Peptic ulcer disease

Alan Cutler MD: Proton pump inhibitors are used to treat reflux disease, ulcer disease, dyspepsia in the stomach and many other upper GI symptoms, including extraesophageal symptoms of reflux disease such as hoarseness, chest pain, asthma. If the treating physician doesn't know what it is and it's upper GI, proton pump inhibitor may be the way to go.

Peptic ulcer disease is caused by a number of agents. Helicobacter pylori and nonsteroidals [Editor's note: NSAIDS] are the two most common. Which one is more predominant depends on the age of your population and where we're talking about, what country we're in and which part of the country.

Nonsteroidal anti-inflammatory drugs can interfere with the prostaglandin system. In doing this, a defensive mechanism of the stomach is weakened; this may lead to an opportunity for erosions and ulcer disease.

Malcolm Robinson MD: Prostaglandins can be protective, but unfortunately have associated symptoms that have made them relatively unpopular. H2 receptor antagonists in usual doses are not very effective for the treatment of NSAID-related damage or prevention, and therefore we're left with proton pump inhibitors as the only modality which can dependably protect against nonsteroidal anti-inflammatory drug-induced damage.

Alan Cutler MD: The pharmacological treatment of choice for nonsteroidal-induced ulcer disease are proton pump inhibitors.

Proton pump inhibitors have been shown to be effective in healing ulcers in patients on nonsteroidals or aspirin who continue taking the offending agent, and in keeping these same patients in maintenance, i.e. without ulcers, even though they continue taking the offending agent. An alternative to proton pump inhibitor addition to nonsteroidal injury is to stop the nonsteroidal and move to a selective COX-2 inhibitor. Proton pump inhibitors are more effective than H2 blockers in preventing the relapse of ulcer disease with or without nonsteroidal and aspirin.

Alan Cutler MD: Helicobacter pylori in general is the primary cause of duodenal ulcers and gastric ulcers. Now it depends a little bit on the area of the country and how old the patient is and what their exposure is to nonsteroidals.

Malcolm Robinson MD: In Oklahoma at this time, Helicobacter pylori is quite uncommon, and this is true in many other urban areas in middle-class populations and upper-class populations, where Helicobacter pylori may only be present in as few as 10% of the population, or perhaps even in smaller numbers.

H. pylori-induced peptic ulcer disease remains a problem, although smaller in magnitude than once was the case. To deal with H. pylori-induced ulcer disease, it is clearly appropriate to identify H. pylori and to eradicate it, and most people would agree that the best line available of therapy for the eradication of Helicobacter pylori involves triple therapy, which includes a proton pump inhibitor and two antibiotics.

Proton pump inhibitors appear to have a direct inhibitory effect against the bacteria themselves, and because of this, proton pump inhibitors, particularly some proton pump inhibitors, may have a direct role in either the stasis or the eradication of these bacteria.

It is thought that the bacteria are approached by PPI therapy in several ways. There are proton pump inhibitor attachments to bacteria that presumably immobilize the bacteria, thereby making them more amenable to the antibiotic therapy. Again, proton pump inhibitors presumably can target the urease in Helicobacter pylori and this urease blockade also can lead to the eventual destruction of the bacteria. Then there are the other mechanisms, less well understood, which are more indirect in the way proton pump inhibitors increase antibiotic concentration and otherwise change the milieu in which the bacteria exist and thereby lead to its destruction.

Alan Cutler MD: The best strategy for treating H. pylori should be a treatment course that's fairly easy to take over a limited period of time and has a good compliance with low side effect profile.

The most effective combination of a proton pump inhibitor with antibiotics is a proton pump inhibitor combined with clarithromycin and amoxicillin. There are alternatives. We can substitute metronidazole for the amoxicillin, but in a patient who may have both metronidazole and clarithromycin resistance, amoxicillin would be a better choice.

Malcolm Robinson MD: The bismuth-ranitidine combination therapy has been mildly effective in the treatment of Helicobacter pylori, but in general either triple therapy, or in some cases quadruple therapy, have been preferred. Quadruple therapy usually is recommended for patients who have failed triple therapy and would involve conventional triple therapy plus a bismuth compound.

Triple therapy has been greatly affected by bacterial resistance. For example, in some countries, where metronidazole resistance has become extremely common, triple therapy involving metronidazole combinations have become almost without value. So there is a risk that antibiotic resistance will be a big problem in this country, as well. We have metronidazole resistance in a growing number of people, and we are beginning to see clarithromycin resistance as well, and this is going to lead to more difficulty in eradicating Helicobacter pylori than we've had up until now.

Alan Cutler MD: Resistance among H. pylori strains is not a population issue; it's an individual issue. In that the rate of transmission from one individual to another as adults is extremely low. So what primarily determines the occurrence of resistance is the previous exposure of the individual to antibiotics. Areas in which Flagyl or metronidazole are used extensively for gynecological or worm infections find that the Helicobacter pylori populations in those regions have very high metronidazole resistance. Similarly, when you use clarithromycin extensively for upper respiratory tract infections-sinusitis and the like-you'll find that there's much more clarithromycin resistance among the H. pylori population.

Malcolm Robinson MD: Compliance with triple therapy is not always good, because patients will experience side effects. The longer the course of therapy, unfortunately, the more side effects are likely and the more likely it is that compliance will suffer. If compliance is poor, and particularly if patients discontinue their therapy prematurely, it is extremely likely that the therapy will fail and the patient will in fact not only fail to be eradicated from their Helicobacter pylori, but also will develop drug resistance to one or more of the drugs given in that combination, meaning that it will be very difficult for that patient to be eradicated later.

Alan Cutler MD: The standard duration for therapy in the United States at this time is 10 to 14 days. There are, however, some new products coming on line, which we believe should be efficacious at a seven-day therapy course.

Triple therapy combination for Helicobacter pylori for seven days should improve patient compliance, should make the regimen easier to take, should reduce the number of side effects and will definitely reduce the cost in treating Helicobacter pylori.