Antifungal
Antifungal
Antifungal
CLASSIFICATION:
1. Antibiotics
A. Polyenes:AmphotericinB (AMB),Nystatin, Hamycin, Natamycin (Pimaricin)
B. Heterocyclic benzofuran: Griseofulvin
2. Antimetabolite : Flucytosine (5-FC)
3 Azoles
A. lmidazoles (topical): Clotrimazole, Econazole, Miconazole, Oxiconazole
(systemic): Ketoconazole
B. Triazoles (systemic): Fluconazole, Itraconazole, Voriconazole
4. Allylamine : Terbinafine
5. Other topical agents: Tolnaftate, Undecylenic acid, Benzoic acid, Quiniodochlor, Ciclopirox olamine,
Butenafine, Sod. thiosulfate.
POLYENE ANTI BIOTICS : The name polyene is derived from their highly double-bonded structure.
Adverse effects:
Acute reaction: – Chills, fever, headache, pain all over, nausea, vomiting, dyspnoea lasting 2-5 hrs because of
release of IL & TNF – can be treated with hydrocortisone 0.6mg/kg
Long term toxicity: – Nephrotoxicity: Azotemia, Hypokalemia, acidosis, Anemia, Hepatotoxicity .
CNS toxicity : intrathecal administration, headache, vomiting, nerve palsies
Uses: Amphotericin B can be applied topically for oral, vaginal and cutaneous candidiasis and otomycosis.
Due to its toxic effects replaced by azoles.
Leishmaniasis: AMB is the most effective drug for resistant cases of kala azar and mucocutaneous
leishmaniasis
PREPARATIONS:
(a) Amphotericin B lipid complex (ABLC)
(b) Amphotericin B colloidal dispersion (ABCD).
(c) Liposomal amphotericin B
NATAMYCIN:
Similar to nystatin, broad spectrum
Used topically 1%, 3% ointment in Fusarium solani keratitis, trichomonas & monilial vaginitis
Mechanism of action: – Griseofulvin interacts with polymerized microtubules and disrupts the mitotic
spindles thus arresting fungal mitosis
Pharmacokinetics: – Oral administration, irregular absorption, increased by fatty food and microfine particles
Gets conc in keratinized tissue , Metabolized in liver, excreted in urine,t1/2=24 hrs.
ADVERSE EFFECTS : – Headache ,GIT disturbances , CNS symptoms: confusion, fatigue, vertigo,
Peripheral neuritis , Rashes, photoallergy , leukopenia, albuminuria
USE : – Systemically only for dermatophytosis, ineffective topically. Duration of treatment depends on site,
thickness of keratin and turnover of keratin.Treatment must be continued till infected tissue is completely
replaced by normal Skin,hair, nail.
➢ Dose: 125-250 mg QID
Duration of treatment:
➢ Body skin = 3 weeks
➢ Palm, soles = 4- 6 weeks
➢ Finger nails = 4- 6months
➢ Toe nails = 8 – 12 months
➢ Griseofulvin should be reserved for nail hair or larger body surface involvement
AZOLES
These are presently the most extensively used antifungal drugs.
The imidazoles and triazoles have broadspectrum antifungal activity covering dermatophytes, Candida, other
fungi involved in deep mycosis (except mucor), Nocardia, some grampositive and anaerobic bacteria, e.g.
Staph. aureus, Strep. faecalis and Leishmania.
TRIAZOLES:
CLOTRIMAZOLE: It is effective in the topical treatment of tinea infections like ringworm.
➢ Athletes foot, otomycosis and oral/ cutaneous vaginal candidiasis.
➢ It is well tolerated.
➢ Local irritation with stinging and burning sensation occurs in some.
➢ No systemic toxicity is seen after topical use.
KETOCONAZOLE
First orally effective broad-spectrum antifungal
Effective against: Dermatophytosis, Deep mycosis, Candidiasis
Effective orally, acidic environment favours absorption
Adverse effects:
➢ Nausea, vomiting, anorexia
➢ Headache, paresthesia, alopecia
➢ reduced steroid, testosterone & estrogen synthesis – Gynaecomastia, oligospermia , loss of libido &
impotence in males – Menstrual irregularities & amenorrhoea in females•
➢ Elevation of liver enzymes
➢ Hypersensitivity reaction - skin rashes, itching
FLUCONAZOLE
➢ Newer water soluble triazole .
➢ Broad spectrum antifungal activity : Candida, cryptococcosis, coccidiodomycosis, Dermatophytosis,
Blastomycosis, Histoplasmosis, Sporotrichosis
➢ Not effective against aspergillosis & mucormycosis.
Adverse effects : GIT upset, Headache, alopecia, skin rashes, hepatic necrosis,Teratogenic effect
Uses: vaginal candidiasis, Oral candidiasis, Tinea infections & cutaneous candidiasis, systemic fungal
infections, candidiasis, cryptococcal, coccidiodal meningitis Meningitis
Eye drops for fungal keratitis.
ITRACONAZOLE
Broadest spectrum of activity also against aspergillus
Fungistatic but effective in immunocompromised
Does not inhibit steroid hormone synthesis and no serious hepatoxicity
Use : Paracoccidomycosis Chromoblastomycosis, Histoplasmosis, Blastomycosis, Esophageal, oropharyngeal
& vaginal candidiasis.
TERBINAFINE
Orally & topically effective drug against candida & dermatophytes
Fungicidal : shorter courses of therapy required . Negligible effect on CYP450
Adverse effects: Nausea , vomiting , Diarrhoea, Taste disturbances
Topical: erythema , itching , dryness , urticaria, rashes.
Uses: Dermatophytosis, Onychomycosis, Candidiasis
TOLNAFTATE: Tinea, cruris, corporis, 1- 3 weeks treatment.
Not effective in hyperkeratinized lesions
Salicylic acid aids its effect by keratolysis
CICLOPIROX OLAMINE: Tinea infections, pitryasis versicolor ,dermal candidiasis, vaginal candidiasis
Penetrates superficial layers
Acts by inhibiting membrane uptake of precursors of macromolecules needed for fungal growth.
BENZOIC ACID: Used in combination with salicylic acid – Whitfields ointment: ( benzoic acid 6% +
salicyclic acid 3 %) – Salicyclic acid due to its keratolytic action helps to remove infected tissue & promotes
penetration of benzoic acid in fungal infected lesion
Adverse events: irritation & burning sensation (Ring cutter ointment)
BUTENAFINE :It is a benzylamine congener of terbinafine with the same mechanism of action.