An Evidence-Based Approach to
Mary Knudtson, MSN, FNP, PNP and Rick H. Davis, Jr, PA-C
LEARNING OBJECTIVES FOR THIS CONTINUING
This Independent Study Activity is Upon completion of this program, participants will be able to:
approved for 1.0 contact hours by the
Washington State Nurses Association, an 1. Differentiate symptoms of frequent heartburn (FHB) from episodic
accredited approver by the American Nurses heartburn.
Credentialing Center’s Commission on
Accreditation (ANCC). The accreditation for 2. Counsel patients appropriately on lifestyle changes and determine
this program expires 1 year from the date of pharmacotherapeutic interventions for FHB.
publication (that is, on January 31, 2006).
3. Evaluate the cost-effectiveness of intermittent therapy for FHB.
This activity is provided to you at no charge
through FnP Associates. To obtain continu-
4. Identify patients who need further evaluation of heartburn symptoms.
ing education credit for this activity:
1. Log on to www.npcentral.net/ce/heartburn.
2. Go to the menu. Heartburn is a sensation of burning discomfort that generally
2. Select the “test only” option. starts in the retrosternal area and moves upward toward the throat.1
It may be accompanied by a sour taste in the mouth (“acid indiges-
3. Register, take the Post-test, and fill out
the Evaluation Form and Registration tion”), and is caused by reflux of gastric contents into the esophagus.
Form. Heartburn may be self-limited, or it may be a symptom of gastroe-
If you score 80% or higher on the post-test, sophageal reflux disease (GERD), a condition characterized by fre-
you will be able to print a Certificate of quent gastroesophageal (GE) symptoms and/or mucosal damage of
Completion. If you do not score 80% or the upper gastrointestinal (GI) tract.2 It may occur on an episodic
higher, you will have a second opportunity basis (eg, after eating a hot spicy meal), an intermittent basis (once
to take the test. monthly to once weekly), or a frequent basis (≥2 times per week).
If you do not have Internet access and need This article focuses on the diagnosis and treatment of frequent heart-
a hard copy of the post-test, evaluation burn (FHB), which may overlap with the approach to GERD.
form, and registration form, please contact
FnP Associates, LLP at fiona@fnpassociates
, Although many patients self-treat their heartburn symptoms with
or call (360) 297-1274. over-the-counter (OTC) medications, they should consult their
healthcare professional for guidance in this regard. Primary care
Full references for this article are also avail- nurse practitioners (NPs) need to be able to distinguish between
able at www.npcentral.net/ce/heartburn.
episodic and frequent heartburn—each has different treatments and
This program was supported by an unre- health implications—and then guide patients in choosing the best
stricted educational grant from Procter & agent for them, one that is not only effective but is also cost-effective
Gamble. in “extinguishing” the problem.
Vol. 9 No. 1 January 2005 The American Journal for Nurse Practitioners I 137
PREVALENCE AND emotional role limitations, and men- for reflux in monozygotic pairs, as com-
DEMOGRAPHICS tal health.10 pared with dizygotic pairs, suggesting
Heartburn afflicts nearly two thirds of US This same group of patients had genetic, rather than environmental,
adults at some point in their lives.3 lower scores on a test of emotional effects.13 The investigators stated that her-
According to a large survey conducted well-being than did patients with itability accounted for 31% (23%-39%)
16 years ago by the Gallup Organization, diabetes or hypertension.10 of the tendency to develop reflux disease
44% of adults suffer from heartburn at The 2000 Gallup survey showed in this population. Finally, estrogens
least once a month, 20% experience it at that, among 1000 respondents with may exacerbate the risk: A population-
least once a week, and 7% have it every heartburn, the following proportions based, cross-sectional, case-control
day.4 In 1997, a population-based study reported moderate to severe impair- study revealed that the association
of 2200 residents of Olmstead County, ment in their: between obesity and reflux symptoms
Minnesota, came up with the same find- – ability to eat/drink what they want: was significantly stronger among pre-
ings in terms of the proportion of US 46% menopausal women than among post-
adults who experience heartburn and/or – ability to get a good night's sleep: menopausal women, and that the use of
acid regurgitation on at least a weekly 40% hormone replacement therapy (HRT) in
basis: 19.8%.5 In 2004, a cross-sectional – ability to sleep when they want to: the postmenopausal group significantly
survey of 496 employees at a Veterans 36% increased the strength of the association.14
Administration medical center revealed – ability to eat/drink when they
that heartburn occurring at least weekly want: 36% PHYSIOLOGY AND
was reported by 27% of blacks, 23% of – mood and general well-being: 35% PATHOPHYSIOLOGY
whites, and 24% of members of other – day-to-day functioning: 25% In normal, healthy individuals, billions
racial groups; thus the rate of heartburn – social activities: 23% of tiny pumps in the stomach manufac-
was similar across racial lines.6 – functioning at work: 23% ture hydrochloric acid, which breaks
Heartburn does show a “preference” for – spouse’s sleep: 18%.9 down food. The lower esophageal
gender, though: Among persons with sphincter (LES) in these individuals
If FHB is a manifestation of full-blown keeps the acidic gastric contents from
FHB—that is heartburn occurring at GERD, then patients are at risk for the
least twice a week, 58% are female and rising back into the esophagus. In some
sequelae of prolonged esophageal injury.11 individuals, however, the LES temporar-
42% are male.7,8 The average FHB suf-
ferer is between the ages of 45 and 50.7 ily relaxes, allowing reflux of the acidic
RISK FACTORS gastric contents into the esophagus,
In 2000, the American Gastroenter- The aforementioned study of people in
ological Association (AGA) commissioned which causes the sensation of heartburn.
Olmstead County, Minnesota, revealed Transient LES relaxation may be
the Gallup Organization to conduct a poll that obesity and a positive family history
of individuals with heartburn occurring caused by eating certain foods or bever-
were the main risk factors for frequent ages or by pressure on the stomach.
on at least a weekly basis to find out more reflux symptoms.12 Other risk factors
about the pattern of their symptoms.9 Increased abdominal pressure may be
cited in this study included a past his- caused by frequent bending and lifting,
Among 1000 respondents, 79% reported tory of smoking, consuming seven or vigorous exercise, or pregnancy.15-17
having nocturnal heartburn—with 60% more drinks per week, and a higher psy- Conditions such as hiatal hernia, gastro-
experiencing symptoms that were severe chosomatic symptom checklist score. paresis, defective esophageal acid clear-
enough to disturb their sleep and com- The following diet/lifestyle choices and ance, impaired mucosal defense, and
promise their work and quality of life behaviors are also associated with an delayed gastric emptying can also pre-
(QoL) the next day. increased risk of heartburn: dispose individuals to heartburn and
exercising after eating; GERD. In addition, certain medica-
ADVERSE CONSEQUENCES OF tions, including calcium antagonists (eg,
UNTREATED HEARTBURN lying down shortly after meals;
bending over or straining soon after amlodipine [Norvasc ®], diltiazem
At the very least, FHB can restrict nor- [Cardizem®], nifedipine [Adalat®, Pro-
mal activities and have an adverse meals;
cardia®], verapamil [Calan, Isoptin]),
impact on QoL: drinking several alcoholic, carbon-
theophylline, HRT, and muscle relax-
One study showed that patients who ated, and/or caffeinated beverages
ants, can reduce LES pressure.17
had a history of heartburn for at least daily;
Not all reflux is pathologic: Normal
6 months, when compared with a eating fried, fatty, acidic, or spicy persons may experience up to 50 episodes
random sample of healthy US adults, foods; and of reflux per day, with acid present in the
fared significantly worse on all eight eating chocolate or spearmint/ esophagus for up to 4% of a given 24-hour
scales of the Medical Outcomes peppermint candy. period.18 In healthy persons, gravity and
Study short-form 36 Health Survey: Genes may play a major role in deter- peristalsis clear the refluxed material, and
physical function, bodily pain, physi- mining heartburn risk. A study of more bicarbonate ions in the saliva and secre-
cal role limitations, vitality, general than 8000 twin pairs aged 55 years or tions from submucosal glands in the
health perceptions, social function, older showed an increased concordance esophagus neutralize the acid that remains
138 I The American Journal for Nurse Practitioners January 2005 Vol. 9 No. 1
in the esophagus. Heartburn and, in to distinguish between episodic or inter- “alarm” symptoms (anemia, bleed-
many cases, GERD develop when these mittent heartburn (1 episode/week) and ing, chest pain, dysphagia [difficulty
protective mechanisms and/or mucosal FHB (≥2 episodes per week), because swallowing], hematemesis, involun-
defenses are impaired. That is, peristalsis the treatment approaches differ. In the tary weight loss, melena, odynopha-
may be ineffective, or salivary or subset of patients with FHB, they may gia [severe pain on swallowing],
esophageal secretions may be reduced, need to determine whether other patho- persistent vomiting) are present.25
leading to inadequate clearance or neu- physiologic processes are going on, and Endoscopy—Routine endoscopy is not
tralization of refluxate. whether damage to esophageal tissue recommended for patients with heart-
It is important to note that not all has occurred. burn and regurgitation only;25 most
patients with heartburn or even GERD patients who have heartburn more than
Differential Diagnosis—In taking the
have esophageal damage: 53% to 71% twice per week have no endoscopic
history, NPs need to distinguish heart-
of heartburn sufferers have endoscopi- esophageal mucosal damage.26 However,
burn/GERD from entities such as gastri-
cally normal esophageal mucosa.19 This patients who have symptoms for 7 to 10
condition is sometimes called nonero- tis, infectious esophagitis (typically
caused by Candida species), peptic ulcer years should undergo screening endos-
sive reflux disease, or NERD.20 Some copy for Barrett's esophagus. Endoscopy
patients with NERD experience heart- disease (typically caused by Helicobacter
pylori infection), non-ulcer dyspepsia, is also recommended in patients who
burn symptoms despite having normal are experiencing alarm symptoms
levels of esophageal acid exposure as biliary tract disease, coronary artery dis-
ease, and esophageal motor disorders.23 and/or extra-esophageal manifestations
assessed by 24-hour pH study (see sec- of GERD (eg, asthma; chronic bronchi-
tion on “Ambulatory Esophageal pH Another common cause of heartburn-
like pain is pill esophagitis, which occurs tis, cough, or sinusitis; noncardiac
Monitoring”); these patients, may, in chest pain; excessive throat clearing;
fact, have esophageal hypersensitivity to when a pill is swallowed into the esoph-
agus but gets “stuck” on the esophagus hoarseness; otalgia; pharyngitis; stri-
physiologic degrees of acid reflux. Other dor).27 This test is particularly useful for
patients with NERD have abnormal acid wall and burns the lining of the esopha-
gus, causing chest pain and esophageal diagnosing GERD complications,
exposure but have not developed overt although it is neither highly sensitive
mucosal injury. ulcers. Medications associated with pill
esophagitis include non-steroidal anti- nor highly specific for GERD itself.11,23
DIAGNOSIS inflammatory drugs (NSAIDs) such as Ambulatory Esophageal pH Moni-
HISTORY ibuprofen (Motrin®), naproxen sodium toring—According to guidelines from the
When patients present with typical symp- (Aleve®), aspirin, and celecoxib (Cele- American College of Gastroenterology
toms of heartburn and no complications, brex®), and bisphosphonates such as (ACG), ambulatory esophageal pH moni-
the diagnosis is usually straightforward alendronate (Fosamax®) and risedronate toring helps to confirm GE reflux in
and can be made from the medical his- (Actonel®). Pill esophagitis can be avoid- patients with persistent symptoms with-
tory.11 Most patients with heartburn ed if patients swallow pills according to out evidence of mucosal damage.24 A pH
describe the following symptoms: the package directions. monitor is placed in the esophagus above
the LES for 24 hours. While the monitor is
a retrosternal burning sensation DIAGNOSTIC TESTING in place, patients keep a diary of symptom
that radiates toward the throat; It is not necessary to perform a diagnos- occurrence. This test is highly sensitive
a sensation that food is “coming tic evaluation in all patients who com- and specific, but it is not widely available
back up”; plain of heartburn, particularly in those and it is invasive, time-consuming, and
a sour or bitter taste in the throat with infrequent symptoms.22 Even with expensive. The AGA recommends pH
and/or mouth; and/or GERD, symptom analysis offers reason- recording for patients with equivocal or
pain that increases when bending able sensitivity and specificity, and most abnormal endoscopy results and persis-
over, lying down, exercising, or typical cases can be diagnosed on the tent reflux symptoms that are refractory to
lifting heavy objects.21 basis of symptoms alone. Diagnostic proton pump inhibitor (PPI) therapy.28 It is
Symptom Duration and Severity— testing is recommended in the following also beneficial in patients with atypical or
Symptoms may last a few minutes to a cases: extra-esophageal symptoms.
few hours. Their severity depends on the history is atypical and the diag- Barium X-rays—An upper GI series is
the reason for LES relaxation, the nosis is unclear; taken after patients drink a barium solu-
amount of acid entering the esophagus, symptoms are long-term, frequent, tion. Only one third of patients with
and the degree to which the patient's and/or refractory to treatment; GERD, and an even smaller minority of
saliva is able to neutralize the acid.21 Of continuous long-term therapy is patients with documented abnormal
note, patients without macroscopic likely needed; pH, have radiologic signs of esophagi-
mucosal lesions do not necessarily have
complications arise (eg, adenocarci- tis.11 Therefore, this test is considered to
milder symptoms than those with more
noma of the esophagus, Barrett’s be of little practical value in patients
esophagus, esophageal bleeding and with FHB or GERD, although it may be
Symptom Frequency: Episodic Versus ulcers, esophagitis, strictures, ulcera- helpful in the detection of esophageal
Frequent Heartburn—NPs will need tions);11,23,24 and/or strictures or hiatal hernias in patients
Vol. 9 No. 1 January 2005 The American Journal for Nurse Practitioners I 139
with dysphagia. It may also be helpful in
identifying pathologies unrelated to TABLE 1. MANAGING HEARTBURN IN “THE REAL WORLD”:
GERD, including diverticula, swallowing EASY-TO-DIGEST PRACTICE TIPS
dysfunction, and motility dysfunction. I Encourage patients who present with episodic, intermittent, or frequent heartburn to
institute lifestyle modifications to reduce or eliminate heartburn triggers.
MANAGEMENT I Recommend use of an antacid or OTC H2RA in patients whose episodic or intermittent
Goals of heartburn management are to heartburn persists despite lifestyle changes.
reduce inappropriate LES relaxation, to
I Recommend a PPI (either OTC or prescription) in patients with FHB.
reduce production of gastric acid, to neu-
tralize gastric acid, and, in some cases, to I Make sure that PPI users are using the product correctly.
promote gastric emptying. A broader goal I Counsel patients about the basic mechanics of reflux, the importance of lifestyle adjust-
is to prevent complications such as ments, the reason for taking the PPI, and the dosing recommendations for the PPI.
esophageal stricture and Barrett's esopha- I Instruct patients with FHB who are using the OTC PPI to take omeprazole magnesium
gus. These goals may be accomplished to once daily, 30-60 minutes before the first meal of the day, for 14 days.
some extent by lifestyle modifications, I Ask patients whose symptoms persist beyond 2 weeks to contact you for further
although hard evidence is lacking that instructions.
these interventions work.25,29 If patients
OTC = over-the-counter; H2RA = histamine H2-receptor antagonist;
have difficulty instituting these changes, PPI = proton pump inhibitor; FHB = frequent heartburn.
then they may try one or more of three
classes of OTC medications. The efficacy
of these agents has been supported by sci- TABLE 2. LIFESTYLE MODIFICATIONS TO EASE HEARTBURN11,24,30
entific research. Of note, one of these
classes has been shown to be particularly
Avoid or limit ingestion of caffeinated products, alcohol, carbonated soft drinks, chocolate,
cost effective for patients with FHB. Patient tomato-based products, spearmint, peppermint, spicy foods, fatty or greasy foods, onions,
education, counseling, and encourage- garlic, and citrus fruits and juices.
ment should be ongoing throughout the
Avoid eating before bedtime or 3 to 4 hours before lying down.
course of therapy. Patients whose symp-
toms or treatment refractoriness suggests Avoid eating large-volume meals.
that their condition is more serious than Lose weight if necessary.
FHB may need to undergo a full round of
diagnostic tests and be referred to a gas-
Elevate the head of the bed by 4 to 8 inches (in patients with nocturnal symptoms).
troenterologist or other specialist. Table 1
offers NPs practical tips for the general Avoid wearing clothing that is tight around the waist.
management of heartburn. Avoid excessive bending over (eg, gardening) or lifting, especially after meals.
Review medications that may potentiate heartburn symptoms, including calcium antagonists,
A variety of lifestyle alterations can, at
bisphosphonates, and theophylline.
least in theory, mitigate, alleviate, or
even prevent heartburn (Table 2). Stop smoking.
Despite the lack of extensive evidence Chew gum or suck on hard candy or lozenges to stimulate saliva production.
supporting the effectiveness of these Eat several small meals instead of three large meals throughout the day.
changes as the sole approach, they will
likely enhance the effectiveness of phar-
own from one of the many medications 47% self-medicated for more than 2
macotherapy. In fact, the ACG recom-
available OTC (Table 3). According to days in a row;
mends that lifestyle modification be
one data set, more than 86% of FHB 34% had used a prescription med-
initiated and continued throughout the
course of therapy.24 The college also sufferers report using OTC medica- ication to manage heartburn; and
asserts that, despite the lack of data, it is tions.33 Before the US Food and Drug 4% used OTC histamine H2-recep-
reasonable to educate patients about fac- Administration (FDA) approved an tor antagonists (H2RAs).34
tors that may precipitate reflux. Because OTC PPI (Prilosec OTC™) specifically
Of interest, approximately 25% of
many patients will not be able to insti- for the treatment of FHB symptoms,
patients with FHB use 70% of the OTC
tute or maintain these lifestyle changes, 80% of patients with FHB used heartburn products.
periodic drug therapy for symptom antacids; OTC medications are divided into
relief is in order. 58% had spoken to their healthcare two main groups: antacids, which neu-
OTC MEDICATIONS provider about heartburn; tralize gastric acid,31,32 and acid suppres-
Patients with mild and/or intermittent 55% took medications for heartburn sants, which reduce gastric acid
heartburn typically seek relief on their prevention; secretion and include H2RAs and PPIs.
140 I The American Journal for Nurse Practitioners January 2005 Vol. 9 No. 1
TABLE 3. OTC HEARTBURN MEDICATIONS: FHB INDICATION, DURATION AND MECHANISM OF
ACTION, ADVERSE EFFECTS
Medication Trade Name(s) Indicated Duration of Mechanism of Action Potential Adverse Effects11
Class Specifically Action
for FHB (one dose)
Antacids Tums® No 1-2 hours Rapidly elevate Aluminum salts: constipation,
Rolaids® esophageal pH accumulation in patients with
Maalox® and neutralize renal failure, hypophosphatemia,
Mylanta® esophageal acid osteomalacia (rare); calcium salts:
Gaviscon® for up to 90 minutes constipation, milk-alkali syndrome
and others after dosing31,32 with high doses, rebound hyperacidity
(dose-dependent); magnesium salts: diar-
rhea, accumulation in patients with renal
failure; sodium bicarbonate: milk-alkali
syndrome with high doses (these agents
should be avoided in sodium-restricted
patients); magnesium/aluminum combina-
tions: minor changes in bowel function
H2RAs Tagamet HB 200® No Up to 12 hours Inhibit gastric acid Diarrhea, headache, constipation;
Zantac 75® secretion gynecomastia and low sperm
Pepcid® AC count (in male users of high-dose
Axid AR® cimetidine)
PPI Prilosec OTC™ Yes Up to 24 hours* Shuts down the active Diarrhea, headache, nausea,
pumps that make abdominal pain
*As part of a 14-day course of therapy.
OTC = over-the-counter; FHB = frequent heartburn; H2RA = histamine H2-receptor antagonist; PPI = proton pump inhibitor.
Antacids—Many patients with heart- following medications:35 Antacids are less appropriate for patients
burn self-treat with OTC antacids such as allopurinol (Zyloprim) with FHB: Their short duration of action
Mylanta®, Maalox®, Rolaids®, Tums®, or aspirin, salicylates means that FHB sufferers would need to
Gaviscon®, the lattermost of which also take multiple doses per day, which
benzodiazepines (Valium®, Xanax®)
contains alginic acid. Alginic acid reacts would likely lead to side effects even if
with saliva to produce a foam barrier on patients did adhere to the regimen.11
top of the stomach that buffers the chloroquine (Aralen®)
Another drawback is their inadequacy as
refluxed material. Antacids are composed corticosteroids (prednisone, heartburn prophylaxis.
of different combinations of three salts Deltasone®, Medrol)
(magnesium, calcium, and aluminum) diabetes medicines (Diabinese®, Histamine H2-Receptor Antagonists—
with hydroxide or bicarbonate ions. They Micronase®, Glucotrol®) Three types of receptors trigger produc-
are effective for quick relief of episodic digoxin (Lanoxin®) tion of hydrochloric acid in the stom-
heartburn. For maximum relief, antacids iron (Feosol®, ferrous sulfate, ach. H2RAs block one of these
should be used as needed, and should be Nu-Iron®) receptors—the histamine H2 receptor—
taken immediately after meals if symp- isoniazid (INH) on the gastric parietal cell, thereby
toms occur.13 Many clinical studies con- impeding the formation of hydrochloric
ducted in the 1970s, 1980s, and 1990s acid. H2RAs that are available OTC
penicillamine (Depen®, Cuprimine®)
have shown that antacids are more effec- include cimetidine (Tagamet HB 200®),
phenothiazines (Thorazine® , ranitidine (Zantac 75®), famotidine
tive than placebo in relieving heartburn. Stelazine®, Compazine®)
However, in addition to having side (Pepcid® AC), and nizatidine (Axid
phenytoin type drugs (Dilantin®, AR®). Dosages of these OTC versions are
effects in some patients (eg, diarrhea,
Mesantoin®, Peganone®, Cerebyx®) one half of the standard lowest prescrip-
abdominal discomfort, constipation),
antacids can interact adversely with a quinidine (Quinidex®, Quinaglute®) tion dosage. (OTC famotidine was
host of other drugs by preventing or lim- tetracycline recently approved at the original pre-
iting their absorption. For example, a thyroid hormone (Synthroid®, scription dosage.) Although these four
combination OTC antacid containing levothyroxine) agents differ somewhat in potency, they
aluminum hydroxide, magnesium ticlopidine (Ticlid®) can be used interchangeably according
hydroxide, calcium carbonate, and sime- ulcer medications (Tagamet®, to the ACG.24 They are particularly use-
thicone may interact adversely with the Zantac®, Pepcid®, Axid®) ful in patients with episodic heartburn
Vol. 9 No. 1 January 2005 The American Journal for Nurse Practitioners I 141
who take the medication before an activ- in 355 patients with symptomatic GERD (Prilosec®), this drug class includes lan-
ity that is likely to produce reflux symp- without esophagitis.46 On days 7 and 27, soprazole (Prevacid®), pantoprazole (Pro-
toms (eg, eating a heavy or spicy meal). respectively, daily proportions of tonix®), esomeprazole (Nexium®), and
Comparisons between antacids and patients who were heartburn-free were rabeprazole (Aciphex®). PPIs are highly
the H2RAs are limited, but it has been higher in the 20-mg omeprazole group effective in controlling symptoms and
suggested that the former provide a more (62% and 74%) than in the 10-mg healing esophagitis, and are used as
rapid response (onset of action, 30 min- omeprazole group (41% and 49%) or maintenance therapy to prevent GERD
utes vs up to 90 minutes),36 whereas the the placebo group (14% and 23%). flare-ups.30 In general, standard-dose
latter are generally more effective and Clinical trials and post-marketing PPIs will relieve symptoms and heal
have a much longer duration of action.24,36 surveillance of the prescription formula- esophagitis in 85% to 90% of patients.50
Efficacy trials have shown that the H2RAs tion of omeprazole have demonstrated Patients with GERD are advised to take
are superior to placebo for the relief of the excellent safety profile of this agent.47 the PPI immediately before breakfast.50
episodic heartburn.37-40 Placebo-con- No new safety issues have emerged with Prokinetic Agents—Instead of neutral-
trolled studies have also demonstrated the OTC formulation. PPI-related side izing stomach acid, prokinetic agents
the efficacy of these agents in preventing effects include diarrhea, headache, nau- increase LES pressure, enhance gastric
heartburn.41,42 sea, and abdominal pain, and occur in emptying, and improve peristalsis.
Side effects of H2RAs include diarrhea, fewer than 10% of users.44 As an Older prokinetics such as bethanechol
headache, and constipation.11 In males, inhibitor of CYP-2C19, omeprazole may (Urecholine®) and metoclopramide
high-dose cimetidine may cause gyneco- increase serum levels of other drugs (Reglan®) are rarely used because of their
mastia and/or a decreased sperm count.43 metabolized by 2C19, including war- side-effect profiles.23 Although cisapride
Drug interactions occur more frequently farin (Coumadin®), phenytoin (Dilan- (Propulsid®) has been found to be equiv-
with cimetidine than with the other tin®), and diazepam (Valium®), and it alent to standard-dose H2RAs in reliev-
H2RAs because cimetidine impedes may alter absorption of medications such ing reflux symptoms and healing
hepatic metabolism of these other drugs.11 as itraconazole (Sporanox®) and digoxin esophagitis, this medication has been
This list of drugs includes warfarin, (Lanoxin®). However, many patients can associated with cardiac arrhythmias and
theophylline, phenytoin, diazepam, pro- use PPIs safely with oral contraceptives is available on a limited basis. The manu-
pranolol, calcium channel blockers, and with medications for hypertension, facturer recommends that a baseline
metronidazole, lidocaine, certain tricyclic arthritis, and angina.43,48,49 electrocardiogram be performed before
antidepressants (TCAs), and other drugs cisapride therapy is started.51 Concurrent
metabolized by the hepatic cytochrome P use of cisapride with agents that increase
Most patients with typical symptoms of
(CYP)-450 isoenzyme system.11 In addi- cisapride blood levels (eg, macrolides,
GERD do not have esophagitis;23 as
tion, any H2RA may decrease the nefazodone, antifungals, certain AIDS
mentioned earlier, many clinicians rec-
bioavailability of drugs whose effects medications) or that predispose patients
ognize this as a separate entity called
depend on an acidic gastric pH.44 to fatal arrhythmias (eg, class IA or class
nonerosive reflux disease or NERD. NPs
III antiarrhythmics; certain TCAs, tetra-
Proton Pump Inhibitor—Like H2RAs, must ascertain whether FHB is self-lim-
cyclic antidepressants, or antipsychotics)
PPIs suppress gastric acid production. ited or a presenting symptom of GERD
However, they do so at the source, by so that treatment can focus not only on
blocking parietal cell hydrogen/potas- relieving heartburn, but also on healing Comparative Trials—Many studies
sium ion adenosine triphosphatase, the mucosal damage to the esophagus and two meta-analyses involving pre-
known as the proton pump. This is the and preventing further damage. Along scription-strength medications have
final common pathway in the process of with long-standing FHB, other signs and demonstrated that PPIs are more effec-
gastric acid secretion. Only one PPI, symptoms of GERD include regurgita- tive than other drug classes or placebo in
omeprazole, is available over the tion of sour-tasting material into the relieving heartburn in patients with
counter: Prilosec OTC™. This medica- throat or mouth and frequent belching. GERD or NERD.
tion contains the equivalent of prescrip- Various prescription medications are A randomized, double-blind trial
tion-strength omeprazole, although it is FDA approved for GERD treatment. conducted on 310 patients who
formulated as a magnesium salt tablet. received omeprazole 20 mg daily or
H2RAs—When given in standard
Bioavailability of omeprazole is similar cimetidine 400 mg 4 times daily
dosages used for peptic ulcer disease,
in both formulations.45 Omeprazole revealed that after 4 weeks of treat-
H2RAs can alleviate mild to moderate
magnesium is the only OTC medication ment, a significantly larger propor-
symptoms of GERD.24 In fact, before the
specifically indicated for FHB. tion of omeprazole recipients than
introduction of PPIs, these agents were
According to the package labeling, this cimetidine recipients were asympto-
the treatment of choice for reflux and
medication is to be taken once daily for matic (46% vs 22%; P <0.001).52 In
erosive esophagitis.24 However, they are
14 days. addition, diary cards completed dur-
not as effective in either domain as the
The efficacy of omeprazole 20 mg ing the first 2 weeks showed that
was demonstrated in a study comparing omeprazole users experienced fewer
it with omeprazole 10 mg and placebo PPIs—In addition to omeprazole daytime and night-time symptoms.
142 I The American Journal for Nurse Practitioners January 2005 Vol. 9 No. 1
A meta-analysis of 43 studies that of published economic studies of which entails a 7-day course of
enrolled 7635 patients with GERD GERD treatments showed that PPIs high-dose omeprazole followed by a
showed that PPIs, relative to H2RAs, were more cost-effective than H2RAs step-down approach (sequential
provided faster and more complete because of their fast healing of therapeutic trials with less intensive
relief of heartburn.53 A much larger esophagitis, early relief of symptoms, therapy), with sequential invasive
proportion of PPI recipients than and prevention of recurrent esophagitis diagnostic testing in nonresponders.
H2RA recipients were rendered and development of complications.57 Over 1 year, the PPI test strategy, as
heartburn free during the treatment In 2000, researchers at Stanford compared with the traditional strate-
period (77.4% vs 47.6%). University sought to determine the gy, resulted in greater symptom relief
A randomized, double-blind, multi- cost-effectiveness of various first-line and improved QoL, as well as more
center trial was conducted on 677 empiric therapies for patients with appropriate utilization of invasive
patients with GERD (heartburn and typical symptoms of GERD.58 The six diagnostic testing.
normal endoscopy findings or mild treatment arms included (1) lifestyle Because many patients with mild
erosive changes) who received therapy, including antacids; (2) GERD and infrequent symptom
omeprazole 10 to 20 mg daily or ran- H2RA therapy, with endoscopy per- relapses use a PPI only when symp-
itidine 150 mg twice daily for 2 formed in nonresponders; (3) step- toms demand, one researcher looked
weeks.54 Participants were followed up therapy with H2RAs followed by at the results of four randomized,
for 12 months, during which time PPIs in nonresponders; (4) step- controlled studies, and found that
they could reinstitute therapy for down therapy with a PPI followed by the use of on-demand or intermittent
heartburn recurrences. Omeprazole an H2RA as needed; (5) PPI on- PPIs reduced symptoms, improved
20 mg daily, as compared with the demand therapy (8 weeks of treat- QoL, and was cost-effective.61
H2RA, provided faster relief of heart- ment for symptomatic recurrence, A summary of findings to date states
burn in patients with erosive or with no more than 3 treatments/ that, “in terms of economics, the
nonerosive disease. Intermittent year); and (6) PPI continuous thera- management strategies that appear to
treatment was effective in managing py. Results showed that the PPI on- result in the most cost-efficient gains
symptoms in half of the patients with demand therapy was the most in health appear to be PPI-based
uncomplicated GERD. cost-effective approach. step-down or ‘on-demand’ strategies”
The Dutch Reflux Study Group eval- Another 2000 study entailed a cost- [versus H2RAs and prokinetics].62
uated acute and long-term treatment utility analysis of four alternatives to
of 446 patients with mild GERD with Table 4 lists the cost of a 2-week
treat uncomplicated heartburn:
standard-dose omeprazole or high- course of various OTC H2RAs and the
empiric PPI with dose escalation for
dose ranitidine, and found that the OTC PPI. These prices are approxima-
nonresponders, empiric H2RA with
proportions of patients who were tions, and may not reflect the cost of
PPI for nonresponders, esophagogas-
asymptomatic after 4 and 8 weeks of each medication in every part of the
troduodenoscopy (EGD) followed by
treatment were 61% and 74% for country. The concept of cost-effective-
treatment, and upper GI series fol-
omeprazole recipients, respectively, ness represents not only the actual cost
lowed by treatment.59 Empiric treat-
and 31% and 50% for ranitidine of the medication, but also the amount
ment appeared to be the optimal
recipients, respectively.55 of time that patients are rendered symp-
initial management strategy for
Another Dutch team performed a tom free after the course of therapy such
patients with heartburn, with a PPI
meta-analysis of 23 trials in which that further medication is not needed, at
projected to provide the greatest qual-
nearly 9000 patients underwent least in the short run.
ity-adjusted survival and an H2RA
empiric treatment for heartburn
projected to be less costly. In other REFERRAL
associated with GERD or treatment
words, the choice of a PPI versus an NPs can diagnose and manage most
for NERD (these patients had under-
H2RA should depend on the impact cases of FHB, and even GERD, especially
gone endoscopy).56 PPIs were superi-
of heartburn on a patient’s QoL. when no other symptoms are present
or to both H2RAs and prokinetic
agents in achieving heartburn remis- In 2002, investigators at the Cedars- and the problem can be controlled with
sion. H2RAs were also effective in Sinai Health System in Los Angeles medication. NPs should refer patients
promoting symptom remission, but used decision analysis to assess the with alarm symptoms, GERD complica-
the prokinetics were less helpful. clinical and economic impact of two tions, a prolonged history of GERD
competing management strategies for symptoms, an uncertain diagnosis, or
COST-EFFECTIVENESS DATA GERD.60 They studied the “tradition- treatment-refractory symptoms to a gas-
Several studies have focused on the cost- al” strategy, which incorporates a troenterologist.63 Patients with extra-
effectiveness of various strategies for step-up approach (sequential thera- esophageal symptoms should be advised
treating heartburn, which is usually in peutic trials with more intensive to see an otorhinolaryngologist, pulmo-
the setting of GERD: therapy), followed by sequential nologist, or other specialist. Finally, a
In 1996, when H2RAs and PPIs were invasive diagnostic testing in nonre- surgical consult may be indicated in
available by prescription only, a review sponders; and the “PPI test” strategy, patients with:
Vol. 9 No. 1 January 2005 The American Journal for Nurse Practitioners I 143
TABLE 4. OTC H2RAs AND PPI: DOSAGE AND COST bureau for Procter & Gamble Pharmaceu-
ticals and Abbott Laboratories, Inc. Rick H.
Medication Dosage Cost ($)* Davis, Jr., serves on the speaker bureau for
H2RAs Procter & Gamble Pharmaceuticals and Astra
Cimetidine (generic) 200 mg 1 or 2 times daily PRN 4.29 Zeneca Pharmaceuticals.
Tagamet HB 200® 200 mg 1 or 2 times daily PRN 8.59
Ranitidine (generic) 75 mg 1 or 2 times daily PRN 4.25 MAJOR REFERENCES*
Zantac 75® 75 mg 1 or 2 times daily PRN 8.49 American Gastroenterological Association
Famotidine (generic) 10 mg 1 or 2 times daily PRN 6.99 medical position statement: guidelines on
Pepcid® AC 10 mg 1 or 2 times daily PRN 7.97 the use of esophageal pH recording. Gastro-
Axid AR® 75 mg 1 or 2 times daily PRN 8.39 enterology. 1996;110:1981.
OTC PPI Bardhan KD, Muller-Lissner S, Bigard MA, et
al. Symptomatic gastro-oesophageal reflux
disease: double blind controlled study of
(omeprazole magnesium) 20.6 mg once daily 9.99
intermittent treatment with omeprazole or
Prescription PPIs ranitidine. The European Study Group. BMJ.
Omeprazole (Prilosec®) 20 mg daily 59.26 1999;318(7182):502-507.
Lansoprazole (Prevacid®) 30 mg daily 71.96 Bardhan KD. Intermittent and on-demand
Rabeprazole (Aciphex®) 20 mg daily 69.48 use of proton pump inhibitors in the man-
Pantoprazole (Protonix®) 40 mg daily 57.02 agement of symptomatic gastroesophageal
Esomeprazole (Nexium®) 40 mg daily 72.05 reflux disease. Am J Gastroenterol. 2003;98(3
*Cost for 2 weeks' treatment with the highest dosage (discount pharmacy in New Jersey).
Berardi RR. Heartburn self-treatment: focus
The prescription PPIs are generally given for 4 to 8 weeks, depending on the indication.
on nonprescription omeprazole. Rx Con-
OTC = over-the-counter; H2RA = Histamine H2-receptor antagonist; PRN = pro re nata (as
needed); PPI = proton pump inhibitor.
DeVault KR, Castell DO, and the Practice
Parameters Committee of the American
documented GERD symptoms that duced OTC PPI does not act as quickly as College of Gastroenterology. Updated guide-
lines for the diagnosis and treatment of gas-
are responsive to medical therapy but antacids and H2RAs, but it is more effec- troesophageal reflux disease. Practice
who do not wish to continue long- tive and longer-lasting than the other two Guidelines. 1999;94(6):1434-1442.
term medical therapy; medication classes, and it will likely prove The Gallup Organization. A Gallup Survey on
documented GERD symptoms that cost-effective in the long run because it Heartburn Across America. Princeton, NJ;
are unresponsive to medical therapy prevents heartburn from occurring. 1988.
because of patient noncompliance, Although all of these medications are The Gallup Organization. A Gallup Survey on
inability to afford medications, or available OTC, it is optimal for NPs to Heartburn Across America. Princeton, NJ;
May 1, 2000.
relapse; guide patients in their use, and to make
Heidelbaugh JJ, Nostrant TT, Kim C, Van
complications of GERD such as sure that patients do not have a more seri-
Harrison R. Management of gastroe-
Barrett's esophagus or grade III or IV ous underlying condition or complica- sophageal reflux disease. Am Fam Physician.
esophagitis; tions that warrant further attention. 2003;68(7):1311-1318.
peptic stricture; Finally, NPs should counsel patients in Heudebert GR, Centor RM, Klapow JC, et al.
recurrent symptomatic aspiration; terms of lifestyle modifications that will What is heartburn worth? A cost-utility
medical complications attributable to mitigate, if not eliminate, FHB symptoms. analysis of management strategies. J Gen
Intern Med. 2000;15(3):175-182.
a large hiatal hernia such as bleeding Mary Knudtson is a professor in the Kahrilas P. Clinical manifestations and diag-
or dysphagia; Department of Family Medicine at the nosis of esophageal reflux. UptoDate.
atypical symptoms such as asthma or University of California, Irvine. She is Over-the-counter omeprazole (Prilosec
chest pain with abnormal 24-hour nationally certified as a family and a pedi- OTC). Med Lett Drugs Ther. 2003; 45(1162):
pH monitoring study results; or atric nurse practitioner. She is a practicing 61-62.
severe symptoms that they would clinician in primary care at UCI and is the Locke GR 3rd, Talley NJ, Fett SL, et al.
prefer to have treated surgically Prevalence and clinical spectrum of gastroe-
director of their family nurse practitioner sophageal reflux: a population-based study
rather than medically.11,25 program. Rick H. Davis, Jr, is a senior in Olmsted County, Minnesota. Gastro-
CONCLUSION physician assistant at the University of enterology. 1997;112(5):1448-1456.
Patients suffering from heartburn have a Florida, Department of Medicine, Division Scott M, Gelhot AR. Gastroesophageal reflux
number of OTC treatments from which of Gastroenterology, Hepatology, and disease: diagnosis and management. Am Fam
Nutrition, in Gainesville, Florida. Physician. 1999;59(5):1161-1169.
to choose. For those with episodic heart-
Wolfe MM. Overview and comparison of the
burn, antacids and H2RAs provide fast proton pump inhibitors for the treatment of
and reliable relief. For those with frequent DISCLOSURE STATEMENTS
Mary Knudtson has current consulting agree- acid-related disorders. UpToDate.
episodes of heartburn, however, omepra- ments with Procter & Gamble Pharma- *Full references corresponding to the
zole magnesium, taken once daily for 14 ceuticals, Eli Lilly and Company, and numbers in the text are available at
days, is preferred. The recently intro- GlaxoSmithKline, and serves on the speaker www.npcentral.net/ce/heartburn
144 I The American Journal for Nurse Practitioners January 2005 Vol. 9 No. 1