Antifungal Agents Flashcards
Classification by Mechanism of Action
- Polyenes (Amphotericin B, Nystatin)
- Antimetabolite (5 Flucytosine, Terbinafine)
- Echinocandins
- Azoles (Triazoles, Imidazoles)
Classification by Site of Infection
- Subcutaneous and Systemic Mycotic Infections (Amphotericin B, 5 Flucytosine, Echinocandins, Triazoles)
- Cutaneous Mycotic Infections (Nystatin, Imidazoles, Terbinafine)
Parenteral Antifungals
- Amphotericin B
- Echinocandins
Oral antifungals
- 5 Flucytosine
- Itraconazole
Oral and parenteral antifungals
Triazoles
Topical and Vaginal Suppositories
- Imidazole
- Nystatin (Oral also)
- Terbinafine (Oral also)
Terbinafine MOA as Squalene epoxidase inhibitor and Administration?
Inhibit squalene conversion to lanosterol and thus biosynthesis of ergosterol, reducing cell membrane function. Toxic accumulation of squalene increases membrane permeability and fungal cell death
Oral and Topical (Cream, gel)
Terbinafine antifungal activity against _______ and is indicated in treatment of ___________________
Trichophyton - Cause tinea
Onychomycosis, Tinea capitis (Scalp) - Oral
Tinea corporis (Ringworm), Tinea cruris (Groin), Tinea pedis (Foot) - Topical
Why are onychomycosis and tinea capitis treated by terbinafine orally?
Accumulation in the keratin is necessary
Can terbinafine be used in renal and hepatic impairment?
To be avoided
Why is terbinafine bioavailability 40%?
Extensive CYP450 metabolism and excretion by urine
Terbinafine ADR?
- GI disturbance
- Headache, rash
- Elevated LFTs
Terbinafine is contraindicated in ________ but is it safe in pregnancy?
Breastfeeding (Accumulation in milk)
Safe in pregnancy
Nystatin oral administration instructions
Swish and swallow or Swish and spit
Nystatin is indicated for use in …
- Oropharyngeal candidiasis (Thrush)
- Vulvulovaginal candidiasis
- Cutaneous candidiasis
Why is nystatin not given parenterally?
Acute infusion-related adverse effects and nephrotoxicity can occur (Systemic toxicity)
Nystatin ADR
Well tolerated. Some skin irritation for topical and vaginal formulations
How long does miconazole stay on the skin and how deep it penetrates?
Stratum corneum for more than 4 days
Miconazole is indicated in …
- Tinea pedis (Foot)
- Tinea cruris (Groin)
- Tinea versicolor
- Vulvulovaginal candidiasis
Clotrimazole is used for …
- Dermatophyte infections (Cutaneous candidiasis)
- Vulvulovaginal candidiasis
- Oropharyngeal candidiasis
Imidazole ADRs
Contact dermatitis, vulvulovaginal irritation, edema
GI disturbance
Elevated liver enzymes (Clotrimazole oral)
Which triazole requires dose adjustment in renal impairment?
Fluconazole
How are each triazole cleared?
- Fluconazole - Renally excreted unchanged
- Posaconazole - Fecal excretion
- Itraconazole - Hepatic metabolism and renally excreted
- Voriconazole - Hepatic metabolism and renally excreted
Which triazole is taken orally only?
Itraconazole
Oral administration counselling points for posaconazole, itraconazole and voriconazole?
Take with high fat meal (Dairy product) - Posaconazole
Avoid antacids, PPI, H2RAs
Best taken on empty stomach - Itraconazole, Voriconazole
Azole inhibit hepatic CYP450 3A4 and enhance the activity of which drugs?
Warfarin, cyclosporine, oral hypoglycemic agents
Can azoles be used in pregnancy?
Teratogenic - Avoid in pregnancy
How are echinocandins cleared?
Hepatic metabolism by hydrolysis and N-acetylation and excreted in urine and feces
Echinocandin ADR
Well tolerated, sometimes GIT, fevers, chills, rashes, skin flushing, thrombocytopenia
Mycotic Drugs with good CSF penetration
Fluconazole, Voriconazole, 5 Flucytosine
How does conventional amphotericin B cause nephrotoxicity?
Despite low drug levels excreted in the urine, conventional amphotericin B causes renal vasoconstriction and reduces GFR by more than half
Amphotericin B ADRs
Fever and chills, Nephrotoxicity, Electrolyte imbalances (Hypotension), Thrombophlebitis, Bone Marrow Suppression (Anemia)
