Medication for Treatment of GERD - Proton Pump Inhibitors (PPI)






		Prescribed Medications for Treatment of GERD PRESCRIPTION MEDICATIONS Sometimes the self help measures do not provide adequate symptom relief. The treating physician may start you on prescription strength H₂-RA Blockers or an even stronger acid reducing group of medications called Proton Pump Inhibitors (PPI). These medications are relatively safe when taken under the supervision of a physician, and their effect is somewhat dose dependent., i.e. if one tablet or capsule is not strong enough two or more will reduce symptoms. Prokinetic drugs like metoclopramide and cisapride are used in conjunction with other measures in patients who are suffering from nausea or bloating in addition to heartburn. Cisapride (Propulsid) causes less diarrhea and extra-pyramidal side effects than Metoclopropamide (Reglan). However, Cisapride can cause life threatening cardiac arrhythmias, especially in patients with cardiac or renal diseases, those with prolonged QT interval on their EKG, patients who are on anti-fungal, anti-viral and Mycin types of antibiotics like erythromycin and clarithromycin. (Beacause of this side-effect, Cisapride is no longer availabe in the US.) PROTON PUMP INHIBITORS (PPI) PPI class of drugs, i.e. Prilosec, Nexium and Prevacid are the agents of choice in achieving symptom relief, improving quality of life, healing, and prevention of mucosal injury in GERD patients. As a class, these drugs are extremely safe. PPIs have been used extensively for the treatment of GERD. The currently available PPIs are Prilosec (omeprazole) 10, 20 and 40mg capsules, Protonix (pantoprazole) 40mg tablet, AcipHex ( rabeprazole sodium) 20mg tablets, Nexium (esomeprazole) 20 and 40mg capsules, and Prevacid (lansoprazole)15 and 30mg capsules. Except for AcipHex the rest of them are taken 30-60 minutes before breakfast with a glass of water. For children and those unable to take the capsules, the capsules can be opened, the content mixed with a tablespoonful of applesauce and taken immediately. The most common reported adverse events associated with PPIs include headache, diarrhea, abdominal pain, and nausea and constipation and bloating. PPIs may interact with other medications by affecting the absorption of drugs for which bio-availability is dependent upon gastric pH (e.g. iron, ampicillin, and ketokonazole). PPIs may also inhibit cytochrome P-450 metabolism to various degrees. However dose adjustment is rarely necessary in the elderly, patients with renal insufficiency, or those who have mild to moderate hepatic impairment. Protonix , the currently least expensive, and in my clinical experience the least effective of PPIs, is reported to have the least effect on other drugs metabolized by the cytochromeP-450. Protonix is available in IV form. Please refer to What's New section. Recommended Strategy for Using PPIs for treatment of GERD (Omeprazole = Prilosec, Esomeprazole = Nexium, Lansoprazole = Prevacid, Pantoprazole = Protonix, and Rabeprazole = Aciphex): Take twice daily for the first 2-3 days of therapy. First dose should be 30-60 minutes before breakfast with a glass of water. Second dose, if necessary, should be before dinner. Not effective when taken at time of heartburn. Should not be administered with H₂-RA and somatostatins concurrently. They will put arietal cells into a nonsecretory state, markedly reducing PPI effect. Points to Remember about PPIs (Omeprazole = Prilosec, Esomeprazole = Nexium, Lansoprazole = Prevacid, Pantoprazole = Protonix, and Rabeprazole = Aciphex): PPIs are pro drugs, which are activated in the acidic canalicular space of the parietal cell, therefore they should not be co-administered with H₂-RAs. PPIs block final pathway of acid release and prevent stimulated acid secretion. PPIs permanently inhibit proton pump and suppress gastric acid for several days, not taking it daily still effective. Unlike H₂-RAs (Ranitidine = Zantac, Cimetidine = Tagamet, Nizatidine = Axid, Famotidine=Pepcid), PPIs are not effected by increasing Histamine release, so tolerance will not develop. Omeprazole (Prilosec), Esomeprazole (Nexium) and Lansoprazole (Prevacid) are metabolized by CY P450 system. 13-23% Asians are slow metabolizers (CYP2 C19 gene polymorphism). PPIs are potent agents, offer ease of dosing with favorable drug interaction and extreme safety profile. GERD patients should be managed with appropriate therapy proportional to the frequency and severity of their symptoms. Symptom severity neither predict severity of disease, nor Erosive Esophagitis. Symptom relief and mucosal healing are closely related to the dose and potency of the acid reducing medication and the duration of therapy. In uncomplicated GERD use the least frequent dosing that provides adequate symptom relief. H. Pylori is an unsafe biological antisecretory agent with high morbidity and must be eradicated whenever and wherever it is discovered. Potential Side Effects of Long-Term PPI Therapy for Treatment of GERD (Omeprazole = Prilosec, Esomeprazole = Nexium, Lansoprazole = Prevacid, Pantoprazole = Protonix, and Rabeprazole = Aciphex): Gastric nodules and Fundic type Polyps Parietal cell hyperplasia Antral Gastritis Hypergastrinemia Increased risk of community acquired pneumonia (X 2.3) Increased risk of clostridium difficile Diarrhea in hospitalized patients on PPIs NO increased risk of carcinoid and adenocarcinoma of the stomach WHO NEEDS PROTON PUMP INHIBITORS Those with endoscopically proven Erosive Esophagitis and Peptic Stricture. Those with ENT symptoms of GERD, i.e. chronic sore throat, frequent dry cough or throat clearing, and hoarseness of voice (reflux laryngitis), require higher doses i.e. 40 mg of Omeprazole once or twice daily for several months. Those with severe symptoms that do not respond to less intense measures. All of the above for maintenance of healing or symptoms. A cost effective approach for patients with moderate to severe symptoms of GERD and a relatively normal endoscopy is to take PPIs on demand. However, in patients with erosive esophagitis the healing dose is the maintenance dose (see selected reference No. 9). SYMPTOMS WHILE ON PPIs Patients who develop symptoms several hours after taking a PPI, require one of several therapeutic approaches depending upon their symptoms. If they develop heartburn while on PPIs, an adjustment of the PPI dose ( increasing strength or b.i.d dosing), or using a PPI with longer half-life may be necessary. Most PPIs keep intra-gastric pH above 4 for about 10-12 hours except for esomeprazole (Nexium 40 mg capsule) that keeps pH above 4 for more than 16 hours. Occasionally supplementation with H₂-RA, i.e. over the counter Cimetidine or Ranitidine, at bedtime may be all that is needed. 70% of normal subjects taking PPIs twice daily have periods of gastric pH less than 4 for 60 minutes or longer during the night. This phenomenon, which is of potential clinical importance when accompanied by reflux of acid into the esophagus is infrequent in normal subjects but it may be seen in up to 50% of patients with Barrett’s esophagus and scleroderma. In GERD patients with nocturnal acid breakthrough we add a bedtime H₂-RA to twice-a-day PPI or switch to esomeprazole 40 mg once or twice daily. If patient complains about nausea, bloating or early satiety, a prokinetic agent will be the added drug of choice. If you have increased the PPI dose and have added metoclopropamide and the patient still complains about heartburn, burping or regurgitation, these symptoms may be due to the bile reflux - as PPIs do not eliminate bile reflux. In these situation antacids may be helpful in order to neutralize bile acids. Occasional patients suffer from visceral hypersensitivity syndrome plus GERD. Their symptoms fail to respond adequately to the above treatment modalities. These rare patients may benefit from the additional prescription of low dose tricyclic antidepressants like amitriptyline 10-50 mg daily. Tricyclic antidepressants can help more than two-thirds of patients with functional esophageal complaints resistant to antireflux therapy.