antifungals Flashcards
fungal infections
Mainly seen as?
* Cutaneous infections:
* Systemic infections:
Mainly seen as opportunistic or “superinfections”
* Cutaneous infections: common, chronic, seldom dangerous
* Systemic infections: difficult to diagnose, treat, and often lethal
Visible fungal infection of the mouth can tell you:
- Immune status
- Drugs they are taking
● Daily oral steroids?
● Immunosuppressive drugs: transplant?
● Antibiotics, Augmentin?
● Leukemia, lymphoma?
● Chemotherapy drugs – neutropenia?
● HIV/AIDS?
Treating Fungal Infections- Selective Toxicity
- Rigid cell walls contain chitin and the cell membrane contains ergosterol
- Selective toxicity achieved by targeting ergosterol
yeast and mold fungi spp
Molds (Dermatophytes)
Yeasts (Candida, Cryptococcus, Aspergillus)
Dermatophytes: Subgroup of ?
Normal inhabitants of ?
Produce ?
Hyphal filaments?
Invades ?
Dermatophytes: Subgroup of molds that live on skin.
Normal inhabitants of skin, contagious, spread by contact.
Produce keratinases that dissolve keratin
Hyphal filaments penetrate into keratin
Invades hair shafts & nail beds
Dermatophyte (Tinea) infections affect what tissues
Dermatophyte (Tinea) infections affect keratinized tissues
– skin, nails, hair, etc.
Three common pathogenic dermatophytes:
Trichophyton Common
Epidermophyton
Microsporum
“Tinea” diseases: (“cutaneous mycoses”)
Tinea capitis – scalp, common in children
Tinea corporis – body
Tinea pedis – athlete’s foot
Tinea cruris – groin
Tinea unguium – toenails (onychomycosis)
ALLYLAMINES
»Terbinafine (Lamisil oral or topical)
»Naftifine (Naftin)
»Terbinafine (Lamisil oral or topical) and Naftifine (Naftin) moa
Binds/inhibits squalene epoxidase
* Squalene precursors build up and are also toxic aiding toxicity
* Requires actively growing fungi
»Terbinafine (Lamisil oral or topical)
»Naftifine (Naftin)
ALLYLAMINES
allylamines only work on:
- Fungicidal against Dermatophytes Only.
- Weak fungistatic activity against Candida
allylamines adrs/ddi
- Little drug interaction potential
- Few side-effects
Candida albicans
Candida albicans
Candida: Most common fungal infection in mouth
» C. albicans normal habitat is the human oral cavity
» propensity to invade and cause disease when an imbalance is created
Oropharyngeal candidiasis (thrush)
Symptoms:
Many patients are
Immunosuppressed patients with thrush often have?
Oropharyngeal candidiasis (thrush)
Symptoms: cottony feeling in the mouth, loss of taste, and/or painful eating and
swallowing.
Many patients are asymptomatic
Immunosuppressed patients with thrush often have concomitant Candida esophagitis
Oropharyngeal thrush tx options
fluconazole tx of esphogeal thrush
Fluconazole - 400 mg as a loading dose and then 200 to 400 mg daily for 14 to 21days given orally
Clotrimazole (Mycelex) pros of use
highly efffective
Clotrimazole (Mycelex) cons of use
- Ease of use (5x /day)
- Expense
- Drug interactions possible
- Irritating to mucosa
- Alters taste
- Contains sugar
Miconazole (Oravig)
Pro:
- Ease of use (daily troche)
- Highly effective
- Tasteless
- No sugar
Miconazole cons
- Expense
- Drug Interactions
possible
Nystatin pros
- No drug interactions
- Inexpensive
- Not irritating to mucosa
nystatin cons
- Ease of use (QID)
- Ease of use (swish contact
time) - Less effective
- High sugar content
Angular cheilitis
Acute or chronic inflammation of lateral
commissures
Caused by excessive moisture and maceration
from saliva
Angular cheilitis
Angular cheilitis tx
- Topical barriers keep moisture out, prevent
reoccurrences - Barrier creams (eg, zinc oxide paste) or
petrolatum
angular chelitis could be a sign of
May have Candida superinfection
azoles moa
First Generation Azoles
Miconazole, Clotrimazole: Not taken systemically
Clotrimazole & miconazole oral formulations less cariogenic; better tolerated vs Nystatin.
Miconazole (Oravig) dosage
50 mg (1 tablet) applied to upper gum once daily for 7-14 days
* Apply in morning after brushing. Alternate sides of mouth with each application; do not crush, chew, or swallow. Avoid chewing gum while in place.
* If the tablet does not adhere to gum or falls off within 6 hours of application, same tablet should be repositioned immediately.
* Exposure time important: goal entirety of waking hours.
Clotrimazole (Mycelex) dosage
* Metabolized in? contraindicated in?
* Avoid in combination with?
* Oral Troche?
10mg (1 troche) dissolved slowly 5 times daily for 7-14 days
* Metabolized in liver – 3A4. Contraindicated in liver disease.
* Avoid in combination with benzodiazapines; HIV
* Oral Troche for management of oral candidiasis
pt education with clotrimazole
- Patient Education: 5 times daily. Swallow the saliva. No eating or drinking for 30min following medication
- Dissolves over 30 minutes and remains in saliva for up to 3 hours
Second Generation Azole: Triazoles
Fluconazole (Diflucan), itraconazole, voriconazole, posaconazole, isavuconazole
First line drugs for systemic fungal infections
Second Generation Azole: Triazoles
triazoles ddi
Fewer drug-drug interactions and expanded spectrum
* Still metabolized via the cytochrome P450 enzyme system
* All azole agents are both metabolized by and slow down hepatic cytochrome P450 activity
triazole side effect profiles
Safer side-effect profiles than ketoconazole for systemic use