Dr. Mrinmayee GhatakDept of Ophthalmology,

K.I.M.S. Hospital,Bangalore (India)

Dr.mrin@gmail.com

Polyenes

1st effective antifungals Bind preferentially to ergosterol in the

fungal plasma membrane > alters membrane permeability > disrupts the fungal cell

Use is restricted due to insolubility, irritation on application and instability

Nystatin

1st polyene antibiotic in 1950 Derived from Streptomyces noursei Affective against Candida infections Topical ointment 100,000 IU, 4-5

times/day Allergic hypersensitivity reactions

Amphotericin B Streptomyces nodosus Insoluble in water, unstable at 37 degree Degrades rapidly is exposed to light Effective against Candida, Aspergillus,

Cryptococcus, Coccidioides, Sporothrix, Blastomycosis, Histoplasma, Mucormycosis

Topical/s.c./intracameral/i.v. Topical – 0.075%-0.3% hourly S.c. 0.8-1.0mg 1-2 doses i.v. 1-1.5mg/kg/day in 5% dextrose over 4 hrs with

pretreatment with hydrosortisone Adverse reactions: anaphylaxis, headache, nausea,

vomoting, fever, nephrotoxicity

Natamycin Only antifungal commercially available for

topical administration Derived from Streptomyces natalenses Most effective against filamentous fungi Also for fusarium, aspergillus and most of

other fungi 5% topical suspension drops 4-6 times/day Adverse reactions: irritation, burning, PEK,

allergic reactions

Imidazoles

1st imidazole was Clotrimazole Inhibition of fungal ergosterol synthesis Interference with mitochondrial oxidative

and peroxisomal enzymes resulting in accumulation of lethal by-products

Affinity for fungal cytochrome P450

Clotrimazole Chlorinated trityl imidazole Borad antifungal activity Specially for aspergillus Also for Candida, fusarium, penicillium,

clasporium and actenomyces 1% eye drops to be used hourly Sckin cream 1% well tolerated by eye Poorly soluble in water Can not be given parenterally Irritation, punctate keratopathy, hepatotoxicity,

diarrhoea

Miconazole Phenethyl imidazole Broad spectrum Causes alteration in fungal cell wall >

induces permeability changes 1% Topical instilled every hourly Sub conj 5-10mg every 48 hrs for 2-3

doses Conjunctival injection, PEE, pruritus,

erythema, local irritation

Econazole

Dichlorimidazole Broad spectrum Low toxicity Interference with membrane sterol

formation 1% ointment and drops 4-6times daily Effective in only superficial infections of

the eye

Ketoconazole Highly effective for treatment of keratomycosis Inhibits ergosterol synthesis More water soluble Enhanced absorption capacity Affective against Candida, Aspergillus, Fusarium Oral: 200-800mg/24hrs single daily dose for a week Topical 1-5% drops Reactions: relatively safe, GIT upset, abnormal LFT,

hypersensitivity Reversible hepatotoxicity Topical well tolerated

Fluconazole 1st antifungal with good pharmacokinetic profile

& relative low side effect Water soluble Exhibits low binding to proteins Most effective against yeasts. Also few dimorphic fungi Most important application : systemic use in

Candida endophthalmitis in combination with Amphotericin B

Oral 200-600mg/day for 3 weeks for candida and 10-12 weeks in cryptococcus infection

Topically 0.3% eye drop every 4hrly

Voriconazole Good bioavailability Good tolerability Good therapeutic concentrations Completely inhibits ergosterol synthesis, more

effectively than fluconazole Commonly used for invasive systemic and ocular

infections specially aspergillosis and candidiasis 200-400mg BD with maintaininace with half dose Transient visual disturbances, fever, rash, vomiting,

headache, abdominal pain, rare but serous hepatotoxicity

Faster and deeper penetration Highly effective in fungal keratitis with

deep abscess Outclasses all other antifungals IV 100ug at conc of 1000ug/ml in

candida endophthalmitis – non-toxic to retina

Itraconazole Well distributed in lipid-rich tissues Lack of intravenous preparation Primarily for aspergillus, histoplasma,

blastomycosis, onychomycosis Moderate for candida & fusarium Orally 200mg BD for a week Topically – to be freshely prepared Subconj is safe GI upset and hypersensitivity

FLUCYTOSINE Fluorinated pyrimidine Effective against Candida, Cryptococcus,

Aspergillus, Clasporium, Penicillium Transported across fungal cell membrane by a

specific permease In cell it is deaminated to fluorouracil that blocks

fungal thymidine synthesis Orally 50-150mg/kg/day divided in 4 doses for a

week Topically 1% drops every hourly Not used alone as poor penetration in certain fungal

cell membranes Topically causes irritation, itching, burning.

Systemically causes nausea, vomiting, diarrhoea

Caspofungin Inhibits 1,3 beta glucan synthase Disrupts the integrity of fungal cell wall Administered IV Effective for invasive aspergillosis,

candidemia Initial dose 70mg iv-infusion followed by

50mg iv daily Relatively low incidence of side effects

including GI disturbances, headache, fever, anemia, hypokalemia, tachycardia, hypersensitivity

SILVER COMPOUNDS

Silver Sulphadiazine Highly effective against Candida,

Aspergillus, Fusarium Topically well tolerated Fungistatic For both superficial and deep infections 1% drops hourly Local irritation, FB sensation, tching

NEWER HORIZONS TERBINAFINE (LAMISIL)

AllylamineBroad spectrum, highly effectiveLow toxicity, high cure ratesPrimary fungicidal action even at low concHighly selective for single fungal enzymeHighly lipophilicMycological cure achieved before clinical cure250mg/day for 2-4 weeksTopical 1% ointmentSystemic side effect include GI upset, skin reactions,

taste disturbances, liver dynfunction, blood disorders.

Topical may cause irritaiton, itching, redness

Caspofungin