Gastroesophageal Reflux Disease

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Gastroesophageal Reflux Disease

• Scott Stolte, Pharm.D.
• Shenandoah University

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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

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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)

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

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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

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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

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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

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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

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Typical Symptoms

• Common symptoms most common when pHlt4
• Heartburn
• Belching and regurgitation
• Hypersalivation
• May be episodic or nocturnal
• May be aggravated by meals and reclining position

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Atypical Symptoms

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

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Complications

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

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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 lt
  1 yr.)
• Patients with GERD 1-5 years 3.0
• Patients with GERD gt 10 years 6.4
• More frequent, more severe, and longer-lasting
  the symptoms of reflux, the gt the risk of cancer

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Warning Signs

• If present, consider an endoscopy
• Dysphagia
• Odynophagia
• Bleeding
• Unexplained weight loss
• Choking
• Chest pain

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Diagnosis

• Clinical symptoms and history
• Presenting symptoms and associated risk factors
• Give empiric therapy and look for improvement
• Endoscopy if warning signs present

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Refer

• Chest pain
• Heartburn while taking H2RAs or PPIs
• Or heartburn that continues after 2 weeks of
  treatment
• Nocturnal heartburn symptoms
• Frequent heartburn for gt 3 months
• GI bleeding and other warning signs
• Concurrent use of NSAIDS
• Pregnant or nursing
• Children lt 12 years old

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Therapy Goals

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

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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

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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

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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

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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

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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

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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

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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

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Esophageal mucosal resistance
Alginic acid, Sucralfate
Esophageal clearance Cisapride
LES pressure MetoclopramideCisapride
Gastric emptying Metoclopramide Cisapride
Gastric acid Antacids H2RAs PPIs
http//www.gerd.com/intro/noframe/grossovw.htm
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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

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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

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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

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Drug Therapy H2RAs
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Drug Therapy H2RAs

• Response to H2RAs dependent upon
• 1) Severity of disease
• 2) Duration of therapy
• 3) Dosage regimen used
• Tolerance to effect develops

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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

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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

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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

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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

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Drug Therapy - Prokinetics

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

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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

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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

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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

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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

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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

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GERD in the Elderly

• In the US, 20 report acid reflux
• Worldwide, 3X prevalence in gt 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

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GERD in the elderly

• Symptoms
• Dysphagia
• Vomiting
• Weight loss
• Anemia
• Anorexia
• Typical symptoms are less frequent

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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

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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

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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

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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.

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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?

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Questions???