Gastroesophageal reflux disease (GERD)

Gastroesophageal reflux disease (GERD) characterized by heartburn and/or regurgitation symptoms

is one of the most common gastrointestinal disorders managed by gastroenterologists and primary
care physicians.
GERD results from imbalance between aggressive and protective factor affecting GI mucosa
Protective factors Aggressive factors
- Lower esophageal sphincter o Gastric acid
(LES) o Pepsin
- Esophageal acid clearance o Bile salts
- Gastric emptying
- Mucosal resistance
o Types of heartburn:
1. Simple: mild and infrequent , associated with diet
2. Frequent: 2 or more days per week
3. Persistent: lasting more than 3 months with typical GERD symptoms
o Risk factors:

Diet Lifestyle Medications Diseases Others

Alcohol Obesity Calcium channel Motility disorders Genetics

Caffeine Smoking blockers Peptic ulcer disease Pregnancy
Beverages Stress Beta-agonists (PUD)
Chocolate Supine position Alpha-adrenergic Scleroderma
Citrus food Tight fitting clothes agonists Zollinger-Ellison
Fatty meals Theophylline syndrome
Garlic and onion Nitrates, PDE-5
Pipperemint inhibitors
Tomato NSAIDS
Salty and spicy food Benzodiazepines
Bisphosphonate

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o Cardinal symptoms:
1. Heartburn and regurgitation
2. Water brash
3. Belching and bloating
4. Epigastric pain
5. In addition, patients may experience extraesophageal symptoms like cough, hoarseness,
throat clearing, throat pain or burning, wheezing, and sleep disturbances.
o Alarming symptoms:
1. Chest pain (could be ischemic heart disease)
2. Dysphagia and odynophagia
3. Signs of upper GI bleeding
4. Nausea and vomiting
o Establishing the diagnosis of Gastroesophageal Reflux Disease (GERD)

o Goals of treatment:
- Relief symptoms
- Prevent meal or exercise related symptoms
- Improve quality of life
o Non- pharmacological treatment (Lifestyle modifications):
- Elevate head 6-8 inches
- Decrease fatty meals
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 - Stop eating before 3 hours of sleep
- Smoking cessation and limit alcohol consumption
- Avoid sleeping on additional pillows
- Avoid triggering food : chocolate, peppermints, caffeine, beverages, onion, garlic, fatty food,
citrus and tomato
- Avoid late and large meals
- Weight loss (for overweight and obese patients)
- Avoid taking NSAIDS as pain killers
- Stress reductions
- Wear loose fitting clothing
o Pharmacological treatment
A. Antacids
o Non-prescription antacids contain at least one of these salts
1. Magnesium hydroxide, magnesium carbonate
2. Aluminum (hydroxide or phosphate)
3. Calcium carbonate
4. Sodium bicarbonate
o Antacids brands:
Brand name Dosage form Components
Actonorm® Suspension Aluminium hydroxide - 220mg/5ml, Magnesium
hydroxide - 200mg/5ml, Simethicone - 25mg/5ml
Chooz® Chewing gum Calcium carbonate 500 mg
Diovol plus® Chewable tablet Simethicone - 25mg, Aluminium hydroxide - 165mg,
Suspension Magnesium hydroxide - 200mg
Gaviscon® Powder for Sodium alginate - 225mg, Magnesium alginate -
infant suspension 87.5mg
Gaviscon® Liquid Sodium alginate - 500mg/10ml, Sodium bicarbonate -
267mg/10ml, Calcium (carbonate) - 160mg/10ml
Maalox® Tablet, chewable Aluminium hydroxide - 400mg, Magnesium hydroxide
- 400mg

Maalox plus® Tablet, chewable Dimethicone - 25mg, Aluminium hydroxide - 200mg,

Magnesium hydroxide - 200mg
Maalox plus® Suspension Dimethicone - 0.5g/100g, Aluminium hydroxide -
3.25g/100g, Magnesium hydroxide - 3.65g/100g
Rennie®: Tablet, chewable Magnesium carbonate - 80mg, Calcium carbonate -
680mg

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 o Mechanism: Relieve heartburn by neutralizing gastric acid (buffering agent)
o Pharmacokinetics:
- Minimal absorption to the circulatory system
- Rapid onset: 5 minutes (liquid antacids  faster onset)
- Short duration: 20-30 mins
- Aluminium hydroxide, calcium carbonate  slower onset, more potent and longer
duration
o Dosing and administration:
- Take product at the onset of symptoms
- Dosing may be repeated in 1 to 2 hours, if needed, but don’t exceed maximum daily
dosage for a particular product
- Duration ma by prolonged up to 3 hours by taking it 1 hour after a meal
- When used in recommended dosage, available antacids are interchangeable despite
differences in salts and potency
- Frequent users may need to be switched to a longer acting product with or without
antacid
o Side effects:
- Diarrhea: magnesium salt (dose related)
- Constipation: aluminium salt (dose related)
- Belching and flatulence (mainly with sodium bicarbonate and calcium carbonate)
- Renal accumulation: (aluminium. Magnesium, calcium)
- Hypophosphatemia (aluminium)
o Caution when taking calcium supplement with calcium containing antacids
o Drug interactions:
- Decrease absorption of: tetracyclines, fluoroquinolones, azithromycin, digoxin,
azole antifungals, iron, levothyroxine
 Separate by at least 2 hours

B. Histamine2- receptor antagonists (H2RAs)

o These medications are available over the counter and by prescription. Common H2
receptor blockers include:
1. nizatidine (Axid®)
2. famotidine (Pepcid®, Pepcid AC®)
3. cimetidine (Tagamet®)
o Mechanism: inhibit histamine on histamine2 receptor of the parietal cell.
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o Pharmacokinetics: fast onset but long duration (cimetidine shortest acting). According to
the National Institutes of Health, H2 receptor blockers decrease stomach acid secretions
over a 24-hour period by 70 percent.
o H2RAs are effective in relieving fasting and nocturnal symptoms
o Dosing: (for >12 years old )
Brand name Active ingredient Adult dose (maximum daily dosage)
Tagmet® Cimetidine 200 mg 1 tablet (2 tablets)
Axid® Nizatidine 75 mg 1 tablet (2 tablets)
Pepcid® Famotidine 10 mg 1 tablet (2 tablets)
Pepcid® Famotidine 20 mg 1 tablet (2 tablets)

o Administration:
- Take a tablet with a glass of water
- Used at the onset of symptoms or 1 hour prior meal or exercise
- When used in recommended doses, H2RAs are considered interchangeable.
- Dose adjustment in renal impairment (CrCL< 50 ml/min)
o Side Effects: constipation, diarrhea, difficulty sleeping, dry mouth, dry skin, headaches,
ringing in the ears, trouble urinating, thrombocytopenia
o In rare cases, H2 receptor blockers might cause more serious side effects, such as:
blistered, burning, or scaling skin, changes in vision, confusion, difficulty breathing, chest
tightness, irregular heartbeat, hallucinations, suicidal thoughts
o Drug interactions:
- Decrease absorption of drugs that require acidic medium (azoles, iron)
- Cimetidine is potent CYP450 inhibitor  lot of drug interaction that is metabolized
via CYP450 isoenzymes
o Patient counseling :
- Take 1 tablet with a glass of water
- This drug should be taken after at least one 1 hour after iron or azole antifungals
- Take before an anticipating event (meals, exercise) 30 min to 1 hour
- When rapid relief is desired  take antacids initially then H2RAs to achieve longer
duration (may use a combination product)
- Preferred to be taken PRN (not scheduled) to prevent tolerance
- Self-treatment should be limited to 2 time per day (to prevent tolerance)
- Use lower dose (famotidine 10 mg bid) for mild infrequent heartburn to reserve
- higher OTC dose (famotidine 20 mg bid) for moderate symptoms

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C. Proton pump inhibitors (PPI)
o Mechanism: block the gastric H, K-ATPase, inhibiting gastric acid secretion. It provide
superior symptomatic relief and longer duration of action

o Pharmacokinetics:
- Onset: 2 to 3 hours
- Absorbed by circulatory system (more side effects)
- Duration of action: 24 hours (once daily dosing usually)
o PPIs are available both over-the-counter and by prescription.
Over-the-counter PPIs Prescription
o Lansoprazole 15 mg o Lansoprazole 30 mg
(lanzor®,lanzoprazol®, LPZ®) o Omeprazole 40 mg (omepral®,
o omeprazole 20 (Prilosec) omiz plus®, risek®)
o Esomeprazole 20 mg (Nexium®) o Esomeprazole 40 mg
o Dexlansoprazole
o Pantoprazole sodium
o Rabeprazole sodium
o Dosing and administration: (adults>18 years)
PPI name Adult dose
Omeprazole 20 mg 1 capsule 30 mins before morning meal QD for 14 days
Lanzoprazole 15 mg 1 capsule 30 mins before morning meal QD for 14 days
Esomeprazole 20 1 capsule 30 mins before morning meal QD for 14 days
mg
o Side effects:
- Similar GI side effect to H2RAs
- Hypomagnesaemia, increased risk of bone fracture, Clostridium difficile
gastroenteritis, community acquired pneumonia , rebound acid hyper secretion
(with long term use)
- Omeprazole may cause gynecomasteia and hyperprolactenemia
o Patient counseling :
- Take 1 tablet with a glass of water 30 mins before morning meal
- Complete relief will be achieved after 1-4 days
- Tablets should not be chewed or crushed (enteric coated)
- Not intended to be used as needed
- Self-treatment PPI use should be limited to a duration of 14 days (if more than 14
days  refer to primary care professional)
o Potential risks associated with PPIs
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 - Switching PPIs can be considered in the setting of side-effects.
- Patients with known osteoporosis can remain on PPI therapy. Concern for hip
fractures and osteoporosis should not affect the decision to use PPI long-term
except in patients with other risk factors for hip fracture.
- PPI therapy can be a risk factor for Clostridium difficile infection, and should be
used with care in patients at risk.
- Short-term PPI usage may increase the risk of community-acquired pneumonia. The
risk does not appear elevated in long-term users.
- PPI therapy does not need to be altered in concomitant clopidogrel users as there
does not appear to be an increased risk for adverse cardiovascular events.

o Comparison between GERD OTC medication

Drug class Antacid H2RAs PPIs

Onset of action Fastest (5 minutes ) 30 – 45 minutes 2 – 3 hours
Duration 20- 30 minutes 4 – 10 hours 12 – 24 hours
Dosing Frequency PRN (q 1-2 hours ) PRN (max. BID) QD on empty stomach
Place in therapy Immediate relief Nocturnal Scheduled for 14 days
symptoms
Systemic No/ low Minimal Highly absorbed
Absorption
Side effects Local (GI ) Mainly local (GI) C.diff, CAP,
Osteoporosis …
Drug interaction Many DDI Mainly CYP DDI Less than antacids
Renal Avoid Adjust dose No adjustment
impairment

o Exclusion criteria for OTC treatment or when to refer to Specialist

o Frequent heartburn > 3 months
o Heart burn while taking PPI OTC dose (with H1RAs or antacid)
o Heartburn that occur after 2 weeks of treatment with PPI or H2RAs
o Severe heartburn and dyspepsia
o Nocturnal heartburn
o Heart burn with dysphagia or odynophagia or with vomiting or diarrhea
o Chronic wheezing, hoarseness, coughing or chocking
o Unexplained weight loss (not intentional)
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 o Adult >45 years with new onset symptoms
o Chest pain accompanied by sweating and radiating to neck, jaw, arm, shoulder and
shortness of breath
o Pregnancy and nursing mothers
o Children:
- <2 years for antacids usage (as OTC)
- <12 years for H2RAs usage (as OTC)
- <18 years for PPIs usage (as OTC)
o Treatment recommendations
o Antacids and OTC H2RAs should be recommended only for patient with mild infrequent
heartburn and dyspepsia
o An 8-week course of PPIs is the therapy of choice for symptom relief and healing of
erosive esophagitis. There are no major differences in efficacy between the different PPIs.
o Traditional delayed release PPIs should be administered 30 – 60 min before meal for
maximal pH control.
o PPI therapy should be initiated at once a day dosing, before the first meal of the day.
o For patients with partial response to once daily therapy, tailored therapy with adjustment
of dose timing and / or twice daily dosing should be considered in patients with night-time
symptoms, variable schedules, and / or sleep disturbance.
o Non-responders to PPI should be referred for evaluation.
o In patients with partial response to PPI therapy, increasing the dose to twice daily therapy
or switching to a different PPI may provide additional symptom relief.
o Maintenance PPI therapy should be administered for GERD patients who continue to have
symptoms after PPI is discontinued, and in patients with complications including erosive
esophagitis and Barrett’s esophagus. For patients who require long-term PPI therapy, it
should be administered in the lowest effective dose, including on demand or intermittent
therapy.
o H 2-receptor antagonist (H 2RA) therapy can be used as a maintenance option in patients
without erosive disease if patients experience heartburn relief.
o Bedtime H 2RA therapy can be added to daytime PPI therapy in selected patients with
objective evidence of night-time reflux if needed, but may be associated with the
development of tachyphlaxis after several weeks of use.
o Therapy for GERD other than acid suppression, including prokinetic therapy and / or
baclofen, should not be used in GERD patients without diagnostic evaluation.
o There is no role for sucralfate in the non-pregnant GERD patient.
o PPIs are safe in pregnant patients if clinically indicated.
o Surgical options for GERD
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 o Surgical therapy is a treatment option for long-term therapy in GERD patients.

o Treatment Algorithm

Patient has none of the

exclusion criteria

Epsodic Frequent (>2days per week

with PPI use )

Mild Moderate Refer to primacy care

after 14 days

Antacid OTC H2RAs (high dose)

Antacid + algininc OTC H2RA + OTC PPI
OTC H2RAs (low dose ) OTC PPItreatment
+ OTC antacid
After 14 days
OTC H2RA + Antacid
Or if symptoms become severe

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Refer to Primary care Physician
o Special populations
o Pregnancy:
- Should be referred to a primary care for further evaluation
- Lifestyle modification is always the first line treatment
- Calcium carbonate (CHOOZ®) and magnesium antacids as well as H2RAs are listed
as category B
o Breastfeeding :
- Lifestyle modification is always the first line treatment
- Magnesium hydroxide and aluminium hydroxide aren’t secreted in breast milk 
recommended
- Ranitidine and famotidine are less concentrated via breast milk  recommended
- Omeprazole: not well established but can be used
o Patient with renal impairment
 Caution when prescribing H2RAs and antacids
o Patients that are receiving calcium supplementation
 Calcium citrate (Ci-CAL®) is the preferred calcium supplement given because it
doesn’t require acidic medium for dissolution and absorption
o Extraesophageal presentations of GERD: Asthma, chronic cough, and laryngitis
o GERD can be considered as a potential co-factor in patients with asthma, chronic cough, or
laryngitis. Careful evaluation for non-GERD causes should be undertaken in all of these
patients.
o A diagnosis of reflux laryngitis should not be made based solely upon laryngoscopy findings.
o A PPI trial is recommended to treat extraesophageal symptoms in patients who also have
typical symptoms of GERD.
o Upper endoscopy is not recommended as a means to establish a diagnosis of GERD-related
asthma, chronic cough, or laryngitis.

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o Reflux monitoring should be considered before a PPI trial in patients with extraesophageal
symptoms who do not have typical symptoms of GERD.
o Surgery should generally not be performed to treat extraesophageal symptoms of GERD in
patients who do not respond to acid suppression with a PPI.

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