Gastroesophageal

Reflux Disease
Scott Stolte, Pharm.D.
Shenandoah University

Overview of GERD
Definition

Symptoms or mucosal damage produced by

the abnormal reflux of gastric contents into
the esophagus

Classic symptom is frequent and

persistent heartburn
44 % of Americans experience heartburn
at least once per month
7 % have daily symptoms

Normal Function
Esophagus

Transports food from mouth to stomach through

peristaltic contractions

Lower esophageal sphincter (LES)

Relaxes, on swallowing, to allow food to enter

stomach and then contracts to prevent reflux

Normal to have some amount of reflux multiple

times each day (transient relaxation of LES not
associated with swallowing)

http://www.gerd.com/intro/noframe/grossovw.htm

Pathogenesis
3 lines of defense must be impaired for
GERD to develop

LES barrier impairment

Relaxation of LES
Low resting LES pressure
Increased gastric pressure

Decreased clearance of refluxed materials

from esophagus
Decreased esophageal mucosal resistance

Contributing Factors
Decrease LES
pressure

Chocolate
Alcohol
Fatty meals
Coffee, cola, tea
Garlic
Onions
Smoking

Directly irritate the gastric

mucosa

Tomato-based products
Coffee
Spicy foods
Citrus juices
Meds: NSAIDS, aspirin, iron,
KCl, alendronate

Stimulate acid secretions

Soda
Beer
Smoking

Contributing Factors
Drugs that decrease LES pressure

Alpha-adrenergic agonists
Anti-cholinergic agents (e.g. TCAs, antihistamines)
Beta-adrenergic agonists
Calcium channel antagonists (nifedipine most reduction)
Diazepam
Dopamine
Meperidine
Nitrates/Other vasodilators
Estrogens/progesterones (including oral contraceptives)
Prostaglandins
Theophylline

Lines of Defense
Clearance of refluxed materials from
esophagus

Primary peristalsis from swallowing increases

salivary flow
Secondary peristalsis from esophageal distension
Gravitational effects

Esophageal mucosal resistance

Mucus production in esophagus

Bicarbonate movement from blood to mucosa

Pathogenesis
Amount of esophageal damage seen
dependent on:

Composition of refluxed material

Which is worse: acid or alkaline refluxed material?

Volume of refluxed material

Length of contact time
Natural sensitivity of esophageal mucosa
Rate of gastric emptying

Typical Symptoms
Common symptoms most common when
pH<4

Heartburn
Belching and regurgitation
Hypersalivation

May be episodic or nocturnal

May be aggravated by meals and reclining
position

Atypical Symptoms
Nonallergic asthma
Chronic cough
Hoarseness
Pharyngitis
Chest pain (mimics angina)
May be only symptoms omeprazole
test

Complications
Esophagitis
Esophageal strictures and ulcers
Hemorrhage
Perforation
Aspiration
Development of Barretts esophagus
Precipitation of an asthma attack

Barretts Esophagus
Highest prevalence in adult Caucasian males
Histologic change

Lower esophageal tissue begins to resemble the epithelium in

the stomach lining

Predisposes to esophageal cancer (30-60x) and

esophageal strictures (30-80% increased risk)
Odds ratio for development (compared with GERD < 1
yr.)

Patients with GERD 1-5 years 3.0

Patients with GERD > 10 years 6.4

More frequent, more severe, and longer-lasting the

symptoms of reflux, the > the risk of cancer

Warning Signs
If present, consider an endoscopy:
Dysphagia
Odynophagia
Bleeding
Unexplained weight loss
Choking
Chest pain

Diagnosis
Clinical symptoms and history

Presenting symptoms and associated risk

factors

Give empiric therapy and look for

improvement
Endoscopy if warning signs present

Refer
Chest pain
Heartburn while taking H2RAs or PPIs

Or heartburn that continues after 2 weeks of

treatment

Nocturnal heartburn symptoms

Frequent heartburn for > 3 months
GI bleeding and other warning signs
Concurrent use of NSAIDS
Pregnant or nursing
Children < 12 years old

Therapy Goals
Alleviate or eliminate symptoms
Diminish the frequency of recurrence and
duration of esophageal reflux
Promote healing if mucosa is injured
Prevent complications

Therapy
Therapy is directed at:

Increasing LES pressure

Enhancing esophageal acid clearance
Improving gastric emptying
Protecting esophageal mucosa
Decreasing acidity of reflux
Decreasing gastric volume available to be
refluxed

Treatment
Three phases in treatment

Phase I: Lifestyle changes 2 weeks

Lifestyle modifications
Patient-directed therapy with OTC medications

Phase II: Pharmacologic intervention

Standard/high-dose antisecretory therapy

Phase III: Surgical intervention

Patients who fail pharmacologic treatment or have severe
complications of GERD
LES positioned within the abdomen where it is under positive
pressure

Treatment Selection
Mild intermittent heartburn (Phase I)

Treat with lifestyle changes plus antacids

AND/OR low dose OTC H2-receptor
antagonists (H2RAs) as needed

Symptomatic relief of mild to moderate

GERD (Phase II)

Treat with lifestyle changes plus standard

doses of H2RAs for 6-12 weeks OR proton
pump inhibitors (PPIs) for 4-8 weeks

Treatment Selection
Healing of erosive esophagitis or
treatment of moderate to severe GERD
(Phase II)

Lifestyle modifications plus PPIs for 8-16

weeks OR high dose H2RAs for 8-12
weeks
PPIs preferred as initial choice due to more
rapid symptom relief and higher rate of healing

May also add a prokinetic/promotility agent

Treatment Considerations
Prokinetic agents are an alternative to
H2RAs

Efficacy similar to prescription dose H2RAs

Used as a single agent only in mild to
moderate, nonerosive GERD
May be more expensive and use is limited
by side effects

Treatment Considerations
Maintenance therapy may be needed

Large % of patients experience recurrence

within 6-12 months after DC of therapy
Goal is to control symptoms and prevent
complications
May use antacids, PPIs or H2RAs
In patients with more severe symptoms, PPI most
effective

Lifestyle Modifications
Elevate the head of the bed 6-8 inches
Decrease fat intake
Smoking cessation
Avoid recumbency for at least 3 hours post-prandial
Weight loss
Limit alcohol intake
Wear loose-fitting clothing
Avoidance of aggravating foods
These changes alone may not control symptoms

Esophageal
clearance:
Cisapride

Esophageal mucosal
resistance:
Alginic acid, Sucralfate

Gastric emptying:
Metoclopramide
Cisapride

LES pressure:
Metoclopramide
Cisapride

Gastric acid:
Antacids
H2RAs
PPIs
http://www.gerd.com/intro/noframe/grossovw.htm

Drug Therapy - Antacids

Antacids with or without alginic acid

Antacids increase LES pressure and do not promote

esophageal healing
Neutralize gastric acid, causing alkalinization

Alginic acid (in Gaviscon) forms a highly viscous

solution that floats on top of the gastric contents
Dose as needed typical action 1-3 hours
Not best choice for nocturnal symptoms because pH
suppression cannot be maintained

Drug Therapy - Antacids

Products: Magnesium salts, aluminum salts,

calcium carbonate, and sodium bicarbonate
Dosing: Initially 40-80 mEq prn (no more than
500-600 mEq per 24 hours)
Maalox/Mylanta 30 ml prn or PC & HS
Maalox TC/Mylanta II 15 ml prn or PC & HS
Gaviscon 2 tabs PC & HS
Tums 0.5-1 gm prn

Drug Therapy H2RAs

H2RAs
Mainstay of treatment for mild to moderate
GERD
H2RAs equally efficacious

Select based on pharmacokinetics, safety profile

and cost

Timing

Give in divided doses for constant gastric acid

suppression
May give at night if only nocturnal symptoms
Give before an activity that may result in reflux
symptoms

Drug Therapy H2RAs

Cimetidine Famotidine Nizatidine Ranitidine
Low dose 200 mg
(qd to
bid)

10 mg

75 mg

75 mg

Standard 400 mg
dose
(bid)

20 mg

150 mg

150 mg

High
dose

40 mg bid

150 mg
qid

150 mg
qid

400 mg
qid or 800
mg bid

Drug Therapy H2RAs

Response to H2RAs dependent upon:
1) Severity of disease
2) Duration of therapy
3) Dosage regimen used

Tolerance to effect develops

Drug Therapy - PPIs

Proton Pump Inhibitors
Used to treat moderate to severe GERD
More effective and faster healing than H2RAs

May be used to treat esophagitis refractory to H2RAs

All agents effective - choose based on cost

Prilosec released OTC 2003

Use for heartburn that occurs 2 days/week

Label - Dont use for more than 14 days

Drug Therapy - PPIs

Standard dosing

Esomeprazole 20 mg qd
May 2006: FDA approved Nexium for adolescents 12-17
years for the short-term (up to 8 weeks) treatment of GERD

Lansoprazole 15-30 mg qd
Omeprazole 20 mg qd
Pantoprazole 40 mg qd
Rabeprazole 20 mg qd

Timing

Best is 30 minutes prior to breakfast

Drug Therapy - PPIs

May give higher doses bid for

Patients with a partial response to standard

therapy
Patients with breakthrough symptoms
Patients with severe esophageal dysmotility
Patients with Barretts esophagus

Always give second dose 30 minutes prior

to evening meal

Drug Therapy - Prokinetics

Prokinetic Agents -- MOA

Enhances motility of smooth muscle from

esophagus through the proximal small bowel
Accelerates gastric emptying and transit of
intestinal contents from duodenum to
ileocecal valve

Drug Therapy - Prokinetics

Prokinetic Agents

Results of therapy
Improved gastric emptying
Enhanced tone of the lower esophageal sphincter
Stimulated esophageal peristalsis (cisapride only)

Prokinetic Agents - Products

Metoclopramide (Reglan)

Dopamine antagonist
Only use if motility dysfunction documented
Administer at least 30 minutes prior to meals
Dose - 10 to 15 mg AC and HS
Adverse Effects limit use
diarrhea
CNS - drowsiness, restlessness, depression
extrapyramidal reactions dystonia, motor restlessness,
etc.
breast tenderness

Prokinetic Agents - Products

Cisapride
Was removed from the market July 14,
2000 due to adverse cardiovascular
effects (i.e. ventricular arrhythmias)
Available only through an investigational
limited access program for patients who
have failed all other treatment options

Drug Therapy
Mucosal Protectants
Sucralfate

Very limited value in treatment of GERD

Comparisons
Similar healing rate to H2RA in treatment of mild
esophagitis
Less effective than H2RAs in refractory esophagitis

Only use in mildest form of GERD

Special Populations
Infants can experience a form of GERD

Postmeal regurgitation or small volume vomiting

Occurs due to a poorly functioning sphincter
Treatment
Supportive therapy

Diet adjustments smaller, more frequent feedings;

thickened feedings
Postural management

H2RAs have been used (e.g. ranitidine 2 mg/kg) and

antacids

Special Populations
Pregnancy

Common, due to decreased LES pressure

and increased abdominal pressure
Nearly half of all pregnant women experience
Antacids other than sodium bicarbonate
generally considered safe, but avoid chronic
high doses

GERD in the Elderly

In the US, 20% report acid reflux
Worldwide, 3X prevalence in > 70 yo of
patients younger than 39 yo
More likely to develop severe disease
More likely to be poorly diagnosed or
underdiagnosed

Due to atypical symptoms

Always look for medication causes

GERD in the elderly

Symptoms

Dysphagia
Vomiting
Weight loss
Anemia
Anorexia

Typical symptoms are less frequent

GERD in the Elderly

Diagnosis should always include
endoscopy
Prokinetic agents should be avoided
PPIs are medications of choice for acute
episodes and prevention of recurrence
due to efficacy, safety, and tolerability

Step down approach is preferred more

clinically effective and more cost effective

PPIs in the Elderly

Decreased clearance with omeprazole,
lansoprazole, rabeprazole
Little effect on clearance with
pantoprazole
Dosage adjustments not necessary
Pantoprazole lower affinity for CYP450