3B CTC08 Gerd 10.01.16

Pamantasan ng Lungsod ng Maynila
(University of the City of Manila)

Intramuros, Manila
COLLEGE OF MEDICINE
Department of Pharmacology, Toxicology, and Therapeutics
Section of Medical Therapeutics and Clinical Pharmacology
CLINICOTHERAPEUTIC CONFERENCE
CASE NO. 8
GASTROESOPHAGEAL REFLUX DISEASE
In Partial Fulfilment of the Requirements in

Medical Therapeutics and Clinical Pharmacology
Date Submitted:
October 1, 2016
Submitted by:
3rd YearSection B
Group 8
Butial, John Rex C. Approach, Introduction, Non-pharma, Suitability
Garcia, Leslie Noelle P. Pathophysiology, Safety
Monteverde, Michael Robert Q. Diagnostics, Affordability
Sabater, Enrico P. Epidemiology, Etiology/Risk Factors, Efficacy

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CASE
A 30 year old male was complaining of chest pain. He was cleared by the cardiologist and
pulmonologist. He underwent upper GI endoscopy revealing esophagitis, rule out Barrett's. Give
the prescription.
SALIENT FEATURES
Chest pain
Cardiopulmonary pathologies - cleared
Esophagitis; r/o Barretts esophagus
APPROACH TO DIAGNOSIS
Figure 1. Diagnostic Algorithm
GASTROESOPHAGEAL REFLUX DISEASE

INTRODUCTION
Currently, GERD is conceptualized to encompass a family of conditions that are thought
to be similarly caused by gastroesophageal reflux which then result to troublesome symptoms,
or esophageal and extraesophageal manifestations. The injuries that may result from GERD
include esophagitis, stricture, Barretts esophagus, and esophageal adenocarcinoma. Typical
symptoms of GERD are heartburn and regurgitation. Less common symptoms include chest
pain and dysphagia. The primary management in these patients are acid inhibitors. However, in
patients presenting with chest pain and persistent dysphagia, cardiac disease for the former,
and a peptic stricture or adenocarcinoma secondary to chronic reflux for the latter, should be
carefully considered and evaluated (Kahrilas& Hirano, 2015).
Extraesophageal syndromes associated with GERD are chronic cough, laryngitis,
asthma, and dental erosions. Other conditions that have proposed associations with GERD
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include pharyngitis, chronic bronchitis, pulmonary fibrosis, chronic sinusitis, cardiac arrhythmias,
sleep apnea, and recurrent aspiration pneumonia. Potential mechanisms for extraesophageal
symptoms are either regurgitation and subsequent contact of the refluxate and the
extraesophageal structure, or via vagovagal reflex which trigger bronchospasm, cough, and
arrhythmias (Kahrilas& Hirano, 2015).
Differential diagnoses of GERD include infectious pill, eosinophilic esophagitis, peptic
ulcer disease, dyspepsia, biliary colic, coronary artery disease, and esophageal motility disease.
It is especially important to rule out coronary artery disease because of its lethal implications. To
evaluate these conditions, diagnostic examination include endoscopy, upper gastrointestinal
series, or biliary tract ultrasonography. Etiologies of esophagitis are made distinct by endoscopy
with mucosal biopsies. When GERD is not treated, complications may arise including bleeding
and strictures from chronic esophagitis, and adenocarcinoma. The most severe histologic
complication of GERD is Barretts metaplasia with associated risk of adenocarcinoma. Barretts
esophagus can progress to adenocarcinoma through the intermediate stages of low- and high-
grade dysplasia. Most important risk factors for developing adenocarcinoma include obesity,
race (white), male, and age being in the sixth decade (Kahrilas & Hirano, 2015).
EPIDEMIOLOGY
GERD is an increasingly common disorder that is encountered in the daily practice.
While it is initially thought as a disease common in the West, there has been an increasing trend
in Asia, including the Philippines, with a prevalence rate of erosive esophagitis increasing from
1.8% in 1995 to 12.6% in 2002. In our country, the prevalence of erosive esophagitis has
increased from 2.9% (1994-1997) to 6.3% (2000-2003). It is also estimated that around 11-12%
of the general population have non-erosive reflux disease (NERD) (Sollano, et al., 2015).
ETIOLOGY AND RISK FACTORS

A subset of GERD patients have esophagitis, which occurs when refluxed gastric acid
and pepsin cause necrosis of the esophageal mucosa causing erosion and ulcers. Esophagitis
results from excessive reflux, often accompanied by impaired clearance of the refluxed gastric
juice. Three dominant mechanisms of esophagogastric junction incompetence are recognized:
(1) transient LES relaxation, (2) LES hypotension, or (3) anatomic distortion of the
esophagogastric junction inclusive of hiatus hernia (Kasper, et al., 2015).
Factors tending to exacerbate reflux regardless of the said mechanisms are abdominal
obesity, pregnancy, gastric hypersecretory states, delayed gastric emptying, disruption of
esophageal peristalsis and gluttony (Kasper, et al., 2015).
PATHOPHYSIOLOGY
The esophagus has two physiologic sphincters, namely, the upper and lower
esophageal sphincter. The distal esophagus and LES are composed of smooth muscle and are
controlled by excitatory and inhibitory neurons within the esophageal myenteric plexus.
Medullary preganglionic neurons from the dorsal motor nucleus of the vagus trigger peristalsis
via these ganglionic neurons during primary peristalsis. Neurotransmitters of the excitatory
ganglionic neurons are acetylcholine and substance P; those of the inhibitory neurons are
vasoactive intestinal peptide and nitric oxide. Peristalsis results from the patterned activation of
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inhibitory followed by excitatory ganglionic neurons, with progressive dominance of the inhibitory
neurons distally. Similarly, LES relaxation occurs with the onset of deglutitive inhibition and
persists until the peristaltic sequence is complete.
At rest, the LES is contracted because of excitatory ganglionic stimulation and its
intrinsic myogenic tone, a property that distinguishes it from the adjacent esophagus. The
function of the LES is supplemented by the surrounding muscle of the right diaphragmatic crus,
which acts as an external sphincter during inspiration, cough, or abdominal straining. Transient
lower esophageal sphincter relaxation defines the pathogenesis of gastroesophageal reflux.
Some degree of gastroesophageal reflux is normal, physiologically intertwined with the
mechanism of belching (transient LES relaxation), but esophagitis results from excessive reflux,
often accompanied by impaired clearance of the refluxed gastric juice (Kasper, et al., 2015).
Three dominant mechanisms of esophagogastric junction incompetence are recognized:
(1) transient LES relaxations (a vagovagal reflex in which LES relaxation is elicited by gastric
distention), (2) LES hypotension, or (3) anatomic distortion of the esophagogastric junction
inclusive of hiatus hernia. Transient LES relaxations account for about 90% of reflux in normal
subjects or GERD patients without hiatus hernia, but patients with hiatus hernia have a more
heterogeneous mechanistic profile (Kasper, et al., 2015).
Gastroesophageal reflux can also occur following swallow-induced lower esophageal
sphincter relaxations or due to forceful opening of a relatively hypotensive lower esophageal
sphincter by an abrupt increase in intraabdominal pressure, such as that due to coughing,
straining, or bending. Other conditions that decrease lower esophageal sphincter tone or
increase abdominal pressure and contribute to GERD include alcohol and tobacco use, obesity,
central nervous system depressants, pregnancy, hiatal hernia, delayed gastric emptying, and
increased gastric volume. In many cases, no definitive cause is identified. Reflux of gastric
juices is central to the development of mucosal injury in GERD. In severe cases, reflux of bile
from the duodenum may exacerbate the damage.
Figure 2. Model of GERD Pathogenesis in Adults

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After acid reflux, peristalsis returns the refluxed fluid to the stomach and acid clearance
is completed by titration of the residual acid by bicarbonate contained in swallowed saliva.
Inherent in the pathophysiologic model of GERD is that gastric juice is harmful to the
esophageal epithelium. However, gastric acid hypersecretion is usually not a dominant factor in
the development of esophagitis. Pepsin, bile, and pancreatic enzymes within gastric secretions
can also injure the esophageal epithelium, but their noxious properties are either lessened
without an acidic environment or dependent on acidity for activation. Bile warrants attention
because it persists in refluxate despite acid-suppressing medications. Bile can traverse the cell
membrane, imparting severe cellular injury in a weakly acidic environment, and has also been
invoked as a cofactor in the pathogenesis of Barretts metaplasia and adenocarcinoma. Hence,
the causticity of gastric refluxate extends beyond hydrochloric acid (Boeckxstaens, 2014).
The best-defined subset of GERD patients, albeit a minority overall, have esophagitis,
which is evident in the patient in this case. Esophagitis occurs when refluxed gastric acid and
pepsin cause necrosis of the esophageal mucosa causing erosions and ulcers.
Another complication is Barretts esophagus is a complication of chronic GERD that is
characterized by intestinal metaplasia (squamous to columnar) within the esophageal
squamous mucosa due to constant insult from the refluxed gastric acid. The incidence of
Barretts esophagus is rising, and it is estimated to occur in as many as 10% of individuals with
symptomatic GERD. Barrett esophagus is most common in white males and typically presents
between 40 and 60 years of age. The greatest concern in Barrett esophagus is that it confers an
increased risk of esophageal adenocarcinoma (Kumar, et.al., 2015).
DIAGNOSTICS
The presence of the classical symptoms of gastroesophageal reflux disease, such as
water brash and substernal heartburn, are sufficient for the presumptive diagnosis and empirical
treatment (Kasper, et al., 2015). The following diagnostic tests are used to support the
diagnoses:
24-hour pH Monitoring
The 24-hour ambulatory pH monitoring is the most sensitive test for the diagnosis of
GERD (Kasper, et al., 2015). It is accepted as the gold standard for establishing or
excluding the presence of GERD in patients who do not possess mucosal changes.
However, it provides information on the amount of esophageal reflux but not non-acid reflux.
In this test the pH within the esophageal lumen will be monitored for at least 24
hours. The two kinds of systems in used are the catheter-based and wireless based.
Traditional systems use a long transnasal catheter that is connected directly to the recording
device. The wireless ones uses a capsule directly attached to the esophageal mucosa under
endoscopic visualization and the data are transmitted by radiotelemetry to the recording
device.
Barium Study
A Barium study can be used to demonstrate well the anatomy and possible
complications of a reflux disease. However, a conclusive diagnosis of reflux disease cannot
be made using barium esophagography. Barium swallow is not sensitive in the detection of
actual reflux, except in the occasional patient who has a wide-open LES and free reflux.
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During a barium esophagogram, a high-density barium suspension is administered,

and double-contrast views are used for images taken with the patient in the upright position.
Prone-positioned images are typically obtained with single contrast and a lower-density
barium suspension.
Manometry
Also known as motility testing, it entails positioning a pressure-sensing catheter
within the esophagus and then observing the contractility following test swallows. This test is
used to diagnose motility disorders and to assess peristaltic integrity prior to the surgery for
reflux disease.
Esophagogastroduodenoscopy (EGD)
Esophagogastroduodenoscopy is most useful for evaluating the proximal
gastrointestinal tract. It produces high-quality colored images of the esophagus, stomach,
and duodenal lumen. Moreover, it has an instrumentation channel through which biopsy
forceps, injection catheters for local delivery of therapeutic agents, balloon dilators, or
hemostatic devices can be used.
The main advantages of this procedure is that it increases the sensitivity of detection
of abnormalities mainly identifiable by color such as Barretts metaplasia or vascular lesions.
Also, it provides the ability to obtain biopsy specimens for histologic examinations of
suspected abnormalities. However, the downside is that it is costly and requires the use of
sedatives or anesthetics.
THERAPEUTIC GOALS
1 Alleviate or eliminate patients symptoms
1. Decrease the frequency or recurrence and duration of gastroesophageal reflux
2. Promote healing of injured mucosa (esophagitis)
3. Prevent the development of complications
NON-PHARMACOLOGIC MANAGEMENT
As part of the non-pharmacological management of GERD, lifestyle modifications are
routinely and strongly advocated. These include avoidance of refluxogenic foods which
include: fatty foods, alcohol, spearmint, peppermint, tomato-based foods, and possible coffee
and tea; avoidance of acidic foods that are inherently irritating; and adoption of behaviors to
minimize reflux and heartburn. It is also encouraged for patients to consume smaller meals
rather than large meals. For patients with sleep disturbance because of nighttime heartburn, it
will be beneficial for that patient to elevate the head of bed (by putting a foam wedge under the
mattress to elevate head of bed by 6 to 8 inches) and to avoid eating before lying down. Weight
reduction has also been shown to be broadly applicable for GERD patients. Avoidance of
alcohol, alcohol, and tight-fitting clothes is also encouraged (Kahrilas& Hirano, 2015).
Aside from lifestyle modifications, it is also important to evaluate patient profiles and
medications taken by the patient. Medications that can decrease LES pressure are
anticholinergics, barbiturates, calcium channel blockers, and theophylline. Medications that can
be a direct mucosal irritant are aspirin, iron, NSAIDs, quinidine, potassium chloride, and
bisphosphonates. For patients taking bisphosphonates, they should be instructed to drink 6 to 8
oz of plain tap water and remain upright for 30 minutes after taking the medication. Smoking can
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also cause aerophagia which can lead to increased belching and regurgitation (Williams
&Schade, 2011).
PHARMACOLOGIC MANAGEMENT
Figure 3. Therapeutic Interventions for GERD (Source: Williams &Schade, 2011).
The general drug groups considered are antacids

, histamine-2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), prokinetics,
and sucralfate. Antacids have been used for centuries in treatment of patients with dyspepsia
and acid-peptic diseases. Antacids react with hydrochloric acid to form a salt and water which
effectively buffers the acidity. H2RAs exhibit competitive inhibition at parietal cell H2 receptor
and suppress both basal and meal-stimulated acid secretion. PPIs form a covalent disulfide
bond with the H+/K+ ATPase which irreversible inactivates the enzyme. Mucosal protective
agents act by, being negatively charged, binding to positively charged proteins at the base of
erosions or ulcers which lead to the formation of a protective barrier as well as stimulation of
prostaglandin production and bicarbonate secretion. Lastly, the role prokinetic agents in the
management of GERD is by stimulating esophageal peristaltic amplitude, LES sphincter
pressure, and enhance gastric emptying (McQuaid, 2015).
DRUG GROUP SELECTION

ESSA CRITERIA
A. EFFICACY
Table 1.Criteria for Efficacy scoring
CRITERION # CRITERIA CONSIDERED POINTS
1 Able to reduce or eliminate symptoms +

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2 Able to promote healing of injured mucosa or esophagitis +

(Another + if has the highest remission rate among the
drug classes)
3 Able to decrease recurrence of gastroesophageal +

symptoms or esophagitis
(Another + if it results to lowest recurrence among the
drug classes)
4 Able to prevent complications of GERD +
B. SAFETY
Table 2.Criteria for Safety scoring
1 Minimal and reversible side effects +
2 No associated severe adverse drug reactions +
3 Minimal drug-drug/food interaction +
4 Less risk for organ toxicity/damage +
C. SUITABILITY/NECESSITY
Table 3. Criteria for Suitability/Necessity scoring
1 Indicated as first line therapy +
2 No contraindications for use in the case +
3 Can be used as stand-alone drug for the case +
4 Compliance to treatment +
D. AFFORDABILITY
Table 4. Criteria for Affordability scoring
1 Available locally in generic form +
2 Cost-effectiveness +
3 Total drug regimen cost less than ave OOP expenditure +

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(Php 2,191.9/year or Php 182.66/month)
EFFICACY
ANTACIDS
Antacids are weak bases that react with gastric HCl to form a salt and water. They are
composed of different combinations of acid-neutralizing agents such as aluminum and
magnesium hydroxide, calcium carbonate, sodium citrate and sodium bicarbonate. The principal
mechanism of action of antacids is to reduce intragastric acidity (Katzung, et al., 2012).
A single dose of 156 mEq of antacid given 1 hour after a meal effectively neutralizes
gastric acid for up to 2 hours. Because antacids provide rapid acid neutralization, they afford
faster symptom relief than H2 antagonists. However the effect of antacids is short-lived (1-2
hours) (Katzung, et al., 2012).In a study conducted by Weberg and Berstad (1989), it was
shown that during the treatment with antacids, there were lower global symptomatic scores, less
acid regurgitation and fewer days and nights with heartburn than during placebo therapy.
According to Hirschcovici and Fass (2011), while antacids provide rapid but transient
symptom relief, they do not contribute to healing of erosive esophagitis (EE) or prevention of
GERD complications.
Table 5. Efficacy scoring for Antacids

Criteria Criteria Considered Points
2 Able to promote healing of injured mucosa or esophagitis

(Another + if has the highest remission rate among the drug
classes)
3 Able to decrease recurrence of gastroesophageal symptoms

or esophagitis
(Another + if it results to lowest recurrence among the drug
classes)
4 Able to prevent complications of GERD
TOTAL 1
HISTAMINE-2 RECEPTOR ANTAGONISTS
The H2 antagonists exhibit competitive inhibition at the parietal cell H2 receptor and
suppress basal and meal-stimulated acid secretion in a linear, dose-dependent manner
(Katzung, et al., 2012). They are highly selective and do not affect H1 or H3 receptors. Reduction
of acid secretion by H2 receptor antagonists can be accomplished through two mechanisms.
First, histamine released from ECL cells by gastrin or vagal stimulation is blocked from binding
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to the parietal cell H2 receptor, making them very effective at inhibiting nocturnal acid secretion
that largely depends on histamine. Secondly, they also have a modest impact on meal-
stimulated acid secretion that depends on stimulation by gastrin, acetylcholine and histamine
because direct stimulation of the parietal cell by gastrin or acetylcholine has a diminished effect
on acid secretion in the presence of H2-receptor blockade (Katzung, et al., 2012).
When given in usual prescription doses, they inhibit 60-70% of total 24-hour acid
secretion. The effect of H2RAs lasts for 6-10 hours. Empiric treatment of GERD with PPI
provides sustained symptomatic relief in 70-80% of patients (Katzung, et al., 2012).
Three RCTs reported a dichotomous outcome, evaluating 610 participants at six weeks
(Moayyediet al., 2010). Overall, symptoms persistence in the group taking H2RA therapy was
57.7% compared to 83.7% in the placebo group. There was statistically significant benefit of
taking H2RA compared to placebo in symptom relief (RR of persistence at six weeks 0.67, 95%
CI 0.48 to 0.95).
In patients with erosive esophagitis, which happens in approximately 50% of patients
with GERD, H2RA afford healing in less than 50% of patients (Katzung, et al., 2012). Ten RCTs
reported a dichotomous outcome for H2RA versus placebo, evaluating 1241 participants at six
weeks (Moayyediet al., 2010). Overall, esophagitis persistence in the group taking H2RA was
59.0% compared to 79.7% in the placebo group. There was statistically significant benefit of
taking H2RA compared to placebo in healing of esophagitis (RR of persistence at four weeks
0.74, 95% CI 0.66 to 0.84).
Two RCTs reported a dichotomous outcome for symptom relief evaluating 451 patients
(Donnellan, et al., 2005). Overall 28% had significant symptoms in the group taking H2RAs
compared to 50.4% in the placebo group. H2RAs were significantly better than placebo at
maintaining remission of symptoms (RR of relapse = 0.52; 95% CI 0.41 to 0.67) with a NNT of
4.0 (95% CI 2.9 to 6.7).
Four RCTs reported a dichotomous outcome for H2RA therapy versus placebo in the
maintenance therapy of esophagitis (Donnellan, et al., 2005). Overall 26.6% of participants
relapsed in the group taking H2RAs, compared to 47.3% in the placebo group. There was
marginal statistically significant benefit of taking H2RA therapy compared to placebo to maintain
remission of esophagitis (RR of relapse 0.57; 95% CI 0.32 to 1.01).
Table 6. Efficacy scoring for Histamine-2 Receptor Antagonists


classes)
3 Able to decrease recurrence of gastroesophageal symptoms +

or esophagitis
classes)
Page 10 of 40
TOTAL 3
PROTON PUMP INHIBITORS
PPIs are lipophilic weak bases. PPIs are prodrugs that after absorption in the intestines,
they diffuse readily across lipid membranes into acidified compartments like the parietal cell
canaliculus (Katzung, et al., 2012). The prodrug then becomes protonated within the canaliculus
and is concentrated more than 1000-fold by Henderson-Hasselbalch trapping. There, it is
rapidly converted to its active form, a reactive thiophilic sulfonamide cation, which forms a
covalent disulfide bond with the H+/K+-ATPase, irreversibly inactivating the enzyme. Because
they block the proton pump itself, PPIs can inhibit both nocturnal and meal-stimulated acid
secretion (Katzung, et al., 2012).
In standard doses, PPIs can inhibit 90-98% of 24-hour acid secretion. Owing to the
irreversible inactivation of the proton pump, acid inhibition by PPIs can last up to 24 hours. PPIs
are the most effective agents for the treatment of nonerosive and erosive reflux disease. Empiric
treatment of GERD with PPI provides sustained symptomatic relief in 70-80% of patients
(Katzung, et al., 2012).
One RCT reported a dichotomous outcome evaluating 50 participants at eight weeks
(Moayyedi et al., 2010). Overall in 60.0% of participants symptoms persisted in the group taking
standard dose PPI compared to 96.0% in placebo group at the end of treatment. There was a
statistically significant benefit of taking healing dose PPI therapy compared to placebo in
symptom relief (RR of persistence of symptoms at eight weeks 0.63; 95%CI 0.5-0.9).
Once daily dosing provides effective symptom relief and tissue healing in 85-90% of
patients with GERD. Five RCTs have been selected by Moayyediet al. (2010) which reported a
dichotomous outcome for standard dose of PPI versus placebo in the short term treatment of
esophagitis; evaluating 645 participants at eight weeks. Overall in 16.8% of participants
esophagitis persisted in the group taking a standard dose of PPIs, compared to 71.7% in the
placebo group. There was a statistically significant benefit of taking standard dose PPI therapy
compared to placebo in healing of esophagitis; RR of esophagitis persistence at eight weeks
0.24 (95% CI 0.19-0.31).
Nine RCTs reported a dichotomous outcome for symptom relief, evaluating 1334
participants between 26 and 52 weeks (Donnellan, et al., 2005). Overall 29.4% had had
significant symptoms in the group taking a healing dose of PPI compared to 76.3% in the
placebo group. There was a significant benefit of taking healing dose PPI therapy compared to
placebo to maintain remission of symptoms (RR of relapse 0.34; 95% CI 0.25 to 0.46).
Nine RCTs reported a dichotomous outcome for healing dose of PPI versus placebo in
the maintenance therapy of esophagitis (Donnellan, et al., 2005). Overall 21.7% of participants
relapsed in the group taking a healing dose of PPIs, compared to 78.8% in the placebo group.
There was a significant benefit of taking healing dose PPI therapy compared to placebo to
maintain remission of esophagitis (relative risk of relapse (RR) 0.26; 95% confidence interval
(CI) 0.19 to 0.36.
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While long-term studies are lacking regarding the effect of medical treatment in the
prevention of GERD complications such as strictures and Barretts esophagus, some studies
show that omeprazole can resolve many peptic strictures associated with esophagitis and keep
the patients dysphagia free for up to 6 months (Marks et al., 1992). A study by Dent, et al.
(1990) supports the use of aggressive acid suppression in patients with severe esophagitis,
either high dose H2-blockers or omeprazole and reported that Barrett's esophagus rarely
develops de novo or progresses after effective control of esophagitis.
Kaynard and Flora (2001) reported that PPI therapy is especially appropriate for patients
with strictures or Barrett's esophagitis and should also be strongly considered in patients with
atypical manifestations of GERD, such as asthma, chronic cough, or laryngitis.
According to Scholten (2007), proton pump inhibitors are widely recognized as the most
effective agents for treating GERD. They are the mainstay of initial GERD management and are
the preferred agents for maintenance therapy in patients with healed erosive esophagitis. PPIs
also provide more rapid symptom control and better healing of erosive esophagitis than both H2
-receptor antagonists and antacids.
Table 7. Efficacy scoring for Proton Pump Inhibitors

2 Able to promote healing of injured mucosa or esophagitis ++

classes)
3 Able to decrease recurrence of gastroesophageal symptoms ++

or esophagitis
classes)
TOTAL 6
PROKINETICS
Metoclopramide and domperidone are dopamine D2receptor antagonists. Within the

gastrointestinal tract, activation of dopamine receptors inhibits cholinergic smooth muscle
stimulation; blockade of this effect is believed to be the primary prokinetic mechanism of action
of these agents. These agents increase esophageal peristaltic amplitude, increase lower
esophageal sphincter pressure, and enhance gastric emptying but have no effect on small
intestine or colonic motility (Katzung, et al., 2012). It has been proposed that prokinetic drugs
improve GERD by increasing LES basal pressure, improving esophageal peristalsis,
accelerating esophageal acid clearance and facilitating gastric emptying (Hirschcovici and Fass,
2011).
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The benefit of these compounds in controlling heartburn and in healing erosive

esophagitis has been relatively modest. According to Moayyediet al. (2010), one RCT reported
a dichotomous outcome for prokinetic versus placebo, evaluating 322 participants at eight
weeks. Heartburn persistence in the group taking prokinetic therapy was 75.5%, compared to
81.1% in the group taking placebo. There was no statistically significant benefit of taking
prokinetic therapy compared to placebo in heart burn relief (RR of persistence at eight weeks
0.93, 95% CI 0.83 to 1.04).
Three RCTs regarding the effects of prokinetics versus placebo have been identified by
the review of Moayyediet al. (2010), evaluating 198 participants at 12 weeks. Overall
esophagitis persistence in the group taking prokinetics was 53.1%, compared to 67.6% in the
group taking placebo. It was concluded that there was no statistically significant benefit of taking
prokinetic therapy compared to placebo in healing of esophagitis (RR of persistence at 12
weeks 0.71, 95% CI0.46 to 1.10).
Four RCTs reported a dichotomous outcome for symptom relief evaluating 1101
participants over 24 to 52 weeks (Donnellan, et al., 2005). All trials presented results in terms of
GSRS. Overall 45.1% had significant symptoms in the group taking prokinetics compared to
68.3% in the placebo group. There was no significant benefit of taking prokinetic therapy
compared to placebo to maintain remission of symptoms (RR of relapse 0.77; 95% CI 0.56 to
1.07).
Four RCTs reported a dichotomous outcome for prokinetics versus placebo in the
maintenance therapy of esophagitis, evaluating 1011 participants between 24 and 52 weeks
(Donnellan, et al., 2005). Overall 40.5% of participants relapsed in the group taking prokinetics,
compared to 64.7% in the placebo group. There was a significant benefit of taking prokinetic
therapy compared to placebo to maintain remission of esophagitis (RR of relapse 0.65; 95% CI
0.50 to 0.84).
Table 8. Efficacy scoring for Prokinetics


classes)
3 Able to decrease recurrence of gastroesophageal symptoms

or esophagitis
classes)
TOTAL 1
MUCOSAL PROTECTIVE AGENTS
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Sucralfate, an aluminum salt of a sulfated disaccharide, is considered a mucosal

protectant that binds to inflamed tissue to create a protective barrier. It is supposed to block
diffusion of gastric acid and pepsin across the esophageal mucosa and inhibit the erosive action
of pepsin and possibly bile (Hirschcovici and Fass, 2011). In water or acidic solutions it forms a
viscous, tenacious paste that binds selectively to ulcers or erosions for up to 6 hours. While the
precise mechanism of action is still unclear, it is believed that the negatively charged sucrose
sulfate binds to positively charged proteins in the base of ulcers or erosion, forming a physical
barrier that restricts further caustic damage and stimulates mucosal prostaglandin and
bicarbonate secretion (Katzung, et al., 2012).
One RCT reported a dichotomous outcome, evaluating 78 participants at six weeks
(Moayyediet al., 2010). Overall symptoms persistence in the group taking mucosal protecting
agent therapy was 72.5%, compared to 89.5% in the group taking antacid. There was no
statistically significant benefit of taking mucosal protecting agent therapy compared to antacid in
symptom relief (RR of persistence at six weeks 0.81, 95% CI 0.65 to 1.01).
Three RCTs reported a dichotomous outcome for mucosal protecting agent versus
antacid or placebo, evaluating 266 participants at six weeks (Moayyediet al., 2010). Overall
esophagitis persistence in the group taking mucosal protecting agent was 53.8% compared to
65.2% in the group taking antacid or placebo. There was no statistically significant benefit of
taking mucosal protecting agent therapy compared to antacid or placebo in healing of
esophagitis (RR of persistence at six weeks 0.82, 95% CI 0.67 to 1.01).
Two RCTs reported a dichotomous outcome for sucralfate versus placebo in the
maintenance therapy of esophagitis, evaluating 201 participants over 26 weeks (Donnellan, et
al., 2005). Overall 29.0% of participants relapsed in the group taking sucralfate, compared to
52.5% in the placebo group. There was a significant benefit of taking sucralfate compared to
placebo to maintain remission of esophagitis (RR of relapse 0.56; 95% CI 0.39 to 0.80) with a
NNT of 4.3 (95% CI 2.8 to 10).
Table 9. Efficacy scoring for Mucosal Protective Agent


classes)

or esophagitis
classes)
TOTAL 2
Page 14 of 40
Table 10. Summary of scores for efficacy of different drug classes

SUMMARY OF SCORES FOR EFFICACY
DRUG CLASS 1 2 3 4 Total
Antacids + 1
H2RA + + + 3
PPI + ++ ++ + 6
Prokinetics + 1
Mucosal Protective + + 2
Agent
SAFETY
ANTACIDS
Sodium bicarbonate (eg, AlkaSeltzer) reacts rapidly with hydrochloric acid (HCL) to
produce carbon dioxide and sodium chloride. Formation of carbon dioxide results in gastric
distention and belching. Unreacted alkali is readily absorbed, potentially causing metabolic
alkalosis when given in high doses or to patients with renal insufficiency. Sodium chloride
absorption may exacerbate fluid retention in patients with heart failure, hypertension, and renal
insufficiency. Calcium carbonate (eg, Tums) is less soluble and reacts more slowly than sodium
bicarbonate with HCl to form carbon dioxide and calcium chloride. Like sodium bicarbonate,
calcium carbonate may cause belching or metabolic alkalosis.
Calcium carbonate is used for a number of other indications apart from its antacid
properties Excessive doses of either sodium bicarbonate or calcium carbonate with calcium-
containing dairy products can lead to hypercalcemia, renal insufficiency, and metabolic alkalosis
(milk alkali syndrome).Formulations containing magnesium hydroxide or aluminum hydroxide
react slowly with HCl to form magnesium chloride or aluminum chloride and water. Because no
gas is generated, belching does not occur. Metabolic alkalosis is also uncommon because of
the efficiency of the neutralization reaction. Because unabsorbed magnesium salts may cause
an osmotic diarrhea and aluminum salts may cause constipation, these agents are commonly
administered together in proprietary formulations (eg, Maalox) to minimize the impact on bowel
function. Both magnesium and aluminum are absorbed and excreted by the kidneys. Hence,
patients with renal insufficiency should not take these agents long-term (Katzung, 2012).
All antacids are weak bases and may affect the absorption of other medications by
binding the drug (reducing its absorption) or by increasing intragastric pH. Therefore, antacids
should not be given within 2 hours of doses of tetracyclines, fluoroquinolones, itraconazole, and
iron. In general, antacids have rare adverse reactions leading to organ toxicity. However, the
fluid retention, hypercalcemia and milk-alkali syndrome brought about by excessive doses of
Page 15 of 40
calcium carbonates, and its drug-drug interaction affecting the absorption of other drugs, it only
scored 2 points on its safety profile.
Table 11. Safety scoring for Antacids

3 Minimal drug-drug/food interaction
One of the reasons for the widespread use of H2-receptor antagonists is their
remarkably low toxicity. H2 antagonists are extremely safe drugs. However, adverse effects
occur in less than 3% of patients and include diarrhea, headache, fatigue, myalgias, and
constipation. Mental status changes (confusion, hallucinations, agitation) may occur with
administration of intravenous H2 antagonists, especially in patients in the intensive care unit who
are elderly or who have renal or hepatic dysfunction but rarely occur in ambulatory patients
(Katzung, 2012).
Cimetidine, in particular, when used long-term or in high doses, may cause
gynecomastia or impotence in men and galactorrhea in women. These effects are specific to
cimetidine and do not occur with the other H2 antagonists. Although there are no known harmful
effects on the fetus, H2 antagonists can cross the placenta and is secreted into breast milk.
Therefore, they should not be administered to pregnant and lactating women unless absolutely
necessary. H2 antagonists may rarely cause blood dyscrasias (Katzung, 2012). 85 reported
cases of blood cytopenias attributed to these drugs are reviewed, of which 75 (88%) were
associated with cimetidine therapy. In postmarketing surveillance studies, the incidence of
cimetidine-associated blood cytopenia has been evaluated at about 2.3 per 100,000 patients.
Neutropenia and agranulocytosis are by far the most frequently encountered. Whatever the drug
or the type of cytopenia, this adverse effect is almost always rapidly reversible when treatment
is stopped (Aymard, 1988).
Cimetidine interferes with several important hepatic cytochrome P450 drug metabolism
pathways, including those catalyzed byCYP1A2, CYP2C9, CYP2D6, and CYP3A4.Hence, the
half-lives of drugs metabolized by these pathways (phase I reactions) maybe prolonged, leading
to potentially toxic plasma concentrations of therapeutic agents such as some oral
anticoagulants, beta-blockers, anticonvulsants, benzodiazepines and xanthenes (Penston,
1986). H2 antagonists (cimetidine and ranitidine) compete with creatinine and certain drugs (eg:
procainamide, quinine) for renal tubular secretion resulting in reduced urinary excretion and
hence potentially toxic plasma concentrations of these drugs (Penston, 1986). All of these
agents except famotidine inhibit gastric first-pass metabolism of ethanol, especially in women.
Page 16 of 40
Table 12. Safety scoring for Histamine-2 Receptor Antagonists

Proton pump inhibitors (PPIs) are generally safe but associated adverse events from
long-term use have generated concerns, i.e, vitamin B12deficiency; iron deficiency; increased
susceptibility to pneumonia, enteric infections, and fractures; and drug interactions. Long-term
administration of PPI is safe; however, careful consideration is needed in patient groups at risk
for complications (Sollano et al, 2015).
Proton pump inhibitors are extremely safe. Diarrhea, headache, and abdominal pain are
reported side effects in 15% of patients, although the frequency of these events is only slightly
increased compared with placebo. Increasing cases of acute interstitial nephritis have been
reported (Katzung, 2012).One drug-drug interaction specific to PPIs is its ability to attenuate
metabolism of clopidogrel to its active metabolite by inhibiting various hepatic CYP450
enzymes, mainly CYP2C19. Concomitant use of a PPI with clopidogrel reduces clopidogrel
active metabolite generation and subsequent platelet inhibition. Evidence from the only
randomized trial studying the clinical implications of the PPI-clopidogrel interaction did not
demonstrate any difference in cardiovascular outcomes but did show a reduction in
gastrointestinal bleeding with use of a PPI (Depta, 2012).
Recently, the use of proton pump inhibitors (PPIs) has been associated with an
increased risk of pneumonia. A study made by Gulmez, et al in 2007, tried to confirm this
association and identify the risk factors. The adjusted odds ratio (OR) associating current use of
PPIs with community-acquired pneumonia was 1.5 (95% confidence interval [CI], 1.3-1.7).
Recent initiation of treatment with PPIs (0-7 days before index date) showed a particularly
strong association with community-acquired pneumonia (OR, 5.0; 95% 2.1-11.7), while the risk
decreased with treatment that was started a long time ago (OR, 1.3; 95% CI, 1.2-1.4). Subgroup
analyses revealed high ORs for users younger than 40 years (OR, 2.3; 95% CI, 1.3-4.0). No
dose-response effect could be demonstrated. In conclusion, the use of PPIs, especially when
recently begun, is associated with an increased risk of community-acquired pneumonia.
According to the FDA (2012), reviewed reports from its Adverse Event Reporting System
(AERS) and found medical literature for cases of Clostridium difficile-associated diarrhea
(CDAD) in patients undergoing treatment with PPIs. Many of the adverse event reports involved
patients who were elderly, had chronic and/or concomitant underlying medical conditions, or
Page 17 of 40
were taking broad spectrum antibiotics that could have predisposed them to developing CDAD.
Patients who have one or more of these risk factors may have serious outcomes from CDAD
with concomitant PPI use. FDA also reviewed a total of 28 observational studies described in 26
publications. Twenty-three of the studies showed a higher risk of C. difficile infection or disease,
including CDAD, associated with PPI exposure compared to no PPI exposure. Although the
strength of the association varied widely from study to study, most studies found that the risk of
C. difficile infection or disease, including CDAD, ranged from 1.4 to 2.75 times higher among
patients with PPI exposure compared to those without PPI exposure.
Several publications in the late 2000s reported an association of PPI use with an
increased risk of osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture
was increased in patients who received high-dose, defined as multiple daily doses, and long-
term PPI therapy appropriate to the condition being treated. FDA evaluated the new safety
information to determine if necessary to require a safety labeling change. Majority of studies
reported an increased risk of fractures with the use of proton pump inhibitors. Kaye et al. (2008)
excluded patients with major risk factors for fracture and did not find a relationship between
proton pump inhibitor use and fractures. Two studies (Yang, 2006; Corley 2010) reported an
increase in fractures with higher doses of proton pump inhibitors. Two studies (Yang, 2008;
Targownik, 2008) reported an increase in fractures with longer duration of use. This led to a
safety labeling change by the FDA in 2010. Following a thorough review of available safety
data, FDA has concluded that fracture risk with short-term, low dose PPI use is unlikely and
because of this we have awarded 4 points for the safety profile of PPIs. Analysis of the
Manitoba Bone Mineral Density Database concluded that the association between PPI use and
hip fracture was probably due to other risk factors independent of osteoporosis (Sollano et al,
2015).
Table 13. Safety scoring for Proton Pump Inhibitors

PROKINETICS
The most common adverse effects of metoclopramide involve the central nervous
system. Restlessness, drowsiness, insomnia, anxiety, and agitation occur in 1020% of
patients, especially the elderly. Extrapyramidal effects (dystonias, akathisia, parkinsonian
features) due to central dopamine receptor blockade occur acutely in 25% of patients given high
doses and in 5% of patients receiving long term therapy. Last 2009, FDA warned against the
long-term use of drugs that contain Metoclopramide. It is approved for the short-term (no longer
Page 18 of 40
than 3 months) treatment of gastrointestinal disorders, such as gastroesophageal reflux disease

(GERD) in people who havent responded to other treatments. Frequent and long-term use of
metoclopramide has been linked to tardive dyskinesia, a disorder that causes uncontrollable,
repetitive movements of the body such as lip smacking, grimacing, tongue protrusion, puckering
and pursing of the lips, rapid eye movements or blinking, and rapid movements of the fingers,
arms, legs, and trunk. Increased risk is associated with older women and those on long term
therapy. Elevated prolactin levels (caused by both metoclopramide and domperidone) can
cause galactorrhea, gynecomastia, impotence, and menstrual disorders. Domperidone is
extremely well tolerated. Because it does not cross the blood-brain barrier to a significant
degree, neuropsychiatric and extrapyramidal effects are rare.
Table 14.Safety scoring for Prokinetics

2 No associated severe adverse drug reactions
4 Less risk for organ toxicity/damage
MUCOSAL PROTECTIVE AGENT
Sucralfate is only minimally absorbed from the gastrointestinal tract. The small amounts
of the sulfated disaccharide that are absorbed are excreted primarily in the urine. Because it is
not absorbed (Less than 3%), sucralfate is virtually devoid of systemic adverse effects.
Constipation occurs in 2% of patients due to the presence of aluminum salts. However, because
a small amount of aluminum is absorbed, it should not be used for prolonged periods in patients
with renal insufficiency (Katzung, 2012). Concomitant use of sucralfate with other products that
contain aluminum, such as aluminum-containing antacids, may increase the total body burden
of aluminum Aluminum accumulation and toxicity (aluminum osteodystrophy, osteomalacia,
encephalopathy) have been described in patients with renal impairment. Sucralfate should be
used with caution in patients with chronic renal failure (FDA, 2013). It may also bind to other
medications like, fluoroquinolones, digoxin, ketoconazole, sulpiride, levothyroxine, phenytoin,
warfarin, theophylline SR, impairing their absorption and decreasing their bioavailability (MIMS,
2015).
Table 15. Safety scoring for Mucosal Protective Agents

2 No associated severe adverse drug reactions

Page 19 of 40
4 Less risk for organ toxicity/damage
Table 16. Summary of scores for Safety of Drug Groups

SUMMARY OF SCORES FOR SAFETY
DRUG 1 2 3 4 Total
Antacids + + + 3
H2RA + + + 3
PPI + + + + 4
Prokinetics + 1
Mucosal + 1
Protective Agent
SUITABILITY
ANTACIDS
Antacids can reduce gastric acid for up to 3 hours in presence of food (Wallace &
Sharkey, 2011). However, its use in patients with GERD are only indicated for those with mild,
infrequent episodes of heartburn (McQuaid, 2015; Wallace & Sharkey, 2011). For patients with
erosive esophagitis, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists are
indicatedwith the former being superior (Wallace & Sharkey, 2011).
The use of antacids is contraindicated to those with hypersensitivity and those with
chronic renal failure (lack of excretion of aluminum may lead to encephalopathy and
osteomalacia) and hypophosphatemia (MIMS, 2014). Antacids are usually taken on-demand,
orally, 1 to 3 after meals and/or at bedtime (McQuaid, 2015; Wallace & Sharkey, 2011), and are
still commonly used by patients as nonprescription remedies for intermittent heartburn and
dyspepsia.
Table 17. Suitability scoring for Antacids

1 Indicated as first line therapy

Page 20 of 40
3 Can be used as stand-alone drug for the case
Although histamine-2 receptor antagonists (H2RAs) are effective therapy for GERD, it is
still inferior to proton pump inhibitors (PPIs) (Kahrilas& Hirano, 2015; Sollano, et al., 2015).
However, if the patient cannot tolerate PPIs, H2RAs can be used instead as monotherapy for
GERD (Sollano, et al., 2015). H2RAs, when used as monotherapy agent, can provide relief for
for up to 10 hours. Thus, it is usually taken orally, twice daily (McQuaid, 2015) for a duration
similar to that recommended for PPIs which is eight weeks (Sollano, et al, 2015). H2RAs can
also be taken on-demand in mild, infrequent heartburn and dyspepsia, with a longer duration of
symptom relief (6-10 hours) than antacids (1-2 hours) albeit slower onset of action (McQuaid,
2015).
Like the PPIs, H2RAs also have low incidence of adverse reactions and are also well-
tolerated (Wallace & Sharkey, 2011).The use of H2-blockers is contraindicated to those with
known hypersensitivity to H2-receptor antagonists. It is used in caution among those with renal
impairment since dosage adjustment is recommended in moderate to severe renal impairment
(Creatinine clearance <50 mL/min) (MIMS, 2014).
Table 18. Suitability scoring for Histamine-2 Receptor Antagonists

Proton pump inhibitors have consistently shown to be superior over other drugs
indicated for GERD, such as antacids, H2RAs, prokinetics, and sucralfate. Furthermore, it
shows superior and faster healing rates for erosive esophagitis. Thus, it is the recommended
first-line treatment for GERD and even for extraesophageal symptoms of GERD (McQuaid,
2015; Sollano, et al., 2015).
Contraindications in the use of proton pump inhibitors include those who have known
hypersensitivity to the active ingredient of proton pump inhibitors (MIMS, 2014). Moreover,
these should be used with caution in patients with severe hepatic disease. It is not
recommended for use in breastfeeding mothers (Vanderhoff&Tahboub, 2002).
Page 21 of 40
The acid inhibition of PPIs usually last up to 24 hours owing to its irreversible inhibition of
the proton pumps and it takes around 18 hours for the synthesis of new proton pumps
(McQuaid, 2015; Wallace & Sharkey, 2011). Thus, a once-daily dosing is the initial
recommendation for GERD with erosive esophagitis (Sollano, et al., 2015) which is sufficient
already to provide symptomatic relief and tissue healing in 85-90% of patients.PPIs also cause
remarkable few adverse reaction and thus, are well-tolerated (Wallace & Sharkey, 2011).
Table 19. Suitabiliity scoring for Proton Pump Inhibitors

PROKINETICS
The local clinical practice guidelines recommend proton pump inhibitors as the first line
medication for GERD (Sollano, 2015). Furthermore, prokinetics, such as metoclopramide and
domperidone have limited use for symptomatic GERD and are not effective for patients with
erosive esophagitis. Because of this and the superior efficacy and safety profile of anti-secretory
agents, prokinetic agents are mainly used as an adjunct to these anti-secretory agents
(McQuaid, 2015). Prokinetics are usually taken 15-30 minutes before a meal, orally, thrice daily.
Contraindications in the use of prokinetics include hypersensitivity to the specific drug
(e.g., metoclopramide), presence of gastrointestinal hemorrhage, mechanical obstruction, or
any perforation. In the use of metoclopramide, it is also contraindicated to those with
pheochromocytoma, epilepsy and other extrapyramidal diseases of the CNS (MIMS, 2014).
Table 20. Suitability scoring for Prokinetics

3 Can be used as stand-alone drug for the case
Page 22 of 40
Sucralfate has been used historically to treat peptic acid disease (Wallace & Sharkey,
2011). It also has been used in the management of GERD but is presently considered
outmoded Nevertheless, a meta-analysis of medications used in the management of GERD
show that monotherapy with sucralfate shows benefit over placebo (Donnellan, et al., 2005). In
another study, sucralfate, comparing with cimitedine (a histamine-2 receptor antagonist), has
shown nearly similar endoscopic improvement and a higher rate for healing of the esophagitis
(Tytgat, 1987). Sucralfate is usually taken 4 times daily, orally, at least an hour before meals
(McQuaid, 2015; MIMS, 2014) or 2 hours after meals (MIMS, 2014).
Contraindications in the use of sucralfate include those who have known hypersensitivity
to the active ingredient of sucralfate. It is also contraindicated to patients who are undergoing
hemodialysis (MIMS, 2014).
Table 21.Suitability scoring for Mucosal Protective Agent.

4 Compliance to treatment
Table 22. Summary of scores for Suitability of Drug Groups

SUMMARY OF SCORES FOR SUITABILITY
DRUG 1 2 3 4 Total
Antacids + + 2
H2RA + + + 3
PPI + + + + 4
Prokinetics + + 2
Mucosal + + 2
Protective Agent
AFFORDABILITY
According to the 2012 Family Income and Expenditure Survey, an average Filipino
household has an average out-of-pocket expenditure (OOPE) of about Php 3,415.1 for medical
Page 23 of 40
products, Php 2,191.9 of which are pharmaceutical products per year (Ulep and Dela Cruz,
2014).
ANTACIDS
Different formulations of antacids are available in the Philippines. The combination of

Aluminum Hydroxide + Magnesium Hydroxide is available as 200mg/100mg tablet for Php
1.50/tablet, if taken three times daily = Php 4.5/day or Php 126.00/month or Php 1,512 a year.
Antacids do not usually provide sufficient acid suppression for patients with GERD
(Scholten, 2007). This regimen is deemed to be cost-ineffective for it is suitable only for short-
term use and/or immediate relief of symptoms and does not address other therapeutic goals
such as: recurrence and duration of reflux, promotion of healing of the mucosal injury,
prevention of complication.
Table 23. Affordability Scoring for Antacids

2 Cost-effectiveness -

Ranitidine HCl 300 mg is available for as low as P4.75/tablet. Regimen normally lasts 8-
12 weeks. Hence, Ranitidine 300 mg po once daily is given for 8 weeks with a total cost of Php
266.00/regimen in two months.
An over-the-counter form of it exists as Ranitidine HCl (Zantac/Zantac 75).
H2RAs are considered to be the second-best treatment next to PPIs for GERD.
Table 24. Affordability scoring for Histamine-2 Receptor Antagonists


Page 24 of 40
Omeprazole 20 mg capsule (ULZOL) is available in the Philippines for Php 5.25/capsule.

A 4-week treatment regimen of Omeprazole 20 mg taken once daily will have a total computed
cost of Php 147.00 in a month/4-week regimen and Php 1,764.00 in a year.
RiteMed Omeprazole 20 mg capsule can be purchased over-the-counter.
Proton pump inhibitors are generally more expensive than H2RAs for the treatment of
GERD. However, there is no doubt about the superiority of the PPIs over other agents as the
most effective therapy in the management of GERD and the associated complications of reflux
disease, in terms of clinical endpoints (Schellack and Meyer, 2016).
Table 25. Affordability scoring for Proton Pump Inhibitors


PROKINETICS
Domperidone (Motilium), arguably the most popular form of Domperidone in the country,
is available as a 10 mg tablet to be taken three times daily costing Php = 2,772 per 100 tablet
(10 mg x 100s) with prescription. However, a cheaper, over-the-counter form exists as
Domperidone (Toridon) 10 mg to be taken three times daily (maximum of 2 weeks) costing Php
739.2 per month/2-week regimen or Php 17.60 per tablet.
This regimen is not cost-effective for it only address the relief of symptoms despite being
the 2nd most costly treatment. Other treatment goals were not met such as: recurrence and
duration of reflux, promotion of healing of the mucosal injury, prevention of complication.
Others OTC Domperidones:

Domperidone (GI NORM) 10 mg x 10s (Php 1,669.92)
Domperidone (TORIDON) tid 10 MG X 100S (Php 1,760.07)
Domperidone (ZYDOM 10) 1 tab tid 10 mg x 100s
Page 25 of 40
Table 26. Affordability scoring for Prokinetics

3 Total drug regimen cost less than ave OOP expenditure -

Sucralfate is only available in the Philippines as 1 g tablet to be taken four times daily. It
is marketed as 1 g x 100s for Php 4,262.40 or Php 42.624 per tablet or Php 4,773.89 a
month/4-week regimen. It is also the least effective treatment while, at the same time, being the
most expensive.
Table 27. Affordability scoring for Mucosal Protective Agent.

1 Available locally in generic form -
3 Total drug regimen cost less than ave OOP expenditure -

Table 28. Summary of scores for Affordability of Drug Groups

SUMMARY OF SCORES FOR AFFORDABILITY
DRUG 1 2 3 Total
Antacids + - + 2
H2RA + + + 3
PPI + + + 3
Prokinetics + - - 1
Mucosal - - - 0
Protective Agent
Page 26 of 40
SUMMARY OF ESSA CRITERIA (DRUG GROUPS)
Table 29. Summary of drug group selection

DRUG CRITERIA TOTAL
E S S A
ANTACIDS 1 3 2 2 8
H2RA 3 3 3 3 12
PPI 6 4 4 3 17
PROKINETICS 1 1 2 1 5
SUCRALFATE 2 1 2 0 5
P-DRUG SELECTION
Six proton pump inhibitors are available for clinical use: omeprazole, esomeprazole,
lansoprazole, dexlansoprazole, rabeprazole, and pantoprazole. All are substituted
benzimidazoles that resemble H2 antagonists in structure but have a completely different
mechanism of action (Katzung, et al., 2012).
Figure 4. Structures of proton pump inhibitors

Page 27 of 40
Table 30. Pharmacokinetic properties of Proton Pump Inhibitors
ESSA CRITERIA
A. EFFICACY
Table 31.Criteria for Efficacy scoring

(Another + if has the highest remission rate among the
drug classes)
3 Able to decrease recurrence of gastroesophageal +

symptoms or esophagitis
B. SAFETY
Table 32. Criteria for Safety scoring

Page 28 of 40
C. SUITABILITY/NECESSITY
Table 33. Criteria for Suitability/Necessity scoring
D. AFFORDABILITY
Table 34. Criteria for Affordability scoring
2 Available in non-prescription form +

(Php 2,191.9/year or Php 182.66/month/4-week regimen)
EFFICACY
The effect on symptom relief and healing of esophagitis by the different PPIs will be
discussed in the subsequent context. For the scoring of the criteria on the prevention of
recurrence and prevention of GERD-related complications, all drugs were given + on each
criterion since according to a study (Consumer Reports Best Buy Drugs, 2013; Shin and Kim,
2013), generally, there was no significant difference in the percentage of recurrence of GERD
symptoms and esophagitis among the different drugs; and for the prevention of complications,
recommendations do not specify a certain PPI to be used so it was assumed that a long-term
therapy of any of the PPIs has an effect on the prevention of GERD-related complications such
as strictures and Barretts esophagus.
DEXLANSOPRAZOLE
Dexlansoprazole is the R-isomer of lansoprazole (Katzung, et al., 2012). It is the most

recent PPI approved for clinical use. The reported advantage of dexlansoprazole compared to
other PPIs is the dual delayed-release system which is aimed at improving treatment of GERD
(Kasper, et al., 2015).
Page 29 of 40
Dexlansoprazole is a dual release formulation of 60 mg of PPI with normal enteric

coating release at around pH 5.0 and a coating labile at pH 7.0 releasing dexlansoprazole some
hours later to try to provide night time drug levels (Shin and Kim, 2013).
Dexlansoprazole delayed-release (DR) 60 mg gave better control of intragastric pH than
esomeprazole 40 mg (Shin and Kim, 2013). Mean gastric pH values for dexlansoprazole DR
and esomeprazole were 4.3 and 3.7 respectively. Night time pH control was significantly
improved with dexlansoprazole. At 12-24 hours post-dose, mean percentage of time with pH
4 and average of mean pH were 60% and 4.5 respectively. Under the same situation,
esomeprazole showed 42% of mean percentage of time with pH 4 and an average of mean
pH 3.5 (Shin and Kim, 2013).
In patients with GERD, standard doses of esomeprazole and dexlansoprazole maintain
intragastric pH above 4 for significantly longer periods compared with standard doses of other
PPIs after 5 days of treatment (Shin and Kim, 2013).
Table 35. Efficacy scoring for Dexlansoprazole

Criterion # Criteria Considered Points

classes)

or esophagitis
TOTAL 5
ESOMEPRAZOLE
Esomeprazole is the S -isomer of omeprazole. While it is available as an oral

formulation, it is also available in intravenous formulations (Katzung, et al., 2012). The
pharmacokinetic properties of Esomeprazole are presented in Table 36.
According to a review (Therapeutics Initiative, 2016), based on 26 RCTs in 23,789
patients, esomeprazole was not significantly different from other PPIs for most outcome
measures: time to first resolution of symptoms. In a meta-analysis conducted by Edwards in
2006 regarding the healing rates of esomeprazole 40 mg compared with standard dose proton
pump inhibitors, results showed: at 4 weeks [relative risk (RR) 0.92; 95% CI: 0.90, 0.94; P <
0.00001], and 8 weeks (RR 0.95; 95% CI: 0.94, 0.97; P < 0.00001). It was concluded that
esomeprazole consistently demonstrates higher healing rates when compared with standard
dose proton pump inhibitors. This conclusion was also observed in one RCT reviewed by
Moayyedi, et al. (2010) which reported a dichotomous outcome for standard dose omeprazole
Page 30 of 40
versus standard dose Esomeprazole, evaluating 1306 participants at four weeks. Esophagitis
persisted in 35.2% participants in omeprazole group compared to 29.6% in Esomeprazole
group. Result showed statistically significant benefit of taking standard dose Esomeprazole
therapy compared to standard dose omeprazole in healing of esophagitis. According to a study
conducted by Shin and Kim in 2013, all studies related with esomeprazole demonstrated that
esomeprazole 40 mg once daily is superior to all other PPIs at standard doses in terms of
achieving higher 24-hour median intragastric pH and the number of patients achieving
intragastric pH 4.0 for at least 12 hours per day. Since esomeprazole was superior to other
PPIs for acid suppression, better healing rates on acid-related diseases were achieved.
Moreover, clinical studies demonstrated that esomeprazole 40 mg od for up to 8 weeks
provided higher rates of healing of erosive GERD, along with a greater proportion of patients
with sustained resolution of heartburn, than omeprazole 20 mg, lansoprazole 30 mg, or
pantoprazole 40 mg OD.
Table 36. Efficacy scoring for Esomeprazole


classes)

or esophagitis
TOTAL 5
LANSOPRAZOLE
Lansoprazole is a racemic mixture of R- and S-isomers. The pharmacokinetic properties

of Lansoprazole are presented in Table 37.
Together with Omeprazole, they have been the PPIs used for the longest time. It is acid-
labile and is administered as enteric-coated granules in a sustained-release capsule that
dissolves within the small intestine at a pH of 6 (Katzung, et al., 2012). Lansoprazole is also
available as a tablet formulation that disintegrates in the mouth, or it may be mixed with water
and administered via oral syringe or enteral tube (Katzung, et al., 2012). This formulation has an
advantage for individuals who have significant dysphagia (Kasper, et al., 2015).
According to a review (Therapeutics Initiative, 2016), based on 13 RCTs in 7,532
patients, lansoprazole was not significantly different from other PPIs for most outcome
measures: total relief of symptoms; relief of retrosternal pain; relief of dysphagia; time to first
resolution of symptoms; endoscopic healing of esophagitis; and recurrence or relapse of
symptoms.
Page 31 of 40
Table 37. Efficacy scoring for Lansoprazole


classes)

or esophagitis
TOTAL 4
OMEPRAZOLE
Omeprazole and lansoprazole are racemic mixtures of R- and S-isomers. The

pharmacokinetic properties of Omeprazole are presented in Table 38.
Like Lansoprazole,it is acid-labile and is administered as enteric-coated granules in a
sustained-release capsule that dissolves within the small intestine at a pH of 6 (Katzung, et al.,
2012). Omeprazole is also available as a powder formulation (capsule or packet) that contains
sodium bicarbonate (11001680 mg NaHCO3; 304460 mg of sodium) to protect the naked
(non-enteric-coated) drug from acid degradation (Katzung, et al., 2012). The sodium
bicarbonate has two purposes: to protect the omeprazole from acid degradation and to promote
rapid gastric alkalinization and subsequent proton pump activation, which facilitates rapid action
of the PPI (Kasper, et al., 2015).When administered on an empty stomach by mouth or enteral
tube, this immediate-release suspension results in rapid omeprazole absorption (Tmax< 30
minutes) and onset of acid inhibition (Katzung, et al., 2012).
Table 38. Efficacy scoring for Omeprazole


classes)

or esophagitis

Page 32 of 40
TOTAL 4
PANTOPRAZOLE
The pharmacokinetic properties of Pantoprazole are presented in Table 39.

Esomeprazole and pantoprazole are also available in intravenous formulations.
One RCT reported a dichotomous outcome, evaluating 286 participants at four weeks
(Moayyedi, et al., 2010). Overall in 22.1% of participants symptoms persisted in the group taking
a standard dose omeprazole compared to 26.2% in the standard dose pantoprazole group.
There was no statistically significant benefit of taking standard dose omeprazole therapy
compared to standard dose pantoprazole in symptom relief (RR of persistence at four weeks =
0.84, 95% CI 0.54 to 1.32).
Four RCTs reported a dichotomous outcome for standard dose omeprazole versus
standard dose pantoprazole, evaluating 881participants at four weeks (Moayyedi, et al., 2010).
Overall in 26.5% of participants esophagitis persisted in the group taking a standard dose
omeprazole, compared to 27.6% in the standard dose pantoprazole group. There was no
statistically significant benefit of taking standard dose omeprazole therapy compared to
standard dose pantoprazole in healing of esophagitis (RR of persistence at four weeks 1.00,
95% CI 0.80 to 1.25).
Table 39. Efficacy scoring for Pantoprazole


classes)

or esophagitis
TOTAL 4
RABEPRAZOLE
Rabeprazole is available as enteric-coated tablets with the same mechanism of action

as with the other PPIs. While others have pKa of 4, Rabeprazole has a pKa of around 5.
Rabeprazole are available as enteric-coated tablets.
One RCT reported a dichotomous outcome; evaluating 200 participants at four weeks
(Moayyedi, et al., 2010). Overall in 26.5% of participants reported symptoms persistence in the
group taking a standard dose omeprazole, compared to 29.6% in the standard dose
Page 33 of 40
rabeprazole group. There was no statistically significant benefit of taking standard dose
omeprazole compared to standard dose rabeprazole in symptom relief.
Three RCTs reported a dichotomous outcome for standard dose omeprazole versus
standard dose rabeprazole, evaluating 469 participants at eight weeks (Moayyedi, et al., 2010).
Overall in 8.9% of participants esophagitis persisted in the group taking a standard dose
omeprazole compared to 9.8% in the standard dose rabeprazole group. There was no
statistically significant benefit of taking standard dose omeprazole therapy compared to
standard dose rabeprazole in healing of esophagitis (RR of persistence at eight weeks 0.92,
95% CI 0.52 to 1.62).
Table 40. Efficacy scoring for Rabeprazole

Criteria # Criteria Considered Points

classes)

or esophagitis
TOTAL 4
Table 41. Summary of Scores for Efficacy of Different Proton Pump Inhibitors
SUMMARY OF SCORES FOR EFFICACY
Drug 1 2 3 4 Total
Dexlansoprazole + ++ + + 5
Esomeprazole + ++ + + 5
Lansomeprazole + + + + 4
Omeprazole + + + + 4
Pantoprazole + + + + 4
Rabeprazole + + + + 4
SAFETY
In general, all Proton pump inhibitors (PPIs) are generallysafe but associated adverse
events from long-termuse have generated concerns, i.e, vitamin B12deficiency; iron deficiency;
Page 34 of 40
increased susceptibility to pneumonia, enteric infections, and fractures; and drug interactions.
Long-term administration of PPI is safe; however,careful consideration is needed in patient
groups atrisk for complications (Sollano et al, 2015).
Their short half-lives make clinically significant drug interactions rare. However, if
present in high doses and long term use each of the PPIs differ in the drugs that they affect.
Omeprazole may inhibit the metabolism of warfarin, diazepam and phenytoin. Esomeprazole
also may decrease metabolism of diazepam. Lansoprazole may enhance clearance of
theophylline. Rabeprazole and pantoprazole have no significant drug interactions (Katzung,
2012).
Many studies have also reported about the interaction between Clopidogrel and PPIs. It
remains uncertain whether the addition of a PPI to clopidogrel therapy adversely affects
cardiovascular outcomes and it is unclear if there is a difference in the risk of an interaction
between specific PPIs and Clopidogrel. Despite this uncertainty, the prescribing information for
clopidogrel advises against the concurrent use of a strong or moderate cytochrome P450 2C19
inhibitor (eg: omeprazole) because of a possible reduction in the antiplatelet activity of
clopidogrel leading to possible cardiovascular events. If a PPI is indicated, the selection of a PPI
with a lower propensity for Cytochrome P450 2C19 inhibition (eg: pantoprazole) (BCPAD,
2015).
Table 42. Summary of Scores for Safety of Different Proton Pump Inhibitors
SUMMARY OF SCORES FOR SAFETY
DRUG CRITERIA TOTAL

RATING
1 2 3 4
Dexlansoprazole + + + + 4
Esomeprazole + + + + 4
Lansoprazole + + + + 4
SUITABILITY
The cornerstone of therapy for patients with GERD with erosive esophagitis is a proton-
pump inhibitor (PPI) (Sollano, et al., 2015; Wallace & Sharkey, 2011) because it has
consistently shown considerable difference in terms of benefit when compared against other
drug class like histamine-2 receptor antagonist (H2RA), antacids, sucralfate, and prokinectics
(Sollano, et al., 2015). It is also the most effective therapeutic agent for non-erosive reflux
disease, esophageal complications of reflux disease (Barretts esophagus), and
Page 35 of 40
extraesophageal manifestations of reflux diseaseThere are six PPIs available for clinical use:
omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, and pantoprazole
(McQuaid, 2015). However, among the PPIs, there are no major difference in terms of efficacy
in the management of GERD (Spielberg, 2013).
Contraindications in the use of proton pump inhibitors include those who have known
hypersensitivity to the active ingredient of proton pump inhibitors (MIMS, 2014). Moreover,
these should be used with caution in patients with severe hepatic disease. It is also not
recommended for use in breastfeeding mothers (Vanderhoff&Tahboub, 2002). Its safety during
pregnancy is not established (McQuaid, 2015). In the recent local clinical practice guideline,
short-term PPI regimen is an option during the last two trimesters of pregnancy. PPIs are have
been all labeled as Class B drugs, except for omeprazole which has been classified as Class C.
Nonetheless, a meta-analysis have shown that the use PPIs do not pose an increased risk for
major fetal abnormalities, spontaneous abortion, and pre-term deliveries.
Additionally, it should be noted that the bioavailability of PPIs are decreased by as much
as 50% by food; therefore, it should be taken 30 minutes to 1 hour before a meal (McQuaid,
2015). Also, the use of acid suppressant drugs concomitantly with PPIs are thought to reduce
the activation and absorption of PPIs; however, the potential significance of this interaction is
yet to be established (Wallace & Sharkey, 2011).
The recommended therapy for GERD of the local clinical practice guidelines and the
American Journal of Gastroenterology is monotherapy with PPI, taken 30 minutes before a
morning meal, for 8 weeks. Standard or usual dosage of PPIs is 20-40 mg, except for
dexlansoprazole which is 30-60 mg. All six of the available PPIs are available in oral form.
Table 43. Summary of Scores for Suitability of Different Proton Pump Inhibitors
SUMMARY OF SCORES FOR SUITABILITY
DRUG CRITERIA TOTAL

RATING
1 2 3 4
Dexlansoprazole + + + + 4
Esomeprazole + + + + 4
Lansoprazole + + + + 4
Page 36 of 40
AFFORDABILITY
Dexlansoprazole (Dexilant)
Dexlansoprazole is only available in the country as a prescription of Dexlansoprazole

(Dexilant) 30mg or 60 mg capsule; taken once daily for up to 4 or 8 weeks. The 30 mg dose 4
week regimen is given for the maintenance of healed erosive esophagitis, while the 60 mg 8
week regimen is for the healing of erosive esophagitis.
While dexlansoprazole has its advantages with its dual delayed release system; PPIs in
general do not differ in effectiveness or safety, but they do differ in price (Spielberg, 2013).
Locally, Dexilant cap 30 mg costs Php 2,051.64/box/month/4-week regimen (Php 73.27/tablet).
No generic form of Dexilant is present for it is a relatively new drug that is protected by
patents until December 2020.
Esomeprazole
Esomeprazole can be given as a 20 mg capsule once daily for 4 weeks. It is packaged

as 20 mg x 40 capsules for Php 13.00/capsule or Php 364.00/month/4-week regimen or Php
4,368/year. There is no over-the-counter form of this drug.
Esomeprazole, along with pantoprazole, and rabeprazole is said to be superior to other
PPIs when it comes to providing better healing from esophagitis (Kasper, et al., 2015).
Lansoprazole
Lansoprazole is available in the Philippines as 30 mg capsule once daily for 4 weeks

costing Php 34.00 per capsule or Php 952/month/4-week regimen or Php 11,424 per year.
Omeprazole
Omeprazole 20 mg capsule (ULZOL) is available in the Philippines for Php 5.25/capsule.

A 4-week treatment regimen of Omeprazole 20 mg taken once daily will have a total computed
cost of Php 147.00/month/4-week regimen and Php 1,764.00 in a year.
RiteMed Omeprazole 20 mg capsule can be purchased over-the-counter.
Pantoprazole
Pantoprazole is available 20-40 mg tablet, given once daily for 4 weeks. A 40 mg tablet
costs Php 20.00 or Php 560/month/4-week regimen. No over-the-counter forms are available.
Rabeprazole
Rabeprazole 100 mg capsule is be taken daily for 4-8 weeks is available at Php
17.00/capsule or Php 476/month/ 4 week regimen. There are no over-the-counter forms
available for this drug.
Page 37 of 40
Table 44. Summary of Scores for Suitability of Different Proton Pump Inhibitors
SUMMARY OF SCORES FOR AFFORDABILITY
DRUG CRITERIA TOTAL

RATING
1 2 3 4
Dexlansoprazole - - - - 0
Esomeprazole + - + - 2
Lansoprazole + - - - 1
Pantoprazole + - + - 2
Rabeprazole + - + - 2
SUMMARY OF ESSA CRITERIA (P-DRUG)
Table 45. Summary of p-drug selection

P-DRUG CRITERIA TOTAL
E S S A
Dexlansoprazole 5 4 4 0 13
Esomeprazole 5 4 4 2 15
Lansoprazole 4 4 4 1 13
Omeprazole 4 4 4 4 16
Pantoprazole 4 4 4 2 14
Rabeprazole 4 4 4 2 14
SAMPLE PRESCRIPTION
Page 38 of 40
REFERENCES
Aymard B, Netter P, Bannwarth B, Trechot P, Streiff F. 1988. Haematological adverse effects of

histamine H2-receptor antagonists. Nov-Dec;3(6):430-48.
Boeckxstaens G., El-Serag H.B., Smout A.J.P.M., Kahrilas P.J. 2014. Symptomatic reflux
disease: the present, the past and the future / Gut;63:1185-1193
Consumer Reports Best Buy Drugs. 2013. Using the proton pump inhibitors to treat: heartburn
and stomach acid reflux.
Dent J., Bremner C. G., Collen M. J., Haggitt R. C., Spechler S. J. 1991. Barrett's esophagus.
Working party report to the World Congress of Gastroenterology. J GastroenterolHepatol
6:1-22
Depta JP1, Bhatt DL. 2012. Antiplatelet therapy and proton pump inhibition: cause for concern?.
Nov;27(6):642-50. doi: 10.1097/HCO.
Donnellan, C., Preston, C., Moayyedi, P., & Sharma, N. (2005). Medical treatments for the
maintenance therapy of reflux esophagitis and endoscopic negative reflux disease.
Cochrane Database Systematic Review, 2. CD003245.
Edwards, S. J., Lind, T., Lindell, T. 2006. Systematic review proton pump inhibitors (PPIs) for
the healing of reflux oesophagitis- a comparison of esomeprazole with other PPIs.
Aliment PharmacolTher24:743-750
Page 39 of 40
FDA Drug Safety Communication (2012): Clostridium difficile-associated diarrhea can be

associated with stomach acid drugs known as proton pump inhibitors (PPIs).
FDA. 2013. Safety Labeling Changes Approved By FDA Center for Drug Evaluation and
Research (CDER). Carafate (sucralfate) suspension.
Kahrilas, P., & Hirano, I. (2015). Diseases of the esophagus. In D. Kasper, A. Fauci, S. Hauser,
D. Longo, JL. Jameson, & J. Loscalzo (Eds.), Harrisons principles of internal medicine
(19thed.). New York: McGraw-Hill Education.
Kasper, D. L., Hauser, S. L., Jameson, J. L., et al. 2015. Harrisons principles of internal
medicine. 19th ed. McGraw-Hill Education.
Katzung, B. G., Masters, S. B., Trevor, A. J.. 2012. Basic and clinical pharmacology. 12thed.
McGraw-Hill Companies, Inc.
Kaynard, A. Flora, K. 2001. Gastroesophageal reflux disease. Postgraduate Medicine 110(3)
Kumar, V, Abbas, A, Aster, J, 2015. Robbins and Cotran Pathologic Basis of Disease 9th edition.
Elsevier Saunders.
Marks R., Richter J. E., Koehler R., Spenney J., Mills T. 1992. Does medical therapy improve
dysphagia in patients with peptic strictures and esophagitis? Gastroenterology
102:A118.
McQuaid, K. (2015). Drugs used in the treatment of gastroesophageal reflux disease. In B.
Katzung& A. Trevor (Eds.), Basic and clinical pharmacology (13thed.). New York:
McGraw-Hill Education.
MIMS. (2014). Master index of medical specialties (140thed). Manila: Medical Publications
Worldwide.
MIMS Philippines. 2015. Drug Reference: Concise Prescribing Information. 143rd Ed. Page 6
Moayyedi, P., Santana, J., Preston, C., Donnellan, C. 2010. Medical treatments in the short
term management of reflux oesophagitis (review). John Wiley & Sons, Ltd.
Penston J, Wormsley KG.1986. Adverse reactions and interactions with H2-receptor
antagonists. May-Jun;1(3):192-216.
Shin, J. M., Kim, N. 2013. Pharmacokinetics and pharmacodynamics of the proton pump
inhibitors. NeurogastroenterolMotil19(1):25-35
Sollano, J., Romano, R., Ibanez-Guzman, L., Lontok, MA., de Ocampo, S., Policarpio, A., de
Guzman, R., Dalupang, C., Galang, AJ., Olympia, E., Chua, MA., Moscoso, B., Tan, J.,
Pangilinan, JA., Vitug, A., Naval, M., Encarnacion, D., Sy, P., Ong, E., Cabahug, O.,
Daez, M., Ismael, A., &Bocobo, M. (2015). Clinical practice guidelines on the diagnosis
and treatment of gastroesophageal reflux disease (GERD). Philippine Journal of Internal
Medicine, 53(3), 1-16.
Spielberg, B. (2013). Corrigendum: Guidelines for the diagnosis and management of
gastroesophageal reflux disease. The American Journal of Gastroenterology, 108, 308-
328
Therapeutics Initiative. 2016. A systematic review of the comparative effectiveness of proton
pump inhibitors for the treatment of adult patients with gastroesophageal reflux disease
or peptic ulcer disease. British Columbia Ministry of Health, Pharmaceutical Services
Division. http://www2.gov.bc.ca/assets/gov/health/health-
drugcoverage/pharmacare/derp-ppi.pdf (Accessed September 30, 2016)
Tytgat, GN. (1987). Clinical efficacy of sucralfate in reflux esophagitis. Comparison with
Page 40 of 40
cimitedine. Am J Med, 28;83(3B), 38-42.

Vanderhoff, B. &Tahboub, R. (2002). Proton pump inhibitors: an update. American Association
of Family Physicians, 66 (2), 273 281.
Wallace, J., & Sharkey, K. (2011). Pharmacotherapy of gastric acidity and peptic ulcers, and
gastroesophageal reflux diseases. In L. Brunton, B. Chabner, & B. Knollman (Eds.),
Goodman & Gilmans The pharmacological basis of therapeutics (12th edition). New York: The
McGraw-Hill Companies, Inc.
Williams, D. &Schade, R. (2011). Gastroesophageal reflux disease. In J. DiPiro, R. Talbert, G.
Yee, G. Matzke, B. Wells, & LM Posey, Pharmacotherapy: A pathophysiologic approach
(8thed.). United States: McGraw-Hill Education, LLC.

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Pamantasan ng Lungsod ng Maynila

(University of the City of Manila)

In Partial Fulfilment of the Requirements in

Butial, John Rex C. Approach, Introduction, Non-pharma, Suitability

Garcia, Leslie Noelle P. Pathophysiology, Safety

Monteverde, Michael Robert Q. Diagnostics, Affordability

Sabater, Enrico P. Epidemiology, Etiology/Risk Factors, Efficacy

Figure 1. Diagnostic Algorithm

GASTROESOPHAGEAL REFLUX DISEASE

ETIOLOGY AND RISK FACTORS

Figure 2. Model of GERD Pathogenesis in Adults

During a barium esophagogram, a high-density barium suspension is administered,

Figure 3. Therapeutic Interventions for GERD (Source: Williams &Schade, 2011).

The general drug groups considered are antacids

DRUG GROUP SELECTION

1 Able to reduce or eliminate symptoms +

2 Able to promote healing of injured mucosa or esophagitis +

3 Able to decrease recurrence of gastroesophageal +

4 Able to prevent complications of GERD +

1 Minimal and reversible side effects +

2 No associated severe adverse drug reactions +

3 Minimal drug-drug/food interaction +

4 Less risk for organ toxicity/damage +

1 Indicated as first line therapy +

2 No contraindications for use in the case +

3 Can be used as stand-alone drug for the case +

1 Available locally in generic form +

3 Total drug regimen cost less than ave OOP expenditure +

(Php 2,191.9/year or Php 182.66/month)

Table 5. Efficacy scoring for Antacids

1 Able to reduce or eliminate symptoms +

2 Able to promote healing of injured mucosa or esophagitis

3 Able to decrease recurrence of gastroesophageal symptoms

4 Able to prevent complications of GERD

HISTAMINE-2 RECEPTOR ANTAGONISTS

Table 6. Efficacy scoring for Histamine-2 Receptor Antagonists

1 Able to reduce or eliminate symptoms +

2 Able to promote healing of injured mucosa or esophagitis +

3 Able to decrease recurrence of gastroesophageal symptoms +

4 Able to prevent complications of GERD

PROTON PUMP INHIBITORS

Table 7. Efficacy scoring for Proton Pump Inhibitors

1 Able to reduce or eliminate symptoms +

2 Able to promote healing of injured mucosa or esophagitis ++

3 Able to decrease recurrence of gastroesophageal symptoms ++

4 Able to prevent complications of GERD +

Metoclopramide and domperidone are dopamine D2receptor antagonists. Within the

The benefit of these compounds in controlling heartburn and in healing erosive

Table 8. Efficacy scoring for Prokinetics

1 Able to reduce or eliminate symptoms +

2 Able to promote healing of injured mucosa or esophagitis

3 Able to decrease recurrence of gastroesophageal symptoms

4 Able to prevent complications of GERD

Sucralfate, an aluminum salt of a sulfated disaccharide, is considered a mucosal

Table 9. Efficacy scoring for Mucosal Protective Agent

1 Able to reduce or eliminate symptoms +

2 Able to promote healing of injured mucosa or esophagitis

3 Able to decrease recurrence of gastroesophageal symptoms +

4 Able to prevent complications of GERD

Table 10. Summary of scores for efficacy of different drug classes

DRUG CLASS 1 2 3 4 Total

Table 11. Safety scoring for Antacids

1 Minimal and reversible side effects +