Histamine_2-receptor antagonists: Rapid development of tachyphylaxis with repeat dosing

Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The aim of this review is to assess the publishedevidence regarding the development of tachyphylaxiswith repeat usage of H_2RAs. PubMed and SCOPUS were searched across all years to identify clinical studies thatexamined the development of tachyphylaxis with repeated dosing of H_2RAs. Although a single (first) doseof an H_2RA can be effective for controlling gastric acidand preventing or relieving food-related heartburn, numerous studies confirm that tachyphylaxis, also knownas tolerance, is consistently detected at the first timepoint assessed after the first dose, including the second day and/or second dose. Even if symptom relief isachieved with an H_2RA, it may be due to desensitizationof the esophagus to acid exposure, potentially providingsymptom relief without significantly decreasing esophageal acid exposure. When recommending OTC drugsfor treatment of frequent heartburn, clinicians shouldbe aware of the potential for rapid development oftachyphylaxis in patients who use H_2RAs for 2 or more consecutive days. Even if symptom relief is achieved, it may be due to desensitization of the esophagus to acid by the H_2RA, potentially providing symptom relief without significantly decreasing esophageal acid exposure. Other strategies, such as an OTC proton pump inhibitor, may be needed to optimize management of frequent heartburn.

Effects of Repeated Injection of Local Anesthetic on Sciatic Nerve Blocks Response

In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression compound action potentials (CAP), rats were anesthetized with halothane, ventilated, monitored and supported with stable hemodynamics and temperature. Posterior tibial nerve distally and sciatic nerve in thigh were exposed, placed on bipolar silver electrodes for stimulation and recording respectively. Three sequential sciatic nerve blocks were performed between these electrodes using 0.15 ml of 3 % chloroprocaine. Nine rats were chosen to observe the effects of repeated sciatic nerve blocks on CAP. In another 18 rats, a second investigator exposed the sciatic nerve near its origin at spinal cord and randomly performed nerve cut and sham (n=9), and closed the incision blinding the electrophysiologic investigator. The results showed that electrical stimulated tibial nerve induced sciatic nerve Aα/β, Aδ, C fiber mediated CAP waves. CAP amplitudes were remained stable during whole experimental procedure. CAP amplitudes were decreased completely with 3% chloroprocaine blocked sciatic nerve and recovered fully. The duration of CAP depression were reduced with repeated blocks. There were no selective blocked effects on Aα/β, Aδ, C fiber mediated CAP. With sciatic nerve cut proximally, there was no statistical significant tachyphylaxis with 3 % chloroprocaine repeated blocked sciatic nerve, and the duration of first and third blocked Aδ fiber mediated CAP was 108±20 and 92±14 min respectively (P>0.05). In normal rats the duration of first and third blocked Aδ fiber mediated CAP was 110±20 and 75±16 min respectively (P<0.05). It was suggested that tachyphylaxis to local anesthetics can occur in rats repeated blocked sciatic nerve when assayed in vivo by duration of depression CAP. The continuity of sciatic nerve with spinal cord is one of the important factors affecting the development of tachyphylaxis.