*Review of Gastroesophageal Reflux Pharmacotherapy Management DOI: http://dx.doi.org/10.5772/intechopen.106338*

higher pH makes the stomach more hospitable for the pathogenic organisms to grow [20]. Additionally, some have proposed that since gastric acid usually may stimulate the cough reflex, allowing for the clearing of infectious agents from the respiratory tract, an increase in pH leads to a decrease in this mechanism of clearing pathogens [20]. Finally, another proposed mechanism is AST causing a decreased immune response due to the potential impairment of white blood cells [20].

As with other medications, there are several drug interactions with H2RAs [15]. Since H2RAs increase gastric pH, they may affect medications that require an acidic environment for proper absorption [15]. Some medications requiring an acidic environment for absorption include itraconazole, ketoconazole, ampicillin, cephalosporins, sulfonylureas, dasatinib, iron salts, gefitinib, enteric-coated budesonide, and cyanocobalamin. Additionally, cimetidine inhibits several CYP450 isoenzymes (CYP1A2, CYP3A4, CYP2C19, and CYP2D6) and thus should be avoided while taking other medications metabolized by these enzymes [15]. Examples of such drugs include warfarin, selective serotonin reuptake inhibitors (SSRIs), and theophylline [15]. Consequently, famotidine has become the preferred H2RA for GERD due to lesser side effects and lesser drug interactions compared with cimetidine [15].

While PPIs are preferred over H2RAs due to more robust evidence for their use, H2RAs can be added to PPI monotherapy in certain situations [4, 16, 21]. If there is objective evidence of night-time reflux, H2RA therapy can be added at bedtime to PPI monotherapy taken during the day in select patients. However, tachyphylaxis may develop after several weeks of use [4]. Since basal acid secretion is highest in the evening, H2RA administration in the evening may be beneficial. Additionally, H2RAs may also play a role in PPI step-down therapy. Finally, tachyphylaxis is a concern for H2Ras, if administered consecutively for 14 days or more and has also been linked to extended H2RA treatment [4].
