GERD and PUD: Therapeutics PDF

GERD and PUD: Therapeutics Meagan A. Brown, PharmD, BCACP Clinical Associate Professor and Community Pharmacy Development, Department of Pharmacy Practice [email protected] Objectives › Identify treatment goals for GERD and PUD. › Discuss the different pharmacological treatment options for GERD and P...

GERD and PUD: Therapeutics Meagan A. Brown, PharmD, BCACP Clinical Associate Professor and Community Pharmacy Development, Department of Pharmacy Practice [email protected] Objectives › Identify treatment goals for GERD and PUD. › Discuss the different pharmacological treatment options for GERD and PUD. › Discuss when self-care is appropriate for the treatment of GERD, and when patients should be referred. › Identify key patient counseling for patients with GERD. › Recognize Special populations – – – – Use of PPI’s in the elderly Stress ulcer prophylaxis Pregnancy Children? Quick Review › What’s the difference between GERD and PUD? Clinical Presentation › GERD – Common Symptoms(esophageal): heartburn, dyspepsia, acid regurgitation, dysphagia, reflux chest pain syndrome – Extra esophageal: chronic cough, laryngitis, sinusitis, dental erosion › ALARM symptoms: – Hematemesis, anemia, melena, unintentional weight loss, vomiting, dysphagia, odynophagia, back pain, obstruction, diarrhea, perforation of pancreas or liver (spreading upper abdominal pain) – Seek immediate care Complications of GERD › Erosive esophagitis › Esophageal strictures › Barrett’s esophagus – 30-60x increased risk of adenocarcinoma › Esophageal adenocarcinoma and laryngeal cancers › anemia Diagnosis › Clinical history including presenting symptoms together with risk factor assessment › 24 hr pH monitoring in the lower esophagus › Radiographic testing with barium swallow › Endoscopy + biopsy › Ambulatory esophageal pH monitoring › Esophageal manometry › May need further testing if: – Lack response to empiric therapy – Extraesophageal syndrome or chronic symptoms Treatment Goals- GERD › Reduce frequency and duration of reflux › Symptom reduction or elimination › Prevent disease progression and the development of complications › Promote healing of injured mucosa Non Pharmacologic Treatment › Avoid reflux-inducing foods/beverages – Chocolate, peppermint, onion, garlic, citrus juices, caffeine, alcohol › May reduce LES pressure – Spicy foods, colas, red wines, and tomato juice › Cause direct irritation – Refrain from assuming a supine position after food consumption avoid food temporally within 3 hours close to bedtime – Reduce intake of fatty foods – Reduce portion size › Smoking cessation › Avoid garments that fight tightly › Elevate the head of the bed › Weight loss › Promotion of salivation (gum chewing, lozenges) for those with mild symptoms Pharmacological Treatment Options for GERD › Step up approach – Start with antacids (do not heal erosions) or H2RA’s and lifestyle modifications and increase › Step down approach – Start with PPI’s and lifestyle modifications and decrease – Extra esophageal › PPI BID for 2 months › Use stepdown approach Pharmacological Treatment Options for GERD › Antacids › H2- receptor antagonists (H2RA’s) › Proton pump inhibitors (PPI’s) › Promotility agents › Surgery Antacids › Aluminum, calcium, and magnesium antacid preparations (OTC) › MOA: Neutralize acid and raise intragastric pH; results in a decreased activation of pepsinogen and increased LES pressure › Role: First line for mild intermittent symptoms or breakthrough for those on H2RA or PPI therapy › Dosing: Take 1-3 hours after meals and other medications to avoid potential DI’s › Adv Events: Constipation (aluminum), chalk taste, abdominal cramps, diarrhea (magnesium), accumulation in renal dysfunction › Examples: sodium bicarbonate (Alka-Seltzer), Calcium Carbonate (TUMS), mag OH/AlOh (Maalox), alginic acid containing (Gaviscon) H2RA’s › MOA: Blocks histamine-2 receptors in gastric parietal cells thereby decreasing gastric acid secretion (reversible blockade) › Role: empiric therapy for mild, troublesome GERD symptoms: ondemand, intermittent, and meal/exercise-provoked symptoms › Faster symptomatic relief than PPI (slower than antacids) – Onset relief: 30-45 mins – Generally last 6-12 hours – Lower healing rate than PPI’s › Dosing: varies, but BID typically. Well absorbed; absorption delayed by admin with antacids but not by food – Prolonged use may lead to decreased efficacy and tolerance – Renal impairment: Generally reduce dose/hepatic impairment- adjust dose H2RA’s › Adv Events: well tolerated! CNS- HA, dizziness, fatigue, confusion- increased in elderly and renally/hep impaired; Tolerance › May be useful in combo with PPI’s at nighttime; but limited data to support this › DDI’s: drugs that depend on a lower gastric pH for absorption may be impaired (ketoconazole, itraconazole, protease inhibitors) › ***Cimetidine: inhibits CYP450 enzymes, drugs metabolized by these enzymes might be affected (theophylline, cyclosporine, nifedipine, propranolol, phenytoin, warfarin) H2RA’s › Cimetidine (Tagamet)* – 400 mg BID – Lots of DDI’s › Famotidine (Pepcid) – 20 mg BID (has IV and PO formulation) › Nizatidine (Axid) – 150 mg BID › Ranitidine (Zantac) – 150 mg BID (has IV and PO formulation) › Some combos: – Pepcid Complete: famotidine, Ca carbonate, Mg oxide PPI’s › MOA: accumulate in acidic region of parietal cells, where they undergo an acid- catalyzed conversion to a reactive species, (rate of conversion varies between agents). Reactive species irreversibly interacts with the H-K-ATPase; resulting in a long-lasting impairment of acid secretion › Role: most potent inhibitors/most effective tx for mod to severe GERD, erosive esophagitis, and complications – All generally equally potent › Dosing: Once-daily in trials; although BID may be used if night sx present; or in refractory GERD – – – – Long term and maintenance therapy is often indicated Administer before the first meal of the day (30 mins before breakfast) Onset of relief: 2-3 hours; Duration- 24 hrs Duration: OTC’s marketed for 14 days; depends on what we are treating PPI’s › Side effects: HA, dizziness, somnolence, diarrhea, dyspepsia, › Can switch to another PPI or try a diff drug class if needed › Potential risks: – Decreased Ca absorption Hip fractures/osteoporosis – pneumonia – enteric infections (C. diff increased risk) › Drug-drug interactions: reduced gastric pH may affect bioavailability of other meds such as azoles, digoxin and Protease inhibitors, warfarin › Plavix + esomeprazole and omeprazole  2C19 PPI’s PPI Dosing Notes Omeprazole (OTC) Prilosec Omeprazole + sodium bicarbonate (OTC) Zegerid Lansoprazole (OTC) Prevacid Rabeprazole Aciphex Pantoprazole Protonix Esomeprazole (OTC) Nexium Dexlansoprazole Dexilant 20 mg daily Admin at bedtime Class C pregnancy (all others B) Co-formulated for immediate pH neutralization; capsule and powder available 40 mg daily 30 mg daily Oral capsule, powder, ODT 20 mg daily 40 mg daily IV formulation available 40 mg daily IV formulation available 30 mg daily Take any time of day; L-isomer of lansoprazole Nocturnal GERD › Lots of patients also have nighttime symptoms – Continued acid production through the night › Management: – Once or twice daily PPI’s OR – Twice daily H2RA’s Approach to Refractory GERD › From 10-40% do not respond to standard-dose PPI therapy and continue to have GERD symptoms and or endoscopic evidence of esophagitis › Evaluate reason for PPI failure – – – – – Optimize antisecretory therapy (BID dosing of PPI’s, witch to diff agent) Add-on therapy (bedtime H2RA or bile acid therapies for bile acid reflux) Lifestyle modifications Perform esophageal testing (EGD, etc) Tx of delayed gastric emptying with promotility agents › Antireflux surgery: should be considered in young patients requiring high-dose therapy for symptom control and those unresponsive to therapy. Promotility agents › Used to improve gastric emptying in select patients; typically in addition to acidsuppressive therapy – Metoclopramide: dopamine antagonist; prokinetic › Dose 10-15 mg fup to QID; 30 mins before meals, dose adjustment necessary for renal impairment › Therapy >12 weeks of duration not recommended due to risk of irreversible tardive dyskinesia › Adv events: several- confusion, dizzy, drowsy, fatigue, HA, hyperprolactinemia, extrapyramidal symptoms (avoid in Parkinson’s disease) – Bethanechol: cholinergic agonist › › › › Stimulates gastric motility, increases gastric tone, and restores peristalsis 25 mg QID 1 hour before or 2 hours after meals Adv events: blurred vision, HA, tachycardia, cramping, diarrhea Poor patient tolerability; use limited – Cisapride: cholinergic agonist › Increases LES pressure and lower esophageal peristalsis, accelerating gastric emptying › Dosed QID; 15 mins before meals › Withdrawn from market due to DDI from CYP3A4; now available only from manufacturer through special program Special Populations › Elderly – Avoid use of PPI’s › Pregnant Women – Very common, especially in the later trimesters (3rd) – Antacids or H2RA’s; PPI use data is limited › Children – Can occur, especially early on in life – May resolve in first 18 months of life – PPI’s (sprinkle formulation) Drug Interactions- from Handbook of Non RX drugs Antacid/Acid Reducer Antacids Drug Itraconazole, ketoconazole, iron, indinavir, atazanavir Antacids Amphetamines Antacids Enteric-coated medications Calcium carbonate, magnesium hydroxide, aluminum hydroxide Calcium carbonate, magnesium hydroxide, aluminum hydroxide Calcium carbonate, magnesium hydroxide, aluminum hydroxide Magnesium hydroxide, aluminum hydroxide Aluminum hydroxide Levothyroxine Sodium bicarbonate Sodium bicarbonate H2RAs H2RAs, PPIs Cimetidine Tetracyclines Fluoroquinolones Azithromycin Isoniazid Potential Interaction Increased gastric pH may decrease disintegration, dissolution, or ionization of drug leading to decreased absorption. Absorption of amphetamines is increased. Increased gastric pH may cause premature breakdown of enteric coating. Absorption of levothyroxine is delayed or impaired. Absorption of antibiotic is decreased. Absorption of antibiotic is decreased. Absorption of antibiotic is decreased. Absorption of isoniazid is decreased. Management/Preventive Measures Separate doses by at least 2 hours. Separate doses by at least 2 hours. Separate doses by at least 2 hours. Separate doses by at least 4 hours. Separate doses by at least 4 hours. Take antibiotic 2 hours before or 6 hours after taking antacid. Separate doses by at least 2 hours. Take isoniazid at least 1 hour before taking antacid. Quinidine Increased urinary pH may decrease Avoid concurrent use or monitor renal excretion of quinidine. response to therapy. Salicylates Increased urinary pH may increase Avoid concurrent use or monitor for renal excretion of salicylates. decreased response to salicylates. Nifedipine Serum concentration of nifedipine is Monitor for increased effects of increased. nifedipine. Itraconazole, ketoconazole, indinavir, Increased gastric pH may decrease Avoid concurrent use or monitor atazanavir, iron sulfate, calcium disintegration, dissolution, or response to therapy. carbonate ionization of drug leading to decreased absorption. Phenytoin, warfarin, amiodarone, Cimetidine inhibits CYP450 3A4, Avoid use of cimetidine in patients clopidogrel, theophylline, tricyclic 2D6, 1A2, and 2C9. taking medications metabolized by antidepressants, others these CYP enzymes. Exclusions for Self Care PEPTIC ULCER DISEASE (PUD) › Major causes: H. Pylori, NSAID use › Other causes: critical illness, surgery, hypovolemia, malignancy, stress and tobacco use › Symptoms: Duodenal Ulcer (DU) Gastric Ulcer (GU) - Sharp burning epigastric pain, point tenderness - Pain 1.5-3 hours after meal - Eating lessens the pain - Episodic, may persist for months - Nocturnal wakening - Diffuse lower abdominal pain, less localized than DU - Pain precipitated by meals (esp. large meals) - Continuous pain - Obstructive symptoms (n/v, anorexia, weight loss, hematemesis) PUD Alarm Symptoms › Refer patients with any of these symptoms for immediate care including endoscopy: – – – – – – – – – – Anemia Hematemesis Melena Unintentional weight loss Vomiting Dysphagia or odynophagia Back pain Obstruction Diarrhea Perforation of pancreas or liver (spreading upper ab pain) Diagnosis- PUD › Esophagogastroduodenoscopy (EGD) – For patients with alarm symptoms, older than 55 years of age, weight loss, tx failure – high sensitivity/specificity › Barium contrast radiography – For patients who can’t tolerate EGD or may have obstruction – Less sensitivity and specificity Diagnosis- PUD (H. Pylori Suspected) H. Pylori Tests- Endoscopic Rapid Urease Test Culture Histology PCR - No PPI for 1-2 weeks or abx/bismuth for 2-4 weeks prior; high accuracy Allows for sensitivity of H. pylori, $$$ Gold standard, evaluates pathologic changes due to H. pylori Not widely available, antibiotic sensitivities H. Pylori Tests- Nonendoscopic Urea Breath Test Identifies active H. pylori infection Fecal antigen test Low accuracy, for confirmation of eradication Antibody testing Inexpensive, not useful after PPI use Complications from PUD › Hemorrhage (bleeding) – Most common › Penetration – Risk of peritonitis and shock without treatment › Gastric outlet obstruction – Bothersome GI symptoms 6 hours or more after meals › Gastric cancer – H. Pylori responsible for 36-74% of all gastric cancers Goals of Therapy › Relieve pain › Promote healing of ulcer › Removal of causative pathogen (H. Pylori) › Prevent recurrence of ulcer › Reduce acid production Treatment Options for PUD https://justinhealth.com/the-truth-about-h-pylori-infections-and-functional-medicine-podcast-90/ Pharmacological Treatment for PUD › Triple Therapy (first line) › Quadruple Therapy (first line) – Eradication of H. Pylori with both of these 70-85% – Selection of therapy: cost, tolerability, DDI’s, abx resistance › Standard Treatment Time: 10-14 days › Recurrent infections Pharmacological Treatment for PUD › TRIPLE: › Metronidazole 500 mg BID OR amoxicillin 1000 mg BID + PPI (any PPI, typically BID) + clarithromycin 500 mg BID › Quadruple: › Any PPI (typically BID)+ Bismuth subsalicylate 525 mg QID + Metronidazole 250-500 mg QID + Tetracycline 500 mg QID OR Amox 500 QID OR Clarithromycin 250-500 QID Pharmacological Treatment of PUD: Antibiotics Antibiotic Side Effects Comments Amoxicillin Rash, N/V, diarrhea Tetracycline Diarrhea, photosensitivity PCN allergy Renally dose adjusted Can’t be sub’d for doxycycline Metronidazole Metallic taste, diarrhea, nausea TID dosing; no alcohol! Levofloxacin N/V, diarrhea, HA Clarithromycin Taste disturbance, nausea, diarrhea Renally dose adjusted BBW: tendon rupture, myasthenia gravis IR formulation, can’t be sub’d Salvage Therapy › 20% failure rate after first treatment › Regimen should include agents not previously used › Includes drugs with more side effects and non-validated regimens Maintenance Therapy › Can be considered for patients with: – Successful eradication of H, pylori – History of recurrent H. pylori related ulcers – PUD related complications › Can use H2RA or PPI’s Treatment of Ulcer (Non H. Pylori) › Gastric Ulcer: Treat with BID PPI for 6-8 weeks › Duodenal ulcer: Treat with PPI BID for 4 weeks › H. Pylori testing should be done before patient gets started on PPI – PPI’s can inhibit growth of H. pylori and may cause a false negative test result › NSAID-induced PUD: – Tobacco cessation – Check for H. pylori – Reduction or cessation of NSAIDs › Switch to selective NSAID or APAP › Can coadminister NSAID with PPI daily or H2RA BID; 8 weeks – Surgery Treatment of Stress Ulcers › Superficial lesion of the gastric lining › Risk factors: ICU, coagulopathy, shock, resp failure, hepatic/renal failure, burns, hypotension › Prophylaxis suggested for those with risk factors – IV H2RA’s have most amount of data › Continuous or bolus – PPI’s › Less data – Sulcrafate MAYBE if others not tolerated Patient Education › Stress adherence to prevent treatment failure › Educate patients on S&S of bleeding and alarm symptoms and worsening of symptoms › Adverse effects of pharmacological agents › Non-Pharm therapy › Discontinuation of NSAIDS › Reduce factors leading to PUD/GERD Nonpharm Treatment: PUD › Smoking cessation › Avoid NSAID use (including aspirin) › Avoiding foods that exacerbate symptoms › Eliminating or reducing physiological stress Overall Assessment: A Case-Based Approach › Collect › Assess › Plan › Implement › Follow Up QUESTIONS?