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Safety considerations for the management of cholestatic itch.

Abstract
Introduction: Pruritus is adisabling symptom common to cholestatic liver disorders. Its pathophysiology has not been completely elucidated and although multiple mediators have been identified, only lysophosphatidic acid (LPA) and its synthetizing enzyme autotaxin (ATX) appear to consistently correlate with symptom intensity. This review aims to summarize the most relevant safety and efficacy data regarding both standard and new medications utilized to treat pruritus in cholestatic liver disease.Areas covered: International societies like the AASLD and EASL recommend astepwise approach for the management of cholestatic itch. However, therapeutic response is variable. Cholestyramine is considered first-line, followed by rifampicin, naltrexone and sertraline. When used appropriately, these medications have afavorable adverse events profile with most side effects related to drug class and not to the underlying etiology of liver disease.Expert opinion: Although conventional therapies seem to be effective in aproportion of patients, asizable number of cases remain refractory and require the utilization of experimental treatments. Multiple potential targets, especially in the ATX-LPA axis have yet to be pharmacologically explored, with ongoing translational and clinical research. Novel drugs are currently being developed for the management of cholestatic itching with promising results and afavorable safety profile.
AuthorsJuan Trivella, Cynthia Levy
JournalExpert opinion on drug safety (Expert Opin Drug Saf) Vol. 20 Issue 8 Pg. 915-924 (Aug 2021) ISSN: 1744-764X [Electronic] England
PMID33836644 (Publication Type: Journal Article, Review)
Chemical References
  • Antipruritics
  • Lysophospholipids
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase
  • lysophosphatidic acid
Topics
  • Animals
  • Antipruritics (administration & dosage, adverse effects, pharmacology)
  • Cholestasis (complications, drug therapy)
  • Drug Development
  • Humans
  • Lysophospholipids (metabolism)
  • Phosphoric Diester Hydrolases (metabolism)
  • Pruritus (drug therapy, etiology, physiopathology)

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