Anti-Fungal Drugs Sush

8/13/2019 Anti-Fungal Drugs Sush

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Anti-Fungal drugs

Dr Sushela Devi

Classify the different antifungals based on their

mechanisms of action

Describe the mechanism of action of antifungalsRelate the importance of antifungals to diabetic patients

Summarise the principles of antifungal treatment


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Relevance of antifungals in diabetesImmunologic research has demonstrated several defects in hostimmune defense mechanisms in diabetic subjects.

Several PMN defects occur in diabetic subjects: impaired migration,

phagocytosis

intracellular killing

anatomically specific factors may contribute to an increasedinfection risk.

Examples

Macrovascular disease and microvascular dysfunction may resultin compromised local circulation leading to delayed response to

infection Unawareness of lower extremity trauma due to sensory

neuropathy may result in inadequate attention to minor woundsand subsequent increased infection

Incomplete bladder emptying due to autonomic neuropathy

permits urinary colonization by microorganisms


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Infections in diabetic patients

Genitourinary infections

Foot and lower extremity infections

Respiratory infections-diabetics are morelikely to be hospitalised for pneumoniathan

non-diabetics

A higher risk for TB Group B streptococcal infections

Fungal infections


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Fungal infections

Athletes foot

Jock itch

Onychomycosis (nail infections)

Thrush

Pityriasis versicolor- This fungal infection causes lightskinnedpeople to have dark spots on their skin. Darkskinnedindividuals will find light patches on their skin.

Mucormycosis- frequently involves the sinuses, thebrain and the lungs. If left untreated can be lifethreatening.


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Classification of antifungals based on their

mechanism of action

Agent

Polyene antibiotics

Azoles

Terbinafine

Griseofulvin

Flucytosine

Mechanism of action

Disruption of fungal cell

membrane

Inhibition of mitosis

Inhibition of DNA synthesis


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Polyene antibioitics Nystatin- no injectable formulations of the drug. It may be

used orally or topically due to its minimal absorption across

the mucous membranes

Amphotericin B-antifungal and an anti-protozoan. Can be

used to treat visceral leishmaniasis.

Azoles

Antifungal:

Antibacterial:

Antiprotozoal:

Anthelminthic


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Antifungal azolesImidazoles Triazoles

Ketoconazole Fluconozole

Miconozole Itraconazole

Clotrimazole

Fungal infections

Superfical fungal infections

Affects the skinand mucous membranes

Systemicfungal infections

Affects deeper tissues eg. heart, brain

Drugs for superficial fungal infections

Nystatin

Amphotericin Azoles

Terbinafine Griseofulvin


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Topical antifungal drugs/medicines

Nystatin

Only for candidiasis

Onlyfor topical use

Skin

Mouth and intestines

Vaginal candidiasis

Amphotericin: new topical

preparations available


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Topical antifungal drugs/medicinesAzoles For dermatophytes-microspora, ep-dermophyton, trichophyton

(Tinea/ringworm) Tinea versicolor

Candidiasis--- 7 taginal typesvaginal thrust

Topical antifungal drugs Whitfields ointment

for dermatophytes

Composition Salicylic acid 3%

Benzoic acid 6%

Emulsifying ointment 91%


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Case history 55-year old male diabetic with nosocomial urinary tract infection was

treated with antibiotics. He presented with severe throat pain a week after

treatment.Reflect on what you would do in this case?---oral thrust


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Mechanism of action:

polyene antibiotics

The drug binds to ergosterol, specific to fungal

membranes, and

changes the membrane permeability, ----form spores in

ergpdterol ,this leads to

leakage of ions and enzymes from fungal cells

Causes cell death of fungi

Ergosterol is not found in mamalian cell

membranes


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Topical antifungal drugs:

Nystatin

Preparations (dosage forms) Mouth washes

Mouth paints

Oral tablets/lozenges

Creams

Vaginal pessaries

Amphotericin: lozenges

Side effects Nausea

Vomiting

Diarrhoea

Severe skin rashes

Mild gastrointestinaldisturbances


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Fungal infections:

dermatophytes (ringworm, tinea)

Tinea coporis---on body

Tinea capitison scalp

Tinea pedis (athletes foot)

Tinea unguiumfinger/hand


15/31 scalp


16/31On UV light, shiny scalp with ringworm


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18/31Athlete foot


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i l if l d A l


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Topical antifungal drugs:AzolesPreparations

Creams

Ointments Dusting powders

Shampoos

Mechanism of action:Azoles Interferes with fungal oxidative enzymes causing lethal

accumulation of hydrogenperoxide,also

Reduced formation of ergosterol (nescessary for theformation of the fungal wall)

Damage the fungal membrane by inhibiting ademethylase enzyme.responsible for formation ofergosterol


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Drugs for systemic fungal infections

Amphotericin B

Ketoconazole

Fluconozole(for Candida albicans)

preventresistance

Itraconazole

Voriconazole (broad spectrum) Flucytosine (often given in combination with

amphotericin B)


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Amphotericin B

The drug of choice for most systemic fungalinfections

Has many side effects

Fever, chills

Anorexia, nausea, vomiting

Renal impairment

Hypokalaemia

The toxic effects may have to be identified andtreatedin life threatening infections.

Lipid formulationsless toxic(expensive)


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Ketoconazole Metabolised in the liver, excreted in the bile Azoles are toxic to liver It is a hepaticmicrosomal enzyme inhibitor, Inhibits metabolism of warfarin, phenytoin sodium and

cyclosporinCauses above drug toxicity if given concurrently

Oral preparation should not beused for superficialfungal

infections Oral formis contraindicated in pregnancy & breast feeding

Fluconozole

Well absorbed after oral administration

Good penetration into CSF

Effective in fungal meningitis (IV)caused bystreptococcus neoformans, capsulated yeast

Hepatotoxicity is less


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Itraconazole Improved absorption with food, reduced absorption with fatty meals

Risk of Liver damage

Caution in heart failure with prolonged use or IV use

Griseofulvin:mechanism of actiontreat ringworm, x kill fungi

Dermatophytesspecifically infect keratinous tissues

Griseofulvin binds to keratinas it is being formed in the cells of the nail

bed, hair follicles and skin

Preventsinfection of new keratin

Does notkill already established fungi

Causes liver enzyme induction

Contraindicated in pregnancy avoid pregnancy for one month after treatment.

Men should not father children within 6months of treatment

Prolonged treatment is necessary until infected keratin is shed.


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Griseofulvin

Given orally better absorbed with fatty food

Only effective dosage form is oral tablets


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Terbinafine

A New drug for superficial dermatophyteinfections

Dosage forms:

1. Topical preparations

2. Oral tablets

Side effects: liver toxicity,

Skin rashes, blood dyscrasias


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Griseofulvin and Terbinafine

Effective onlyfor superficial dermatophyte infections

Not effective in

Superficial candidiasis

Tinea versicolor

Systemic fungal infections


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Factors predisposing to fungal

infections

Diabetesmellitus

Use of broad spectrum antibiotics, cytotoxics (anti

cancer drugs)

Immune deficiency-congenital, acquired, drug induced(steroids), due to malignancy

Repeated trauma,foreign bodies, IV lines

Prolongedimmersion in water

Infancy, old age, pregnancy


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Principles of antifungal treatment

Drugs used depend on the type of infection

Superficial? or deep?

If superficial infection:

topical therapysufficient or

oral therapyis required?

Do not use oral drugs for trivial (minor)infections

Look for risk factorsand correct


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Principles of antifungal treatment ctd..

Look for an animal sourcefor dermatophyte

infections

Toxicity is lesswith topicalazoles

Azolesare toxic to liverwhen given orally, monitorliver functions

Prolonged treatmentis necessary for infections

affecting the stratum corneum.

Most systemic antifungals; caution in prgnancy.

Avoid, unless benefit outweighs the risks


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Thank you for listening

Hope you enjoyed the lecture

Anti-Fungal Drugs Sush

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