THEME OF THE LECTURE:
GASTRO-OESOPHAGEAL REFLUX DISEASE.
CHRONIC GASTRITIS.
Plan of the lecture:
Gastro-oesophageal reflux disease, gastric dyspepsia
Chronic gastritis.
Etiology
Pathogenesis
Diagnosis
Complications
Differential Diagnosis
Treatment
Gastro-oesophageal reflux disease
Gastro-oesophageal reflux disease (GORD) is the most common cause of indigestion, affecting up to 30% of the general population. GORD develops when gastric or duodenal contents flow back into the oesophagus. Oesophageal reflux is only considered a pathological condition when it causes undesirable symptoms.
Clinical features of GORD
The most common symptoms of oesophageal reflux are dyspepsia, heartburn and regurgitation, which can be provoked by bending, straining or lying down. Waterbrash, which is salivation due to reflex salivary gland stimulation as acid enters the gullet, is often present. A history of weight gain is common. Some patients are woken at night by choking as refluxed fluid irritates the larynx. Other less common symptoms include dysphagia (difficulty swallowing), odynophagia (pain on swallowing), and symptoms of anaemia. A small number of patients present with atypical chest pain, which may be severe, can mimic angina and is probably due to reflux-induced oesophageal spasm.
Pathophysiology of GORD
Occasional episodes of GORD are common in health, particularly after eating. Gastro-oesophageal reflux disease develops when the oesophageal mucosa is exposed to gastric contents for prolonged periods of time, resulting in symptoms and, in a small proportion of cases, this leads to oesophagitis.
Normally, prevention of acid damage is achieved by a combination of physiological barriers. The LOS is a 3-
There is also extrinsic pressure exerted from the crura of the diaphragm at the same point and the angle of His (the angle of entry of the oesophagus into the stomach) which both help retain acid within the stomach. Periods of LOS relaxation occur in all individuals and allow transient reflux of acid into the oesophagus. This initiates a distal oesophageal peristaltic wave which progressively clears the acid. Swallowed saliva is alkaline and also helps neutralise oesophageal acid.
Abnormalities of the lower oesophageal sphincter related to GORD
In health the lower oesophageal sphincter is tonically contracted, relaxing only during swallowing. Some patients with GORD have reduced lower oesophageal sphincter tone, permitting reflux when intra-abdominal pressure rises. In others basal sphincter tone is normal but reflux occurs in response to frequent episodes of inappropriate sphincter relaxation.
Hiatus hernia
A hiatal hernia occurs when part of the stomach protrudes through the diaphragm and into the thoracic cavity. Such hernias are extremely common in older people and more common in women than in men. A hiatus hernia causes reflux because the pressure gradient between the abdominal and thoracic cavities, which normally pinches the hiatus, is lost. In addition the oblique angle between the cardia and oesophagus disappears. Many patients who have large hiatus hernias develop reflux symptoms, but the relationship between the presence of a hernia and symptoms is poor. Hiatus hernias are very common in individuals who have no symptoms, and some symptomatic patients have only a very small or no hernia.
Important features of a hiatus hernia include:
• Occur in 30% of the population over the age of 50 years.
• Often asymptomatic.
• Heartburn and regurgitation can occur.
• Gastric volumes may complicate large hernias.
The role of gastric contents in GORD
Gastric acid is the most important oesophageal irritant and there is a close relationship between acid exposure time and symptoms. Alkaline reflux, due to bile reflux following gastric surgery, is of uncertain importance.
Increased intra-abdominal pressure
Pregnancy and obesity are established predisposing causes. Weight loss commonly improves symptoms and patients should be encouraged to avoid tight-fitting garments.
Dietary and environmental factors
Dietary fat, chocolate, alcohol and beverages such as tea and coffee relax the lower oesophageal sphincter and may provoke symptoms. There is little evidence to incriminate smoking or non-steroidal anti-inflammatory drugs (NSAIDs) as causes of gastro-oesophageal reflux disease.
Delayed oesophageal clearance
Defective oesophageal peristaltic activity can be seen in patients who have GORD. Poor oesophageal clearance leads to increased exposure to acid from the stomach.
Complications of GORD
Oesophagitis
Reflux oesophagitis is a chronic inflammatory process mediated by gastric acid and pepsin from the stomach as well as bile from the duodenum, which can result in ulceration of the mucosa and secondary fibrosis in the muscular wall. A range of endoscopic findings, from mild redness to severe bleeding ulceration with stricture formation, is recognised. There is a poor correlation between symptoms and histological and endoscopic findings. A normal endoscopy and normal oesophageal histology are perfectly compatible with significant gastro-oesophageal reflux disease
Other causes of oesophagitis: infectious diseases. Viruses, bacteria, fungi and mycobacterium can all cause oesophageal infection. The most common of these are candida. Oesophageal candidiasis occurs in debilitated patients and those taking broad-spectrum antibiotics or cytotoxic drugs. It is a particular problem in AIDS patients, who are also susceptible to a spectrum of oesophageal infections. Oesophageal candidiasis rarely develops in patients who do not have an underlying disease such as diabetes, immune deficiency or malignancy. The main symptoms of oesophageal candidiasis are dysphagia and odynophagia. Severe infection of the gullet can destroy oesophageal innervation, causing abnormal motility
Corrosives
Accidental or suicidal ingestion of highly alkaline or acidic substances may result in injury to the oesophagus. The most common symptom is odynophagia, but patients may also complain of dysphagia and chest pain. Ingestion of caustic compounds is followed by painful burns of the mouth and pharynx and by extensive erosive oesophagitis. At the time of presentation, management is conservative, based upon analgesia and nutritional support. Vomiting should be avoided and endoscopy should not be done at this stage because of the high risk of oesophageal perforation. Following the acute phase, a barium swallow and X-ray examination is performed to demonstrate the extent of stricture formation. Endoscopic dilation is usually necessary, although it is difficult and hazardous because strictures are often long, tortuous and easily perforated.
Barrett’s oesophagus
Barrett’s oesophagus is defined as epithelial metaplasia in which the normal squamous epithelium of the oesophagus is replaced by one or more of the following types of columnar epithelium: a specialised columnar epithelium, a junctional type of epithelium; and/or a gastric type of epithelium. Barrett’s oesophagus is thought to be a consequence of chronic gastro-oesophageal reflux.
Diagnosis of Barrett’s oesophagus is made by endoscopic visualisation of the oesophageal mucosa, supported by examination of tissue biopsies. Barrett’s oesophagus is recognised endoscopically as confluent areas or fingers of pink, gastric-like mucosa extending from the cardia of the stomach into the oesophagus. The prevalence of adenocarcinoma in patients with Barrett’s oesophagus is reported to be in the region of 30 to 50 times that of the general population (Clark et al. 2000). Consequently patients discovered to have Barrett’s changes during endoscopy are considered for endoscopic surveillance programmes. Patients with moderate dysplasia should undergo repeated biopsies at 6 to 12-monthly intervals. Patients found to have severe dysplasia usually have associated cancer and are usually referred for oesophageal surgery.
Anaemia
Iron deficiency anaemia occurs as a consequence of chronic, insiduous blood loss and can result from longstanding oesophagitis.
Benign oesophageal stricture
An oesophageal stricture is an abnormal formation of fibrous tissue that is usually at the lower end of the oesophagus. Fibrous strictures develop as a consequence of longstanding oesophagitis. Most patients are older and have poor oesophageal peristaltic activity. Progressive dysphagia is the most common clinical feature. Diagnosis is made by endoscopy and biopsies of the stricture are taken to exclude malignancy.
Treatment of strictures may involve the use of weighted bougies, pneumatic balloon dilators or graduated plastic Savary-Gillard dilators. Subsequent treatment usually involves long-term therapy with a proton pump inhibitor drug (i.e. omeprazole or lansoprazole) which should be prescribed to reduce the risk of recurrent oesophagitis and stricture formation. The patient should be advised to chew food thoroughly and it is also important to ensure that dentition is adequate.
Investigations for GORD
Investigation is advisable if patients present in middle or late age, if symptoms are atypical or if a complication is suspected. Endoscopy is the investigation of choice. This is done to exclude other upper gastrointestinal diseases that can mimic gastro-oesophageal reflux, and to identify complications. A normal endoscopy in a patient with compatible symptoms should not preclude treatment for gastro-oesophageal reflux disease. When, despite endoscopy, the diagnosis is unclear or if surgical intervention is under consideration, 24-hour pH monitoring is indicated. This involves tethering a slim catheter with a terminal radiotelemetry pHsensitive probe above the gastro-oesophageal junction. The intraluminal pH is recorded whilst the patient undergoes normal activities, and episodes of pain are noted and related to pH. A pH of less than 4 for more than 4% of the study time is diagnostic of reflux disease.
Management of GORD
The first-line nursing of patients with GORD should relate to behaviour modification and nurses should encourage the following recommendations:
• weight loss
• avoidance of tight-fitting garments
• avoidance of dietary items which the patient finds worsens symptoms
• elevation of the bed-head in those who experience nocturnal symptoms
• avoidance of late meals
• cessation of smoking
Antacids, which are said to produce a protective mucosal ‘raft’ over the oesophageal mucosa, are taken with considerable symptomatic benefit by most patients. H2 receptor antagonist drugs, which reduce gastric acid secretion, help symptoms without healing oesophagitis. They are well tolerated and the timing of medication and dosage should be tailored to individual need. Proton pump inhibitors are the treatment of choice for severe symptoms and for complicated reflux disease. These drugs irreversibly inhibit the proton pump, reducing the transport of hydrogen (H) ions out of parietal cells. Symptoms almost invariably resolve and oesophagitis heals in the majority of patients. Recurrence of symptoms is almost inevitable when therapy is stopped, and some patients require lifelong treatment. Patients who fail to respond to medical therapy, those who are unwilling to take long-term proton pump inhibitors and those whose major symptom is severe regurgitation are considered for anti-reflux surgery.
Non-Ulcer Dyspepsia
Definition
It is not unusual for there to be confusion when a diagnosis is based on symptoms alone. This is undoubtedly the case with non-ulcer dyspepsia (NUD), but it is an essential diagnostic group because it represents up to 40% of patients who present with ‘persistent or recurrent pain or discomfort that is centred in the upper abdomen or epigastrium’ (dyspepsia), and in whom upper GI endoscopy and radiology are normal. Symptoms can be subdivided into:
· Ulcer-like dyspepsia
Epigastric pain relieved by food, often occurring at night
· Dysmotility-like dyspepsia
Upper abdominal discomfort, worse after meals, accompanied with bloating, early satiety and nausea
· Reflux-like dyspepsia
Upper abdominal pain with associated reflux symptoms. This classification has not proved to be helpful in tailoring therapy, except for reflux-like symptoms which might be better treated as for GORD. The pathology responsible for causing the symptoms of NUD has focused on two main areas:
1. Gastric dysmotility
2. Helicobacter pylori-related gastritis.
During fasting, the stomach exhibits migrating motor complexes (MMCs) along with the rest of the GI tract and post-prandially shows relaxation of the gastric fundus to accommodate the food bolus. The antrum has high amplitude contractions to reduce particle size and the pylorus has phasic contractions to allow slow emptying of the stomach. There may be decreased compliance of the gastric fundus in NUD patients but this does not correlate well with symptoms, particularly nausea and early satiety, nor does it predict a good outcome with treatment using promotility agents.
H. pylori-related gastritis has come under close scrutiny in patients with NUD. There appears to be no benefit accrued by eradicating H. pylori in patients with NUD. Gastric acid hypersecretion does not cause NUD as basal and peak acid output is similar in both patients and controls
Table
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Sensitivity (%) |
Specifity (%) |
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Non-invasive |
|
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Serology |
88-99 |
86-95 |
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Urea breath test |
90-97 |
90-100 |
|
Invasive (requiring endoscopy) |
|
|
|
Rapid urease test (CLO test) |
89-98 |
93-98 |
|
Histology |
93-99 |
95-99 |
|
Culture |
77-92 |
100 |
|
* Includes cost of endoscopy |
|
|
|
Taken from Secrets in Gl/liver disease |
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Dyspepsia
· Non-ulcer dyspepsia is a diagnostic term that may encompass a number of conditions including gastritis and gastric dismotility. Peptic ulceration may be the real cause of symptoms if endoscopy has been performed at a time when the ulcer has healed.
· Gastritis is a histological or endoscopic description which may or may not be associated with dyspeptic symptoms. There are many causes including drugs, alcohol and H. pylori and all shoul considered.
· H. pylori is an infection usually acquired in childhood and which persists through life.
· H. pylory is closely associated with gastritis, and duodenal and gastric ulceration and may be important in the development of gastric cancer.
· Eradication of H. pylori results in ulcer healing and vastly lower recurrence rate compared to ulcers healed simply with acid suppression therapy.
Treatment
After the diagnosis of NUD, subsequent further investigation should be avoided as it implies diagnostic uncertainty and may worsen therapeutic outcome. Minimum treatment required should be adopted with simple antacids. More intractable cases may be treated with H2 receptor antagonists or PPIs for 4-6 weeks and then discontinued and reserved for symptom recurrence. Promotility agents may be beneficial and are best taken shortly before meals. Evidence supporting the usefulness of H. pylori eradication in NUD patients is lacking but as peptic ulcer disease is periodic, it is possible that patients were in remission at the time of endoscopy. Consequently, it may be appropriate to offer H. pylori eradication therapy in patients showing relevant symptoms
The treatment of the patients suffering from fuctional dyspepsia syndrome must be complex and include life style normalization, dietary recommendations and drug therapy.
Adequete life style means to avoid harmful habits, situations causing stress (negative emotions, physical and emotional overstrain).
Dietary treatment such patients is if great importance, meaning that the patients should intake small portions of meals with a low fat content 405 times a day.
In case of H-pylori eradication antihelicobacteria therapy is indicated according to one of the schemes (
While treating patients with functional dyspepsia antacids are widely used as they are able to reduce gastric content acidity. They are divided into two groups: soluble and insoluble. Soluble ones are rarely used becouse they can cause different side effects. Maaloks is one of the most often used insoluble drugs.
Renny is often used too.
If it is necessary inhibiting proton, pump is indicated (omeprazol, lankoprazol, pantoprazol, rabeprazol, ezomeprzol – standard dose or a half of a dose).
The patients with functional dyspepsia often suffer from gastric movements disorders, so, prokinetyks are of great importance contributing to gastric movements normalization. Metoklopramid, domperydon are widely used. Prokinetyks are prescribed 3 times a day (10 mg) 15 min. before meals.
Chronic gastritis
Chronic gastritis is common in adults and may be associated with a number of conditions including gastric ulcers and Helicobacter pylori (HP). It usually involves the gastric body and antrum of the stomach. Most patients are asymptomatic and do not require any treatment. At present there is no indication for widespread use of HP eradication therapy in patients with chronic gastritis but without evidence of peptic ulcer disease.
Chronic gastritis can be classified as:
• Type A (autoimmune)
• Type B (bacterial infection)
• Type C (reflux gastritis)
Type A: autoimmune chronic gastritis (ACG)
ACG involves the body of the stomach but does not affect the antral region and results from autoimmune activity against parietal cells. The histological features are diffuse chronic inflammation, atrophy and loss of fundi glands, intestinal metaplasia and sometimes hyperplasia of enterochromaffin-like (ECL) cells. In some patients the degree of gastric atrophy is severe and loss of intrinsic factor secretion leads to pernicious anaemia. The gastritis itself is usually asymptomatic but some patients have evidence of other organ-specific autoimmunity, particularly thyroid disease. There is a fourfold increase in the risk of gastric cancer development.
Type B: bacterial infection
HP infection is present in about 90% of Type B gastritis cases. It provokes an acute inflammatory response. Type B gastritis can affect the entire stomach.
Type C: reflux gastritis
Reflux gastritis is caused by the regurgitation of duodenal contents into the stomach through the pylorus. It may be present with dyspepsia and bilious vomiting.
The early phase of chronic gastritis is superficial gastritis. The inflammatory changes are limited to the lamina propria of the surface mucosa, with edema and cellular infiltrates separating intact gastric glands. Additional findings may include decreased mucus in the mucous cells and decreased mitotic figures in the glandular cells. The next stage is atrophic gastritis. The inflammatory infiltrate extends deeper into the mucosa, with progressive distortion and destruction of the glands. The final stage of chronic gastritis is gastric atrophy. Glandular structures are lost; there is a paucity of inflammatory infiltrates. Endoscopically the mucosa may be substantially thin, permitting clear visualization of the underlying blood vessels.
Signs and Symptoms
Deficiencies of intrinsic factor lead to vitamin B12 deficiency and a condition of pernicious anemia. Deficiencies of hydrochloric acid (hypochlorhydria) induce the production of G (Gastrin producing) cells. Increased proliferation of G cells causes excess gastrin production, which in turn increases the risk for development of gastric polyps and gastric adenocarcinoma (stomach cancer).
Early in the course of the disease, symptoms rarely occur although mild symptoms of indigestion may be present. Autoimmune atrophic gastritis is the most frequent cause of pernicious anemia in temperate climates. The risk of gastric adenocarcinoma is reported to be at least 2.9 times higher in patients with pernicious anemia than in the general population. Patients with pernicious anemia are also at increased risk for esophageal squamous-cell carcinomas.
Autoimmune atrophic gastritis typically causes symptoms related to vitamin B12 (cobalmin) deficiency, including anemia, gastrointestinal symptoms, and neurologic symptoms including dementia. Megaloblastic anemia may develop, and rarely platelet deficiency (thrombocytopenia) may occur. Symptoms of anemia include weakness, light-headedness, vertigo, tinnitus, palpitations, angina and symptoms of congestive heart failure. Other symptoms include sore tongue, weight loss, irritability, mild jaundice, and heart enlargement.
ACG involves the body of the stomach but does not affect the antral region and results from autoimmune activity against parietal cells. The histological features are diffuse chronic inflammation, atrophy and loss of fundi glands, intestinal metaplasia and sometimes hyperplasia of enterochromaffin-like (ECL) cells. In some patients the degree of gastric atrophy is severe and loss of intrinsic factor secretion leads to pernicious anaemia. The gastritis itself is usually asymptomatic but some patients have evidence of other organ-specific autoimmunity, particularly thyroid disease. There is a fourfold increase in the risk of gastric cancer development.
Type C: reflux gastritis
Reflux gastritis is caused by the regurgitation of duodenal contents into the stomach through the pylorus. It may be present with dyspepsia and bilious vomiting.
Chronic gastritis is identified histologically by an inflammatory cell infiltrate consisting primarily of lymphocytes and plasma cells, with very scant neutrophil involvement. Distribution of the inflammation may be patchy, initially involving superficial and glandular portions of the gastric mucosa. This picture may progress to more severe glandular destruction, with atrophy and metaplasia. Chronic gastritis has been classified according to histologic characteristics. These include superficial atrophic changes and gastric atrophy.
The early phase of chronic gastritis is superficial gastritis. The inflammatory changes are limited to the lamina propria of the surface mucosa, with edema and cellular infiltrates separating intact gastric glands. Additional findings may include decreased mucus in the mucous cells and decreased mitotic figures in the glandular cells. The next stage is atrophic gastritis. The inflammatory infiltrate extends deeper into the mucosa, with progressive distortion and destruction of the glands. The final stage of chronic gastritis is gastric atrophy. Glandular structures are lost; there is a paucity of inflammatory infiltrates. Endoscopically the mucosa may be substantially thin, permitting clear visualization of the underlying blood vessels. Gastric glands may undergo morphologic transformation in chronic gastritis. Intestinal metaplasia denotes the conversion of gastric glands to a small intestinal phenotype with small-bowel mucosal glands containing goblet cells. The metaplastic changes may vary in distribution from patchy to fairly extensive gastric involvement. Intestinal metaplasia is an important predisposing factor for gastric cancer.
Treatment of the gastritis.
Treatment in chronic gastritis is aimed at the sequelae and not the underlying inflammation. Patients with pernicious anemia will require parenteral vitamin B12 supplementation on a long-term basis. Eradication of H. pylori is not routinely recommended unless PUD or a low-grade MALT lymphoma is present.
Miscellaneous Forms of Gastritis. Lymphocytic gastritis is characterized histologically by intense infiltration of the surface epithelium with lymphocytes. The infiltrative process is primarily in the body of the stomach and consists of mature T cells and plasmacytes. The etiology of this form of chronic gastritis is unknown. It has been described in patients with celiac sprue, but whether there is a common factor associating these two entities is unknown. No specific symptoms suggest lymphocytic gastritis. A subgroup of patients has thickened folds noted on endoscopy. These folds are often capped by small nodules that contain a central depression or erosion; this form of the disease is called varioliform gastritis. H. pylori probably plays no significant role in lymphocytic gastritis. Therapy with glucocorticoids or sodium cromoglycate has obtained unclear results.
Marked eosinophilic infiltration involving any layer of the stomach (mucosa, muscularis propria, and serosa) is characteristic of eosinophilic gastritis. Affected individuals will often have circulating eosinophilia with clinical manifestation of systemic allergy. Involvement may range from isolated gastric disease to diffuse eosinophilic gastroenteritis. Antral involvement predominates, with prominent edematous folds being observed on endoscopy. These prominent antral folds can lead to outlet obstruction. Patients can present with epigastric discomfort, nausea, and vomiting. Treatment with glucocorticoids has been successful.
Several systemic disorders may be associated with granulomatous gastritis. Gastric involvement has been observed in Crohn’s disease. Involvement may range from granulomatous infiltrates noted only on gastric biopsies to frank ulceration and stricture formation. Gastric Crohn’s disease usually occurs in the presence of small-intestinal disease. Several rare infectious processes can lead to granulomatous gastritis, including histoplasmosis, candidiasis, syphilis, and tuberculosis. Other unusual causes of this form of gastritis include sarcoidosis, idiopathic granulomatous gastritis, and eosinophilic granulomas involving the stomach. Establishing the specific etiologic agent in this form of gastritis can be difficult, at times requiring repeat endoscopy with biopsy and cytology. Occasionally, a surgically obtained full-thickness biopsy of the stomach may be required to exclude malignancy.
Antibiotic treatment should therefore be considered in all H. pylori-infected patients with chronic H. pylori-induced gastritis
Antibiotic therapy for H. pylori is evolving. Single agents should not be used because no single antibiotic can predictably cure most H. pylori infections. Initially, bismuth-based triple therapy was recommended. This approach is being challenged by simpler dual drug regimens, which include the use of acid-blocking drugs. Regardless of which therapy is used, antibiotic resistance, physician counseling, and patient compliance determine its success.
H2 blockers have a role in the treatment of chronic H. pylori-induced gastritis but are no longer primary therapy when used alone; they are frequently used as antisecretory drugs in an anti–H. pylori regimen. With differing potencies and half-lives, each drug (cimetidine, ranitidine, famotidine, and nizatidine) is a competitive inhibitor of histamine at the H2 receptor. Histamine plays an important role in vagal and gastrin-stimulated acid secretion, thereby making H2 blockers effective suppressors of basal gastric acid output and acid output stimulated by food, the vagus nerve, and gastrin. Gastric juice volume is proportionately reduced. Histamine-mediated pepsin secretion is also decreased.
H2 blockers are well absorbed from the GI tract, with 37 to 90% bioavailability. Onset of action is 30 to 60 min after ingestion, and effects peak at 1 to 2 h. I/V administration produces a more rapid onset of action. Duration of action is proportional to dose and ranges from 6 to 20 h. Several hepatic metabolites, inactive or less active than the parent compound, are produced, but much unchanged drug is eliminated via the kidney, requiring dose adjustment for renal function. Hemodialysis removes H2 blockers, and redosing is necessary after dialysis. Doses often should be reduced in the elderly.
Cimetidine has minor antiadrenergic effects expressed as reversible gynecomastia and, less commonly, impotence in a few patients on high doses for prolonged periods (eg, hypersecretors). Mental status changes, diarrhea, rash, drug fever, myalgias, thrombocytopenia, and sinus bradycardia and hypotension after rapid I/V administration have been reported with all H2 blockers, generally in < 1% of treated patients but more commonly in the elderly.
Cimetidine and, to a lesser extent, other H2 blockers interact with the P-450 microsomal enzyme system and may delay metabolism of other drugs eliminated through this system (eg, phenytoin, warfarin, theophylline, diazepam, lidocaine).
Proton pump inhibitors are potent inhibitors of the proton (acid) pump (ie, the enzyme H+,K+-ATPase), located in the apical secretory membrane of the parietal cell. Proton pump inhibitors can completely inhibit acid secretion and have a long duration of action.
Proton pump inhibitors are key components of many anti–H. pylori regimens. In active H. pylori-induced gastritis, omeprazole 20 mg/day orally or lansoprazole 30 mg/day orally is usually continued for 2 wk after completion of antibiotic therapy to ensure complete healing of the H. pylori-induced gastritis.
Although it was originally surmised that long-term proton pump inhibitor therapy could predispose to the formation of stomach cancer, this does not appear to be the case. Likewise, although patients infected with H. pylori taking proton pump inhibitors develop gastric atrophy, this does not appear to lead to metaplasia or increased risk of gastric adenocarcinoma. Prolonged suppression of gastric acid raises theoretical but undocumented concerns of bacterial overgrowth, susceptibility to enteric infection, and vitamin B12 malabsorption.
Certain prostaglandins (especially misoprostol) can inhibit acid secretion and enhance mucosal defense. The role of synthetic prostaglandin derivatives in the management of peptic ulcer disease is predominantly in the area of N SAID-induced mucosal injury. Patients at high risk for NSAID-in-duced ulcers (ie, the elderly, those with a past history of ulcer or ulcer complication, those also taking corticosteroids) are candidates for misoprostol 200 μg orally 4 times a day along with their NSAID. Common side effects of misoprostol are abdominal cramping and diarrhea, which occur in 30% of patients. Misoprostol is a powerful abortifacient and is absolutely contraindicated in women of childbearing age who are not using contraception.
Sucralfate is a sucrose-aluminum complex that promotes ulcer healing. It has no effect on acid output or gastrin secretion. Its suspected mechanisms of action include inhibition of pepsin-substrate interaction, stimulation of mucosal prostaglandin production, and binding of bile salts. Sucralfate also appears to have trophic effects on the ulcerated mucosa, possibly by binding growth factors and concentrating them at the ulcer site. In the acid milieu of the stomach, sucralfate dissociates and forms a barrier over the ulcer base, protecting it from acid, pepsin, and bile salts.
Systemic absorption of sucralfate is negligible. Constipation occurs in 3 to 5% of patients. Sulcrafate may bind to other medications, interfering with their absorption.
Antacids give symptomatic relief, promote ulcer healing, and reduce recurrence. They are relatively inexpensive but must be taken five to seven times per day. The optimal antacid regimen for ulcer healing appears to be 16 to 30 mL of liquid or 2 to 4 tablets 1 and 3 h after each meal and at bedtime. The total daily dosage of antacids should provide 200 to 400 mEq neutralizing capacity.
In general, there are two types: (1) Absorbable antacids (eg, sodium bicarbonate), which provide rapid, complete neutralization, may occasionally be taken short-term for intermittent symptomatic relief. However, because they are absorbed, continuous use may cause alkalosis or milk-alkali syndrome. (2) Nonabsorbable antacids (relatively insoluble salts of weak bases) are preferred because of fewer systemic side effects. They interact with hydrochloric acid to form poorly absorbed salts, thereby increasing gastric pH. Pepsin activity diminishes as gastric pHl rises to > 4.0, and pepsin may be adsorbed by some antacids. Antacids may interfere with the absorption of other drugs (eg, tetracycline, digoxin, iron).
Aluminum hydroxide is a relatively safe, commonly used antacid. With chronic use, phosphate depletion may rarely develop as a result of binding of phosphate by aluminum in the GI tract. The risk of phosphate depletion increases in alcoholics, malnourished patients, and patients with renal disease, including those receiving hemodialysis. Aluminum hydroxide causes constipation.
Magnesium hydroxide is a more effective antacid than aluminum but may cause diarrhea. To limit diarrhea, many proprietary antacids contain both magnesium and aluminum hydroxides; some contain aluminum hydroxide and magnesium trisilicate. The latter tends to have less neutralizing potency. Because small amounts of magnesium are absorbed, magnesium preparations should be used with caution in patients with renal disease.
Anti–H. pylori therapy (
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Triple therapy
(Lansoprazole 30mg twice daily) |
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Quadruple therapy
(Lansoprazole 30mg twice daily) |
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