GERD

Gastro-Esophageal Reflux
Disease

Hussain Al Awami, B.Sc. Pharm., M.Sc., MBA

 Prevalence
• About 50% of the general population have
GERD symptoms at least once a month.
• Up to 10% will experience those symptoms at
least once weekly.
• Up to 25% of pregnant women suffers from
heartburn.
• More frequent in adults more than 40 YO.
• Most patients seeks community pharmacists
advice for mild symptoms.
 Classical symptoms
• Burning, pressure or pain
• Bitter or acid taste in the mouth
• Heartburn worsen after meal
• Heartburn is not linked to exercise or improve
with rest.
• Dysphagia (difficult swallowing)
• Odynophagia (painful swallowing)
 Atypical symptoms
• Breathing problems such as asthma, cough, or
wheezing
• Aspiration
• Pneumonia
• Interstitial fibrosis
• Laryngitis
• Globus
• Earache
 GERD, complications
• Symptoms causes discomfort
• Slow blood loss which cause anemia
• Esophageal stricture
• Ulceration, bleeding, perforation
• Laryngitis and aspiration
• Barretts esophagus
• Esophageal adenocarcinoma
 GERD, pathophysiology
• Lower esophageal sphinctor LES
• Gastric Emptying Time GET
• Esophageal clearance
• Protective esophageal mucosal layer
• H pylori
 Dietary factors
• Peppermint, spearmint, chocolates, coffee (even
decaffeinated), tomato, citrus fruits, onions, and
spicy foods.
• High fat meals will slow the GET.
• Large meals or high fluid volume.
• Cigarette smoking
• Alcoholic beverages
 Factors associated with GERD
• Obesity
• Drugs
• Bending forward
• Reclining after meal
• Restrictive clothing
 GERD, diagnosis
• Symptoms
• Endoscopy
• 24 hours intraesophageal pH monitoring
• H. pylori test
 Goals of therapy
• Relieve symptoms
• Heal esophagitis
• Maintain patient in symptom free status
• Prevent complication
• Provide cost effective management
 Drugs weaken LES
• α adrenergic agonists
• β adrenergic agonists
• Benzodiazepines
• Calcium channel blockers
• Dopamine
• Theophylline
• TCA
• Birth control pills
 Non pharmacological treatment
• Avoid foods that directly irritate esophageal
mucosa.
• Avoid foods that lower LES tone.
• Avoid high fat meals.
• Do not drink large amount of fluids with meals.
• Try several small meals throughout the day.
• Avoid drugs that lower LES tone.
 Continue
• Remain upright for 2-3 hours after eating.
• Elevate the head of the bed on blocks or use a
wedge pillow.
• Avoid bending forward.
• Wear loose, comfortable clothing.
• Lose weight if appropriate.
• Stop smoking.
• Avoid Alcohol.
 Pharmacological options
• Antacids
• H2RA
• PPIs
• Prokinetic drugs
• Mucosal barrier agents
 Antacids
• ↑ gastric pH
• ↑ gastric pH → ↑ LES pressure
• short duration (up to 1.5 hours)
• Used for mild cases for symptomatic relief
• Do not promote healing of esophagitis
• Should not be used for bedtime
• Ideally Antacids should be used in PRN basis
with other therapy.
 Antacids, continue
• Efficacy seems to be similar among different
products.
• Products containing Alginic acid may provide
additional advantage as it’s a foaming agent
provide physical barrier in top of the stomach.
• The selection is based on SE profile.
 Antacids, types
• Aluminium hydroxide
– Constipation; Small amounts absorbed (watch in
renal failure)
• Magnesium hydroxide
– Diarrhea; Small amounts absorbed (watch in renal
failure)
• Calcium carbonate
– Higher doses might produce paradoxical effect
• Sodium bicarbonate
– Systemic alkalosis
 Antacids, MOA
• Mg(OH)2 + 2H+ → Mg2+ + 2H2O
• Al(OH)3 + H+ → Al(OH)2 + H2O
• CaCO3 + H+ → Ca2+ + HCO3-
 Antacids, drug interaction
• By alteration in gastric pH, it can interfere with
absorption of many drugs:
– Digoxin; phenytoin; isoniazide; ketoconazole.
– ↓ bioavailability of cimitidine by 50%; ranitidine by
30%; famotidine by 20%; and nizatidine by 10%.
• It can form complexation with many drugs:
– Ciprofloxacin bioavailability ↓ by 50%.
– Tetracycline
• Separate the administration by at least 2 hours.
 H2 RA
• Stop stimulation of parietal cells by histamine.
• ↓ acidic media and ↓ acid volume.
• Effective in controlling symptoms.
• ?! Efficacy in healing (! Dose dependent).
• Non prescription Vs prescription H2RA.
• Efficacy seems to be the same among different
agents.
• Selection based on SE profile and cost
effectiveness.
 OTC, H2RA
Drug Strength

Cimitidine 200 mg

Ranitidine 75 mg

Nizatidine 75 mg

Famotidine 10 mg
 Prescription H2RA
Drug/dose GERD Erosive Prevention of
esophagitis GERD
recurrence
Cimitidine 400 mg QID X X
Cimitidine 800 mg BID X X
Ranitidine 150 mg QID X
Ranitidine 150 mg BID X X
Famotidine 20 mg BID X X
Famotidine 40 mg BID X
Nizatidine 150 mg BID X
 PPIs
• Inhibit the final step of acid production (proton
pump) system on the gastric parietal cell surface.
• Approved for wider range from heartburn to
erosive esophagitis.
• It seems to be related to its capacity of keeping
gastric pH within 4 or greater for long time.
• Though PPIs affects the gastric pH, limited
nutrients and drug interactions are reported!
 PPIs, continue
• Short half life and long duration of action.
• Acid suppression is superior to H2RA.
• Acid suppression seems to be similar among
different products.
• Symptoms relief starts within few days.
• Few studies shows that lansoprazole 30 mg,
rabeprazole 20 mg, and esmoprazole 40 mg are
faster in action than omeprazole 20 mg.
 PPIs, continue
• Healing of esophagitis is achieved in 70-95% of
patients within 4-8 weeks treatment.
• Severe forms might need longer duration.
• If healing not achieved, continue for additional
8-12 weeks.
• Higher doses might be even recommended.
• About 80% of patients stays in remission status.
• Whether PPIs is better in preventing long term
complication, still to be studied.
 PPI, SE
• SE occurs in less than 5% of the patients.
• SE includes headache, diarrhea, abdominal pain,
and nausea.
• All SE, except diarrhea, are not related to dose,
duration of treatment, or age.
• Diarrhea seems to be associated with alteration
in the gastric pH which affects the normal flora.
• Contraindicated in patients with hypersensitivity
to those drugs and in severe hepatic disease.
PPIs, dosage and administration
• PPIs are inactivated by gastric acid and its
absorbed in the proximal bowel.
• Omeprazole and lansoprazole are delayed
release gelatine capsules containing enteric
coated granules.
• Rabeprazole and pantoprazole are delayed
release enteric coated tablets.
• Should be swallowed directly and NOT to open,
chew, or crush the capsule or tablet.
 PPIs, continue
• In selected cases, capsules may be opened and
granules sprinkled over tablespoon of
applesauce, pudding, or yogurt.
• The food must be taken without stirring,
crushing, or chewing.
• Patients with nasogastric tubes, the granules of
once capsule can be mixed with 40 ml of apple
juice and injected through the tube.
 PPIs, with food
• Omeprazole and lansoprazole should be taken
30 min before meal.
• Rabeprazole have to be taken after meal.
• Pantoprazole may be taken without regard to
meals.
• Antacids might be taken concomitantly with
PPIs.
 Prokinetic drugs
• Bethanecol
• Cisapride
• Metoclopromide
• Sucralfate (mucosal barrier)
 Bethanechol
• Increases LES pressure
• Improves esophageal clearance
• Not affecting GET
• Increase gastric acid secretion
• It has shown some efficacy in some patients
• Associated with frequent SE such as abdominal
cramping, urinary frequency, blurred vision,
diarrhea, and malaise.
 Cisapride
• Increases LES pressure
• Improves esophageal clearance
• Enhancing GET
• Efficacy is similar to H2RA
• Voluntarily Withdrawn from market due to
cardiac arrhythmia.
 Metoclopromide
• Increasing LES pressure
• Improving GET
• Does not associated with healing
• SE includes sleepness, fatigue, weakness,
depression, nervousness, and dizziness.
• Limited for refractory cases.
 Sucralfate
• Non absorbable local physical barrier.
• Limited studies in GERD which might be
comparable to H2RA.
• 1 gm tablets dissolved in water directly before
administration.
• Administered 1 hr before meal and at bed time.
• SE includes constipation, abdominal cramping,
nausea, and dry mouth.
• Many drug interactions (e.g., digoxin, warfarin,
ciprofloxacin, ketokenazole, etc).
 Surgery
• Only in refractory cases
 Treatment scheme
• Step up approach
• Step down approach
• Continuous PPIs