Gerd

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

Cimitidine 400 mg QID

X

Cimitidine 800 mg BID

X

Ranitidine 150 mg QID

X

Ranitidine 150 mg BID

X

Famotidine 20 mg BID

X

Famotidine 40 mg BID Nizatidine 150 mg BID

Erosive Prevention of esophagitis GERD recurrence X X X X X

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