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Published on 1 May 2005

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Advances in the clinical management of GORD

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Anton Gillesen
MD
Head
Department of Medicine
Herz-Jesu-Krankenhaus Muenster
Teaching Hospital of Westfalian Wilhemls
University of Muenster
Muenster
Germany
E:gillessen@herz-jesu-kh-ms.de

An estimated 20–40% of western populations are thought to experience symptoms of gastro-oesophageal reflux disease (GORD) on a regular basis, and it is therefore likely that large numbers of hospitalised patients will have comorbid GORD. GORD is a highly prevalent disorder, typically characterised by chronic, intermittent acid regurgitation, heartburn and epigastric pain.(1) In addition, many patients experience extra-oesophageal symptoms such as sleep disturbance, asthma and unexplained, noncardiac chest pain. Some of these patients may be receiving prescription medicines, others may self-medicate, and many will have unrecognised and unmanaged symptoms suggestive of GORD. The management of GORD requires effective techniques to control symptoms, maintain remission and prevent complications such as Barrett’s oesophagus, oesophageal adenocarcinoma or oesophageal stricture.(2-4)

GORD: the broader picture
The high prevalence of GORD, its painful and debilitating symptoms and the high rate of extra-oesophageal symptoms(3) have a negative impact on patient quality of life. As many as 70% of patients with GORD report disturbance of sleep,(5,6) and 40–60% of patients with moderate disease (symptoms for two or more days a week) will have endoscopically evident oesophagitis. Patients with severe GORD not well controlled by drug therapy may require investigation for underlying, serious abnormalities and complications.(3,4)

Importantly, however, evidence of oesophagitis is not a prerequisite for diagnosis and treatment of GORD, and all patients with troublesome symptoms should be considered for empirical treatment with therapies proven to reduce and improve GORD symptoms with minimal adverse effects on quality of life.

Proton pump inhibitors
Antacid therapies were the mainstay of treatment until the introduction of histamine-2-receptor antagonists (H2RAs) in the 1970s, and have now been replaced by more effective and better-tolerated drugs. Antacids are now largely used as self-medication and for breakthrough symptom control, and H2RAs have also been superseded by the proton pump inhibitor (PPI) class of drugs.(7)

PPIs selectively inhibit H(+)/K(+)-ATPase in gastric parietal cells, therefore blocking acid secretion under the control of acetylcholine, gastrin and histamine. They are significantly more effective than H2RAs in achieving and sustaining intragastric pH at levels above 4.0, and provide superior and more rapid relief from symptoms and improved healing rates in oesophagitis.(8)

Choosing PPI therapy for hospitalised patients
When considering which agent to prescribe for the management of an acid-related disease, critical factors to consider are the need for rapid, sustained and complete symptom control, high healing rates, a good safety profile and a low potential for drug interactions. This latter point is particularly important in the hospitalised patient, as polypharmacy is commonplace.

Pantoprazole
For the hospitalised patient unable to use or tolerate medication by mouth, the availability of intravenous (IV) PPI preparations allows for treatment flexibility. Pantoprazole is available as a once-daily oral formulation (20 and 40mg) and as an IV formulation, and several recent clinical studies comparing the efficacy of different PPIs suggest that pantoprazole has many of the features of a drug ideally suited for use in hospitalised patients with GORD.

Daily doses of 20mg are typically used in the management of mild GORD, while the 40mg dose is used for the control of moderate to severe oesophagitis.(9–11) Higher doses may be necessary for patients with hypersecretory conditions such as Zollinger–Ellison syndrome.

High healing rates
During sustained use of PPIs, there is evidence that continuous suppression of acid secretion and control of oesophageal reflux can improve oesophagitis and promote mucosal healing. Both pantoprazole and esomeprazole (40mg once daily as oral therapy) lead to 88% healing rates in patients with oesophagitis.(9)

In the hospital setting, the speed of onset and effective control of symptoms is also a crucial feature of PPI efficacy, and, in this setting, differences between the available PPI therapies may be important.

Rapid onset of action
In a study comparing oral pantoprazole (40mg once daily) with oral esomeprazole (40mg once daily) for four weeks in a group of 217 patients with endoscopically confirmed GORD, both PPIs were equivalent in terms of managing the symptom load of GORD. However, pantoprazole provided more rapid relief from both day- and night-time symptoms.

After a mean of 3.7 days, patients receiving pantoprazole reported improvements in GORD, while patients on esomeprazole did not report the same level of symptom relief until they had received treatment for 5.9 days (p=0.034). Differences in the relief of night-time symptoms were also apparent, with pantoprazole-treated patients reporting improvements after a mean of 1.7 days, compared with a mean of 3.5 days among those treated with esomeprazole (p=0.012).(12)

IV and oral switching
Several studies confirm that oral and IV formulations of pantoprazole have similar efficacy. For example, in a study in 63 patients with symptomatic GORD, it was found that oral pantoprazole (20 and 40mg once daily) could be replaced by IV pantoprazole (20 and 40mg once daily) with no change in treatment efficacy.(13)

Other studies in patients with moderate or severe GORD demonstrated that, after five to seven days of IV pantoprazole treatment (40mg once daily), a change to oral therapy (continued for eight weeks) ensures and achieves sustained symptom control.(14,15)

Safety and drug interactions
Pantoprazole has a lower inhibitory potential against cytochrome P450 than other PPIs and, therefore, has a markedly lower potential to interfere with the metabolic elimination of concomitant drugs than omeprazole, esomeprazole or lansoprazole, making it particularly suitable for critically ill patients taking multiple medications or elderly patients, for whom polypharmacy is common.

Pantoprazole is metabolised in the liver, predominantly by CYP 2C19 and CYP 3A4 (cytochrome P450 enzyme subfamilies). Pharmacokinetic and pharmacodynamic interactions between pantoprazole 40mg and other drugs metabolised by these liver enzymes are uncommon.(16)

Conclusions
Effective treatment is important for all patients with GORD, whether or not they have documented evidence of oesophagitis.

Pantoprazole provides high healing rates and a rapid onset of action. In the hospital setting, pantoprazole offers particular advantages, as it can be used as an IV formulation (with the possibility of switching to the oral route when the patient’s condition improves), and the added reassurance that, of all the PPIs, it has the lowest potential for drug interactions.

References

  1. Aliment Pharmacol Ther 2002;16 Suppl 4: 73-8.
  2. Eur J Gastroenterol Hepatol 2001;13 Suppl 1:S5-11.
  3. J Gastroenterol Hepatol 2004;19 Suppl 3:S33-43.
  4. N Engl J Med 1999;340:825-31.
  5. Gastroenterology 2000;118 Suppl 2:A1303.
  6. Am J Gastroenterol 2003;98:1487-93.
  7. Scand J Gastroenterol Suppl 1986;121:46-52.
  8. Digestion 2004;69 Suppl 1:9-16.
  9. J Clin Gastroenterol 2004;38:332-40.
  10. Eur J Gastroenterol Hepatol 2000;12:197-202.
  11. Aliment Pharmacol Ther 2001;15:1585-91.
  12. Aliment Pharmacol Ther 2003;18:587-94.
  13. Gastroenterology 1999;116 Suppl 2:A278.
  14. Hepato-gastroenterology 1999;46:1809-15.
  15. Int J Clin Pharmacol Ther 1996;34:243-62.


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