A REVIEW ON CANDIDIASIS: TYPES AND MEDICATIONS

ABOUT AUTHORS:
V. Sravanthi*¹, Mayure vijay kumar¹, Donthineni Kalyan², C.P.Meher¹, G.J.Finny^1
1Department of pharmaceutical chemistry, Maheshwara College of Pharmacy
²Department of Pharmaceutical Analysis, Saraswathi College of Pharmaceutical Sciences.
Isnapur chitkul ‘X’ road, Patancheru, Hyderabad-502307
*v.sravanthi27@gmail.com

ABSTRACT:
Candida albicans are the most effective organism that makes quite an yeast infection to form a inflammation in the different parts of the body like oral, vaginal, hepatic, renal etc…, During the infection of Candidiasis there are less chances of human death can occur, but in patient with damaged immune systems there is a chance of death, but to the Candidiasis flow to the blood streams and kills. In this review the full outline of the Candidiasis and the types and medication are put forth to be aware on the diseases caused by Candidiasis. According to FDA approval, the Ketoconazole is the first-line drug used for the treatment of the different types of Candidiasis.

INTRODUCTION:
The following are the two types of Candidiasis that are spreading in the current disease conditions.

I) MUCOSAL CANDIDIASIS:
Opportunistic pathogens of the genus Candida is named as Mucosal candidiasis. Were it can be discussed as in two name mucosal and disseminated candidiasis¹. According to oral, oesophageal or vaginal infections, is common in HIV/AIDS Mucosal candidiasis which varies from 7-93% infection². The disseminated candidiasis named as a remarkably uncommon in AIDS. due to relatively adequate neutrophil function in most HIV-infected individuals.

RISK FACTORS: Neutropaenia, Parenteral nutrition, Abdominal surgery, Broad spectrum antibiotics, Cancer and corticosteroid use^3,4

The following are the types of candidiasis that are related to the mucosal candidiasis:
Oropharyngeal Candidiasis:
The fungal infection of Candida species  of mycosisca uses the oral candidiasis. In the presence of Candida albicans were the half the population are caused by these candidiasis⁵.

Pseudomembranous Candidiasis:
It is also a class of oral candidiasis referred as trush. Around 35% of candidiasis are come across these category. Sometimes there will be an occurance of bleeding beneath the mucosa as named as "curdled milk", the location of pseudomembranous candidiasis occurs on the tongue, buccal mucosae or palate⁶.

The following are the cases that come under pseudo membranous Candidiasis:

Vaginal candidiasis	Vaginal candidiasis is an infection of the vagina involving overgrowth of a yeast, or fungus, known as Candida.Over one million women are suffering with this type of candidiasis
Oral candidiasis	Oral candidiasis known as thrush, causes white, curd-like patches in the mouth or throat
Deep organ candidiasis	Candidiasis is a serious systemic infection that can affect the esophagus, heart, blood, liver, spleen, kidneys, eyes, and skin.

Erythematous Candidiasis:
The type of candidiasis which appears as a red, raw-looking lesion is assayed as Erythematous (atrophic) candidiasis. Sub-types of Erythematous candidiasis are denture-related stomatitis, angular stomatitis, median rhombiod glossitis, and antiobiotic-induced stomatitis⁷. Two types of candidiasis can be studied as:
The candidiasis occuried in the dorsum of the tongue in persons taking long term corticosteroids or antibiotics is called as Acute erythematous candidiasis. This is usually termed "antibiotic sore mouth", "antibiotic sore tongue",⁸ or "antibiotic induced stomatitis" because it is commonly painful as well as red. Chronic erythematous candidiasis is more usually associated with denture wearing (see denture-related stomatitis).

Hyperplastic Candidiasis:
According to candidiasis, it is formation of white patch on⁹ the commissures of the oral mucosa were behaved as variant of oral candidosis. The major etiologic agent of the disease is the oral fungal pathogen Candida predominantly belonging to Candida albicans, although other systemic co-factors, such as vitamin deficiency and generalized immune suppression. Lesions are the major formation in this type of candidiasis, if untreated it demonstrate dysplasia and develop into carcinomas, all this conditions are occurred in the Chronic hyperplastic candidosis/candidiasis. According to cernea et al, many oral leukoplakias are associated with Candida infections¹⁰. chronic mucocutaneous candidal lesions, encountered in patients with endocrine and immune defects, and affecting the skin and other mucosae, were also described by some as chronic hyperplastic candidosis. The Group I lesions consist of the classic triad—pseudomembranous, erythematous, and hyperplastic variants¹¹.

Denture Related Stomatitis:
Denture sore mouth/ chronic atrophic candidiasis/ denture-associated erythematous stomatitis is a common condition where mild inflammation and redness of the oral mucous membrane occurs beneath a denture. common form of oral candidiasis (a yeast infection of the mouth). It is more common in elderly people. The following are the types of Denture related stomatitis^12-15:

· Type 1 - Localized inflammation or pinpoint hyperemia.
· Type 2 - More diffuse erythema (redness) involving part or all of the mucosa which is covered by the denture.
· Type 3 - Inflammatory nodular/papillary hyperplasia usually on the central hard palate and the alveolar ridge.

Angular Stomatitis:
Inflammation of the corners of the lips is termed angular stomatitis or angular cheilitis.
· Children = repeated lip-licking.
· Adults = iron deficiency anemia, or vitamin B deficiencies
· Areas: jaws

According to this type of candidiasis, the skin folds around the angle of the mouth which are kept moist by saliva, which in turn favours infection; mostly by Candida albicans or similar species¹⁶.  Medications: nystatin, etc;

Median Rhomboid Glossitis:
Central papillary atrophy is the other name of Median rhomboid glossitis here condition characterized by an area of redness and loss of lingual papillae. Area: dorsum of the tongue, circumvallate papillae^17-19

Candidal Vulvovaginitis(CV):
It Is the another type of candidiasis caused by candida albicans which causes infection to the vaginal mucosa membranes. Disease can be identified by vaginal itching or pain, burning with urination etc., it is also known as Vaginal thrush. The main reason to cause Candidal vulvovaginitis was hormonal imbalance. clotrimazole and fluconazole are used in the severe treatments^20-23.

75%= Affected by CV
5% = Recurring episodes

Candidal Balanitis: Inflammation in the Glans refer to the Candidial Balanitis, 

RISK FACTORS:
· Uncircumcised penis
· Antibiotic use
· Corticosteroid use
· Immunocompromised
· Poorly controlled diabetes

DRUGS: Clotrimazole, Miconazole, Anticoagulants^24-26.

Esophageal Candidiasis (Candid esophagitis):
It is an esophagus inflammation, caused by immune compromised states, also called as monilial esophagitis.^27,28

DRUGS: nystatin, itraconazole, caspofungin, amphotericin etc…,

Candidal Intertrigo:
Inflammation between intertriginous folds of adjacent skin is known as Candidal intertrigo. Intertrigo is also a known symptom of vitamin B6 deficiency²⁹.
DRUGS: fluconazole, griseofulvin, and nystatin.

Candidal Paronychia:
Infection of nails and skin are known as candidal paronychia.
Sudden infection =  Acute paronychia
Gradual infection =  Chronic paronychia^30-32
DRUGS: clindamycin or cephalexin

Perianal Candidiasis:
It is the another type of skin infection present as pruritus anicaused by Candida albicansand named as Perianal candidiasis.³³

Chronic Mucocutaneous Candidiasis:
An immune disorder of T cellsis Chronic mucocutaneous candidiasis. It is caused by also other type of infection called human papilloma virus³⁴.

Congenital Cutaneous Candidiasis: Also known as Beck-Ibrahim disease, occurs in newborn babies caused by premature rupture of membranes³⁵

Erosio Interdigitalis Blastomycetica: Infection extends on the sides of fingers³⁶.

Onychomycosis :Nail infection, "tinea unguium.
This condition may affect toenails or fingernails, 10% of the adult population are suffered with Onychomycosis³⁷

Distal subungual onychomycosis= Tinea unguium
White superficial onychomycosis=  10 percent of onychomycosis
Proximal subungual onychomycosis=  Tinea unguium
Candidal onychomycosis=  Damage of the nail^38,39

Invasive Candidiasis: Invasive candidiasis is a fungal infection that can occur when Candida yeasts enter the bloodstream.

Genitourinary Tract Candidiasis:
It is common fungal infections which lead to life-threatening invasive to non-life-threatening mucocutaneous diseases. Species involved are Candida spp.,Candida albicans⁴²,
Nongenitourinary candidiasis=          Oropharyngeal manifestations
Genitourinary candidiasis=           Vulvovaginal candidiasis⁴³

Renal Candidiasis:
Upper urinary tract that involves the renal pelvis and medulla related to Primary renal candidiasis. Species involved was Candida pyelonephritis, untreated disease may gradually progress to fungus ball (mycetoma) or abscess formation^44,45.

Candidemia:
Candida albicans and Candida parapsilosis are the two most frequent causes of candidemia in pediatric patients.⁴⁶
DRUGS: fluconazole, an echinocandin, amphotericin B

Hepatosplenic Candidiasis:
It is also called as Chronic disseminated candidiasis. It is occurred in patients with hematologic malignancies.⁴⁷

Candidal Onychomycosis:
Onychomycosis is usually caused by a dermatophyte, infections due to Candida species,

DRUGS: griseofulvin, terbinafine or itraconazole⁴⁸,

Candidal Skin Infections and Paronychia:
Non hematogenous primary skin infections typically occur as intertrigo in skin folds, especially in obese and diabetic patients.
DRUGS:  Azoles and polyenes, clotrimazole, miconazole, and nystatin⁴⁸,

Mammary Candidiasis:
Nipple or breast pain in nursing mothers has been linked to the presence of C. albicans,
DRUGS; nystatin and oral fluconazole⁴⁸

Respiratory Tract Candidiasis:
Respiratory tract of a critically ill patient receiving mechanical ventilation (MV) usually indicates colonization rather than infection of the respiratory tract Candidiasis. Thus, Candida colonization of the respiratory tract may predispose to bacterial ventilator-associated pneumonia (VAP).⁴⁹

MEDICATIONS:
FLUCONAZOLE: Diflucan
Fluconazole inhibits the fungal cytochrome P450 enzyme 14α-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol⁵⁰, Side effects are: oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia⁵¹, etc;

2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol

NYSTATIN:Nyamyc
Nystatin binds to fungal cell membrane. When present in sufficient concentrations, it forms pores in the membrane that lead to K⁺ leakage, acidification, and death of the fungus.⁵²side effects are: Hypersensitivity Reactions, including Stevens-Johnson syndrome in some cases ⁵³Rash, itching, burning

(1S,3R,4R,7R,11R,16R,17R,18S,19E,21E,25E,27E,29E,31E,33R,35S,36R,37S,)-33-](3-amino-3, 6-dideoxy-beta-L-mannopyranosyl)oxy]-1, 3,4,7,9,11,17,31-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexane-36-carboxylic acid.

CLOTRIMAZOLE:Desenex:
Clotrimazole works to kill individual Candida or fungal cells by altering the permeability of the fungal cell wall. It binds tophospholipids in the cell membrane and inhibits the biosynthesis of ergosterol and other sterols required for cell membrane production. This leads to the cell's death⁵⁴side effects are:  itching, nausea, and vomiting.  polyuria, vulvar itching, soreness, edema, or discharge ⁵⁵

1-[(2-Chlorophenyl)(diphenyl)methyl]-1H-imidazole

DIFLUCAN:
Mechanism explains same as Flucanozole, side effects are: Nausea, vomiting, diarrhea, stomach upset/pain, headache, dizziness, or hair loss.⁵⁶

2,4-difluoro-α,α¹-bis(1H-1,2,4-triazol-1-ylmethyl)

MICONAZOLE: Monistat
Inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes, side effects are: hypercholesterolemia. Rash, itching, burning.⁵⁷

RS)-1-(2-(2,4-Dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl)-1H-imidazole

GENTIAN:
It is applied to the skin for treating wounds and cancer. used for digestion problems such as loss of appetite, fullness, intestinal gas, diarrhea, gastritis, heartburn, and vomiting. It is also used for fever, hysteria, andhigh blood pressure. Some people use gentian to prevent muscle spasms, treat parasitic worms, start menstrual periods, and as a germ killer.⁵⁸

4-{bis[4-(dimethylamino)phenyl]methylidene}-N,N-dimethylcyclohexa-2,5-dien-1-iminium

NYSTATIN-TRIAMCINOLONE:
It contains antifungal and a corticosteroid medicine, used for fungus infection like Candida (Monilia), side effects are : unusual/extreme tiredness, weight loss, headache, swellingankles/feet, increased thirst/urination, vision problems.⁵⁹

Ketoconazole:
It is a synthetic, imidazole antifungal medication used primarily to treat fungal infections.  used to treat tinea; cutaneous candidiasis, including candidal paronychia; and pityriasis versicolor) and shampoos (used primarily to treat dandruff—seborrhoeic dermatitis of the scalp)⁶⁰some of the side effects are:  liver damage, adrenal problems,

1-[4-(4-{[(2R,4S)-2-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one

Ciclopirox:
It isa synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. It is most useful against Tinea versicolor.⁶¹ loss of function of certaincatalase and peroxidase enzymes has been implicated as the mechanism of action, as well as various other components of cellular metabolism.

6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one

Econazole:
It is an antifungal medication of the imidazole class. Used to treat skin infections such as athlete's foot, tinea, pityriasis versicolor, ringworm, and jock itch. The most common symptoms were burning, itching, erythema, and one outbreak of a pruritic rash.⁶²

(RS)-1-{2-[(4-Chlorophenyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole

Miconazole nitrate:
Miconazole is used to treat skin infections such as athlete's foot, jock itch, ringworm, and other fungal skin infections (candidiasis). This medication is also used to treat a skin condition known as pityriasis (tinea versicolor), a fungal infection that causes a lightening or darkening of the skin of the neck, chest, arms, or legs. symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.⁶³

\(RS)-1-(2-(2,4-Dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl)-1H-imidazole

Fungoid:
Fungoides is also known as Alibert-Bazin syndrome⁶⁴ or granuloma fungoides, is the most common form of Cutaneous T-cell lymphoma. Treatment options include sunlight exposure, ultraviolet light, topical steroids, chemotherapy, and radiation.

Tolnaftate:
It is a synthetic thiocarbamate used as an anti-fungal agent. Tolnaftate is used to treat fungal conditions such as jock itch, athlete's foot and ringworm.

O-2-naphthyl methyl(3-methylphenyl)thiocarbamate

Triple Dye:
It is an  antiseptic consisting of the aniline dyes gentian violet, brilliant green, and acriflavine that was originally used in the treatment of burns and later as a general bactericide

Terbinafine:
Terbinafine hydrochloride is a synthetic allylamine antifungal . It is highly hydrophobic in nature and tends to accumulate in skin,nails, and fatty tissues. ⁶⁶side effects are: Diarrhea, constipation, nausea, sickness, fullness, abdominal pain, indigestion, dyspepsia, gastritis, cholestasis, flatulence, altered stool colour, abdominal muscular pain. Headaches, dizziness, vertigo, light-headedness, decreased concentration levels, paraesthesia (pins and needles)

[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine

Lamisil AT:
These drugs Relieves itching, burning, cracking, and scaling associated with jock itch, athlete's foot, ringworm, and other fungal infections of the skin. Lamisil AT cream is topical antifungal agent. It works by killing sensitive fungi. Severe allergic reactions(rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); new or worsening skin irritation.

(2E)-N,6,6-Trimethyl-N-(1-naphthylmethyl)-2-hepten-4-yn-1-amine hydrochloride (1:1)

Miconazole-lanolin:
Drugs are used to treat Ringworm of Groin Area, Athlete's Foot, Ringworm of the Body, Fungal Infection of the Skin with Yellow Patches, Skin Infection due to a Candida Yeast. Side effects are: Redness of Skin, Small Skin Blister, Rash, Skin Irritation, Reaction due to an Allergy, Numbness and Tingling.

CONCLUSION:
Thrush is the other name of Candidiasis/Candidosis/Moniliasis/Oidiomycosis, as we know that the Candidiasis is the fungal infection caused by C.albicans. Therefore, there are different type of Candidiasis which are harmful for the humans. Several treatments to be taken on the Candidiasis, amongst the all anti-candidiasis agents, ketaconazole is the first-line drugs. As we discussed in the abstract, I in this review demonstrated the key study of the current disease called as a new era disease as Candidiasis can be elaborated with their types of diseases and treatment by suitable agents.

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REFERENCE ID: PHARMATUTOR-ART-2232

PharmaTutor (ISSN: 2347 - 7881) Volume 2, Issue 9 Received On: 14/06/2014; Accepted On: 25/06/2014; Published On: 01/09/2014 How to cite this article: V Sravanthi, VK Mayure, K Donthineni, CP Meher, GJ Finny; A Review on Candidiasis: Types and Medications; PharmaTutor; 2014; 2(9); 36-45

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