ANTIFUNGAL AGENTS презентация

Fungi Very large and diverse group of microorganisms Broken down into yeast and molds Yeast is single cell organism, useful for baking and alcohol beverages Molds are multicellular, characterized by long,

Слайд 1ANTIFUNGAL AGENTS

Dr. Igor Khalin


Слайд 2Fungi
Very large and diverse group of microorganisms
Broken down into yeast and

molds
Yeast is single cell organism, useful for baking and alcohol beverages
Molds are multicellular, characterized by long, branching filaments called hyphae


Слайд 3FUNGAL INFECTIONS
Yeast infections
Candida species
Cryptococcus neoformats
Moulds (filamentous fungi)
Aspergillus sp.
Dermatophytes
Trichophyton
Microsporum


Слайд 4Infection disease caused by fungi called mycoses
Major Types of Mycoses
superficial
cutaneous


subcutaneous
systemic
opportunistic
Symptoms vary from cosmetic to life threatening


Слайд 5 Antifungal agents
Drugs used to treat fungal infection

Systemic: amphotericin B, fluconazole,

ketoconazole, itraconazole, caspofungin


Topical: terbinafine, clotrimazole, grizeofulvin, nistatin

Слайд 6Antifungal agents
Polyene antibiotics
Nystatin
Amphotericin B
Imidazoles and triazoles* =AZOLES
Ketoconazole Fluconazole *
Clotrimazole Itraconazole*
Mebendazole


Allylamines
Terbinafine
Echinocandins
Caspofungin


Слайд 7 Mechanism of action


Слайд 8Amphotericin B
Pharmacokinetics

is an amphoteric polyene macrolide
is insoluble in water
is poorly

absorbed from the GIT
more than 90% bound by serum proteins




Слайд 9Amphotericin B
Mechanism of action
Binds to sterols in the cell membrane lining
Allow

to K+ and Mg2+ to leak out, altering fungal cell metabolism
Result fungal cell death




Слайд 10Amphotericin B
A-Aspergillus
B-Blastomyces
C-Coccoides
C-Candida
C-Can not cross BBB
INTRATHECALLY
FLUCONAZOLE


Слайд 11Amphotericin B
Adverse effects
“Shake and bake” (fever, chills), headache, tachycardia, hypotension, muscle

pain, anemia
Renal toxicity (Mg/K suppl), neural toxicity (seizures, parestesias)



Слайд 13 Flucytosine (5-FC)
Synthetic pyrimidine, used in combination with

amphotericin B
Amphotericin B increases cell permeability
5-FC forms false nucleotide
Disrupts nucleic acid and protein synthesis
Bone marrow depression, dyspepsia, hepatic dysfunction



Слайд 14Ketoconazole
Mechanism of action
Inhibits an enzyme, resulting in cell wall leaking
Blocks demethylation of lanosterol

to ergosterol
Leads to altered cell membrane (unstable)
Result: fungal cell death
Spectrum
Both topical and oral forms used for wide spectrum mycoses


Слайд 15Ketoconazole
Drug interactions
Inhibits CYP450
Adverse effects
Alters synthesis of gonadal and adrenal steroid

hormones
Allergy
Dyspepsia
Anorexia
Gynecomastia
Impotence
Menstrual irregularities

Слайд 16Caspofungin
Belongs to Echinocandis
Inhibits β(1,3)-D-glucan synthesis destroying cell wall, resulting in lysis

and cell death
Effective mostly against Aspergillus and Candida
Second line drug
Fever, rush, nausea and phlebitis are common adverse reactions


Слайд 17Terbinafine
Oral form is essential for the treatment of onychomycoses
Cream of solution

useful for skin infection


Слайд 18Mechanism of action
Terbinafine inhibits squalene epoxidase of the fungi, which leads

to decreasing of ergosterol synthesis


Слайд 19Terbinafine
Has fungicidal action, mostly active against Trychophyton
Half life from 200 to

400 hours
Adverse effects
Dyspepsia
Rash
Neutropenia
Hepatotoxicity
Visual disturbances


Слайд 20Griseofulvin
Is fungistatic and used for dermatophytosis
Causes disruption of the mitotic spindle,

inhibiting mitosis
Induces hepatic CYP450 activity
Unwanted effects
Dyspepsia
Fatigue
Allergy


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