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 Directly irritate the gastric

pressure mucosa
 Chocolate  Tomato-based products
 Alcohol  Coffee
 Spicy foods
 Fatty meals
 Citrus juices
 Coffee, cola, tea
 Meds: NSAIDS, aspirin, iron,
 Garlic KCl, alendronate
 Onions Stimulate acid secretions
 Smoking  Soda
 Beer
 Smoking
 Contributing Factors
Drugs that decrease LES pressure
 Alpha-adrenergic agonists
 Anti-cholinergic agents (e.g. TCA’s, 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 Barrett’s esophagus
Precipitation of an asthma attack
 Barrett’s 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 (H2RA’s) as needed
Symptomatic relief of mild to moderate
GERD (Phase II)
 Treat with lifestyle changes plus standard
doses of H2RA’s for 6-12 weeks OR proton
pump inhibitors (PPI’s) for 4-8 weeks
 Treatment Selection

Healing of erosive esophagitis or

treatment of moderate to severe GERD
(Phase II)
 Lifestyle modifications plus PPI’s for 8-16
weeks OR high dose H2RA’s for 8-12
weeks
PPI’s 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

H2RA’s
 Efficacy similar to prescription dose H2RA’s
 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 D’C 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 mucosal
resistance:
Esophageal Alginic acid, Sucralfate
clearance:
Cisapride
LES pressure:
Gastric emptying: Metoclopramide
Metoclopramide Cisapride
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 – H2RA’s

H2RA’s
Mainstay of treatment for mild to moderate
GERD
H2RA’s 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 – H2RA’s
Cimetidine Famotidine Nizatidine Ranitidine

Low dose 200 mg 10 mg 75 mg 75 mg

(qd to
bid)
Standard 400 mg 20 mg 150 mg 150 mg
dose
(bid)
High 400 mg 40 mg bid 150 mg 150 mg
dose qid or 800 qid qid
mg bid
 Drug Therapy – H2RA’s
Response to H2RA’s dependent upon:
1) Severity of disease

2) Duration of therapy

3) Dosage regimen used

Tolerance to effect develops

 Drug Therapy - PPI’s
Proton Pump Inhibitors
Used to treat moderate to severe GERD
More effective and faster healing than H2RA’s
 May be used to treat esophagitis refractory to H2RA’s
All agents effective - choose based on cost
Prilosec released OTC 2003
 Use for heartburn that occurs ≥ 2 days/week
 Label - Don’t use for more than 14 days
 Drug Therapy - PPI’s
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 - PPI’s
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 Barrett’s 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
H2RA’s 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
PPI’s 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
 Counseling Questions
Before recommending a therapy, ask:
 Duration and frequency of symptoms
 Quality and timing of symptoms
 Use of alcohol and tobacco
 Dietary choices
 Medications already tried to treat symptoms
 Other disease states present and medications
being used
 Case Study
BT, a 45 year old male postal worker,
complains of heartburn 3-4 times per
month. The pain typically appears after
meals. He has tried Tums with varying
degrees of success. He would like
something “more effective.”
 Case Study
What questions should you ask BT first?
What would cause you to refer BT to a
physician?
What type of GERD do you think BT has-
mild, moderate or severe?
What treatment should you recommend?
Questions???