28 - 188 - ANTIFUNGALS Flashcards
systemic antifungals are indicated in what?
onychomycosis and tinea capitis
the main target of both systemic and topical antifungals
Ergosterol - which is the fundamental mycotic cell membrane sterol
what are the 3 main antifungal categories targeting ergosterol?
(1) allylamines and benzylamines,
(2) azoles (imidazole and triazoles), and
(3) polyenes.
examples of allylamines
Terbinafine
Naftifine
What is the first line of treatment of dermatophytosis?
Terbinafine
MOA of Terbinafine
inhibits squalene epoxidase enzyme leading to accumulation of squalene (fungicidal) and deficiency of ergosterol (fungistatic)
the only FDA approved drugs for the treatment of tinea capitis in children
Terbinafine and griseofulvin
terbinafine is **less effective **than griseofulvin in eradicating ectothrix tinea capitis in the pediatric population, particularly, that caused by Microsporum canis and Trichophyton tonsurans, because of its high tendency to accumulate in sebum
mechanism of action of azoles
inhibition of lanosterol demethylase enzyme (14α-demethylase), a fungal cytochrome P450 (CYP)–dependent enzyme that catalyzes the conversion step of lanosterol into ergosterol, thereby blocking the biosynthesis of ergosterol.
considered the best choice in treatment of Candida and nondermatophyte onychomycosis
Itraconazole
the only FDA-approved treatment for pediatric onychomycosis,
Griseofulvin
mainstay treatment of tinea capitis and onychomycosis
Systemic antifungals
Overall, this structure is the main target of both systemic and topical antifungals
ergosterol
the fundamental mycotic cell membrane sterol
3 main antifungal categories targeting ergosterol
(1) allylamines and benzylamines,
(2) azoles (imidazole and triazoles), and
(3) polyenes
- allylamines, benzylamines, and azoles block the biosynthesis of ergosterol,
- polyenes bind the molecule with high affinity, creating cell membrane pores
this class of antifungal exhibit superior activity against yeasts compared to allylamines
azoles
but less activity against dermatophytes
examples of ALLYLAMINES
terbinafine and naftifine
are allylamines fungistatic or fungicidal against Candida and dermatophytes?
Candida species (fungistatic),
dermatophytes (fungicidal)
They act through the suppression of ergosterol synthesis by** inhibiting the action of squalene epoxidase enzyme, **the enzyme that catalyzes the conversion of squalene precursors into ergosterol.
ALLYLAMINES
terbinafine and naftifine
what is responsible for the fungistatic and fungicidal effects of allylamines?
The resultant deficiency of ergosterol is responsible for the fungistatic effect, while the buildup of squalene accounts for fungicidal activity
In addition to its antifungal activity, this allylamine has antibacterial activity (gram-positive and gram-negative) as well as antiinflammatory properties secondary to its ability to suppress the synthesis of leukotrienes and prostaglandins
naftifine
first line treatment of dermatophytosis
terbinafine
how do you give oral terbinafine for tinea unguium?
how long should you give terbinafine in tinea unguium of the fingernails?
6 weeks
how long should you give terbinafine in tinea unguium of the toenails?
9 - 12 weeks
how do you give oral fluconazole in onychomycosis?
150-300 mg/wk
Fingernail for 6-9 mo
Toenail for 9-15 mo
how long do you give oral fluconazole in onychomycosis of the fingernails?
6 - 9 months
how long do you give oral fluconazole in onychomycosis of the toenails?
9 - 15 months
how do you give oral itraconazole in onychomycosis?
Continuous: **200 mg/d **
Fingernail for 6 wk
Toenail for 12 wk
Pulse:** 400 mg/d for 1 wk/mo **
Fingernail 2 pulses
Toenail 3 pulses
unique side effect of terbinafine
altered taste
most common terbinafine adverse effects
Minimal GI tract upset (eg, abdominal pain, nausea, vomiting, diarrhea), appetite changes, and weight gain
the only available antifungal derivative of benzylamine
Butenafine
subclassifications of azoles
- imidazoles
- triazoles
Examples of Imidazoles
ketoconazole, butoconazole, clotrimazole, econazole, luliconazole, miconazole, and sertaconazole,
examples of triazoles
fluconazole, itraconazole, efinaconazole, and isavuconazole
azoles inhibit what enzyme?
lanosterol demethylase enzyme (14α-demethylase)
The only category D antifungal
amorolfine
the prescription of oral preparations of this antifungal has now been markedly restricted by the FDA and other health organizations due to drug interaction and serious side effects on the liver and adrenal glands.
Ketoconazole
how do you use ketoconazole shampoo in pityriasis versicolor and scalp seborrheic dermatitis
- PV: once daily (left for 5-10 minutes) for 1 to 4 weeks and once weekly for prophylaxis
- Scalp seborrheic dermatitis: twice a week for 4 weeks
difference of imidazoles and triazoles
Imidazoles have 2-ring nitrogen atoms, whereas triazoles contain 3 and are less prone to metabolic degradation.
Fluconazole is efficacious against all Candida except?
C. krusei
considered the best choice in treatment of Candida and nondermatophyte onychomycosis
Itraconazole
Elderly patients on itraconazole often experience a triad of?
edema, hypertension, and hyperkalemia
topical polyene derived from Streptomyces spp
Nystatin
- has both **fungistatic and fungicidal **activity.
- It acts through binding to the mycotic ergosterol, for which its affinity is higher than that of the cholesterol found in mammalian cells.
- This binding will result in **creation of pores in the cell membrane **with subsequent leakage of essential fungal intracellular components, resulting in cell death
Nystatin
- exhibits broad-spectrum fungicidal and fungistatic, antibacterial, and antiinflammatory activities.
- It acts through the inhibition of the transmembrane uptake of RNA, DNA, and protein precursors.
Ciclopirox
- novel oxaborole antifungal drug that encloses a fluorine atom, decreasing the pH of the boronic center, which inhibits fungal peptide synthesis
- acts through inhibiting a new target, aminoacyl transfer RNA synthetase (AARS), for which its affinity is a thousand times that of the mammalian cell and thereby selectively inhibits the mycotic protein synthesis
Tavaborole
binds tubulin- and microtubule-associated proteins (MAPs) along the polymerized microtubules, suppressing the formation of the mitotic spindle at the G2/M phase of the cell cycle
Griseofulvin
remains the first line of treatment for tinea capitis caused by Microsporum species owing to its higher efficacy compared to terbinafine, and similar efficiency yet lower cost compared to itraconazole and fluconazole
Griseofulvin
the only FDA-approved treatment for pediatric onychomycosis, though its efficacy is limited to dermatophytes only
Griseofulvin
