Antifungals ALLYLAMINES Flashcards
Griseofulvin is a metabolic derivative of what?
Penicillium Griseofulvum
Griseofulvin is classically used for the treatment of what?
Dermatophytes
Does Griseofulvin have an activity against yeast and molds?
NONE
Is Griseofulvin fungicidal or fungistatic?
FUNGISTATIC
Where does Griseofulvin bind?
It binds tubulin and
microtubule- associated proteins (MAPS) along the polymerized microtubules–> suppressing formation of the mitotic spindle at the G2/M phase of the cell cycle (THIS INHIBITS cell division and forces the cell to undergo apoptosis)
Is Griseofulvin water soluble or insoluble?
it is water insoluble
Does Griseofulvin have a low or a high bioavailability?
LOW
Where does drug absorption happen in griseofulvin?
Duodenum
Better absorption of griseofulvin can occur either when coated with?
Polyethylene glycol or on coadministration with fatty meals
Griseofulvin is characterized by?
Its accumulation in the keratin-producing tissues, where it is adherently bound to the newly formed keratin. Rendering it resistant to fungal penetration
What enzyme is responsible for the accumulation of Griseofulvin in the liver?
6-desmethyl enzyme
How is Griseofulvin eliminated from the body?
Through the kidney in the form of metabolites
Griseofulvin remains the first line of treatment for?
Tinea capitis caused by Microsporum species
Griseofulvin
The cutaneous elimination of the drug is slower than its elimination from plasma, allowing for extended drug activity even after its discontinua- tion.
Griseofulvin
- has higher efficacy compared to terbinafine
- similar efficiency yet lower cost compared to itraconazole and fluconazole
what is the only FDA-approved treatment for pediatric onychomycosis?
Griseofulvin (though its efficacy is limited to dermatophytes only)
What are the allylamines? (TN)
Terbinafine and naftifine
Is terbinafine available in topical or oral or both?
BOTH
Is naftifine available for topical or oral or both?
TOPICAL
Are allylamines fungistatic or fungicidal?
BOTH-
it has antifungal activity against Candida species (fungistatic)
dermatophytes (fungicidal)
What is the mechanism of action of allylamines?
inhibit squalene epoxidase enzyme (responsible for catalyzing squalene precursors into ergosterol)
They act through the suppression of ergosterol synthesis
In allylamines, the resultant deficiency of ergosterol is responsible for what?
FUNGISTATIC effect
In allylamines the buildup of squalene accounts for what?
FUNGICIDAL ACTIVITY
In addition to Naftifine antifungal activity what are the other mechanism of action?
1) Antibacterial activity (gram-positive and gram-negative)
2) Anti-inflammatory properties secondary to its ability to suppress the synthesis of leukotrienes and prostaglandins
Naftifine has antiinflammatory properties secondary to its ability to suppress what?
synthesis of leukotrienes and prostaglandins
Describe the pharmacokinetics of Naftifine
> the lipophilic properties of naftifine account for its efficient penetration through the stratum corneum
therapeutic drug levels can persist in stratum corneum up to 5 days following a single application
only 3% to 6% of the applied drug can be systemically absorbed
What are the clinical indications of naftifine?
1) Interdigital tinea pedis
2) Tinea cruris
3) Tinea corporis
4) tinea versicolor
5) Candida infections
Naftifine is commercially available as what?
1% gel or cream
How do you give naftifine?
once-twice daily for 2-6 weeks (sa table) or 2-4 weeks ba
What are the side effects of naftifine?
MINOR LANG
dryness
pruritus
local irritation
erythema
What is the mechanism of action of terbinafine?
1) It works through the suppression of squalene epoxidase enzyme, blocking the formation of ergosterol
