Building a clinical pharmacology framework for the safe and effective use of antifungal agents
Year: 2016
Type: dissertation
Abstract: Echinocandins inhibit ß -(1,3) -glucan synthesis Flucytosine interferes with DNA and RNA synthesis Polyenes bind to ergosterol Azoles inhibit CYP -450 enzyme responsible for ergosterol synthesis Ergosterol Mannoproteins Glucan synthase Therapeutic drug monitoringIn general, drugs used for life-threatening diseases with a proven PK/PD relationship, small therapeutic range, large interindividual variation in pharmacokinetics and pharmacodynamics, and severe adverse effects are particular good candidates for TDM [37] .By performing TDM, Section II. Antifungal drug-drug interactionsAlthough prophylactic or therapeutic use of antifungal drugs has substantially improved treatment outcome of IFD, effective treatment is complicated by the high potential for drug interactions.In particular, the antifungal class of triazoles may interfere with the metabolism of many drugs causing clinically significant drug interactions [34] .In chapter 5, we provide guidance for adequate management of drug interactions between azoles and immunosuppressants.The myriad of potential drug interactions between antifungal drugs and concomitant medications make it almost impossible for the clinician to be conversant with these possible drug interactions.Their potential consequences should be assessed in the light of the individual patient, and failure to recognise a drug interaction may produce deleterious consequences to the patient.We describe the development of a real-time knowledgebase of drug interactions with antifungal agents and concomitant medications (available at http://www.fungalpharmacology.com), providing expert recommendations to clinicians on how to handle interactions with these drugs (chapter 6).Although many drug interactions involving antifungal drugs are caused by inhibition of CYP-enzymes, inhibition of ABC-transporters is also a common mechanism underlying drug-drug interactions (see Antifungal drug-drug interactions).These efflux pumps are also thought to play a crucial role in the inexplicable (non-CYP mediated) drug interactions with antifungal agents.In chapter 7, we investigated the inhibitory potential of antifungal drugs on ABC transporters P-gp, MRP1-5, BCRP and BSEP in vitro.
Author: Vincent J. Lempers
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2407595524