Gastro-Esophageal Reflux Disease (GERD) Pharmaco-therapeutics 2 Gastro-Esophageal Reflux Disease (GERD) Mohammad Ruhal Ain R Ph, PGDPRA, M Pharm (Clin. Pharm) Department of Clinical Pharmacy E-mal: m.alain@sau.edu.sa

Case Study • A .W 75-year-old man with a 3-year history of severe GERD symptoms and Parkinson disease has been taking lansoprazole 30 mg 2 times/day for 5 months. • He has initiated proper nonpharmacologic measures, including elevating the head of his bed, reducing fat intake and portion size, avoiding tight-fitting clothes, and losing weight. •Because he continues to have daily heartburn symptoms, he is referred for endoscopy, which reveals normal-appearing mucosa and no structural abnormalities.

Define GERD ! A condition which develops when reflux of stomach contents causes troublesome symptoms and/or complications

Symptoms of GERD What are the symptoms of GERD ? Extraesophageal symptoms (formerly referred to as atypical) Typical symptoms Heartburn (pyrosis) Regurgitation Acidic taste in the mouth Chronic cough, asthma-like Symptoms recurrent sore throat, laryngitis/hoarseness, dental enamel loss Non cardiac chest pain; sinusitis/pneumonia/bronchitis/otitis media are less common atypical symptoms. Alarm symptoms troublesome dysphagia, odynophagia, bleeding, weight loss, choking, chest pain, and epigastric mass Odynophagia: a dysphagia in which  swallowing causes pain.

Questions: Fill in the blank Pyrosis is ………………. • Regurgitation and Acidic taste in the mouth are ………. Symptoms of GERD ( typical /atypical /alarm ) •GERD stands for …………………………………. •Recurrent sore throat, laryngitis/hoarseness, dental enamel loss are ……………. Symptoms of GERD ( typical /atypical /alarm ) •Troublesome dysphagia odynophagia, bleeding are ………….. Symptoms of GERD ( typical /atypical /alarm )

Questions: Fill in the blank Pyrosis is Heartburn • Regurgitation and Acidic taste in the mouth are Typical Symptoms of GERD ( typical /atypical /alarm ) •GERD stands for Gastro-Esophageal Reflux Disease •Recurrent sore throat, laryngitis/hoarseness, dental enamel loss are atypical Symptoms of GERD ( typical /atypical /alarm ) •Troublesome dysphagia odynophagia, bleeding are alarm Symptoms of GERD ( typical /atypical /alarm )

Aggravating factors in GERD I. Recumbency (gravity) What can aggravate M.W condition ? Aggravating factors in GERD I. Recumbency (gravity) II. Increased intra-abdominal pressure III. Reduced gastric motility IV. Decreased lower esophageal sphincter (LES) tone V. Direct mucosal irritation

Question: Mention 3 aggravating factors in GERD? True or false Questions •(gravity) is considered to be an aggravating factor for GERD ? [T] [F] • Increased lower esophageal sphincter (LES) tone is an aggravating factor for GERD ? [T] [F] •Increased intra-abdominal pressure is a complication for GERD ? [T] [F]

Question: Mention 3 aggravating factors in GERD? True or false Questions •(gravity) is considered to be an aggravating factor for GERD ? [T] [F] • Increased lower esophageal sphincter (LES) tone is an aggravating factor for GERD ? [T] [F] •Increased intra-abdominal pressure is a complication for GERD ? [T] [F]

Long-term complications of GERD are ? I. Esophageal erosion II. strictures/obstruction III. Barrett esophagus, IV. and reduction in patient’s quality of life lining of the esophagus is damaged by stomach acid

Case Study • A .W 75-year-old man with a 3-year history of severe GERD symptoms and Parkinson disease has been taking lansoprazole 30 mg 2 times/day for 5 months. • He has initiated proper nonpharmacologic measures, including elevating the head of his bed, reducing fat intake and portion size, avoiding tight-fitting clothes, and losing weight. •Because he continues to have daily heartburn symptoms, he is referred for endoscopy????????, which reveals normal-appearing mucosa and no structural abnormalities.

Diagnosis I.Based on Symptoms ? ….in uncomplicated cases - it is reasonable to assume a diagnosis of GERD in patient who respond to initial acid-suppressive therapy, particularly proton pump inhibitors (PPIs). Symptoms do not predict the degree of esophagitis or complications secondary to GERD, if present. Patients presenting with extraesophageal symptoms should be assessed on a case-by-case basis to consider the need for referral or alternative/invasive testing. - Cardiac etiologies (ischemic) should be considered and explored before arriving at a diagnosis of reflux chest pain syndrome.

Diagnosis II. Endoscopy ………. - Choice to identify Barrett esophagus (with biopsy) or complications of GERD. - 97% specific for the diagnosis of GERD Most patients with typical/atypical symptoms will have normal-appearing esophageal mucosa on endoscopy I. Age > 45 years, II. Patient with alarm symptoms (particularly troublesome dysphagia III. Refractory to initial treatment, as well as in those with a preoperative assessment or possibly when extraesophageal symptoms are present When to use endoscopy ?

Diagnosis III. Manometry ………. Used to evaluate peristaltic function of the esophagus in patients with normal endoscopic findings

Diagnosis IV. pH testing ………. The main outcome measure of esophageal pH monitoring is the percentage of time the pH value is less than 4 in a 24-hour period. Ambulatory pH testing is useful in the following clinical situations: Patients with no mucosal changes on endoscopy and normal manometry who have continued symptoms (both typical and atypical) ii. Patients who are refractory to therapeutic doses of appropriate pharmacologic agents iii. Monitoring of reflux control in patients with continued symptoms on drug therapy Sensitivity/specificity of 96% reported The PPIs should be withheld for 7 days before pH testing, if possible, for the most accurate results.

True or false Questions - It is reasonable to assume a diagnosis of GERD in patient who respond to initial acid-suppressive therapy, particularly proton pump inhibitors (PPI) ? [T] [F] • Symptoms predict the degree of esophagitis or complications secondary to GERD, if present. ? •Most patients with typical/atypical symptoms of GERD will have abnormal-appearing esophageal mucosa on endoscopy

True or false Questions - It is reasonable to assume a diagnosis of GERD in patient who respond to initial acid-suppressive therapy, particularly proton pump inhibitors (PPI) ? [T] [F] • Symptoms predict the degree of esophagitis or complications secondary to GERD, if present. ? •Most patients with typical/atypical symptoms of GERD will have abnormal-appearing esophageal mucosa on endoscopy

Complete the following •Endoscopy is the choice to identify ………………………… GERD •most patients with typical/atypical symptoms of GERD will have …………………………..on endoscopy •Endoscopy is ……….. (specific /not specific ) for diagnosis GERD

Complete the following •Endoscopy is the choice to identify Barrett esophagus (with biopsy) or complications of GERD •Most patients with typical/atypical symptoms of GERD will have normal-appearing esophageal mucosa on endoscopy •Endoscopy is specific (specific /not specific ) for diagnosis GERD

Case Study • A .W 75-year-old man with a 3-year history of severe GERD symptoms and Parkinson disease has been taking lansoprazole 30 mg 2 times/day for 5 months. • He has initiated proper nonpharmacologic measures??????????, including elevating the head of his bed, reducing fat intake and portion size, avoiding tight-fitting clothes, and losing weight. •Because he continues to have daily heartburn symptoms, he is referred for endoscopy, which reveals normal-appearing mucosa and no structural abnormalities.

Treatment •Treatment options for GERD Nonpharmacologic interventions/lifestyle modifications Pharmacologic therapies

Nonpharmacologic interventions/lifestyle modifications Dietary modifications in patients whose symptoms are associated with certain foods or drinks Avoid aggravating foods/beverages; some may reduce LES pressure (alcohol, caffeine, chocolate, citrus juices, garlic, onions, peppermint/spearmint) or cause direct irritation (spicy foods, tomato juice, coffee). ii. Reduce fat intake (high-fat meals slow gastric emptying) and portion size. iii. Avoid eating 2–3 hours before bedtime. iv. Remain upright after meal

Nonpharmacologic interventions/lifestyle modifications B. Weight loss for overweight or obese patients C. Reduce/discontinue nicotine use in patients who use tobacco products (affects LES). D. Elevate the head of the bed (6–8 in.) if reflux is associated with recumbency E. Avoid tight-fitting clothing (decreases intra-abdominal pressure). F. Avoid medications that may reduce LES pressure, delay gastric emptying, or cause direct irritation: α-Adrenergic antagonists, anticholinergics, benzodiazepines, calcium channel blockers, estrogen, nitrates, opiates, tricyclic antidepressants, theophylline, NSAIDs, and aspirin

Answer the given questions: •Generally , Nonpharmacologic treatment such as dietary modifications of GERD options include ………………… •………… fat intake as dietary modification for GERD patient ( reduce /increase) •………… eating 2–3 hours before bedtime ( avoid/ encourage) as dietary modification for GERD patient •Remain………….after meal as dietery modification for GERD patient (upright /lay down ) • Reduce/discontinue nicotine use in patients who use tobacco products (affects LES). ( T/F) •In GERD patient Elevate the head of the bed (6–8 in.) if reflux is associated with recumbency (T/F)

Pharmacologic therapies Initial treatment will depend on severity, frequency, and duration of symptoms. Strategies “Step-up” treatment “Step-down” treatment Starting with lower-dose OTC products. Starting with maximal therapy, such as therapeutic doses of PPIs, is always appropriate as a first-line strategy in patients with documented esophageal erosion Advantages: Avoids overtreatment, has lower initial drug cost. Advantages: Rapid symptom relief, avoidance of overinvestigation. Disadvantages: Potential undertreatment (partial symptom relief), may take longer for symptom control, may lead to overinvestigation Disadvantages: Potential overtreatment, higher drug cost, increased potential of adverse effects

Contain the anti-refluxant alginic acid, which forms a viscous layer on top of gastric contents to act as a barrier to reflux Aluminum hydroxide, magnesium hydroxide and simethicone.

2. Symptomatic relief of GERD

3. Healing of erosive esophagitis or treatment of patients presenting with moderate to severe symptoms or complications

True or false Questions PPIs are more effective than histamine2-receptor antagonists (H2RA) ? [T] [F] • All PPIs are similar in efficacy when used for patients with esophageal GERD symptoms. •Maintenance therapy is appropriate for patients with esophagitis in whom PPIs have been effective Titration to the lowest effective dose is recommended.

Drugs Antacids •Calcium-, aluminum-, and magnesium-based products are available OTC in a wide variety of formulations (capsules, tablets, chewable tablets, and suspensions). •Side effects Constipation (aluminum), (magnesium), diarrhea Accumulation of aluminum/magnesium in renal disease with repeated dosing Drug interactions: Chelation (fluoroquinolones, tetracyclines), reduced absorption because of increases in pH (ketoconazole, itraconazole, iron, atazanavir, delavirdine, indinavir, nelfinavir) or increases in absorption leading to potential toxicity (raltegravir, saquinavir)

Drugs H2RAs ( (cimetidine, ranitidine, famotidine, nizatidine)) Side effects: –Headache –Somnolence –Fatigue –Dizziness –Either constipation or diarrhea •Cimetidine may inhibit metabolism of some drugs (e.g., theophylline, warfarin, phenytoin). •They are equally effective; selection of agent based on differences in pharmacokinetics, safety profile, and cost •Elderly patients and those with reduced renal function are more at risk. •Prolonged cimetidine use is associated with rare development of gynecomastia.

Drugs •PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, –Side effects: •Headache •Dizziness •Somnolence •Diarrhea •Constipation •Nausea •Vitamin B12 deficiency –May facilitate Clostridium difficile infection during acid suppression. –Lansoprazole, esomeprazole, and pantoprazole available in IV formulations, but are not more effective than oral preparations and are more expensive.

•New FDA labeling for PPIs as of May 2010 stating that PPIs may increase the risk of hip and spine fracture •Patients should take oral PPIs in morning 15–30 minutes before breakfast; dexlansoprazole can be taken without regard to meals. •If dosed twice daily, second dose should be taken 10–12 hours after morning dose and prior to meal or snack not bed time

Case Study • A .W 75-year-old man with a 3-year history of severe GERD symptoms and Parkinson disease has been taking lansoprazole 30 mg 2 times/day for 5 months. • He has initiated proper nonpharmacologic measures, including elevating the head of his bed, reducing fat intake and portion size, avoiding tight-fitting clothes, and losing weight. •Because he continues to have daily heartburn symptoms, he is referred for endoscopy, which reveals normal-appearing mucosa and no structural abnormalities.

Q- Which one of the following is the best course of action for this patient? Add metoclopramide 10 mg 4 times/day and reassess in 3 months. B. Educate about the proper use of lansoprazole and refer for manometry. C. Add metoclopramide 10 mg 4 times/day and refer for surgical intervention. D. Add famotidine 20 mg/day at bedtime and reassess in 4 months.