GERD, PUD, SUP

• heartburn (pyrosis)
• hypersalivation (water brash)
• belching
• regurgitation
• acid taste in mouth
• nausea

• Nonallergic asthma
• chronic cough
• hoarseness
• pharyngitis
• chest pain
• dental erosions

if pt has chronic cough, ambulatory reflux monitoring is preferred approach for evaluation

if pt has non-cardiac chest pain use 20mg omeprazole BID for 1-8 weeks

• continual pain
• dysphagia
• odynophagia (pain on swallowing)
• unexplained weight loss
• choking
• bleeding

if pt has alarm symptoms, is >45 yo, is refractory to treatment, they should be referred for endoscopy

• peppermint
• spearmint
• chocolate
• coffee, cola, tea
• garlic
• onion
• fatty meals
• chili peppers

• beta blockers
• calcium channel blockers
• nicotine

• NSAIDs, ASA, bisphosphonates, iron salts
• acidic foods, alcohol, spicy foods, coffee

2 weeks

• start with high dose QD to BID PPI then step down to a lower PPI dose, then to an H2RA, then taper off
• used for severe disease

• traditional treatment
• first initiate lifestyle changes, progress to H2RAs, then to PPIs, then to surgery

acid suppression

• antacids
• OTC acid suppressive agents

PPIs

• sodium bicarbonate
• calcium carbonate (tums, maalox)
• magnesium salts (mylanta)
• aluminum salts (maalox, mylanta)

sodium bicarbonate

• Constipation: calcium carbonate, aluminum salts
• Diarrhea: magnesium salts

magnesium salts

aluminum salts because they help to absorb excess phosphate

• neutralize acid and increase gastric pH
• also decrease pepsin and gastrin
• increase LES pressure

• an "inactive" ingredient in many antacids
• it forms a protective barrier between the esophagus and gastric contents

• 1st line for intermittent sx or as breakthrough for PPI/H2RA therapy
• give immediate symptom relief

• chelation with FQs, TCs
• reduced abs d/t pH increases with ketoconazole, itraconazole, iron

• cimetidine (tagamet)
• famotidine (pepcid)
• ranitidine (zantac)
• nizatidine (axid)

competitive (reversible) inhibition of H2 receptors on parietal cell - decrease gastric secretion

treatment of mild symptomatic GERD

treatment of mild-moderate GERD (BID dosing)

to heal erosive esophagitis (QID dosing)

• on-demand therapy for intermittent mild-to-moderate GERD sx
• preventive dosing before meals or exercise
• high doses (Rx) are for severe sx or maintenance therapy

8 weeks +

• begin w/in 1 hr
• last 6-12 hr

• CNS effects - elderly at increased risk
• Hematologic effects - rare - (decr platelets and WBCs - monitor CBC)
• N/V/D/ constipation
• Endocrine - cimetidine assoc with gynecomastia (rare - with prolonged use)

• Ranitidine: if CrCl < 50, give 150 mg qd
• Famotidine: if CrCl < 50, give 20 mg qd
• Cimetidine: if CrCl < 30, give 300 mg q12h
• Nizatidine: if CrCl 20-50, give 150 mg qd. If < 20, give 150 mg QOD

• affect absorption of ketoconazole, itraconazole, iron
• cimetidine inhibits lots of CYP enzymes (affects warfarin, phenytoin, diazepam, theophylline). Use famotidine or ranitidine instead

yes

• omeprazole (prilosec)
• lansoprazole (prevacid)
• esomeprazole (nexium)
• pantoprazole (protonix)
• rabeprazole (aciphex)
• dexlansoprazole (kapidex)

• omeprazole 20 mg
• esomeprazole 20 mg
• rabeprazole 20 mg
• lansoprazole 30 mg
• pantoprazole 40 mg
• dexlansoprazole 60 mg

irreversibly inhibit H+/K+/ATPase - final step in gastric secretion

PPI

PPIs typically do

most effective tx for short-term and long-term mgmt of GERD and erosive disease

30 minutes prior to a meal

• 2-4 h for symptom relief
• 3-5 d for complet relief
• because PPIs only inhibit active proton pumps

4-8 weeks (possibly longer)

• drugs with pH dependent absorption (ketoconazole, itraconazole)
• Omeprazole inhibits 2C19 so can affect warfarin (decr. PT)
• Clopidogrel - is efficacy is decr. with omeprazole. CLINICALLY SIGNIFICANT. If possible use H2RA instead, or pantoprazole or esomeprazole.

none - they are equal

• increase dosing frequency
• increase dose
• add a 2nd drug (hs dose of H2RA, prokinetic)
• switch to different PPI
• for nocturnal sx, may add H2RA
• anti-reflux surgery - last line

• metoclopramide
• bethanechol
• cisapride

facilitate increased gastric emptying

adjunctive therapy for GERD - used in combo with H2RAs in pts with motility probs and in pts who fail high dose PPIs

• the risks outweigh the benefits
• they have lots of SEs
• require multiple daily doses

• promotility agent - dopamine antagonist
• increases LES tone and accelerates gastric emptying
• dosed up to QID
• AEs - dizziness, fatigue, somnolence, drowsiness, EPS, hyperprolactinemia
• CI'd - Parkinsons, mechanical obstruction, other dopamine antagonists or anticholinergics, pheochromocytoma

• promotility agent - cholinergic agonist
• AEs - diarrhea, blurred vision, abdominal cramping
• May increase gastric production

• promotility agent
• efficacy similar to H2RAs
• available on restricted basis only
• AEs - QT prolongation and cardiac arrhythmias when in combo with 3A4 inhibitors

sucralfate

• Dosed QID 30 min prior to meal
• MOA - nonabsorbable aluminum salt - coats stomach
• Place in therapy - not often used in GERD
• AEs - lots of chelation DIs, accumulation of aluminum in renal failure

• anti-reflux surgery
• last line therapy for GERD
• pts still can't d/c meds

• if sx return w/in 3 months of tapering off meds
• if pt has complications (Barretts esophagus, strictures, hemorrhage)

• H2RA (for mild disease) - only ranitidine 150 mg BID is approved for maintenance of healing erosive esophagitis
• PPI (for moderate to severe esophagitis)
• "on-demand" PPI for endoscopy-negative GERD

lifestyle modifications + antacids AND/OR OTC low-dose H2RA (up to BID) OR OTC PPI (QD)

lifestyle modifications + rx-strength acid suppression therapy (H2RA for 6-12 weeks OR PPI for 4-8 weeks)

lifestyle modifications + PPIs for 4-16 weeks up to BID OR high-dose H2RAs for 8-12 weeks

• duodenal ulcer
• gastric ulcer

• Duodenal: H. pylori infx (95%), NSAIDs (less common - Zollinger-Ellison syndrome, hypercalcemia, neoplasia, CMV, herpes)
• Gastric: H. pylori infx, NSAIDs, stress (less common - Crohn's, CMV, herpes)

• Both: epigastric pain, heartburn, belching, bloated feeling, nausea, anorexia, GI bleeding/hematemesis
• Duodenal: worse at night and the pain occurs 1-3 hours post meal. Relieved by eating.
• Gastric: pain is worse with eating.

• uncomplicated duodenal ulcer 4+ weeks
• uncomplicated gastric ulcer 6+ weeks

• Age > 60 years
• increased NSAID dose
• longer duration of treatment
• intrinsic NSAID toxicity
• hx of PUD
• concurrent use of corticosteroids or anticoagulants
• underlying CV or rheumatologic disease
• use of multiple NSAIDs

• G (-) bacteria found between gastric epithelial cells and the mucus layer
• it increases ulceration and damage
• can lead to gastric cancer

• active ulcer disease
• history of PUD
• MALT lymphoma

• Only if it is known to be susceptible to the agents
• Triple therapy is one antisecretory agent (PPI preferred) + 2 antibiotics

10-14 d

• Use if initial tx fails or if there's resistance
• Use for 14 days

• Efficacy (should be > 90% and >85% in resistant strains)
• Tolerability
• DIs
• Antibiotic resistance
• cost
• compliance (many multiple daily doses needed)

they make it turn dark in color

• bismuth subsalicylate 525 QID + metronidazole 500 mg TID + tetracycline 500 mg QID + PPI (or ulcer-healing dose of H2RA for 4-6 weeks)
• Duration is 14 days
• can substitute Amoxicillin 500 mg or Clarithromycin 250-500 mg QID for the TC

Amox, clarithromycin, and metronidazole (or tinidazole) + PPI for 10 - 14 d

• Amox + PPI BID x 5 days
• then clarithromycin + metronidazole + PPI BID for 5 more days

• Amox + PPI BID x 7 d
• then Amox, Clarith, and metronidazole for 7 more days

• cause direct or topical damage
• inhibit prostaglandins

• etodolac
• meloxicam
• diclofenac
• celecoxib
• nabumetone

PPI for 4 weeks (would need maintenance therapy if pt continued on NSAID)

• omeprazole 20-40mg qd
• esomeprazole 20-40mg qd
• rabeprazole 20 mg qd
• lansoprazole 15-30 mg qd
• pantoprazole 40 mg qd
• dexlansoprazole 30-60 mg qd
• sucralfate 1 g qid or 2 g bid

• misoprostol
• (+) as effective as PPI for healing/secondary prevention
• (-) MDD, dose dependent AEs - diarrhea, abd pain, nausea, flatulence
• CI - pregnancy Category X d/t bleeding/spontaneous abortion

• inferior in healing and preventing recurrence of gastric ulcers
• standard dose can prevent NSAID induced duodenal ulcers

when symptoms, or the ulcer, or both persist for > 8 weeks for duodenal or > 12 weeks for gastric despite treatment

• Higher PPI
• Maintenance treatment with healing dose of PPI may be needed
• No benefit in switching between different H2RAs or PPIs
• Concurrent PPIs and H2RAs no benefit
• Combo with misoprostol or sucralfate no benefit
• May need surgery

hypergastric secretion with recurrent peptic ulcerations resulting from a gastrin producing tumor (gastrinoma)

• recurrent peptic ulcers
• heartburn
• diarrhea

• PPIs are first line (H2RAs don't work well enough)
• High doses (e.g. 60 mg omeprazole)
• Long term
• May use octreotide to directly inhibit acid secretion. 100-250 mcg SQ TID
• May require surgery or chemotherapy

• PUD
• esophagitis
• erosive disease
• esophageal varices
• stress ulcers

• hematemesis (coffee-ground)
• N/V/D, melena
• Hypotension and assoc organ dysfxn (renal/hepatic/cardiac/cerebral hypoperfusion)
• Sx of blood loss anemia (fatigue, low Hgb/Hct)

• Endoscopy w/in 24 h and ablation if needed
• Remove meds contributing to bleeding
• High dose PPIs (bolus then infusion - can use oral)
• Use of H2RAs or octreotide not recommended

• pts with GERD or ZES and no enteral access
• acute GI bleed
• Prophylaxis of stress ulcers and clinically important bleeding
• prevention of rebleeding from PUD
• induction of anesthesia

acute superficial inflammatory lesions of the gastric mucosa induced when an individual is subjected to abnormally elevated physiological demands

• Stress: multiple, acute, asymptomatic, acid/pepsin secretory mucosa
• Non-stress: usually solitary, chronic inflammation, symptomatic (pain, burning, discomfort), distal stomach/duodenum (e.g. regular PUD ulcers)

• hypoperfusion of GIT - decreases protective mucosal mechanisms
• altered susceptibility to gastric acid
• loss of defense mechanisms (mucous/bicarb layer, prostaglandins, cellular renewal)

• Mechanical ventilation > 48 hours
• Coagulopathy (platelets < 50,000; INR > 1.5)
• GI bleeding/ulceration within past year

• Antacids
• H2RAs
• PPIs
• Sucralfate

• H2RAs
• (+) good efficacy data, inexpensive, easy to add to TPN, available PO and IV
• (-) must dose adjust in renal impairment, higher pH may increase risk of bacterial colonization

Famotidine: normal renal fxn 20 mg BID PO, NG, IV; if CrCl < 30, give 20 mg QD PO, NG, IV

Ranitidine: normal renal fxn 150 mg BID PO or NG, 50 mg q6-8h IV; if CrCl < 50, give 150 mg QD or BID PO or NG or 50 mg q12-24h IV

• No specific guidelines
• H2RAs are 1st line (pt on vent, INR > 1.5, Hx GI bleed)
• PPIs are 2nd or 3rd line
• Sucralfate is 2nd or 3rd line

• when pt is transferred out of ICU
• if pt in ICU has < 2 risk factors
• may need to continue PPI or H2RA if pt has other disease states (GERD, PUD, high-dose steroids)