Histamine 2-Receptor Antagonists Tachyphylaxis: A Scoping Review

Area of Science:

• Gastroenterology
• Pharmacology
• Clinical Medicine

Background:

• Histamine 2-receptor antagonists (H2RAs) are commonly used for gastroesophageal reflux disease (GERD).
• Tachyphylaxis, a rapid decrease in drug efficacy with repeated dosing, is frequently observed with H2RAs but poorly understood.
• Understanding H2RA tachyphylaxis is crucial for optimizing GERD treatment strategies.

Purpose of the Study:

• To conduct a scoping review on the decrease in H2RA efficacy with repeat dosing.
• To investigate the mechanisms, impact, and management of H2RA tachyphylaxis.
• To evaluate the clinical implications of H2RA tachyphylaxis in GERD management.

Main Methods:

• Systematic literature search following PRISMA-ScR guidelines across major databases (PubMed, Embase, Scopus, Web of Science, Cochrane).
• Data extraction by two independent reviewers focusing on mechanisms, impact, and management strategies.
• Inclusion of studies investigating H2RA efficacy and tachyphylaxis in GERD patients.

Main Results:

• H2RAs increase intragastric pH > 4 from 8% to 38% initially.
• Tachyphylaxis begins by day 2, with efficacy reduced by 11.2% by day 3 and 20.3% by day 15.
• Proton pump inhibitors (PPIs) maintain intragastric pH > 4 for 63% of the time without observed tachyphylaxis after 14 days.

Conclusions:

• Tachyphylaxis is a well-documented phenomenon across all H2RAs, causing up to a 25% decrease in absolute efficacy.
• The exact mechanisms driving H2RA tachyphylaxis remain unclear.
• H2RAs should not be first-line treatments for frequent GERD or routinely added to proton pump inhibitor therapy.