Professional Documents
Culture Documents
Treatment Obstacles
Structural characteristics of fungi Slow growth of fungi Infection frequently in poorly vascularized areas Often in immunocompromised patients
Antifungal Overview
Fungal Infections
Superficial/cutaneous
Dermatophytosis (tinea, ringworm) Candidiasis (yeast)
Systemic
Aspergillosis Blastomycosis Coccidiomycosis Histoplasmosis Paracoccydioidomycosis Sporotrichosis
Treatment of Dermatomycosis
Ringworm, athletes foot, jock itch treatment choice may depend on organism, location, level of inflammation, immune status, etc
Systemic Therapy
Antifungal Drugs
ALLYLAMINE Terbinafine ECHINOCANDINS Caspofungin, Micafungin, anidulafungin AZOLES Ketoconazole, Itraconazole, Fluconazole, Voriconazole, Posaconazole PYRIMIDINE ANALOG Flucytosine POLYENE MACROLIDE
Amphotericin B
Terbinafine
Terbinafine
Increases clearance of cyclosporine Rifampin doubles terbinafines clearance rate Cimetidine decreases terbinafine clearance
Terbinafine
Indications
Itraconazole
Itraconazole
Contraindications/Interactions:
Patients w/ heart failure Liver disease Preg cat C Potent inhibitor of CYP 3A4 also inhibits P-gp numerous interactions Avoid drugs which increase QT interval
Itraconazole
Fluconazole
Distribution
Fluconazole
Indications:
Candidiasis (except krusei) Cryptococcosis: Fluconazole is the best azole agent for fungal meningitis because of high CSF levels
Fluconazole
Contraindications / Interactions:
Preg cat C (teratogenic in animals) Inhibits CYP450 enzymes decreased clearance of some drugs Rifampin increase fluconazole clearance Avoid drugs which prolong QT interval
GI effects & headache most common Increased hepatic transaminases QT prolongation and torsades de pointes (rare)
Griseofulvin
Oral administration
Microparticles Enhance with fatty food
Griseofulvin
Undecylenic acid and salts (Desenex: Zn salt) Tolnaftate(Tinactin) -T. pedis, T. cruris Selenium sulfide suspension (Selsun) -for seborrhaic dermatitis of scalp Benzoic and salicylic acids (Antinea) Potassium iodide -also used for cutaneous sporotrichosis
Superficial Candidiasis
Clotrimazole
Topical product Variety of preparations - cream, lotion, solution, oral lozenge (use appropriate prep!) MOA: typical of azoles PK: Poor penetration beyond the skin, 5-10% following intravaginal use
Clotrimazole
Contraindications:
Vaginal - Preg Cat B; not <12 yrs; may interfere w/contraceptive devices & spermicides Lozenges - Preg Cat C; not <3 yrs Topical - Preg Cat B; ok for pediatrics Avoid ocular contact
Cyp3A4 inhibitor --> increased levels of tacrolimus w/ oral lozenges
Interactions:
Nystatin
Polyene macrolide Pharmacokinetics -not absorbed from the GI tract Adverse effects -too toxic for systemic use Indications
Mouth (oral Candidiasis [thrush]) Skin and mucous membranes - Intravaginal (2 week course) Lower GI tract (oral administration)
Cutaneous
Topical azole treatment (clotrimazole [Gyne Lotrimin], miconazole [Monistat]) Systemic azole treatment for extensive infections, immunocompromised, folliculitis
Vaginal Candidiasis:
Topical Azoles (butoconazole, clotrimazole, miconazole, tioconazole, terconazole) Systemic treatment fluconazole, itraconazole
Oral Candidiasis:
clotrimazole lozenges [Mycelex troche] nystatin mild oral fluconazole for moderate to severe
Voriconazole
Administration -oral (96% bioavailability) and IV (beta cyclodextran vehicle) Distribution - generally good, --> CSF Disposition primarily metabolized dose dependent t 1/2
Indications
invasive aspergillosis
Voriconazole
adverse effects
reversible visual disturbances (30%) increased hepatic transaminase activity photosensitivity
Posaconazole
Administration - oral - greatly increased by high fat meal disposition -fecal elimination of unchanged drug and metabolites Prevention of Candida and Aspergillus in severely immunocompromised patients Non responsive aspergillosis and candidosis
Indications
Posaconazole
Contraindications / Interactions
Proton pump inhibitors, H2 receptor blockers and antacids (impair absorption) Inhibits CYP3A4 Drugs which prolong QT interval
GI effects, fatigue & headache most common increased hepatic transaminase activity QT prolongation and torsades de pointes (rare)
Echinocandins
No mammalian equivalents
Pharmacokinetics
Administration -IV Disposition -redistribution and slow hepatic metabolism, fecal elimination
Echinocandins
Contraindications / Interactions
metabolism increased by rifampin, dexamethasone, others levels increased by cyclosporin Caspofungins decrease tacrolimus levels
Indications
Capsofungin
Anidulafungin
Micafungin
esophageal candidiasis prophylaxis against Candida infections in patients undergoing hematopoietic stem cell transplantation
Amphotericin B: Deoxycholate
(Fungizone) or liposomal (Amphotec, Albecet, AmBisome) preparations
Pharmacokinetics
Administration
IV - most common, deoxycholate suspension or liposomal preparations Local application
Distribution:
Wide except for CSF >90% protein bound Binds to cell membrane and tissue lipids
Amphotericin B
Pharmacokinetics
Disposition:
Biphasic:
Initial (distribution) T 1/2 = 24 Hrs Elimination: T 1/2 = 15 Days Metabolism and urinary excretion
Amphotericin B
Therapeutic uses:
Major treatment for most rapidly progressing or severe systemic mycoses despite toxicity Used as induction therapy Used for non-responsive infections Well characterized in pregnant patients
Amphotericin B
Adverse effects: