antifungal drugs used in dentistry

17 Pages·2014·0.64 MB·English

International Journal of Dental and Health Sciences
Review Article Volume 01,Issue 04

ANTIFUNGAL DRUGS USED IN DENTISTRY
Tapaswini Bagh1,Laxmikanth Chatra2, Prashanth Shenai3,Veena K M3

,Prasanna Kumar Rao 4 ,Rachana V Prabhu 5

1.Post Graduate Student, Department of Oral Medicine and Radiology, Yenepoya Dental College,
Yenepoya University, Mangalore, Karnataka, India.
2.Senior Professor and head, Department of Oral Medicine and Radiology, Yenepoya Dental College,
Yenepoya University, Mangalore, Karnataka, India.
3.Professor, Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya
University, Mangalore, Karnataka, India.
4.Associate professor, Department of Oral Medicine and Radiology, Yenepoya Dental College,
Yenepoya University, Mangalore, Karnataka, India.
5.Reader, Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya
University, Mangalore, Karnataka, India

ABSTRACT:
Fungal infections are usually more difficult to treat than bacterial infections because fungal
organisms grow slowly. Oral candidiasis, a frequent and important fungal condition of the
oral cavity is caused by Candida species. There are few local factors that make the oral
tissues susceptible to Candida infection. These factors include acid saliva, xerostomia, night
use of prosthetic dentures, tobacco, carbohydrate rich diets and patients that receive
radiotherapy and chemotherapy in maxillofacial structures and also associated with the use
of broad spectrum antibiotics, corticosteroids, anticancer/immunosuppressant drugs,
emergence of AIDS.Antifungal drugs are used in dentistry in the management of oral
candidal infections. They are available as lozenges, gels, ointments and oral suspension for
topical use. Systemic dosing may also be used when the infection is severe.Three groups of
compounds are used. These are polyenes, imidazoles and triazoles. Amphotericin and
Nystatin are polyenes that are not absorbed after oral administration. The imidazoles and
triazoles achieve their antifungal action by inhibiting the synthesis of ergosterol and it
results in decreased fungal replication.Maintenance of oral hygiene and early diagnosis of
this condition is very important. This article reflects on clinical application of antifungal
drugs in dentistry.
Key words: Antifungal drugs, Oral Candidiasis, Denture stomatitis, Clotriamzole, Nystatin.

INTRODUCTION: immunodeficiency syndrome. The perfect
fungi causing oral infections are
Fungi generally constitute a relatively
Aspergillus, Geotrichium and Mucor
small, proportion of oral microflora. The
species. The imperfect yeasts such as
perfect fungi that divide by sexual
Candida species which divide by asexual
reproduction are rarely isolated from oral
reproduction are found in the mouth.
cavity but occasionally found in infecting
[1]The largest proportion of the fungal
patients with advanced acquired
microflora in the human mouth is made

*Corresponding Author Address: Dr. Tapaswini Bagh,Department of Oral Medicine and Radiology,Yenepoya dental
College.,Yenepoya University,Deralakatte. Mangalore ,PIN: 575018 Karnataka, India.E-mail: [email protected]
Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539
up of Candida species. Candida albicans Newton has classified Denture- sore
are one of the components of normal oral mouth as shown in Table: 3[7]
microflora and around 30% to 50% people
These conditions are treated by antifungal
carry this organism. Rate of carriage
drugs (Nystatin, Amphotericin-B,
increases with age of the patient. Candida
Miconazole and Fluconazole) and
albicans are recovered from 60% of
disinfectants (0.2% Chlorhexidine
dentate patient’s mouth over the age of
gluconate mouth washes 3 or 4 times a
60 years. There are nearly five types of
day). Even though denture stomatitis is
candida species which are seen in the oral
asymptomatic, it should be treated as it
cavity. Candida albicans, Candida
may act as reservoir for infections which
tropicalis, Candida krusei Candida
can become extensive and lead to the
parapsilosis, Candida guilliermondii.
resorption of the alveolar bone. The most
Among these five types, Candida albicans
effective treatment is the eradication and
are commonly seen in the oral
control of the microbial plaque.
cavity.Candida albicans is a dimorphic
fungus that causes severe opportunistic
1. Nystatin:
infections in humans.[2] There are three
It is polyene antibiotic obtained from
general factors which helps the Candida
Streptomyces noursei.
albicans infection to develop in the
patient’s body. They are: Immune status
Trade name: MYCOSTATIN
of the patient , Oral mucosal
environment, Strain of Candida Preparation available:
albicans.The main factors which increase
Oral - 5, 00,000 unit tablets
susceptibility of oral candidiasis are:
Immunosuppression, Topical - 100,000 unit/gm cream and
Endocrinopathies,Nutritionaldeficiencies, ointments, 100,000 units vaginal tablets.
Malignancies,Dental prosthesis, Epithelial It is available currently for topical use in
alteration, high carbohydrate diet, Infancy creams, ointment, suppositories, lotion,
and old age, Poor oral hygiene, heavy suspension, vaginal tablets, and oral
smoking.[3.4] pastille.
Classification of Antifungal drugs: Mechanism of action: Depending upon
concentration used, it can be either
Antifungal drugs are used in both
fungistatic or fungicidal agent. It binds to
superficial and deep fungal infections
the ergosterol and increases the
classified as in different groups shown in
permeability of cell membrane facilitating
Table: 1[5]
pore formation. These microspore
Clinical application in dentistry: formation allow leakage of intracellular
ions and macromolecule leading to cell
Lehnar has classified oral candidiasis as
death.
follows shown in Table: 2 [6]
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Indication: treating denture stomatitis with nystatin
powder, placed on the fitting surface of
Oral candidiasis (Oral thrush):
the denture; three times a day for 14
days. Nystatin is formulated for oral use
Nystatin is drug of choice. It is commonly
as suspension or pastille. [8]
used as topical agent to suppress Candida
infection. It is not administered parentally
Lucio Milillo, Lorengo et al in 2005 had
as it is toxic for systemic use. Thrush is
conducted a study of the efficacy of
treated by holding 5 ml of nystatin
amorolfine anti-fungal varnish in Candida
suspension (for infants- 2 ml) in oral cavity
related denture stomatitis. They had done
for several minutes 4 times daily before
this to avoid the use of systemic
swallowing. Alternative treatment is to
antifungal agents in nystatin resistant
retain vaginal tablet in the mouth until it
cases. [12]
dissolves, at least 4 times a day. Nystatin
oral pastille (200,000 units) dissolved Candidial Angular cheilitis:
slowly in the mouth 5 times a day—can be
Treatment with Nystatin or Mycostatin
mixed with glycerin. Mycostatin creams
yield good result.
and ointments (1 lack units) may be used
in candidiasis with angular cheilitis,
Adverse effect: fever, chills, headache,
stomatitis. Mycostatin oral rinse - 1
hypotension, rashes, nausea, and
teaspoon of nystatin oral suspension
vomiting.
(100,000unit/cc) mixed with ¼ cup of
Contraindication: Hypersensitivity
water is used as oral rinse for 3-4 times a
reaction.
day for 7-10 day
2. Amphotericin-B:
Denture stomatitis (chronic atrophic
candidiasis):
Amphotericin B is an antifungal antibiotic
produced by Streptomyces nodosus.
0.2% chlorhexidine solution with
Mycostatin tablet dissolves in it forming
Trade name:
gel used mainly in such patients. In
denture wearing patients, nystatin Fungizone, Abelcet, Ambisome,
ointments are to be applied to the fitting Amphotec.
surface of clean denture thoroughly and
Preparation available:
regularly and should be left out of mouth
at night keeping it in 0.02% of sodium Parenteral: conventional formulation:
hypochlorite solution. Fungizone 50 mg power for injection.
Nystatin tablets 500,000 units were Lipid formulation: Abelcet -100 mg/20 ml
allowed to dissolve in the mouth three suspension for injection. Ambisome-50
times a day for 14 days. Bergendal and mg powder for inj. Amphotec-50,100 mg
Isacsson reported similar results by powder for inj.
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Topical: 3% cream, lotion, ointment. vomiting, headache, thrombophlebitis
may occur if injected IV.
Mechanism of action:
3. Hamycin:
It binds to the ergosterol. The sterol of cell
membrane of fungi increases the It is polyene antibiotics obtained from
permeability of cell membrane facilitating Streptomyces pimprina.
pore formation. These pore formation
Trade name: HAMYCIN, IMPRIMA
allow loss of cation, intracellular ions and
loss of calcium leading to cell death. It
Preparation available: Topical- 4 lac
acts as fungicidal at high concentration
unit/gm ointment, 5 lac unit vaginal
and fungistatic at low concentration. It is
ovules, 2 lac/ml suspension.
effective against numerous fungi and
Indication:
yeast like Candidia albicans.
Oral thrush (due to Candida albicans):
Indication:
Ointment or suspension is applied to the
Oral candidiasis: Used in Oral candidiasis
affected area of oral mucosa with sterile
(Oral thrush), acute atrophic candidiasis
cotton 2-3 times a day for 7-10 days. It
(antibiotic stomatitis), denture sour
can also be given in cutaneous candidiasis,
mouth (chronic atrophic candidiasis),
monoliasis and otomycosis caused by
chronic hyperplastic candidiasis (candidial
Aspergillus. Dose recommended is 10-20
leukoplakia).
mg/kg daily.
- Amphotericin B is mostly applied
Adverse effect: Mild rashes, irritation.
topically in the form of ointment,
Contraindication: Hypersensitivity.
suspension, drops, cream, and
lotion. It is applied 2-3 times a day.
4. Natamycin:
Mystelicin elixir containing both
tetracyclines vigorously swished in Trade name: NATAMYCIN, PIMAFUCIN
the mouth and then swallowed, 4-
Preparation available: Topical - 5%
5 times for 2-1 weeks.
suspension, 2% cream, 1% ointment and
- In denture wearing patient, 25 mg vaginal tabs.
amphotericin B ointment applied
Indication:
to fitting surface of denture before
it use. • Oral thrush/ Oral candidiasis: Natamycin
vaginal tab or ointment is applied on
Adverse effect: It is toxic drug causes
affected area of oral mucosa for several
impairment of renal and hepatocellular
minutes 3-4 times daily
function, anemia, mental and neurological
changes, renal toxicity. Chills, fever, Adverse effect: Nausea, mild rashes
occasionally.
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5. Flucytosine (5-FC): cream, lotion, solution. Oral: 100 mg, 200
mg, 500 mg tab.
It is oral antifungal agent effective against
systemic infection due to yeast and fungi. Mechanism of action:
Trade name - ANCOBON It inhibits the synthesis of ergosterol by
binding to catalytic haem ion of fungal
Preparation available - Oral: 250, 500 mg
cytochrome resulting in damage to cell
capsule, 100 - 150 mg/kg/day in patient
membrane of fungi.
with normal renal function.
Indication:
Mechanism of action:
Candidiasis caused by Candida albicans,
It has antifungal action. Susceptible fungal
oral candidiasis, cutaneous candidiasis.
cell take up flucytosine, convert it to
fluorouracil, which is converted to 5- For oropharyngeal candidiasis 10 mg
flurodeoyuridylic acid which inhibit DNA troche of clotrimazole is allowed to
and RNA synthesis. But human cells are dissolve in the mouth 3-4 times a day, or
unable to convert parent drug to its active the lotion/ gel is applied/ swirled in the
metabolites, so it is relatively non-toxic. mouth for as long as possible.
Indication: It is also effective in skin infections caused
by Corynebacteria.
It is mainly used as an adjuvant drug.
Flucytosine is used in combination with Adverse effect: Local burning or stinging,
itraconazole. skin irritation, rash, hypersensitivity.
Adverse effect: Prolonged use with high Contraindication: 1st trimester of
doses cause leukopenia, pregnancy.
thrombocytopenia, and anemia due to
7. Econazole:
bone marrow depression, nausea,
vomiting, and skin rashes.
It is antifungal agent mainly used
topically.
6. Clotriamzole:
Trade name: ECANOL, SPECTAZOLE,
It is used exclusively as topical agent. It is
ECODERM, ECONAZOLE
toxic on parental administration.
Preparation available: Topical: 1% cream -
Trade name: MYCOBAN, LOTRIMIN,
10 gm.
MYCELEX, SURFAZ, CLOTRIN, CLODERM,
CANDID.
Mechanism of action: same as
Clotrimazole.
Preparation available:

Topical: Mycoban Gel 12% (30 gm),
Gynostatum vaginal tab, 1% vaginal

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Indication:  Systemic mycosis: Miconazole is
used by intravenous route
Treatment for trichomoniasis-1%
(Monistat).
ointment, 150 mg vaginal tablets is
applied to affected area of skin or oral  Ocular infection: Topical (1%) for
mucosa twice a day for 7-10 days. every hours and subconjunctival
injection of 5 mg miconazole (1%)
Mucocutaneous candidiasis: It is used as
MICOPTIC OPICOPS once/twice a
an oral rinse, cream, ointment as well as
day.
suspension. Vaginal tab dissolved in ¼ cup
of water and used as oral rinse for oral Adverse effects: Chills, fever, itching,
candidiasis. nausea, rashes, phlebitis, anemia,
irritation to skin.
Adverse effect: Local burning or stinging,
skin irritation, rash. 9. Ketoconazole (KTZ):
8. Miconazole: It was first orally effective azole antifungal
agent used in the treatment of systemic
It is used as topical antifungal agent. It is
fungal infection. It is less toxic than
more toxic than ketoconazole.
Amphotericin B. The oral absorption of
Trade name: MICOGEL, MONISTAT, KTZ is facilitated by gastric acidity because
MICATIN, ZOLE, DAKTARIN it is more soluble at lower pH. [9, 10]
Preparation available: Trade name: NIZRAL, TOCON, FUNGICIDE,
FUNAZOLE, KETOVATE, HYPHORAL
Topical: ointment 2%-15 gm, lotion 2%-15
ml, powder 2%-15 gm, cream 2%-15 gm, Preparation available:
gel 2%-15 gm, vaginal suppositories- 100,
Oral- Tab 200 mg, Topical: 2% cream, and
200 mg.
shampoo.
Mechanism of action: same as
Mechanism of action: same as
Clotrimazole.
Cotrimazole.
Indication:
Indication:
 Severe systemic fungal infection:
 Mucocutaneous candidiasis: Tab
In adult, 1200 to 2400 mg/day in
200 mg once a day is very
divided doses.
effective.
 Cutaneous candidiasis: Applied
 Candidiasis, seborrheic dermatitis:
cream, ointment to be affected
Oral dose of 200 mg daily for 2-3
area twice daily for 7days.
weeks can be given. Ketoconazole
(Nizoral) available as a cream for
topical treatment. 3) Shampoo 1%
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is used for seborrheic dermatitis Systemic candidiasis: For systemic
(Nizoral AD Shampoo). infection, 400 mg of ketoconazole either
orally or intravenously on first day then
Adverse effect:
200-400 mg once a day for 15-30 days. For
children: 3-6 mg/kg BW daily in severe life
Nausea, vomiting, loss of appetite,
threatening infection in over 1year.
giddiness, headache, rashes, photophobia,
and paresthesia.It interferes with
 Prophylactic agent for bone
biosynthesis of adrenal and gonadal
marrow transplantation recipients
steroid hormone producing
and AIDS patient. Prophylactic use
gynaecomastia, infertility, menstrual
of fluconazole to reduce fungal
irregularities and GIT upset.
infection is used.
10. Fluconazole:
 Oral fluconazole (150 mg/ day for
It is new antifungal drug which is more 2 weeks) is highly effective in
water soluble and has good penetration oropharyngeal candidiasis, but is
into cerebrospinal fluid, ocular fluid, reserved for cases not responding
vaginal tissue and saliva. It can be to topical antifungals.
administered intravenously or orally.
Adverse effect: Nausea, headache,
Trade name: SYSCAN, DIFLUCAN, ZOCON, abdominal pain.
FORCAN, FLUZON
11. Itraconazole:
Preparation available:
It is newer antifungal drug which is
Oral 50, 100, 150, 200 mg tablets, Topical: administered orally. Its efficiency is
powder for 10, 40 mg/ml suspension. enhanced in combination with flucytosine.
Parenteral-2 mg/ml in 100 and 200 ml [9.10]
vial.
Trade name: ITROLE, CANDITRAL,
Mechanism of action: SPORANOX, CANDISTAT, ITASPOR,
FLUCOVER
It acts by inhibiting the enzyme
demethylase resulting in the damage to Preparation available:
fungus cell membrane. It has fungistatic
Oral- 100 mg, 200 mg Capsule.
action.
Topical: 10 mg/ml solution, Parenteral: 10
Indication:
mg/ml for IV infusion.
Mucosal candidiasis/mucocutaneous
Mechanism of action: same as
candidiasis: Ketoconazole can be given
Fluconazole.
orally in the dose of 50-100 mg daily for
14-30 days or intravenously. For mucosal Indication:
infection, topical application may useful.
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Oropharyngeal candidiasis: Oral liquids  Dermatophytosis, Candidiasis:
and intravenous preparation are quite Topical application of cream or
effective in the dose of 200 mg lotion over skin and oral mucosa,
capsule/tablets twice daily for at least 6 4-5 times/ day yield good results
month, yields good results. due to good penetration power.
Adverse effect: 14. Voriconazole:
Peripheral neuropathy, headache, It is newest trizole to enter clinical trials. It
dizziness, allergic reaction, jaundice, is available in an intravenous and oral
hepatotoxicity. formulation.Recommended dosage is 400
mg/day. It has broad spectrum of action
12. Newer Antifungal drugs: [11]
mainly against Candida species.
Silver sulfadiazine (SSZ): SSZ has broad Voriconazole is most effective than
spectrum of antifungal activity against itraconazole in candidial infection. [11]
Candida Aspergillus, Fusarium, and other
Indication:
fungal infections of the eye.
Oral thrush: Orally or intravenously
Trade name: APLICAPS.
administered in the dose of 400 mg/day.
Preparation: Topical: 1% suspension, Oral: Mucocutaneous preparation: Topical 10%
250 mg tablets. ointment, cream.
Indication: 15.Brazilian Green Propolis:
It is used in fungal infection of the eye Propolis is a resinous material collect by
caused by Candida, Aspergillus, and bees from various plants, and this
Fusarium. 1% suspension is used, 5 times chemical composition depends on its
a day. SSZ is also available in1% eye drops origin area. Extract of Propolis contains a
and ointment 1% - applied topically 4-5 wide variety of components like
times daily. flavonoids and phenolic acids. The
flavonoids in Propolis, mainly
13. Ciclopirox olamine:
pinocembrin, have been considered to be
responsible for its inhibitory effect on
It is newer antifungal agent with high cure
Candida. Antifungal activity is one of the
rates. It has good penetration power.
most extensively investigated biological
Trade name: LAPROX, BATRAFEN, OLAMIN actions of Propolis. Recently a study was
done to comparison of the efficacy of a
Preparation: 1% cream, lotion.
new form of Brazilian green propolis,
Indication: using a formula propylene glycol
contrasting it with miconazole gel in the
 It is used in Tinea infections,
topical treatment of Candida-associated
denture stomatitis. The overall results
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showed that propylene glycol Brazilian Mycostatin as mouth rinses and denture
green propolis has an antifungal activity soaks over a period of 28 days resulted in
similar to miconazole, in the C. albicans a significant reduction in palatal
colonies decrease and in the erythema inflammation and candidal colonization of
reduction of patients with Candida- dentures and palatal mucosa, although
associated denture stomatitis. Brazilian denture plaque scores did not differ
green propolis that has antifungal significantly.In another study a 0.2%
properties is a safe, affordable, and chlorhexidine gluconate mouth rinse used
natural product without well-known side three times daily significantly reduced
effects up to now. [12] plaque, but there was no significant effect
on the number of Candida organisms.[14,15]
16. Amorolfine:
Peridex: Epstein has described the use of
Amorolfine varnish is a medicine used in
Peridex containing chlorhexidine
the topical treatment of onychomycosis
gluconate, in the treatment of oral
caused by dermatophytes, yeasts and
candidosis. The drug is a broad spectrum
moulds. The varnish contains 5% w/v
mouthrinse which is adsorbed on the
amorolfine (as hydrochloride) as active
surfaces of microorganisms, increasing
ingredient in an ethanol base. The active
permeability of cell membranes and
substance Amorolfine belongs to the
causing precipitation of cytoplasmic
morpholines derivatives class of
contents. It was found that chlorhexidine
antifungal substances. It has got
bound to salivary pellicles as well as hard
antifungal and fungistatic effect. The
tissues in the oral cavity, resulting in
ingredients of locetar 5% varnish are
chlorhexidine titres in saliva for 12 hours
amorolfine chloride, copolymer of
or more after rinsing. Although effective
methacrylic acid, triacetin, butyl acetate,
in the treatment of oral candidosis,
ethyl acetate and ethyl alcohol. [13]
unpleasant side effects included staining
of the tooth surfaces and a bitter taste.[16]
Lucio Milillo, Lorengo et al had conducted
a study of the efficacy of amorolfine
Lal et al. investigated the use of
antifungal varnish in Candida related
chlorhexidine gluconate in the form of
denture stomatitis. They had done this to
Peridex both as a mouth rinse and a
avoid the use of systemic antifungal
denture soak in the treatment of denture
agents in nystatin resistant cases. [13]
stomatitis. The study was for a period of
24 days and Peridex oral rinse containing
Antifungal action of antiseptic and
0.12% chlorhexidine gluconate was used
disinfecting agent:
twice daily and dentures soaked overnight
Listerine : An in vivo programme involving
in Peridex solution. It was found that
the use of Listerine*** antiseptic (ethanol
chlorhexidine completely eliminated C.
0.26 mL, benzoic acid 1.5 mg, thymol 0.63
albicans on the acrylic resin denture
mg, eucalytol 0.9 mg per mL) and
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surface and significantly reduced palatal  To eliminate any associated
inflammation. [17] discomfort
Guidelines for treatment and prophylaxis  To reduce load of candida
of invasive fungal diseases: [18, 19]
 Treatment options are mainly
Patient selection criteria may include: categorized in to two lines,
primary & secondary line of
 Clinical history, signs and
treatment
symptoms.
Primary line of treatment:
 Imaging studies
Nystatin is the drug of choice as a primary
 Microscopic findings in suitable
line of treatment. Usually for the mild and
specimens.
localized candidiasis this primary line of
 Rapid diagnostic tests (e.g. treatment is used other drugs includes
Clotrimazole which can be taken as is
exfoliative cytology,tissue
Lozenges and Amphotercin B as oral
biopsy,antigen or nucleic acid
suspension. [4, 5]
detection tests, liver function test,
and renal function test)
Second line of treatment:
 Culture results from suitable
 The second lines of treatment are
specimens.
used for severe, localized,
 Histological findings. immunosuppressed patients and
patients who respond poorly to
 Always continue the treatment for
primary line of treatment. Drugs
2 weeks after resolution of the
mainly used in second line of
lesions. When the topical therapy
treatment are:
fails then one has to start systemic
1. Ketoconazole
therapy because failure of drug
response is the initial sign of
2. Fluconazole
underlying systemic disease.
Follow-up appointment after 3 to 3. Itraconazole
7 days is important to check the
 Drug Interactions and Adverse
effect of drugs. Main Goals of
Effect :[20]
treatment are :
- Warfarin
 To identify & eliminate possible
contributory factors - Interaction with fluconazole,
ketoconazole, itraconazole
 To prevent systemic dissemination
- Increase blood levels and risk
of bleeding
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