GERD and PUD 3.10.2023 SV - Tagged.pdf

Clinical Presentaon › GERD – Common Symptoms(esophageal): heartburn, dyspepsia, acid regurgitaon, dysphagia, re2ux chest pain syndrome – Extra esophageal: chronic cough, laryngis, sinusis, dental erosion › ALARM symptoms: – Hematemesis, anemia, melena, unintenonal weight loss, voming, dysphagi...

Clinical Presentaon › GERD – Common Symptoms(esophageal): heartburn, dyspepsia, acid regurgitaon, dysphagia, re2ux chest pain syndrome – Extra esophageal: chronic cough, laryngis, sinusis, dental erosion › ALARM symptoms: – Hematemesis, anemia, melena, unintenonal weight loss, voming, dysphagia, odynophagia, back pain, obstrucon, diarrhea, perforaon of pancreas or liver (spreading upper abdominal pain) – Seek immediate care Complicaons of GERD › Erosive esophagis › Esophageal strictures › Barre8’s esophagus – 30-60x increased risk of adenocarcinoma › Esophageal adenocarcinoma and laryngeal cancers › anemia Treatment Goals- GERD › Reduce frequency and duraon of re2ux › Symptom reducon or eliminaon › Prevent disease progression and the development of complicaons › Promote healing of injured mucosa Pharmacological Treatment Opons for GERD › Step up approach – Start with antacids (do not heal erosions) or H2RA’s and lifestyle modiCcaons and increase › Step down approach – Start with PPI’s and lifestyle modiCcaons and decrease – Extra esophageal › PPI BID for 2 months › Use stepdown approach Pharmacological Treatment Opons for GERD › Antacids › H2- receptor antagonists (H2RA’s) › Proton pump inhibitors (PPI’s) › Promolity agents › Surgery Antacids › Aluminum, calcium, and magnesium antacid preparaons (OTC) › MOA: Neutralize acid and raise intragastric pH; results in a decreased acvaon of pepsinogen and increased LES pressure › Role: First line for mild intermi8ent symptoms or breakthrough for those on H2RA or PPI therapy › Dosing: Take 1-3 hours aBer meals and other medicaons to avoid potenal DI’s › Adv Events: Conspaon (aluminum), chalk taste, abdominal cramps, diarrhea (magnesium), accumulaon in renal dysfuncon › 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 secreon (reversible blockade) › Role: empiric therapy for mild, troublesome GERD symptoms: ondemand, intermi8ent, and meal/exercise-provoked symptoms › Faster symptomac 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; absorpon delayed by admin with antacids but not by food – Prolonged use may lead to decreased eHcacy and tolerance – Renal impairment: Generally reduce dose/hepac impairment- adjust dose H2RA’s › Adv Events: well tolerated! CNS- HA, dizziness, fague, confusion- increased in elderly and renally/hep impaired; Tolerance › May be useful in combo with PPI’s at nighJme; but limited data to support this › DDI’s: drugs that depend on a lower gastric pH for absorpon may be impaired (ketoconazole, itraconazole, protease inhibitors) › ***Cimedine: inhibits CYP450 enzymes, drugs metabolized by these enzymes might be a#ected (theophylline, cyclosporine, nifedipine, propranolol, phenytoin, warfarin) H2RA’s › Cimedine (Tagamet)* – 400 mg BID – Lots of DDI’s › Famodine (Pepcid) – 20 mg BID (has IV and PO formulaon) › Nizadine (Axid) – 150 mg BID › Ranidine (Zantac) – 150 mg BID (has IV and PO formulaon) › Some combos: – Pepcid Complete: famodine, Ca carbonate, Mg oxide PPI’s › MOA: accumulate in acidic region of parietal cells, where they undergo an acid- catalyzed conversion to a reacve species, (rate of conversion varies between agents). Reacve species irreversibly interacts with the H-K-ATPase; resulng in a long-lasng impairment of acid secreon › Role: most potent inhibitors/most e#ecve tx for mod to severe GERD, erosive esophagis, and complicaons – 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 oBen indicated Administer before the Crst meal of the day (30 mins before breakfast) Onset of relief: 2-3 hours; Duraon- 24 hrs Duraon: OTC’s marketed for 14 days; depends on what we are treang PPI’s › Side e#ects: HA, dizziness, somnolence, diarrhea, dyspepsia, › Can switch to another PPI or try a di# drug class if needed › Potenal risks: – Decreased Ca absorpon Hip fractures/osteoporosis – pneumonia – enteric infecons (C. di# increased risk) › Drug-drug interacons: reduced gastric pH may a#ect 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 bedme Class C pregnancy (all others B) Co-formulated for immediate pH neutralizaon; capsule and powder available 40 mg daily 30 mg daily Oral capsule, powder, ODT 20 mg daily 40 mg daily IV formulaon available 40 mg daily IV formulaon available 30 mg daily Take any me of day; L-isomer of lansoprazole Nocturnal GERD › Lots of paents also have nighJme symptoms – Connued acid producon 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 connue to have GERD symptoms and or endoscopic evidence of esophagis › Evaluate reason for PPI failure – – – – – Opmize ansecretory therapy (BID dosing of PPI’s, witch to di# agent) Add-on therapy (bedme H2RA or bile acid therapies for bile acid re2ux) Lifestyle modiCcaons Perform esophageal tesng (EGD, etc) Tx of delayed gastric emptying with promolity agents › Anre2ux surgery: should be considered in young paents requiring high-dose therapy for symptom control and those unresponsive to therapy. Promolity agents › Used to improve gastric emptying in select paents; typically in addion to acidsuppressive therapy – Metoclopramide: dopamine antagonist; prokinec › Dose 10-15 mg fup to QID; 30 mins before meals, dose adjustment necessary for renal impairment › Therapy >12 weeks of duraon not recommended due to risk of irreversible tardive dyskinesia › Adv events: several- confusion, dizzy, drowsy, fague, HA, hyperprolacnemia, extrapyramidal symptoms (avoid in Parkinson’s disease) – Bethanechol: cholinergic agonist › › › › Smulates gastric molity, increases gastric tone, and restores peristalsis 25 mg QID 1 hour before or 2 hours aBer meals Adv events: blurred vision, HA, tachycardia, cramping, diarrhea Poor paent tolerability; use limited – Cisapride: cholinergic agonist › Increases LES pressure and lower esophageal peristalsis, accelerang 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 Populaons › 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 Crst 18 months of life – PPI’s (sprinkle formulaon)