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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 are usually more difficult to treat than bacterial infections because fungal organisms grow slowly. Oral , 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 . 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 , corticosteroids, anticancer/immunosuppressant drugs, emergence of AIDS. 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, and . Amphotericin and are polyenes that are not absorbed after oral administration. The imidazoles and triazoles achieve their antifungal action by inhibiting the synthesis of 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, , Denture stomatitis, Clotriamzole, Nystatin.

INTRODUCTION: immunodeficiency syndrome. The perfect fungi causing oral infections are Fungi generally constitute a relatively , Geotrichium and Mucor small, proportion of oral microflora. The species. The imperfect 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. 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 and ) 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 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 that causes severe opportunistic 1. Nystatin: infections in humans.[2] There are three general factors which helps the Candida It is polyene obtained from albicans infection to develop in the noursei. 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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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 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 Nystatin is drug of choice. It is commonly days. Nystatin is formulated for oral use [8] used as topical agent to suppress Candida as suspension or pastille. 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 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 water is used as oral rinse for 3-4 times a Contraindication: Hypersensitivity day for 7-10 day reaction.

Denture stomatitis (chronic atrophic 2. Amphotericin-B: candidiasis): is an antifungal antibiotic 0.2% chlorhexidine solution with produced by Streptomyces nodosus. 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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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 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 like Candidia albicans. Indication:

Indication: Oral thrush (due to Candida albicans): 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, suspension, drops, cream, and Contraindication: Hypersensitivity. lotion. It is applied 2-3 times a day. 4. : 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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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 5. (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 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, . skin irritation, rash, hypersensitivity.

Adverse effect: Prolonged use with high Contraindication: 1st trimester of doses cause leukopenia, pregnancy. thrombocytopenia, and anemia due to 7. : 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 527

Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 Indication:  Systemic : 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. (KTZ):

8. Miconazole: It was first orally effective 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% 528

Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 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 Nausea, vomiting, loss of appetite, children: 3-6 mg/kg BW daily in severe life giddiness, headache, rashes, photophobia, threatening infection in over 1year. 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 . administered intravenously or orally. Adverse effect: Nausea, headache, Trade name: SYSCAN, DIFLUCAN, ZOCON, abdominal . 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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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 Oropharyngeal candidiasis: Oral liquids  , 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. :

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. olamine: pinocembrin, have been considered to be It is newer antifungal agent with high cure responsible for its inhibitory effect on rates. It has good penetration power. Candida. Antifungal activity is one of the 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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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 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 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 gluconate, in the treatment of oral caused by , 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 [16] Lucio Milillo, Lorengo et al had conducted of the tooth surfaces and a bitter taste. 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 Antifungal action of antiseptic and 24 days and Peridex oral rinse containing disinfecting agent: 0.12% chlorhexidine gluconate was used 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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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 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 exfoliative cytology,tissue Clotrimazole which can be taken as is biopsy,antigen or nucleic acid Lozenges and Amphotercin B as oral . [4, 5] detection tests, liver function test, suspension 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 therapy because failure of drug 1. Ketoconazole 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 532

Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 - Monitor INR in patients (3.5 microbiota, possess certain characteristics INR safe) effects that are associated with their pathogenicity in medically and . Drug-disease interactions : immunocompromised hosts of the oral - Prolonged use of systemic fungals candidal infections. Denture, oral hygiene may result in renal or hepatic and management of adverse medical dysfunction conditions should be the primary goal of treatment.This should go hand in hand - Administer fluconazole, with the application of topical antifungal ketoconazole, or itraconazole with agents particularly those in the cream or caution in patients with hepatic gel form for better patient’s compliance. disease or when taking other Candida associated denture stomatitis is hepatotoxic (APAP). the commonest and because of the multifactorial nature of the disease, . Review management is complex. Recent research Summary of Antifungal drugs: Shown in has investigated plaque control, removal Table: 6[10] of dentures at night, the use of antiseptic and antimicrobial agents, antifungals and CONCLUSION: microwave irradiation as factors to Candida species, although constituting consider in the treatment of candida only a minor proportion of the oral associated lesion as: denture stomatitis, candidal leukoplakia and angular chelitis.

4. Prasanna Kumar Rao, Oral REFERENCES: Candidiasis – A Review Scholarly Journal of Medicine, Vol. 2(2) pp. 1. Professor Philip D Marsh BSc, Ph 26-30, February 2012. Salisbury Dr Michael V MartinText book of oral microbiology : 5th 5. K.D tripathi, Essential medical edition ch-9 p 166-78 pharmacology ch-57,5th edition jaypee brothers’ publication 1st 2. Gravina, HG, de Morán, EG, January 1985, p757-767. Zambrano, O, Chourio, ML, de Valero, SR, Robertis, S, Mesa L. Oral 6. Malcolm A.Lynch;Red and white Candidiasis in children and lesions of the oral mucosa;Burkets adolescents with cancer. Oral Medicine Diagnosis and Identification of Candida.spp Med Treatment, 9th Edn: Lippincot Raven Oral Patol Oral Cir Bucal, 2007 12: publishers, 2001:51-120 E419-23. 7. George. A.Zarb, Charles L.Bolender 3. Akpan, A, Morgan, R et al. Oral ;Sequelae caused by wearing candidiasis-Review. Postgrad. complete denture ,12th Edn:Elsevier Med.J.,2002 78:455–459 2004 : 34-50

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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 8. William G. Shafer, Maynard.K.Hine, ulcer pat i e n t s. A double-blind Barnet M.Levy; Physical and placebo-controlled cross-over study. chemical injuries of the oral J Clin Periodontol 1987; 14:267-73. cavity,Text book of oral pathology;11th Edn., Elsevier India 16. Epstein JB. Oral and pharyngeal 1997 : 528-593. candidiasis. Topical agents for management and prevention. 9. Crispan scully , Medical problems in Postgrad Med 1989; 85:257-69. dentistry 6th edition 2010, Elsevier Limited; p 493-495 17. Lal K, Santarpia III RP, Pollock JJ, Renner RP. Assessment of 10. Crispan scully, Text book of oral and antimicrobial treatment of denture maxillofacial medicine ; The basis of stomatitis using an in vivo replica diagnosis and treatment 2nd edition, model system: Therapeutic efficacy Edinburgh London New York Oxford of an oral rinse. J Prosthet Dent Philadelphia St Louis Sydney 1992; 67:72-7. Toronto, Elsevier Limited.2008. 18. Guideline on the clinical evaluation 11. Goodman Gillman: Manual of of antifungal agents for the pharmacology and therapeutics sec treatment and prophylaxis of -8; Chemotherapy of Microbial invasive fungal disease: European diseases. P 800-814. medicines agency 22nd April 2010.

12. Hermínia Marques Capistrano, 19. Pappas, PG, Rex, JH, Sobel, JD, Filler, Eliene Magda de Assis: Brazilian SG, Dismukes, WE, Walsh, TJ, Green Propolis Compared to Edwards, JE (2004). Guidelines for Miconazole Gel in the Treatment of Treatment of CandidiasisCID, Candida-Associated Denture 38:161-89 Stomatitis Evidence-Based Complementary and Alternative 20. Parihar Oral Candidiasis- A Review. Medicine: p: 1-7 Volume 2013. WebmedCentral dentistry, 2011; 2: WMC002498. 13. Babu Cherian, S. Sunil et al Use of Amorolfine in Candida –associated 21. B. C. Webb, C. J. Thomas, M. D. P. denture stomatitis. Oral & Willcox, D. W. S. Harty and K. W. Maxillofacial Pathology Journal [ Knox: Candida associated denture OMPJ ] Vol 1 No 1 Jan- Jun 2010 stomatitis. Aetiology and management: A review. Part 3. 14. DePaola LG, Minah GE, Leupold RL, Treatment of oral c a n d i d o s i s Faraone KL, Elias SA.The effect of Australian Dental Journal antiseptic mouthrinses on oral 1998;43:(4):000-000 microbial flora and denture stomatitis. Clin Prev Dent 1986; 8:3- 22. Najla S.Dar-Odeh Osama A. Abu- 8. Hammad: The role of antifungal drugs in the management of 15. Addy M, Hunter L. The effects of a denture-associated stomatitis; the 0.2% chlorhexidine gluconate international Arabic journal of mouthrinse on plaque, tooth antimicrobial agents, vol-2 (1):2012. staining and Candida in aphthous 534

Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539

TABLES:

TABLE: 1 Classification of Antifungal drugs

ANTIBIOTICS : . Amphotericin B [POLYENE] . Nystatin . Hamycin . Natamycin HETEROCYCLIC BENZOFURAN .

ANTIMETABOLITES . Flucytosine

AZOLES Topical: . Clotrimazole . Econazole . Miconazole Systemic: . Ketoconazole

TRIAZOLES Systemic . Fluconazole . Itraconazole Allylamine . OTHER TOPICAL AGENTS . . . Benzoic acid . Cyclopiroxolamine . Quiniodochlor .

TABLE: 2 Classification of oral candidiasis

Primary oral candidiasis . Acute pseudomembraneous candidiasis (thrush). Acute . Acute-atrophic Candidiasis-Antibiotic sore-mouth.

Chronic a.Chronic-atrophic Candidiasis . Denture-Stomatitis (Denture-sore mouth) . Angular chelitis . Median rhomboid glossitis b.Chronic hyperplastic candidiasis

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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 Secondary oral candidosis . Familial mucocutaneous candidiasis . Oral manifestation of . Diffuse chronic mucocutaneous candidiasis systemic . Familial mucocutaneous candidiasis mucocutanous . Chronic granulomatous disease candidosis . Candidosis endocrinopathy syndrome . Acquired immune deficiency syndrome (AIDS)

TABLE -3 Types of denture sore mouth

TYPE-1 A localized simple inflammation or pin point hyperemia

TYPE-2 A more diffuse erythema involving a part or the entire denture covered mucosa and hard palate TYPE-3 A granular type (papillary hyperplasia) commonly involving the central hard palate and alveolar ridges.

TABLE - 4 Topical Antifungal drugs for the management of oral candidiasis

Drug Brand name Form Dosage Adverse effect Monitoring

Nystatin Nystat Cream and Apply to the affected Negligible ,Mycostatin ointment area 3-4 times/day absorption from (100,000U/g) gastrointestinal tract

Pastille(100,000 Dissolve 1 pastille U/ml slowly after meals 4times/day for 7 days Liver function test Nausea, vomiting, diarrhea, stomach pain, contact Oral Apply after meals for dermatitis. suspension(100, 4times/day for 7 days 000U) and continue use for several days after post clinical healing.

Powder(50milli Sprinkle on tissue on U) contact area of denture.

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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 Troche(200,000 200,000-400,000 U U) 4-5 times/day

Clotriamzole Mycelex, Cream Apply to the affected Abnormal liver Gyne- area for 2-3 function Lotrimin, times/day test,nausea,vomiti Candid for 3-4 week. ng,local mild Liver burning,irritation,s function test Solution 5ml 3- 4times/day for tinging 2week

Troche minimum. 10 mg troche: dissolve slowly over 15–30 minutes

Ketoconazole Nizoral Cream 2% of cream rub Irritation, pruritus, Liver gently into the stinging, function test affected area 1-2 Avoid contact times daily. with eyes.

200-400mg tablet Tablet taken once or twice daily with food for 2 weeks

TABLE -5 Systemic Antifungal drugs for the management of oral candidiasis

Drugs Brand Form Dosage Adverse effect Monitoring name Fluconazole Diflucan Capsules 50-100mg capsules once Liver and daily for 2-3 weeks renal function tests, potassium

Tablet 200mg on day1 then 100mg daily for 7-14 day Headache,nausea,abdominal pain,vomiting,rash, taste perversion, dyspepsia, diarrhea,left ventricular dysfunction,congestive,anap Powder Powder for oral suspension hylactic reaction 10mg/mL

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Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 Itraconazole Sporanox Capsules 100mg capsules taken daily Nausea,edema,hypertension, immediately after meals for2 headache,fever,dizziness,ras weeks. h,pruritus,hyperkalemia Liver ,libido,hepatitis,liver function tests dysfunction ,adrenal after 1 month Solutions 10mg/ml : 100-200mg/10ml supression ,steven-johnson of treatment once a day for 1–2 wk; if syndrome refractory to fluconazole Ketoconazole Nizoral Tablets 200–400 mg/d as single dose Hypersensitivity to azole Liver for 7–14 days drugs ,Pruritus, nausea, function test vomiting, abdominal pain, gynecomastia, headaches, hemolytic anemia, hepatotoxicity, impotence, leukopenia, photophobia, somnolence, thrombocytopenia

TABLE: 6 Summary of Antifungal drugs

Antifungal drugs Dosage and duration (continue for Possible drug interactions and at least 48 hours after lesions have contraindications cleared)

Chlorhexidine 0.12–0.2% mouth rinse twice daily Tooth staining, especially if the patient drinks tea, coffee or red wine Amphotericin 10mg lozenge, 100mg/ml suspension, 10– Topical use – no problems 400 mg 6-hourly for at least 14–21 days Amphotericin 0.5mg/kg for at least 10–14 days Expensive. Nephrotoxicity, arrhythmias, (i.v.) neuropathies, anaphylactoid reactions. Avoid in pregnancy. Liposomal amphotericin may be safer Nystatin 500 000IU lozenge, 100 000IU pastille, Topical use often no problems but may be (topical) 100 000IU per ml of suspension. 100 unpleasant taste, nausea or gastrointestinal 000IU 6 hourly for at least 14–21 days. disturbance. suspension contains sucrose Clotrimazole 10mg 6-hourly for at least 14 days. Difficult to dissolve if mouth dry ( topical) Contains sucrose. Available in INDIA

Miconazole 250mg tablet, 25mg/ml gel. May interact with many drugs, including (topical) 250mg 6-hourly for at least 14–21 days. antidiabetic drugs, anticoagulants, phenytoin, midazolam, cyclosporin, 50mg/g denture lacquer; apply cisapride and terfenadine. Avoid in Weekly for at least 2 weeks. pregnancy, porphyria. May impair oral contraceptive. Even topical agent may be absorbed systemically. Fluconazole 50-200 mg/day for at least 14 days May interact with many drugs, including 538

Bagh T. et al., Int J Dent Health Sci 2014; 1(4):523-539 (oral) antidiabetic drugs, anticoagulants, phenytoin, midazolam, ciclosporin, zidovudine, terfenadine, cisapride. Avoid in pregnancy, porphyria. May sometimes be hepatotoxic and myelosuppressive. Expensive. Avoid in pregnancy, infants, renal disease. Less toxic than ketoconazole Itraconazole 100–200mg/day for at least 14 days. May interact with many drugs, including (oral) 10mg/ml liquid 10ml twice daily for at digoxin, sertindole, anticoagulants, least 14 days. phenytoin, midazolam, ciclosporin, simvastatin, terfenadine, cisapride. Avoid in cardiac disease, pregnancy, and porphyria. Expensive. May impair oral contraceptive Voriconazole 200–400mg/day for at least 14 days. For fluconazole-resistant C. albicans or C. (oral) krusei infections. Contraindicated in cardiac disease, liver disease, and pregnancy. May Prolong QT interval.May cause nausea, neuropathy, rash.Interacts with terfenadine, cisapride and astemizole IV infusion 50mg daily. For fluconazole-resistant C. albicans. Contraindicated in cardiac disease, liver disease, and pregnancy.Adverse effects including anaphylaxis. Interacts with ciclosporin and tacrolimus.

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