activity against dermatophytes and
fungistatic activity against yeasts.
Naftifine is available for topical use only in the treatment of cutaneous
dermatophyte and Candida infections.
Terbinafine (Lamisil®) is available for topical and systemic use (oral tablet)
in the treatment of dermatophyte skin and nail infections.
ALLYLAMINES

22. 5. Echinocandins
Caspofungin is a semisynthetic lipopeptide.
Mechanism of action: It inhibits the synthesis of beta-D-glucan, a cell wall
component of filamentous fungi.
Uses:Caspofungin isapproved for the treatment of invasive aspergillosis in
patients not responding to amphotericin B, and itraconazole.
Adverse effects are mediated through histamine release: facial flushing, rash,
fever, and pruritus.
Dose reductions are required in the presence of moderate hepatic insufficiency.
ECHINOCANDINS

23. 6. Pyridones
Ciclopirox olamine is a pyridone derivative for the treatment of
cutaneous dermatophyte infections, cutaneous C. albicans
infections,
and tinea versicolor caused by Malassezia furfur.
It interferes with fungal growth by inhibiting macromolecule
synthesis.
7. Thiocarbamates
Tolnaftate is an antifungal agent effective in the topical
treatment of dermatophyte infections and tinea.
PYRIDONES & THIOCARBAMATES

24. 8. Nonpolyene antibiotics
Griseofulvin is an oral fungistatic agent .
Uses: dermatophyte infections caused by Epidermophyton, Microsporum, and
Trichophyton spp. Produced by Penicillium
griseofulvin,
Mechanism of action:it inhibits fungal growth by binding to the
microtubules responsible for mitotic spindle formation.
Uses:The drug binds to keratin precursor cells and newly synthesized keratin
in the stratum corneum of the skin, hair, and nails, stopping the progression of
dermatophyte infection. In the treatment of ringworm
of the beard, scalp, and other skin surfaces, 4 to 6 weeks of therapy is often
required.
NON POLYENE ANTIBIOTIC - GRISEOFULVIN

25. -CANDIDIASIS
-BLASTOMYCOSIS
-HISTOPLASMOSIS
-CRYTOCOCCOSIS
-COCCIOIDOMYCOSIS
-ASPERGILLOSIS
-SPOROTRICHOSIS/RHINOSPORIDIOSIS
FUNGAL INFECTIONS OF THE ORAL CAVITY

26. ACUTE : PSEUDOMEMBRANOUS
ATROPHIC
CHRONIC: HYPERPLASTIC
MUCOCUTANEOUS
ATROPHIC
IMMUNOCOMPROMISED HIV ASSOCIATED
CANDIDIASIS
TYPES OF CANDIDIASIS

27. ACUTE PSEUDOMEMBRANOUS
CANDIDIASIS

28. ACUTE PSEUDOMEMBRANOUS CANDIDIASIS

29. ACUTE ATROPHIC
CANDIDIASIS

30. CHRONIC HYPERPLASTIC CANDIDIASIS

31. CHRONIC HYPERPLASTIC CANDIDIASIS

32. CHRONIC ATROPHIC
CANDIDIASIS

33. TREATMENT FOR
CANDIDIASIS

34. BLASTOMYCOSIS

35. BLASTOMYCOSIS

36. ITRACONAZOLE ORALLY 200MG DAILY OR BD
SEVERE INFECTION - Amphotericin B i.v
TREATMENT FOR
BLASTOMYCOSIS

37. HISTOPLASMOSIS

38. ITRACONAZOLE CAPSULES 200mg/daily or BD
Or
KETOCONAZOLE CAPSULES 400mg/day few weeks and
months
Severe infections-Amphotericin iv
after successful outcome ITRACONAZOLE can be continued as
prophylactic measure
TREATMENT FOR
HISTOPLASMOSIS

39. CRYPTOCOCCOSIS
C.neoformans and C.gatti
Superficial ulcers,nodules,granulomas
sites-gingiva,palate,tooth socket after extraction

40. Amphotericin-iv 1mg/20-30 min , then 250mcg/kg
daily , 1mg/kg daily with or without FLUCYTOSINE
or FLUCONAZOLE
AFTER SUCCESSFUL OUTCOME
,FLUCONAZOLE CAN BE CONTINUED AS
PROPHYLACTIC MEASURE.
TREATMENT FOR
CRYPTOCOCCOSIS

41. ZYGORMYCOSIS/MUCORMYCOSIS

42. ZYGORMYCOSIS / MUCORMYCOSIS

43. Amphotericin iv infusion of 1mg over 20-30 min test dose,then
250mcg/kg daily and if tolerated increase to 1mg/kg daily.
(max 1.5mg/kg daily) / Amphotericin newer formulation.
ITRACONAZOLE / VORICONAZOLE / POSACONAZOLE /
CAPSOFUNGIN
TREATMENT FOR
MUCORMYCOSIS

44. ASPERGILLOSIS
caused by A.fumigatus
second most opputunistic fungal infection
marginal gingiva and gingival-portal of entry
painful gingival ulcerations and soft tissue
swellings.

45. Amphotericin iv of , 1mg over 20-30 min test dose , then
250mcg/kg daily and if tolerated increase to 1 mg/kg
daily.(Maximum 1.5mg/kg)
Newer formulation:Amphotericin lipid formulation 1mg over
10 mintest dose , then 5mg/kg for atleast 14 days
ITRACONAZOLE/VORICONAZOLE/POSACONAZOLE/CA
PSOFUNGIN
TREATMENT FOR
ASPERGILLOSIS

46. COCCIDIOMYCOSIS
Caused by C.immitis
Oral lesions are uncommon and are granulomatous
nodules.
Clinically they are non specific

47. Fluconazole 50-400mg oral/iv daily depending on degree of
risk
Or ITRACONAZOLE / KETOCONAZOLE
TREATMENT FOR
COCCIDIOMYCOSIS

48. SPIROTRICHOSIS/RHINOSPORIDIOSIS

49. Rhinosporidiosis is treated with surgical excision because,
generally, medical treatment has not been proven effective.
DAPSONE.
Local surgical excision is the treatment of choice.
Recurrence has been reported with simple excision. Wide
excision with electrocoagulation of the lesional base has
been promoted to decrease recurrences.
TREATMENT FOR
SPIROTRICHOSIS/RHINOSPORIDIOSIS

50. -Immunocompromised patients are at increased risk of
of fungal infections and may need prophylactic
antifungal drugs.
-Management is a challenge and a specialist field.
IMMUNOCOMPROMISED
PATIENTS (HIV,HEPATITIS ETC.)

51. -Oral triazole antifungals are the drugs of choice for prophylaxis.
-Fluconazole is more reliablly absorbed than itraconazole but is
not effective against aspergillus spp.
-Posaconazole can used for prophylaxis in patients who are
undergoing haemopoetic stem cell transplantation or receiving
chemotherapy,if they intolerant to fluconazole or itraconazole.
-Micafungin can be used if all the above cannot be used.

52. -amphotericin B intravenous infusion or capsofungin
is used for the empirical treatment of serious fungal
infections.

53. Itraconazole (capsule) 400 mg per dayhas reduced incidence of
candidiasis,given 2 weeks before chemotherapy.
Itraconazole (oral solution) 2.5 mg/kg twice dailyreduces non-albican sps
of candida,given 1 week before transplantation.
Amphotericin B (i.v.) 0.15–0.25 mg/kg per day
Amphotericin B (aerosol) 10 mg 3 times daily
Fluconazole 100–400 mg per day depending on risk of patientseffective for
prevention of candidiasis in ICP.
PROPHYLACTIC FUNGAL
THERAPY

54. BURKET’S ORAL MEDICINE(DIAGNOSIS &TREATMENT)
SHAFER’S TEXTBOOK OF ORAL PATHOLOGY
ORAL AND MAXILLOFACIAL PATHOLOGY:NEVILLE
GOOGLE.COM
BIBLIOGRAPHY AND SOURCE