Pharmacological and pharmacodynamic essentials of H-2-receptor antagonistsand proton pump inhibitors for the practising physician

The suppression of gastric acid secretion with anti-secretory agents has be en the mainstay of medical treatment for patients with acid-related disorde rs. Although the majority of Helicobacter pylori-related peptic ulcers can be healed with antibiotics, ulcer healing and symptom control can be signif icantly improved when antibiotics are given with anti-secretory agents, esp ecially with a proton pump inhibitor. There is a dynamic relationship betwe en the suppression of intragastric acidity and the healing of peptic ulcer and erosive oesophagitis and control of acid-related symptoms. The suppress ion of gastric acid secretion achieved with H-2-receptor antagonists has, h owever, proved to be suboptimal for effectively controlling acid-related di sorders, especially for healing erosive oesophagitis and for the relief of reflux symptoms. H-2-receptor antagonists are also not effective in inhibit ing meal-stimulated acid secretion, which is required for managing patients with erosive oesophagitis. Furthermore, the rapid development of tolerance to H-2-receptor antagonists and the rebound acid hypersecretion after the withdrawal of an H-2-receptor antagonist further limit their clinical use. Although low-dose H-2-receptor antagonists are currently available as over- the-counter medications for self-controlling acid-related symptoms, their p harmacology and pharmacodynamics have not been well studied, especially in the self-medicating population. Proton pump inhibitors have been proved to be very effective for suppressing intragastric acidity to all known stimuli , although variations exist in the rapidity of onset of action and the pote ncy of acid inhibition after oral administration at the approved therapeuti c doses, which may have important clinical implications for the treatment o f gastro-oesophageal reflux disease and perhaps for eradicating H. pylori i nfection when a proton pump inhibitor is given with antibiotics. Once-daily dosing in the morning is more effective than dosing in the evening for all proton pump inhibitors with respect to the suppression of intragastric aci dity and daytime gastric acid secretion in particular, which may result fro m a better bio-availability being achieved with the morning dose. When high er doses are needed, these drugs must be given twice daily to achieve the o ptimal suppression of 24 hour intragastric acidity. Preliminary results hav e shown that esomeprazole, the optical isomer of omeprazole, given at 40 mg , is significantly more effective than omeprazole 40 mg, lansoprazole 30 mg or pantoprazole 40 mg for suppressing gastric acid secretion. However, mor e studies in different patient populations are needed to compare esomeprazo le with the existing proton pump inhibitors with regard to their efficacy, cost-effectiveness and long-term safety for the management of acid-related disorders.