Download Gastro-oesophageal reflux disease (GORD)

l
REVIEW
Gastro-oesophageal reflux disease
(GORD)
Karen van Rensburg, BPharm
Abstract
Gastro-oesophageal reflux disease is a common gastrointestinal disease. Patients who suffer from this
condition report a broad spectrum of symptoms. The symptom most commonly associated with gastrooesophageal disease is heartburn (usually experienced behind the breastbone) occurring at least two to
three times per week. It usually occurs 30–60 minutes after meals, resolving spontaneously or with the
use of antacids. The goal of the treatment of GORD is to provide adequate symptomatic relief, to heal
oesophagitis if it is present and to prevent complications from developing. Empirical treatment is often
implemented based on an adequate history and presence of the most common symptoms.
Introduction
Gastro-oesophageal reflux disease (GORD) has become one
of the most common gastrointestinal diseases affecting between 10–40% of the population in Western countries.1,2
Patients who suffer from this condition report a broad spectrum
of symptoms, making it difficult to reach a consensus as to what
exactly constitutes typical reflux disease. The American Journal of
Gastroenterology published a definition in 2002 as agreed upon
at a Brazilian consensus conference: “GORD is a chronic disorder
related to the retrograde flow of gastro-duodenal contents into the
oesophagus and/or adjacent organs, resulting in a spectrum of
symptoms, with or without tissue damage”. This definition recognises the chronic character of the disease, and acknowledges that
the refluxate can be gastric and duodenal in origin, with important
implications for the treatment of the disease.3
gastro-oesophageal barrier, and at present, only fundoplication (a surgical procedure to treat gastro-oesophageal reflux
disease and hiatus hernia) is known to correct the functionality
of the sphincter.4,5
Abnormal gastric emptying could also contribute to GORD by
increasing intragastric pressure. Gastroprokinetic agents such
as metoclopramide can improve gastric emptying and should
be considered.3,4
Hiatus hernias occur commonly and are not always associated
with any symptoms. But, in patients with GORD, they are associated with higher amounts of acid reflux and delayed oesophageal
acid clearance leading to oesophagitis. Hiatus hernias are associated with recurrence of failure of medical therapy for GORD.3,4
Aetiology
Signs and symptoms
Various factors contribute to the development of GORD. Under
healthy conditions, a very effective barrier exists between the
stomach and the oesophagus. Firstly, peristalsis and salivary
production promote oesophageal clearance. And secondly, a
valve system exists between the oesophagus and the stomach
to prevent reflux. This valve comprises of the lower oesophageal sphincter (LOS), the diaphragm, the His angle, the Gugaroff valve and the phrenoesophageal membrane.3
The symptom most commonly associated with GORD is heartburn (usually experienced behind the breastbone) occurring
at least two to three times per week. It usually occurs 30–60
minutes after meals, resolving spontaneously or with the use
of antacids. The pain associated with heartburn can often be
confused with angina pectoris.1,4,6
Defective peristalsis can be associated with GORD as it is the
main determinant of oesophageal clearance of the refluxate. In
2001, Diener reported that between 40–50% of patients with
GORD suffer from abnormal peristalsis.3 This causes the refluxate to move through the oesophagus at a slower pace, being
in contact with the mucosa for a longer period of time causing
mucosal damage, often resulting in a dry and irritating cough.4
GORD is also associated with a mechanically incompetent
LOS.3,5 An incompetent LOS is a permanent defect of the
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Dysphagia (difficulty in swallowing) due to erosive oesophagitis and regurgitation (the perception of flow of refluxed gastric
content into the mouth) are also commonly present.1
More recently, various “atypical” symptoms are also being
recognised with increasing frequency, such as asthma, chronic
coughing, sore throat and chronic laryngitis.4
Complications that can occur include oesophagitis, oesophageal ulcers, peptic oesophageal stricture and Barrett’s
metaplasia.
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Diagnosis
GORD is usually diagnosed based upon the symptoms and the
response to treatment. Obtaining a careful history can often point
to the correct diagnosis. Performing tests may not always be
necessary, as patients with reflux who do not suffer from complications, can often be treated simply by making lifestyle changes
or with the use of medications. If the diagnosis is unclear or if
complications are present, specific testing might be required.
Oesophagoscopy
Oesophagoscopy is usually the initial evaluation of suspected
GORD and a biopsy can be performed at the same time if required.
In South Africa, the Los Angeles classification system is used
to grade the severity of oesophagitis (see Table I).
Two thirds of patients have a normal endoscopy and are termed
non-erosive reflux disease.1,7 These patients should however be
treated in a similar fashion to those with erosive oesophagitis as
the other symptoms in these patients are just as difficult to control.
Ambulatory oesophageal pH monitoring1,4,7
This diagnostic guideline helps to confirm GORD in patients
with persistent symptoms without evidence of mucosal damage, especially when a trial of acid suppressing medication has
failed. Ambulatory pH monitoring can be done via a transnasally placed catheter or a wireless capsule shaped device that
is affixed to the distal oesophageal mucosa. Monitoring the pH
this way is useful and indicated:
•• To document abnormal oesophageal acid exposure if a
patient with a normal endoscopy but is being considered for
antireflux surgery.
•• To monitor patients who have been unresponsive to treatment with proton pump inhibitors.
Complications
Barrett’s oesophagus
This condition occurs when the normal squamous cells that line
the lower oesophagus are replaced by intestinal cells. This is
the result of repeated damage to the lining of the oesophagus
after a long period of time. These patients often do not experiTable I: Los Angeles classification of endoscopic grading1
Grade
Description
A
One or more mucosal breaks no longer than 5 mm, none
of which extends between the tops of the mucosal folds.
B
One or more mucosal breaks more than 5 mm long, none
of which extends between the tops of two mucosal folds.
C
Mucosal breaks that extend between the tops of two or
more mucosal folds, but which involve less than 75% of
oesophageal circumference.
D
Mucosal breaks which involve at least 75% of oesophageal circumference.
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ence any symptoms different to that from GORD, other than
dysphagia due to impaired motility. Barrett’s oesophagus can
develop into oesophageal adenocarcinoma.1,4
Stricture
The oesophagus can be scarred due to acid damage, which may
lead to subsequent narrowing (stricture), most commonly at the
gastroesophageal junction. Ironically, this stricture can cause a reduction in heartburn as the stricture can act as a barrier to reflux.4
Treatment
The goal of treatment is to provide adequate symptomatic relief, to heal oesophagitis if it is present and to prevent complications from developing. Empirical treatment is often implemented based on an adequate history and presence of the most
common symptoms. When patients do not respond to empirical
treatment, further examinations may need to be conducted.
The severity of the disease is often an indicator of the type of
treatment required.
Lifestyle changes
Many patients with mild symptoms may benefit from lifestyle
modifications, although on its own, lifestyle changes are not
likely to completely control symptoms in the majority of patients.
Patients should be educated about the factors that can precipitate and aggravate reflux. Various studies have encouraged
elevation of the head of the bed, decreased fat intake, smoking
cessation and weight loss to reduce symptoms of GORD.1,7 Patients should be advised to avoid acidic food (e.g. citrus fruits,
tomato products, spicy foods) and foods that can cause the
LOS to relax (e.g. chocolates, peppermint and alcohol).
Acid suppression through use of medication
There are five main classes of drugs that have been evaluated
for treatment of GORD:
•• Surface agents
•• Antacids
•• Prokinetics
•• Histamine-2 receptor antagonists
•• Proton pump inhibitors
Surface agents4,8
Surface agents create a barrier that helps prevent injury to
mucosal surfaces of the stomach and oesophagus. The two
agents that have been evaluated in the treatment of GORD are
sodium alginate and sucralfate.
Products containing sodium alginate (e.g. Gaviscon®) form a
surface gel that creates a physical barrier against regurgitation
of gastric contents and protects the oesophageal mucosa.
Sucralfate (Ulsanic®) is a sucrose hydrogen sulphate aluminium complex. It acts as a mucosal protective agent and
assists in ulcer healing without altering gastric acid secretion.
It stimulates angiogenesis by binding to injured tissue, delivering growth factor and reducing the access that acid has to the
mucosa.
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REVIEW
Antacids
Most antacids are readily available over the counter. Although
antacids can give rapid relief of pain, their duration of action is
usually relatively short (2 hours).
Many over-the-counter antacids contain a combination of
Al(OH)3 and Mg(OH)2, e.g. Maalox®, Mucaine®. These products
have the advantage that they do not affect bowel function as
much as the individual components on their own would have.
The drugs in this class include omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. (See Table II.)
Surgery3,4,7,8
Surgical fundoplication, although controversial, provides good
to excellent relief of symptoms in over 85% of appropriately selected patients and is more effective than medical management
for the treatment of GORD in the short to medium term.
Surgical treatment should only be considered for: a) Otherwise
healthy patients with extraoesophageal manifestations of reflux,
Prokinetics4,8
Color profile: Generic CMYK printer profile
Promotility drugs like metoclopromide and cisapride
can Default
help screen b) for patients with severe reflux disease who are not willing to
Composite
take medication every day because of the cost, inconvenience
to reduce reflux by increasing the pressure of the LOS thereby
or potential risks thereof, c) patients with
enhancing oesophageal peristalsis and
erosive disease who are intolerant of or
gastric emptying. Because of various
resistant to PPIs.
side-effects associated with these drugs,
they are often used only as a last resort in
patients who have failed antisecretory therConclusion
It's the
apy (proton pump inhibitors and histamine
It is clear that the pathophysiology of GORD
type 2 receptor antagonists) and for pais multifactorial, creating disagreement as
shell that
tients who are healthy (no evidence or acid
to what typically constitutes typical GORD.
makes
reflux or other disease on evaluation) for
It is important to remember that not all pawhom quality of life is adversely affected
tients require diagnostic evaluation such as
safer.
by recurrent vomiting or regurgitation.
endoscopy, and should only be performed
on patients presenting with complications
Cisapride has been known to prolong QT
or patients who have not responded to an
Safety-Coated
intervals, leading to cardiac arrhythmias
empirical trial of PPI therapy.
81mg
and metoclopramide may cause neuropsyThe ORIGINAL low dose aspirin
chiatric side-effects due to its mechanism
Unfortunately, most patients do not respond
for optimum cardio-protection
of action as a dopamine antagonist.
to lifestyle advice and require further
Each tablet contains Aspirin 81mg. Reg.No.: 29/2.7/0767
Pharmafrica (Pty) Ltd, 33 Hulbert Road, New Centre, Johannesburg 2001
therapy. H2RAs and PPIs are better than
Under licence from Goldshield Pharmaceuticals Ltd. U.K.
Histamine type 2 receptor antagonists
placebo in oesophagitis. Most patients need
Patients with uncomplicated GORD with reflux symptoms
that
long-term
treatment
because
the disease usually relapses.
55X75MM
23 September
occur several times a week can be treated empirically
with2008
H2 10:02:46 AM
PPIs are superior to histamine type 2 receptor antagonists
receptor antagonists (H2RAs). The H2RAs inhibit acid secre(H2RAs) in relieving symptoms and healing oesophagitis.
tion by blocking histamine H2 receptors on the parietal cell.
Surgery is still considered to be relatively controversial although
carefully selected patients treated by experienced surgeons
The two main H2RAs used in South Africa include cimetidine
have resulted in excellent outcomes.r
(Lenamet®) and ranitidine (Zantac®, Ranihexal®).
R
R
pH
For reflux oesophagitis, cimetidine should be taken at a dose
of 400 mg four times a day with meals and at bedtime for up to
12 weeks. The indicated dose for ranitidine is 150 mg twice a
day OR 300 mg at bedtime for eight to twelve weeks. It may be
increased to 150 mg four times a day for up to twelve weeks in
moderate to severe GORD.
Studies have shown that H2RAs are superior to placebo for healing
oesophagitis and improving symptoms. Their benefit is greatest
for patients with mild oesophagitis, but unfortunately tolerance can
eventually develop, limiting efficacy for long-term management.8
Proton pump inhibitors
Proton pump inhibitors (PPIs) block acid secretion by irreversibly
binding to and inhibiting the hydrogen-potassium ATPase pump
that resides on the luminal surface of the parietal cell membrane.
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References
1. Kahrilas PJ. Clinical Manifestations and diagnosis of gastroesophageal reflux
in adults. Up to date. Version 18.2 [Cited 2010 August 30]
2. Liakakos T, Karamanolis G, Patapis P, Misiakos EP. Gastroesophageal
Reflux Disease: Medical or surgical treatment. Gastroeneterology Research
and Practice. 2009:Article ID 371580.
3. Patti MG. Gatroesophageal reflux disease: From pathophysiology to treatment. World Journal of Gastroenterology. 2010:16(30):3745-3748
4. Tierney LM, McPhee SJ, Papadakis MA, editors. Current Medical Diagnosis
and Treatment 2003. 42nd edition. New York: McGraw-Hill. 2003.
5. Berkow R, editor. The Merck manual of diagnosis and therapy. 16th edition.
New Jersey: Merck Research Laboratories; 1992.
6. Kahrilas PJ. Patient information: Gastroesophageal reflux disease in adults.
Up to date. Version 17.3 [Cited 2010 Jan 18].
7. DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment
of gastroesophageal reflux disease. American Journal of Gastroenterology.
200;100:190-200.
8. Winter HS. Management of gastroesophageal reflux disease in children and
adolescents. Up to date Version 18.1 [Cited Aug 30]
9. Gibbon CJ, editor. South African Medicines Formulary. 6th edition. Western
Cape: Creda Communications. 2003.
10. Snyman JR, editor. Monthly index of medical specialities. Volume 49 number
9. September 2009
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Table II: Proton pump inhibitors available in South Africa4,5,9,10
Drug
Dose/Indications*
Drug Interactions
Schedule
Side effects
Omeprazole
Losec®
Recurrent reflux oesophagitis:
20 mg daily for 4–8 weeks
Reflux oesophagitis long-term
treatment: 10 mg daily, increase
to 20–40 mg if needed
Can prolong elimination of diazepam,
warfarin, phenytoin
Increases bioavailability of digoxin
S4
Skin rashes, gastrointestinal reactions, insomnia,
vertigo, malaise, muscle
weakness, blurred vision
Esomeprazole
Nexiam®
Erosive reflux oesophagitis:
40 mg once daily for 4–8 weeks
GORD: 20 mg once daily for 4
weeks
Prevention of relapse: 20 mg once
daily
Patients on NSAIDs: 20–40 mg
once daily
Prevention of gastric and duodenal ulcers associated with NSAID
therapy in patients at risk:
20 mg or 40 mg once daily.
IV: indicated where oral therapy is
not appropriate and for the shortest possible time
Erosive reflux oesophagitis:
40 mg once daily for 4 weeks
Long-term management to prevent relapse: 20 mg once daily
Severe reflux: 20 mg once daily
Maintenance of haemostasis and
prevention of rebleeding of gastric
or duodenal ulcers:
80 mg administered as bolus infusion over 30 minutes followed by
a continuous intravenous infusion
of 8 mg/hr given over 3 days
Possible increase/decrease in absorption of drugs influenced by stomach
acid, ketoconazole, itraconazole,
prolonged diazepam clearance,
increased phenytoin plasma concentrations, slight elevation of warfarin
trough plasma concentration
S4
Headache, dizziness,
blurred vision, abdominal
pain, skin reactions, dry
mouth
Lansoprazole
Lanzor®
Oesophagitis due to gastrooesophageal reflux: 30 mg daily
for 4 weeks depending on endoscopic results
Dyspepsia: 15 mg daily for 2–4
weeks
Maintenance for prevention of
gastro-oesophageal reflux:
15 mg daily
Lanzor HB®/Lansoloc OTC®: 15
mg once daily as short-term relief
of heartburn and acid dyspepsia
Bioavailability reduced by sucralfate,
affects absorption of drugs sensitive to
acid environment
S4
Lansoloc OTC® S2
Lanzor HB® S2
Pantoprazole
Pantoloc®
Gastric ulcer and reflux
oesophagitis: 40 mg daily for 4–8
weeks
Mild GORD: 20 mg daily for 4–8
weeks
GORD relapse prevention:
20 mg daily, increase to 40 mg in
case of relapse then reduce to
20 mg daily after healing
Lesions caused by NSAIDs:
20 mg once daily
Possible changes in absorption of
pH-dependant medications e.g.
ketoconazole
S4
GI disturbances, allergic
reactions, headaches,
dizziness, depression,
jaundice
Rabeprazole
Pariet®
Erosive or ulcerative GORD: Oral,
20 mg once daily 4–8 weeks.
Maintenance to prevent relapse:
10–20 mg once daily for up to
twelve months
Ketoconazole, itraconazole, increased
digoxin levels
S4
Headache, GI disturbances, allergic reactions, cough, leg cramps,
dizziness
Abdominal pain, allergic reactions, halitosis,
malaise, arthralgia,
Steven-Johnson
* These products all have additional indications, only those relevant to this article have been highlighted
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