1 / 9

Antifungals 101

Antifungals 101. Dr . Hesham Amgad Senior ICU phamacist / DIC pharmacist CCHE. I. AZOLES . Members of the triazole family are some of the most widely used antifungal agents. Inhibit Ergosterol synthesis (important component of fungal cell membranes).

wilbur
Download Presentation

Antifungals 101

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Antifungals 101 Dr. HeshamAmgad Senior ICU phamacist / DIC pharmacist CCHE

  2. I. AZOLES • Members of the triazole family are some of the most widely used antifungal agents. • Inhibit Ergosterol synthesis (important component of fungal cell membranes). • Fungistaticagainst Candida species. • Voriconazole fungicidal activity against Aspergillusspecies. • Main metabolism is hepatic, main toxicity is elevated LFTs. • Major drug-drug interactions.

  3. A. FLUCONAZOLE • Drug of choice for non-severe Candida infections, including C.albicans, except C.glabrata (can overcome with higher doses) and C.krusei (completely resistant) • Also used for Cryptococcus infections (maintenance phase for cryptococcal meningitis after induction with Ampho B), Coccidioidomycosis, Histoplasmosis, and others. • Toxicity: elevated LFTs, also GI side effects. • Great CSF and urine penetration (only azole with good urine penetration). •  Available in both oral and intravenous preparations.

  4. B. VORICONAZOLE • Cidal for many molds, drug of choice for Invasive Aspergillosis. • Also effective against most Candida, but little reason to use over Fluconazole. • One important hole in coverage is no Zygomycetes (Mucormycosis) • Liver toxicity, also visual toxicity; transient visual changes, but also rare visual hallucinations. •  Available in both oral and intravenous preparations. • Oral bioavailability is reduced by approximately 30% when taken with a high fat meal; must be taken on empty stomach. • Intravenous formulation contains cyclodextrin vehicle which is nephrotoxic. • Good CSF penetration.

  5. C. ITRACONAZOLE • Used for non-severe Histoplasmosis and Blastomycosis. • Toxicity: LFTs and also negative inotrope, can worsen or cause CHF in predisposed patients, GIT side effects with solution form. • Available as a capsule, and an oral solution. • Capsule formulation has a bioavailability of approximately 55%, solution is 30% more. • Capsules require food and an acidic gastric pH for solubilization. • Bioavailability of oral solution is not altered by gastric pH; should be administered on an empty stomach for optimal absorption.

  6. D. POSACONAZOLE • Newest Azole with broad spectrum of activity; yeast, molds, endemic fungi, Zygomycetes (only azole with activity). • Used as 2nd-line / salvage therapy for many severe fungal infections. • Main problem is that it is only available PO, and must be given with fatty foods for maximal absorption.

  7. II. AMPHOTERECIN B • Polyene , binds ergosterol in membrane and forms membrane pores. • Drug of choice for many severe fungal infections: Zygomycetes, Cryptococcal Meningitis (induction phase with flucytosine), Severe Histoplasmosis/Blastomycosis/Coccidioidomycosis. • 2nd-line for invasive aspergillosis (Voriconazole is DOC) • 2nd-line for candida infections (Echinocandins are at least as effective, and less toxic) • Some candida are resistant. • Significant toxicity: Nephrotoxic (including Mg and K wasting), hypotension, bradycardia, fevers/chills during infusion, seizures. • ABELCET (lipid complex), AMBISOME (liposomal): Lipid preparations that are equally effective and much less toxic (esp. renal toxicity), although more expensive. • Allow for much higher doses thanks to lower toxicity. • Only lipid preparations have good CSF penetration.

  8. III. ECHINOCANDINS • New class of antifungals;inhibit beta-(1,3)-D-glucansynthase, an enzyme that is necessary for the synthesis of an essential component of the cell wall of several fungi. • Caspofungin, Micafungin, and Anidulafungin. • All three echinocandins share a similar spectrum of activity, but differ in dosing, pathways of metabolic elimination, and drug interaction profile. • Lower incidence of side effects and drug interactions compared to other antifungals. • Drug of choice for candida infections especially in critically ill and neutropenic patients. • Salvage therapy for Invasive Aspergillosis. • Low CNS penetration. • Toxicity: elevated LFTs, GIT.

  9. Thank You

More Related