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8/13/2019 Gastroesophageal Reflux Disease Pharmacotherapy
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Gastroesophageal Reflux
Disease Pharmacotherapy
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"a condition that occurs when the refluxed stomach
contents lead to troublesome symptoms and/orcomplications. Episodic heartburn that is not frequent enough or painful
enoughto be considered bothersome by the patient is notincluded in this definition of GERD
Gastroesophageal reflux symptoms associated with
disease processes in organs other than the esophagus arereferred to as extraesophageal reflux syndromes. Patientswith extraesophageal reflux syndromes may present withreflux chest pain syndrome, laryngitis, or asthma
Definition
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Esophageal GERD syndromes are classified as either symptom-
basedor tissue injury baseddepending on how the patientpresents. Symptom-based esophageal GERD syndromes may exist with or
without esophageal injury and most commonly present asheartburn, regurgitation or dysphagia. Less commonly,odynophagia (painful swallowing) or hypersalivation may occur
Tissue injurybased syndromes may exist with or withoutsymptoms. The spectrum of injury includes esophagitis(inflammation of the lining of the esophagus), Barrettesophagus (when tissue lining the esophagus is replaced bytissue similar to the lining of the intestine), strictures, andesophageal adenocarcinoma
Clasification
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Gastroesophageal reflux disease occurs in people of all ages but is mostcommon in those older than age 40 years
The true prevalence and incidence of GERD is difficult to assessbecausemany patients do not seek medical treatment, symptoms do not alwayscorrelate well with the severity of the disease, and there is nostandardized definition or universal gold standard method fordiagnosing the disease
10% to 20% of adults in Western countries suffer from GERD symptomson a weekly basis. The prevalence of GERD varies depending on thegeographic region butappears highest in Western countries
does not appear to be a major difference in incidence between menand women. Although gender does not generally play a major role in thedevelopment of GERD, it is an important factor in the development ofBarrett esophagus. Barrett esophagus is most prevalent in white adultmales in Western countries andmay increase the risk foradenocarcinoma of the esophagus especially in white males
Other risk factors and comorbidities that may contribute to thedevelopment or worsening of GERD symptomsinclude family history,
obesity, smoking, alcohol consumption, certain medications and foods,respiratory diseases, and reflux chest pain syndrome.
Epidemiology
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The key factorin the development of GERD is the abnormal reflux ofgastric contents from the stomach into the esophagus
gastroesophageal reflux is associated withdefective lower esophagealsphincter (LES) pressure or function
Problems with other normal mucosal defense mechanisms, such as
abnormal esophageal anatomy, improper esophageal clearance ofgastric fluids, reduced mucosal resistance to acid, delayed orineffective gastric emptying, inadequate production of epidermalgrowth factor, and reduced salivary buffering of acid, may alsocontribute to the development of GERD
Substances that may promote esophageal damage upon reflux into theesophagusinclude gastric acid, pepsin, bile acids, and pancreaticenzymes.
Thus the composition and volume of the refluxate, as well as durationof exposure, are important aggressive factors in determining theconsequences of gastroesophageal reflux.
Rational therapeutic regimens in the treatment of gastroesophagealreflux are designed to maximize normal mucosal defense mechanisms
and attenuate the aggressive factors.
Pathophysiology
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1. Lower Esophageal Sphincter Pressure The sphincter is normally in a tonic, contracted state, preventing the reflux
of gastric material from the stomach but relaxes on swallowing to permitthe free passage of food into the stomach
Although theexact mechanism is unknown, esophageal distension,vomiting, belching, and retching cause relaxation of the LES
decreases in LES pressure is probably dependent on numerous factors,including the degree of sphincter relaxation, efficacy of esophagealclearance, patient position (more common in recumbent position), gastricvolume, and intragastric pressure. Second, reflux may occur followingtransient increases in intraabdominal pressure (stress reflux). An increasein intraabdominal pressure such as that occurring during straining,
bending over, coughing, eating, or a Valsalva maneuver may overcome aweak LES, and thus may lead to reflux. Third, the LES may be atonic, thuspermitting free reflux as seen in patients with scleroderma Althoughtransient relaxations are more likely to occur when there is normal LESpressure, the lattertwo mechanisms are more likely to occur when the LESpressure is decreased by such factors as fatty foods, gastric distension,smoking, or certain medications Various foods aggravate esophageal reflux
by decreasing LES pressure or by precipitating symptomatic reflux by directmucosal irritation (e.g., spicy foods, orange juice, tomato juice, and coffee).
Pathophysiology
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2. Anatomic Factors Disruption of the normal anatomic barriers by a hiatal hernia (when a portion of the
stomach protrudes through the diaphragm into the chest) was once thought to be aprimary etiology of gastroesophageal reflux and esophagitis 3. Esophageal Clearance In many patients with GERD, the problem is not that they produce too much acid but
that the acid produced spends too much time in contact with the esophageal mucosa The esophagus is cleared byprimary peristalsis in response to swallowing, or by
secondary peristalsis in response to esophageal distension and gravitational effects. esophageal damage caused by reflux occurs more often in the elderly and similarly
for patients with Sjgren syndrome or xerostomia Swallowing is also decreased during sleep, making nocturnal GERD a problem in
many patients
Pathophysiology
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4. Mucosal Resistance
Within the esophageal mucosa and submucosa there are mucus-secreting glands that may contribute to the protection of theesophagus
Bicarbonate moving from the blood to the lumencan neutralize acidic
refluxate in the esophagus Saliva is also rich in epidermal growth factor, stimulating cell renewal
5. Gastric Emptying
An increase in gastric volume may increase both the frequency ofreflux and the amount of gastric fluid available to be refluxed
Factors that increase gastric volume and/or decrease gastric emptying,such as smoking and high-fat meals, are often associated withgastroesophageal reflux
The delay in emptying may promote regurgitation of feedings, whichmight, in turn, contribute to two common complications of GERD in
infants (e.g., failure to thrive and pulmonary aspiration)
Pathophysiology
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6. Composition of Refluxate The composition, pH, and volume of the refluxate are important
aggressive factors in determining the consequences ofgastroesophageal reflux
First, if the pH of the refluxate is less than 2, esophagitis may
develop secondary to protein denaturation. In addition,pepsinogen is activated to pepsin at this pH and may also causeesophagitis. Duodenogastric reflux esophagitis, or "alkalineesophagitis," refers to esophagitis induced by the reflux ofbilious and pancreatic fluid
An increase in gastric bile concentrations may be caused byduodenogastric reflux as a result of a generalized motilitydisorder, slower clearance of the refluxate, or after surgery
the percentage of time that the esophageal pH is
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Symptom-based esophageal GERD syndromes (with or without esophageal tissue injury)Typical symptoms (May be aggravated by activities that worsen gastroesophageal reflux
such as recumbent position, bending over, or eating a meal high in fat.) Heartburn (hallmark symptom described as a substernal sensation of warmth or
burning rising up from the abdomen that may radiate to the neck. May be waxingand waning in character.
Water brash (hypersalivation) Belching RegurgitationAlarm symptoms (These symptoms may be indicative of complications of GERD such asBarrett esophagus, esophageal strictures, or esophageal adenocarcinoma.) Dysphagia Odynophagia
Clinical Presentation
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Tissue injurybased esophageal GERD syndromes (with or without esophagealsymptoms)
Symptoms (May present with alarm symptoms such as dysphagia, odynophagia orunexplained weight loss.) Esophagitis Strictures Barrett esophagus Esophageal adenocarcinomaExtraesophageal GERD syndromes
Symptoms (These symptoms have an association with GERD, but causality should only beconsidered if a concomitant esophageal GERD syndrome is also present.) Chronic cough Laryngitis Asthma Dental enamel erosion
Clinical Presentation
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Clinical history Generally sufficient to clinically diagnose GERD for patients with typical symptoms.Endoscopy Preferred for assessing the mucosa for esophagitis, identifying Barrett esophagus and diagnosing
complications. Non-inflammatory GERD and major motor disorders may be missed by endoscopy. If no erosions, does not definitively show symptoms are GERD-related.Ambulatory pH monitoring
Identifies patients with excessive esophageal acid exposure and helps determine if symptoms are acidrelated.
Useful for patients not responding to acid-suppression therapy. Documents the percentage of time the intraesophageal pH is
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Desired Outcomes
(1) alleviate or eliminate the patient's symptoms, (2)decrease the frequency or recurrence and durationof gastroesophageal reflux, (3) promote healing ofthe injured mucosa, and (4) prevent the
development of complications
Treatment
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Therapy is directed at (1) decreasing the acidity of
the refluxate, (2) decreasing the gastric volumeavailable to be refluxed, (3) improving gastricemptying, (4) increasing LES pressure, (5) enhancingesophageal acid clearance, and (6) protecting the
esophageal mucosa.
Treatment
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Evidence Base Medicine
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Non Pharmacologic therapy
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Pharmacologic therapy
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Pharmacologic therapy
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