Anti-Fungals Flashcards
Fungi are eukaryotes with rigid cell walls containing
Chitin and polysaccharide
Antifungals attack this vital fungal membrane component inhibiting synthesis or binding to its pores
Ergosterol
Given for serious systemic infections
Amphotericin B (IV) Itraconazole (PO)
Given to less serious fungal infection
Azoles (PO)
Given for superficial infections
Griseofulvin PO
Nystatin topical
Azole
Naturally occuring
Produced by Streptomyces nodosus
Drug of choice for systemic mycotic infection
Amphotericin B
Binds to ergosterol present in cell membrane disrupting membrane function
Allows electrolytes to leak out from cell resulting in cell death
Amphotericin B
Effective against Candida, Histoplasma, Cryptococcus, Blastomyces, Aspergillus, Coccidiodes
Amphotericin B
Amphotericin B is excreted through
Bile
Amphotericin SE
Hypotension Arrythmia Neurologic effect Nephrotoxic Fever Hypochromic, normocytic anemia
First isolated from a strain of streptomyces noursei
Used for Candida
Administered as an oral agent for treatment of oral candidiasis
Negligibly absorbed from GI tract so adverse effects are rare
Nystatin
Allylamine examples
Naftifine
Terbinafine (Lamisil)
Benzylamine example
Butenafine (Mentax)
Inhibits squalene epoxidase for the synthesis of ergosterol in fungal cell membrane
Accumulation of squalene (a sterol) which is toxic to fungi
Good for nails
SE: headache, GI upset
Terbinafine
Also blocks sterol formation via inhibition of squalene 2,3 epoxidase
Antifungal
Anti inflammatory
Antibacterial
Naftifine
Inhibits sterol synthesis via squalene epoxidase
Butenafine
Obtained from the mold Penicillium griseofulvum
Griseofulvin
Interacts with microtubules within fugus to disrupt the mitotic spindle and inhibit mitosis (arrests cell division in metaphase)
Griseofulvin
Griseofulvin absorption is increased by
fatty acids
Inhibits microtubule function
Griseofulvin
Covers Trichophyton
Microsporum
Epidermophyton
Griseofulvin
Griseofulvin AE
Teratogenic* Hepatotoxic Increases Warfarin metabolism* Headache GI irritation
Similar to 5 FU
Flucytosine
Griseofulvin is an enzyme
inducer
Inhibits thymidylate synthetase
For subcutaneous chronomycoses
Used in combination with Amphotericin B for treatment of systemic mycoses, subcutaneous chronomycoses, and meningitis by Cryptococcus neoformans and Candida* CD4 <100
The combination is
Flucytosine
synergistic
Flucytosine SE
Reversible bone marrow depression
Increased hepatic enzymes
Nausea vomiting diarrhea
Interacts with C14 A Demethylase to block demethylation of lanosterol to ergosterol, the principal sterol in fungal membrane
Alter permeability of fungal cell membrane
Azole
Covers Histoplasma, Candida, Cryptococcus, Blastomycosis, Ketoconazole
Never give with amphotericin B because they
Ketoconazole
will antagonize each other
Ketoconazole AE
Gynecomastia Decreased libido Impotence Menstrual irregularity Milk alkali syndrome
It lacks the endocrinologic effects of ketoconazole
Itraconazole
DOC for subcutaneous chromomycosis (Blastomycosis)
Broad based budding yeast
Itraconazole
Itraconazole AE
Hypokalemia
GI distress
Hypertriglyceridemia
Administered orally and intravenously
Has excellent penetrability into the CSF
Fluconazole
DOC for Cryptococcal meningitis
cryptococcus neoformans
Fluconazole 6 months
Antifungals for superficial infection
Griseofulvin Nystatin Miconazole Clotrimazole Econazole
For subcutaneous and systemic mycoses
Similar to ketoconazole
Ketoconazole
Miconazole
Econazole
Clotramizole
For superficial mycoses
Clotrimazole Miconazole Econazole Griseofulvin Nystatin
Interferes with cell wall synthesis/permeability via inhibition of B 13 D glucan synthesis
Effective against most species of Candida but not Cryptococcus
Echinocandins
capsofungin
micafungin
anidulafungin
Effective in invasive Aspergillosis in patients refractory to or intolerant of other antifungals
Also effective against Candida
Capsofungin
Capsofungin SE
Induration Facial swelling Pruritus Headache Fever Infusion site reactions Nausea Vomiting
Interrupts with active membrane transport of trivalent cations (essential cellular precursor)
Anti-inflammatory
Ciclopirox olamine
Loprox, Penlac
Reversible and noncompetitive inhibitor of squalene epoxidase
Skin infection
Tolnaftate (Tinactin)
Fungistatic
Zinc component in this drug provides astringent component
Unclear MOA
Undecylenic acid (Desenex)
Notorius for arythmia
Amphotericin
Impairs absorption of ketoconazole
Cimetidine
Antacid
Polyene antifungals
Nystatin
Anphotericin B
Griseofulvin
Solid: thyroid, hepatic tumors
Hematologic
Improves survival of C meningitis
Amphotericin B
Flucytosine
+ Fluconazole
Imidazoles
Miconazole
Toconazole
Clotrimazole
Triazole
Itraconazole
Fluconazole
Ketoconazole
Terbinafine SE Blackbox
Tinnitus
Taste disturbance
