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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
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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