Constipation Worsens the Effects of GERD


About 5% of adults suffer from reflux symptoms regularly, i.e. several times a month.1 When typical symptoms such as heartburn and acid regurgitation are prevalent, diagnosis is easy.2 Less characteristic complaints about chest pain, hoarseness or coughing require differential diagnostic differentiation, e.g. from coronary artery disease. Difficulty swallowing and recurrent vomiting or hematemesis suggest a severe course of the disease or complications.

If stomach contents flow back into the esophagus, stomach acid, pepsin and bile damage the mucous membrane. Failure of the lower esophageal sphincter is mainly associated with frequent phases of relaxation, and more rarely with reduced resting tone. In some of those affected, the acid that has returned is only slowly emptied into the stomach.3 Lying flat in the supine position, pressing, being overweight and sliding hiatal hernia as well as lavish late meals, nicotine, alcohol, coffee, fruit juices and spices promote the symptoms. The disease lasts for years with episodes of spontaneous improvement and relapses. Without therapy, it does not necessarily have to worsen.1

The severity of the mucosal damage is usually divided into 5 levels according to endoscopic findings from 0 (no recognizable damage) to 4 (chronic lesions up to the BARRETT esophagus, in which the squamous epithelium of the lower esophagus is replaced by columnar epithelium typical of the stomach; see table). Patients with BARRETT's esophagus have an up to 40-fold increased risk of malignant tumors.4 The intensity of the symptoms does not give a reliable indication of the degree of the lesions. Less than two-thirds of patients with reflux symptoms examined in the clinic have endoscopic evidence of esophagitis.1

The treatment should relieve symptoms, prevent relapses and prevent complications (stenoses, bleeding, degeneration). After successful drug therapy, 50% to 80% recurrences are to be expected within one year, since the underlying motility disorders are not permanently improved.5

NON-DRUG MEASURES: Less pronounced complaints improve when obesity is lost, slept with the upper body elevated at night and refrained from eating late and smoking. Medicines that reduce the tone of the lower esophageal sphincter should be avoided: benzodiazepines, calcium channel blockers, β-adrenergic agents, anticholinergic agents, etc.

An "antireflux operation", e.g. the cuff-like sewing of the lower esophagus with the gastric fundus (fundoplication according to NISSEN), has to be weighed against possible years of therapy with acid blockers, especially in the case of frequent relapses and progressive inflammation. The procedure improves reflux symptoms in nine out of ten patients.1,6 An existing BARRETT esophagus can partially or completely regress.7

MEDICAL THERAPY:Antacids are mainly used in self-medication. Some studies show an effectiveness of the acid buffering agents on symptoms and healing, while in several controlled studies they do not work better than placebo.8

The main disruptive effects are diarrhea (magnesium antacids) and constipation (aluminum and calcium supplements). Antacids containing aluminum favor the development of encephalopathy in dialysis patients. Because of the risk of anemia and osteopathy, they should not be taken continuously for more than eight weeks (a-t 2 [1996], 20).

There is little evidence of the benefit of Sucralfate (ULCOGANT et al.). It should work just as well as H2 antagonists.9 The combination of both active principles does not bring any advantage.

Sucralfate often causes constipation. Similar reservations apply to the aluminum-containing mucosal protective agent as to aluminum-containing antacids.

Prokinetics increase the pressure in the lower esophageal sphincter, increase peristalsis and accelerate the emptying of the stomach. Metoclopramide (PASPERTIN et al.) And domperidone (MOTILIUM et al.) Can improve mild reflux symptoms, but do not contribute to the healing of lesions.10 On the other hand, with 10 mg cisapride (ALIMIX, PROPULSIN) four times a day, mild to moderate inflammation (grade 1-2) heals just as well as with H2 antagonists.11 The combination of both active principles results in higher success rates than H2 blockers alone (70% vs. 46%).12 There is no evidence of the effectiveness of prokinetics in severe inflammation (grade 3-4).

Cisapride mainly causes diarrhea and abdominal pain. Extrapyramidal movement disorders are less common than with metoclopramide. Azole antimycotics such as ketoconazole (NIZORAL) inhibit the breakdown of cisapride with the risk of life-threatening ventricular arrhythmias (a-t 3 [1995], 25).

The different H2 antagonists do not differ in their effectiveness. Ingestion in several single doses per day is intended to ensure lasting acid suppression for 24 hours.1 Satisfactory results can be achieved in the dosages customary for the treatment of peptic ulcers in mild esophagitis. With 300 mg ranitidine (ZANTIC et al.) Daily, 88% of patients with grade 1 esophagitis are cured within 12 weeks.13 In the case of severe inflammation, even high doses only help moderately.

With H2-receptor blockers, central nervous disorders such as headache or fatigue and gastrointestinal disorders such as diarrhea are to be expected, as well as - especially with cimetidine (TAGAMET, etc.) - with gynecomastia and interactions with numerous other drugs.

Proton pump blockers suppress acid secretion more and more persistently and bring better results than H2-receptor blockers in acute therapy as well as for relapse prophylaxis. Usually 20 mg omeprazole (ANTRA, GASTROLOC) once a day is sufficient.14 If it fails, double the dose can still be a cure.15 30 mg of lansoprazole (AGOPTON) works better than 15 mg.16 Higher doses of both blockers have no further advantage. Bland inflammations (grade 1) heal within one month in 90% of patients with 40 mg omeprazole daily compared to 55% with 300 mg ranitidine daily. The two ulcer remedies achieve similar healing rates for higher-grade inflammation (grade 2-3) after 12 weeks (91% and 55%, respectively).13 In 9 (69%) of 13 people with grade 4 reflux disease, 40 mg omeprazole cured largely over eight weeks.17 Complaints that are refractory to H2 antagonists can still respond to proton pump inhibitors.17

The most common disruptive effects are headaches and diarrhea. Proton pump blockers rarely cause visual disturbances up to blindness and hearing loss (a-t 7 [1993], 74; 11 [1994], 110).

Long-term use of proton pump inhibitors, in some cases significantly increased gastrin levels, gives cause for concern. When omeprazole is taken continuously, the glandular parenchyma of the stomach disappears. 18 (30%) of 59 patients who take omeprazole 20 to 40 mg daily for an average of five years for reflux esophagitis and are infected with H. pylori develop chronic atrophic gastritis, which is associated with malignant degeneration. In contrast, after suturing the esophagus (fundoplication), none of 72 people with and without H. pylori infection have atrophic gastritis.18 According to long-term observations available to date, the incidence of endocrine tumors does not appear to be increased.19

RELIABLE PROPHYLAXIS: If there is pronounced inflammation, long-term therapy will help prevent recurrences. The frequency of relapse depends on the severity of the initial findings. Esophagitis that only heals with proton pump inhibitors after unsuccessful treatment with other agents will return quickly.1,10 After discontinuation, a relapse can be expected in up to 80% of patients within six months. H2 antagonists in therapeutic doses for six months prevent relapses by about 60%. A lower dose maintenance therapy is not enough. Relapses of mild esophagitis can be prevented with about the same success with 20 mg cisapride twice a day.1 450 mg ranitidine plus 30 mg cisapride per day provide significantly better protection than ranitidine alone.20 In the case of moderate inflammation, the combination is an alternative to proton pump inhibitors - loaded with a large number of tablets.

Proton pump blockers, e.g. 20 mg omeprazole daily, prevent relapses more reliably than H2 antagonists,21 but remain reserved for severe esophagitis with endoscopically proven lesions because of the risk of atrophic gastritis. Low-dose maintenance therapy with omeprazole 10 mg daily fails in grade 3-4.22 The proton pump inhibitor is only approved for use for a maximum of one year. There are no controlled studies over a longer period of time. If it is unsuccessful, a combination of a proton pump inhibitor and a prokinetic can be considered.

It has not been established whether drug therapy prevents the transition from severe esophagitis into BARRETT syndrome. Dilatations of strictures are required less often with long-term use of omeprazole.23 Comparative studies between long-term use of proton pump inhibitors and surgery are pending.

CONCLUSION: If patients present for the first time with reflux symptoms, a therapy attempt with antacids or prokinetics such as cisapride (ALIMIX, PROPULSIN) in conjunction with accompanying measures such as reducing obesity and sleeping with an elevated upper body is advisable. If there is no success, it is advisable to clarify the findings endoscopically. Mild esophagitis (grade 1-2) can be treated satisfactorily with H2 antagonists. Severe inflammation (grade 3-4) justifies the use of proton pump inhibitors.

Up to four out of five patients suffer a relapse after discontinuation, so that long-term therapy may be necessary. For lighter forms, an attempt with an H2 antagonist or prokinetic can be considered, possibly also combined. The long-term use of proton pump inhibitors should be limited to severe inflammation because of the risk of atrophic gastritis and other harmful effects. If it is unsuccessful, an additional prokinetic can help. Antireflux surgery should be weighed against long-term use of proton pump inhibitors, especially in younger patients with a complicated course.