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antifungalls
UVa med pharmacology black 4
| Question | Answer |
|---|---|
| What is itraconazoles MOST IMPORTANT side effect? | high levels cause prolonged QT interval |
| Why is resistance to Amphotericin B rare? | Mechanism of action, all fungi need ergosterols for their membrane |
| What is the benefit of newer Amphotericin formulations? What is a serious consideration when deciding on their use? | Less noxious effects than the orginial "ampho terrible" VERY EXPENSIVE raising serious cost-benefit issues |
| Why is Terfenadine level elevation an important side effect of Azoles? | Terfenadine is the histamine blocker that can cause torsades-des-pointes |
| What adverse effect of Amphotericin B occurs in 80% of patients? Is it dependent on dose? | Nephrotoxicity YES, dose dependent |
| What drugs increase nephrotoxicity when co-administered with Ampho B? | Aminoglycosides, nitrogen mustard anti-neoplastics, CYCLOSPORIN |
| Where does griseofulvin accumulate? Why is this important to its function? How long does treatment take? | accumulates in keratinocytes as new growth occurs, old infected skin/hair/nails are shed and replaced with griseolfulvin uninfected keratin Tx continues until full replacement (1-12months) |
| What is the therapeutic niche for Griseofulvin? When should it NOT be used? | minor skin infections caused by microsporum, trichophyton, epidermophyton ***AKA --> cause by dermatophytes (ie tinea's) should NOT be used if bugs respond to topical treatment |
| Why do renal and hepatic failure not affect Amphotericin B excretion? | Because it is excreted VERY SLOWLY anyway |
| What patient population is Amphotericin B the DOC for very often? | Immucompromised Remember, they NEED cidal agents |
| What drugs does Fluconazole interact with? | increases Phenytoin and Cyclosporin toxicity increased the action of oral anticoagulation elevates terfenadine levels |
| What is special about Griseofulvin? | used for topical mycoses but THE ONLY ONE IN THIS NICHE that is not applied topically |
| Compare Fluconazoles and Ketoconazoles absortion, adverse effects | Fluco is better absorbed than Keto Fluco generally has less side effects, elevated terfenadine level less than Keto |
| Why is a test dose often administered when using amphotericin B? | To gauge patient tolerance |
| What is the mechanism of Amphotericin B? cidal or static? | Complexes with sterols (primarily ergosterols) and alters membrane permeability fungiCIDAL |
| In general what kind of azole is preferred and why? | Triazoles --> less propensity to interact with human sterol biosynthesis |
| What is griseofulvin's mechanism? | binds to polymerized microtubules and disrupts the mitotic spindle in other words --> INHIBITS MITOSIS |
| What drugs "claim to fame" is its treatment of aspergilliosis? | Voriconazole |
| What is a metabolism difference between Fluconazole and Voriconazole? | Voriconazole is metabolized by MANY p450 isotypes |
| The multiple drug interactions of all azoles derive from what? | Their interactions with the p450 system |
| Compare the azoles to Amphotericin B | Orally available and far less noxious azoles are fungiSTATIC |
| Amphotericin B is the virtually the only drug available for what kind of disease? What type of fungi is it effective against? | CNS and rapidly spreading fungal infections ALL FUNGI (virtually) found clinically |
| What is the main therapy for deep-seated mycoses? | Amphotericin B |
| What effect does Ampho B have when coadministered with cholinergic antagonists? | increased neuromuscular blockade |
| What drug has replaced Ketoconazole in patients with economic means? | Itraconazole |
| What are some adverse reactions of amphotericin? | Fever, hypotension, arrythmias IV phlebitis (ampho terrible) nephrotoxicity (dose-dependent) anemia |
| What is the most common side effect of Fluconazole? What are some others? | GI distress -- MOST COMMON rash - Stevens-Johnson syndrome acute hepatic necrosis |
| Difference between Nystatin and Ampho B? | Nystatin is topical only (too toxic for systemic use) ***swish and swallow for oral candidiasis |
| What is the mechanism of all azoles? | They inhibit fungal 14-a-demethylase Blockage of ergosterol synthesis Build of 14-a-demethylsterols ---> these disrupt packing of the lipid bilayer |
| How is Amphotericin B administered? How is it administered for CNS infections? | IV administration over 2 to 4 hours, poorly water soluble at phyisiological pH CNS infection requires intrathecal administration |
| Adverse effects of Griseofulvin according to class? According to FA? | CLASS: Usually minor (headaches, lethargy, nausea) FA: teratogenic, carcinogenic, confusion, headaches |
| Why have azoles not supplanted Ampho B systemic for fungal infections in the immunocompromised? | because azoles are fungiSTATIC |
| What additional therapeutic niche in addition to Ketoconazole's does Itraconazole have? | Aspergilliosis lymphocutaneous sporotrichosis |
| Under what conditions is Amphotericin B water soluble? | extremes of pH |
| What cardiac drug has an interaction with Ampho B? Why? | Digitalis Hypokalemia |
| What drugs DECREASE itraconazole levels? | isoniazid, phenytoin, rifampin |
| What is ketoconazole used for? | blastomyces, coccioides, histoplasma, candida, hypercortisolism (decrease sterol synthesis) |
| What drugs' acitivity is diminished by griseofulvin? why? | anticoagulants and oral contraceptives increased p450 metabolism |
| What drugs decrease absorption of Griseofulvin? | barbituates |
| What are some adverse effects of Voriconazole? | visual distrubances hallucinations fulminant hepatitis |
| What drugs increase itraconazole levels? | clarithromycin, indinavir, ritonavir |
| What is the therapeutic niche for Fluconazole? | oropharyngeal and esophageal candidiasis cryptococcal meningitis in AIDS patients |
| What are just some of the drugs that Itraconazole increases the metabolsim of? | cyclosporin, digoxin, warfarin, phenytoin |
| How does a fungal strain become resistant to Ampho B in vitro? | Reduced levels of ergosterol or increased levels of ergosterol precursors w/lower affinity for polyene antibiotics |
Created by:
sam.mrosenfeld
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