Transcript Gastroesophageal Reflux Disease

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. 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
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 – 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
(qd to
bid)
Standard
dose
(bid)
High
dose
200 mg
10 mg
75 mg
75 mg
400 mg
20 mg
150 mg
150 mg
400 mg
qid or 800
mg bid
40 mg bid
150 mg
qid
150 mg
qid
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 hasmild, moderate or severe?
What treatment should you recommend?
Questions???