Systemic antifungals Flashcards
What the types of antifungal agents?
1. Azoles
Triazoles - Itraconazole, fluconazole, voriconazole, posconazole, ravuconazole
Imidazole - ketoconazole
2. Allylamines
Terbinafine,
Naftifine.
3. Polyenes
- Nystatin
- Amphotericin B
How does terbinafine reach the stratum corneum? How long does this take?
Passive dermoepidermal diffusion
Through sebum
Migration of basal keratinocytes
High conc are reached in the stratum corneum within hours
After administration of terbinafine 250 mg daily for 12 days, drug concentrations above the MIC for most dermatophytes may be present for 2–3 months after oral therapy is discontinued
False - 2 -3 weeks.
How is itraconazole delivered to the skin?
Passive diffusion from the plasma to the keratinocytes with strong drug adherance to keratin.
Via the sebum
How is fluconazole delivered to the stratum corneum?
through sweat and
by direct diffusion through the dermis and epidermis
How is terbinafine delivered to the nails?
Detected in the distal nail within 1 week of starting therapy
Diffuses to the distal nail via the nail plate and matrix
How is itraconazole delivered to the nail?
Detected wihtin the distal nail within 1 -2 weeks.
via both the nail matrix and the nail bed
How is fluconazole delivered to the nails?
Detected within 1 day
via both the nail matrix and the nail bed
MoA of allyamines
Terbinafine is an allyamine
Inhibits squalene epoxidose
–> accumulation of squalene and a subsequent deficiency of ergosterol.
–> leads to **fungistatic action **
NB; fungicidal action **invitro **
MoA Triazole
Triazole = itraconazole, fluconazole, voriconazole, posaconazole
Inhibits CYP dependent enzyme lanosterol 14a demthylase
Inhbits lonosterol –> ergosterol
= Fungiostatic action
Terbinafine is more effective against Trichophyton sp. than fluconazole
True
Fluconazole is more effective against dermatophytes than itraconazole
False. Terbinafine and itraconazole are more effective against dermatophytes than fluconazole
Fluconazole is more effective against candida than terbinafine
True - has a lower MIC
Oral terbinafine dosing
< 20 kg = 62.5mg / day
20 - 40 kg = 125mg / day
> 40 kg = 250 mg / day
Fluconazole dosing
150 - 300 mg once weekly
Treatment options for onychomycosis secondary to dermatophytes
Terbinafine 250mg daily for 12 - 16 weeks
Itraconazole 200mg daily for 12 weeks
OR
Pulse itraconazole 200mg BD for one week per month for 3 -4 months
Fluconazole 150 - 300mg weekly until nail is normal
Treatment options for onychomycosis caused by candida spp
Itraconazole and fluconazole»_space; terbinafine
Topical antifungal treatment can penetrate the hair shaft
False - hence why oral treatment is often needed for tinea capitus
Adjunct topical therapies for tinea capitus include?
Ketaconazole shampoo
Selenium Sulfide
Povidone-iodine
Treatment of choice for M. Canis tinea capitus infection?
Griseofulvin
Treatment of choice for T. tonsurans dermatophyte infection?
Terbinafine
Dosing of griseofulvin for tinea capitus
20mg / kg /day
Which antifungal agents work best for malassezia spp?
Itraconazole
Ketaconazole
Fluconazole
Terbinafine / Griseofulvin are not effective
Contraindications to Terbinafine?
Allergy
Precautions:
- liver disease
- renal failure
Azole contraindications
Allergy
Ventricular dysfunction
Coadministration of drugs that prolong the QT interval
Terbinafine side effects
Headache
GI symptoms
Cutaneous:
- urticaria
- SJS / TEN
- psoriasis
- EM
- SLE
LFT dysfunction
Taste disturbance
Visual disturbance
Idiosyncratic hepatobilary dysfunction - typically within 4 -6 weeks of treatment
Side effects of Itraconazole?
Headache
GI disturbance
Cutaneous
- pruritis
- TEN / SJS
- AGEP
- Vasculitis
- EM
- Alopecia
- photosensitivity
Abnormal LFTs
Pregnancy category of antifungals?
Terbinafine - B
Itraconazole - C
Fluconazole - D
