Waller GERD treatment DSA

Question 1

Proton-Pump Inhibitors (PPIs)

Answer 1

i) Dexlansoprazole (Dexilant)
ii) Esomeprazole (Nexium)
iii) Lansoprazole (Prevacid)
iv) Omeprazole (Prilosec, Zegerid)
v) Pantoprazole (Protonix)
vi) Rabeprazole (Aciphex)

Question 2

H2-Receptor Antagonists (H2RAs)

Answer 2

i) Cimetidine (Tagamet)
ii) Famotidine (Pepcid)
iii) Nizatidine (Axid)
iv) Ranitidine (Zantac)

Question 3

Antacids

Answer 3

i) Sodium bicarbonate (baking soda, Alka Seltzer)
ii) Calcium carbonate (Tums, Os-Cal)
iii) Magnesium hydroxide/aluminum hydroxide (Mylanta, Maalox)

Question 4

Agents Which Provide Mucosal Protection

Answer 4

a) Bismuth subcitrate
b) Bismuth subsalicylate (Pepto-Bismol)
c) Misoprostol
d) Sucralfate (Carafate)

Question 5

Antibiotic Treatment of Helicobacter pylori Infection

Answer 5

a) PPI or H2RA combined with two or more antibiotics
i) Amoxicillin
ii) Clarithromycin
iii) Metronidazole
iv) Tetracycline

Question 6

Physiology of Acid Secretion

Answer 6

Neuronal (acetylcholine, ACh), paracrine (histamine), and endocrine (gastrin) factors regulate acid secretion through receptor binding on parietal cells.

Question 7

b) Parietal Cell

Answer 7

i) ACh (vagal postganglionic nerves) and gastrin (antral G cells) bind parietal receptors (muscarinic M3 and CCK-B respectively) and stimulate G-protein coupled receptor (GPCR) signaling pathways.
(1) Gq-PLC-IP3-Ca2+ activation leads to an increase in cytosolic Ca2+ which ultimately results in stimulation of acid secretion from H+/K+-ATPase (proton-pump).
(2) H+/K+-ATPase exchanges hydrogen and potassium ions across the parietal cell membrane.
ii) ACh provides potent direct parietal cell stimulation while gastrin effects are primarily mediated through indirect release of histamine from enterochromaffin-like cells.

Question 8

Enterochromaffin-Like Cell (ECL)

Answer 8

i) ACh and gastrin also bind gut endocrine cells called enterochromaffin-like (ECL) cells in close proximity to parietal cells which stimulates histamine release.
(1) Histamine released from ECL cells binds H2 receptors on parietal cells and activates the proton-pump via cAMP-dependent GPCR signaling pathways (Gs-adenylyl cyclase-cyclic AMP-PKA).

Question 9

Somatostatin

Answer 9

(SST), produced by antral D cells, inhibits gastric acid secretion.
i) When gastric pH falls below 3, this stimulates SST release, which suppresses gastrin in a negative-feedback loop.

Question 10

Role of prostaglandins (PGs)

Answer 10

i) Prostaglandins E2 and I2 inhibit the proton-pump by reducing cAMP production (EP3 receptors are GPCRs coupled to Gi on parietal cells).
ii) PGE2 and PGI2 also stimulate production of protective factors (mucus, bicarbonate) by superficial epithelial cells and enhance mucosal blood flow.
iii) Non-steroidal anti-inflammatory drugs (NSAIDs) block PG production resulting in more acid secretion, less mucus and bicarbonate production, and diminished blood flow. Thus, NSAIDs are ulcerogenic and should be avoided or dose reduced in patients with peptic ulcers.

Question 11

Acid-Peptic Diseases

Answer 11

a) Gastroesophageal reflux (GERD), peptic ulcer (gastric and duodenal), and stress-related mucosal injury.
b) Erosions or ulcerations arise when aggressive factors overwhelm defensive factors.
i) Aggressive factors: acid, pepsin, bile.
ii) Defensive factors: mucus and bicarbonate secretion, prostaglandins, blood flow.

Question 12

Gastroesophageal Reflux Disease (GERD) –

Answer 12

symptoms or complications from refluxed gastric contents into the esophagus or beyond (oral cavity or lung).

i) Classification: based on presence of symptoms without erosions (nonerosive disease or NERD) or symptoms with erosions (ERD).
ii) Complications: most cases of GERD follow a relatively benign course, but can be associated with severe erosive esophagitis, stricture formation, and Barrett’s metaplasia, which is associated with a small but significant risk of adenocarcinoma
iii) Causes: transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter tone, delayed gastric emptying, or hormonal changes due to pregnancy.
iv) Symptoms: heartburn, regurgitation, and chest pain.
v) Atypical symptoms (overlap other diseases): dyspepsia, epigastric pain, nausea, bloating, belching.
vi) Alarm symptoms: bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia, recurrent vomiting, family history of gastrointestinal cancer, previous esophagogastric malignancy.
vii) Extraesophageal symptoms: asthma, chronic cough, laryngitis.

Question 13

GERD lifestyle modifications

Answer 13

(1) Weight loss in overweight individuals or those who have recently gained weight.
(2) Head of bed elevation if symptoms associated with recumbency.
(3) Avoid meals 2-3 hours before bedtime in those with nocturnal GERD.
(4) Smoking cessation (tobacco effects lower esophageal sphincter).
(5) Cessation of foods that may aggravate reflux (limited or no clinical evidence but recommended if patient experiences symptom relief after cessation): caffeine, coffee, chocolate, spicy foods, acidic foods, high fat content foods.

Question 14

GERD Pharmacotherapy:

Answer 14

(1) Mild, intermittent symptoms – antacid or H2RA as needed.
(2) Nonerosive disease – antacid or H2RA (PPI may be required in more severe symptoms).
(3) Erosive esophagitis – PPI for 8 weeks.
(4) Pregnancy – most drugs are FDA pregnancy category B; exception – omeprazole (category C; risk cannot be ruled out).
(a) Mild cases – antacid or sucralfate.
(b) Persistent symptoms – H2RA (ranitidine has most safety data available).
(c) Intractable symptoms/complicated reflux – PPI (lansoprazole or pantoprazole preferred).

Question 15

Peptic Ulcer Disease (PUD)

Answer 15

mucosal damage secondary to pepsin and gastric acid occurring in the stomach (gastric ulcer) or proximal duodenum (duodenal ulcer).

i) Over 90% of peptic ulcers are caused by infection with Helicobacter pylori or NSAID use.
ii) Causes: Helicobacter pylori infection, chronic NSAID use, stress-related mucosal injury (due to poor perfusion in critically ill patients), Zollinger-Ellison Syndrome (gastrin producing tumors which stimulate acid secretion).
iii) Symptoms: burning epigastric pain, pain occurring after meals or on an empty stomach, nocturnal pain relieved by food intake (less common symptoms: indigestion, vomiting, heartburn).

Question 16

PUD pharmacotherapy

Answer 16

(1) Initial management – withdrawal of offending/contributing factors, eradication of H. pylori.
(2) Duodenal ulcer – H2RA or PPI for 4 weeks.
(3) Gastric ulcer – PPI for 8 weeks.
(4) H. pylori eradication – has been shown to reduce the risk of recurrence.
(a) Antisecretory agent (PPI preferred) plus at least two antibiotics (see page 10).

Question 17

available drug classes for GERD and PUD

Answer 17

a) Agents which reduce gastric acidity (PPIs, H2RAs, antacids).
b) Agents which promote mucosal defense (bismuth compounds, misoprostol, sucralfate).

Question 18

Proton-Pump Inhibitors (PPIs), agents and MOA

Answer 18

a) Agents: dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.
i) When given in therapeutic equivalent doses, PPIs show little difference in clinical efficacy.
b) MOA: inactive prodrugs, lipophilic weak bases diffuse readily across lipid membranes into acidified compartments (parietal cell canaliculus) from the alkaline intestinal lumen. Rapidly becomes protonated and undergoes conversion to active form which forms a covalent disulfide bond with H+/K+-ATPase, irreversibly inactivating the enzyme.

Question 19

PPIs pharmacokinetics

Answer 19

c) PK: ideal drugs from a PK perspective as they have short serum half-lives, concentrated and activated near site of action, and have a long duration of action.
i) Administered as inactive prodrugs. Oral products are formulated as delayed-release, acid-resistant, enteric-coated capsules/tablets to protect the acid-labile prodrug from destruction in the gastric lumen. Delayed-release products dissolve in the alkaline intestinal lumen and then are absorbed.
ii) Bioavailability – decreased ~50% by food, administer on an empty stomach at least 30 minutes before a meal (breakfast). PPIs only inhibit actively secreting proton-pumps so should preferably be given 1 hour before a meal so peak concentration coincides with max activity of proton-pump.
iii) t1/2 ~1.5 hours; acid inhibition lasts 24 hours due to irreversible inactivation of proton-pump.
(1) At least 18 hours required for new synthesis of H+/K+-ATPase.
(2) Not all proton-pumps inactivated by first dose, requires up to 3-4 days of medication administration for full acid inhibiting potential (should not be taken “on-demand”).
(a) Requires 3-4 days for full acid secretion to return after medication discontinued.
iv) Undergoes rapid first-pass and hepatic metabolism (dose adjust in severe hepatic insufficiency), negligible renal clearance.

Question 20

PPIs PD

Answer 20

inhibits both fasting and meal stimulated acid secretion.

i) Blocks final common pathway of acid secretion – the proton-pump.
ii) Inhibits 90-98% of 24 hour acid secretion in standard doses.

Question 21

PPIs Therapeutic Use

Answer 21

i) GERD – most effective for erosive and nonerosive reflux disease, esophageal complications (peptic stricture or Barrett’s esophagus), and extraesophageal manifestations.
ii) PUD – PPIs provide more rapid symptom relief compared to H2RAs. Also provide faster ulcer healing for duodenal ulcers.
iii) H. pylori infection – promotes organism eradication by direct antimicrobial properties (minor) and by raising intra-gastric pH (lowers minimum inhibitory concentration (MIC) of antibiotics against H. pylori). Reduces risk of ulcer recurrence.
iv) NSAID ulcers – faster healing when aspirin (ASA) or NSAID discontinued. If NSAID or ASA must be continued, PPI (once or twice daily) therapy required.
v) Prevention of re-bleeding – high intragastric pH may enhance coagulation and platelet aggregation in healing ulcers.
vi) Stress-related mucosal injury – omeprazole sodium bicarbonate (only PPI approved for this indication) given per tube in critically ill, ICU patients due to comparable efficacy, lower cost, and ease of administration. Other PPI suspensions, given by nasogastric tube, may also be used (although not FDA approved). Those without nasoenteric tube, H2RA IV preferred over PPI IV.
vii) Zollinger-Ellison syndrome (gastrinomas) and other hyper-secretory conditions.
viii) Over-the-counter (OTC) – short treatment of frequent heartburn.

Question 22

ADRs of PPIs

Answer 22

i) Increased risk (2-3x) of hospital- and community-acquired Clostridium difficile.
ii) Decreased vitamin B12 absorption (potentially leads to subnormal levels with prolonged therapy), modest increased risk of hip fracture, increased risk of nosocomial pneumonia, small increased risk of enteric infections.

Question 23

PPI DDIs

Answer 23

decreased gastric acidity may lead to altered drug absorption (ketoconazole, itraconazole, digoxin, atazanavir).

i) All PPIs metabolized via CYP P450 enzymes (including 2C19 and 3A4) but clinically significant drug interactions are rare due to short t1/2’s.
(1) Omeprazole may inhibit metabolism of warfarin, diazepam, phenytoin, and others.
(2) Rabeprazole and pantoprazole have no significant interactions.
(3) FDA warning – PPIs and clopidogrel.
(a) Clopidogrel is a prodrug requiring CYP2C19 activation. PPIs (omeprazole, esomeprazole, lansoprazole, and dexlansoprazole) could reduce clopidogrel activation thus reducing anti-platelet activity. If co-administration is required, pantoprazole or rabeprazole preferred.

Question 24

H2-Receptor Antagonists (H2RAs)- agents, MOA, PK, PD

Answer 24

a) Agents: cimetidine, famotidine, nizatidine, ranitidine.
i) Potency varies over a 50-fold range, but all H2RAs are roughly equally effective at usual doses; they are not as effective as PPIs.
b) MOA: competitive inhibition at parietal cell H2-receptors (highly selective, does not affect H1- or H3-receptors) blocks histamine released from ECL cells by gastrin or vagal stimulation.
c) PK: cimetidine, famotidine, and ranitidine undergo first-pass metabolism. Bioavailability ~50%.
i) t1/2 1.1-4 hours; however, duration of action dependent on dose.
ii) Cleared by combination of hepatic metabolism, glomerular filtration, and renal tubular secretion [dose reduce in patients with moderate to severe renal (and possibly severe hepatic) insufficiency].
d) PD: suppresses basal more than meal-stimulated acid secretion.

i) Especially effective at inhibiting nocturnal acid secretion (which depends largely on histamine) with modest impact on meal stimulated histamine release (which is stimulated by gastrin and ACh as well as histamine).
ii) Control of nocturnal acid secretion is the most important determinant of duodenal ulcer healing, thus evening dosing is typical.

Question 25

H2 receptor antagonists therapeutic use

Answer 25

i) GERD – used intermittently for infrequent heartburn or dyspepsia (under 3x per week). OTC preparations heavily used.
ii) PUD – largely replaced by PPIs, but still used occasionally for duodenal ulcers as nocturnal acid secretion most important determinant of ulcer healing.
iii) NSAID ulcers – may be used if offending NSAID discontinued. If NSAID or ASA continued, PPI preferred over H2RA.
iv) Stress-related mucosal injury – H2RA preferred IV over PPI in patients, without a nasoenteric tube or significant ileus present, because of proven efficacy and lower cost.

Question 26

H2 receptor antagonists ADRs and DDIs

Answer 26

under 3% experience diarrhea, headache, fatigue, myalgia, constipation.

i) Mental status changes: confusion, hallucinations, agitation, especially in ICU patients who are elderly or who have renal or hepatic dysfunction (rarely occurs in ambulatory setting).
ii) Cimetidine: gynecomastia or impotence in men and galactorrhea in women.
iii) Increased risk of nosocomial pneumonia; rarely causes blood dyscrasias (thrombocytopenia); bradycardia/hypotension with rapid IV infusion (give over 30 minutes).
g) DDIs: interferes with CYP1A2, 2C9, 2D6, 3A4 (cimetidine&raquo_space;> ranitidine; negligible interactions with famotidine and nizatidine). Drugs with a narrow therapeutic window (e.g., theophylline, warfarin, phenytoin, and lidocaine) may result in adverse effects when given with cimetidine.
i) Competes with creatinine and other drugs (procainamide) for renal tubular secretion.
ii) All H2RAs (except famotidine), inhibit gastric first-pass metabolism of alcohol. Could lead to increased ethanol blood levels but importance of interaction debated.

Question 27

Antacid- agents and MOA

Answer 27

a) Agents: sodium bicarbonate, calcium carbonate, magnesium hydroxide/aluminum hydroxide.
b) MOA: weak bases, react with hydrochloric acid (HCl) to form a salt and water. Neutralizes acid and reduces intragastric acidity.

Question 28

antacids- PK

Answer 28

neutralization capacity highly variable depending on – rate of dissolution (tablet vs. liquid), water solubility, rate of reaction with acid, and rate of gastric emptying.

i) Sodium bicarbonate:
(1) Reacts rapidly with HCl to produce carbon dioxide (CO2) and sodium chloride (NaCl).
(2) Formation of CO2 leads to gastric distention and belching. Unreacted alkali (metabolic alkalosis) and NaCl absorption (fluid retention) may pose a risk in patients with heart failure, hypertension, and renal insufficiency. Should not be taken long-term.
ii) Calcium carbonate:
(1) Less soluble and reacts more slowly with HCl to form CO2 and calcium chloride (CaCl2).
(2) May cause belching and metabolic alkalosis. Excessive doses of either sodium bicarbonate or calcium carbonate with Ca2+ containing dairy products can lead to hypercalcemia, renal insufficiency, and metabolic alkalosis. Should not be taken long-term.
iii) Magnesium hydroxide/aluminum hydroxide:
(1) React slowly with HCl to from magnesium chloride (MgCl2) or aluminum chloride (AlCl3) & H2O.

(2) No gas is generated so belching does not occur, metabolic alkalosis also uncommon due to efficiency of neutralization.
(a) Magnesium salts can cause osmotic diarrhea.
(b) Aluminum salts can cause constipation.
(c) Commonly administered in combination to minimize impact on bowel function.
(d) Both Mg2+ and Al3+ absorbed and excreted by the kidneys, should not be taken long term in renal insufficiency.

Question 29

antacids therapeutic use and DDIs

Answer 29

d) Therapeutic Use:
i) Dyspepsia and intermittent heartburn.
e) DDIs: antacids may bind/affect absorption of other drugs or increase intragastric pH so drug dissolution or solubility is altered. Do not give within 2 hours of tetracyclines, fluoroquinolones, and iron.

Question 30

Comparison of PPIs, H2RAs, and Antacids

Answer 30

a) Pharmacokinetics:
i) Onset of action: from fastest to slowest – antacids, H2RAs, then PPIs.
ii) Duration of action: PPIs have shorter t1/2, but duration of action is longer (24-48 hours) due to irreversible inhibition of proton-pumps; H2RAs act longer (6-10 hours) than antacids (1-2 hours).
b) Efficacy:
i) Standard doses of PPIs inhibit 90-98% of daily acid secretion, compared to 60-70% with H2RAs.
ii) PPIs more effectively increase intragastric pH & more rapidly heal peptic ulcers compared to H2RAs.
c) Pharmacodynamics:
i) Antacids neutralize acid; PPIs and H2RAs inhibit acid secretion (“antisecretory”).
ii) H2RAs predominantly inhibit basal (fasting) acid secretion; PPIs block both fasting and food-stimulated secretion.
d) Tolerance and Rebound:
i) Repeated administration of H2RAs leads to reduced effectiveness (mechanism unknown, but may involve stimulation of histamine release from ECL cells by secondary hypergastrinemia; also appears to be more prevalent in patients who are not infected with H. pylori); can occur within 3 days of starting treatment.
ii) Unlike H2RAs, tolerance does not occur with PPIs, probably because the site of action is distal to the action of histamine.
iii) Rebound dyspeptic symptoms and acid hypersecretion have been reported following discontinuation of PPIs and H2RAs.

Question 31

Bismuth compounds- agends, MOA

Answer 31

a) Agents: bismuth subsalicylate and bismuth subcitrate potassium (only available in prescription combination with metronidazole and tetracycline for H. pylori).
b) MOA: precise mechanism unknown; bismuth coats ulcers and erosions creating a protective layer against acid and pepsin. Also stimulates prostaglandin, mucus, and bicarbonate secretion.
i) Salicylate (like ASA) readily absorbed; inhibits intestinal prostaglandin and chloride secretion (reduces stool frequency and liquidity in infectious diarrhea).
ii) Bismuth has direct antimicrobial activity against H. pylori.

Question 32

Bismuth compounds- PK and THerapeutic use

Answer 32

c) PK: undergoes rapid dissociation in the stomach and salicylate absorbed.
i) > 99% of bismuth appears in the stool; although < 1% absorbed, bismuth is stored in tissues and has slow renal excretion.
ii) Salicylate is readily absorbed and excreted in the urine.

d) Therapeutic Use:
i) Dyspepsia and acute diarrhea – widely used OTC (even with lack of comparative trials).
ii) Traveler’s diarrhea.
iii) H. pylori infection – part of 4 drug combination regimen.

Question 33

Bismuth compounds ADRs

Answer 33

: harmless blackening of stool (may be confused with GI bleeding); liquid formulations may also cause harmless blackening of tongue.

i) High doses of bismuth subsalicylate can cause salicylate toxicity, overlap in adverse effects with other forms of salicylates (ASA); do not use in patients with influenza or chickenpox due to risk of Reye’s Syndrome.
ii) Use for short periods (prolonged use may lead to encephalopathy); avoid in renal impairment.

Question 34

Prostaglandin analogs- agents, MOA, PK

Answer 34

a) Agent: misoprostol.
b) MOA: methyl analog of PGE1, mucosal protective and acid inhibitory. May stimulate mucus and bicarbonate secretion and enhance mucosal blood flow. Binds prostaglandin receptors on parietal cells reducing histamine stimulated cAMP production causing modest acid inhibition.
c) PK: methyl analog rapidly absorbed and metabolized to active free acid.
i) t1/2 < 30 minutes, must be given 3-4x daily.
ii) Excreted in urine but does not require dose adjustment in renal impairment.

Question 35

prostaglandin analogs- PD, therapeutic use, ADRs

Answer 35

d) PD: also stimulates intestinal electrolyte and fluid absorption, intestinal motility, uterine contractions.
e) Therapeutic Use:
i) Prevention of NSAID induced ulcers – decreases incidence but is not widely used due to adverse effect profile and need for multiple daily dosing (PPIs may be as effective and are better tolerated).
f) ADRs: 10-20% experience diarrhea and cramping abdominal pain. Not well tolerated.
i) Stimulates uterine contractions; thus, contraindicated in pregnancy or in those of child-bearing years without a negative pregnancy test.

Question 36

Sucralfate- MOA, PK

Answer 36

a) Salt of sucrose complexed to sulfated aluminum hydroxide
b) MOA: precise mechanism unknown; negatively charged sucrose sulfate binds positively charged proteins at base of erosions forming a physical barrier that restricts further damage; also stimulates mucosal prostaglandin and bicarbonate secretion.
c) PK: forms a viscous paste in water or acidic solutions which binds ulcers or erosions for up to 6 hours.
i) Limited solubility, < 3% absorbed (intact drug and Al3+), remainder excreted in feces.

Question 37

Sucralfate- Therapeutic Use, ADRs, DDIs

Answer 37

d) Therapeutic Use:
i) Stress-related mucosal injury – administered as slurry through nasogastric tube (slightly less effective than H2RAs IV).
(1) Used preferentially over acid-inhibitory therapies by some clinicians due to concern for increased risk of nosocomial pneumonia secondary to gastric colonization by bacteria in an alkaline environment.
e) ADRs: not absorbed = virtually no systemic side effects (avoid prolonged use in renal failure/ insufficiency due to small amount aluminum absorption). 2% experience constipation (due to aluminum salt).
f) DDIs: may bind and impair absorption of other drugs, must separate administration times.

Question 38

H. Pylori intro and when to test

Answer 38

1) Introduction
a) H. pylori (spiral-shaped, gram-negative rod) is one of the most common worldwide infections.
b) Incidence in the U.S. population: 30-40%.
2) When to Test for H. pylori
a) Active PUD (regardless of NSAID use status, those with active PUD should be tested and treated for H. pylori if infection found).
b) Past history of documented peptic ulcer (without treatment for H. pylori).
c) Gastric mucosa associated lymphoid tissue (MALT) lymphoma.
d) “Test-and-treat” strategy for patients with uninvestigated dyspepsia, < 55 years old, and have no alarm features (bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia).

Question 39

overview of h pylori treatment

Answer 39

a) First course of therapy for H. pylori, offers the best chance for eradication.
i) If a patient has previous antibiotic exposure, this reduces the likelihood of a successful outcome.
ii) Important to always:
(1) Use treatment regimens proven effective
(2) Prescribe regimens for the appropriate duration
(3) Stress the importance of patient compliance
(4) Counsel on likely side effects so patient more likely to complete recommended regimen
b) Therapeutic goals: heal ulcer and eradicate the organism.

Question 40

H pyloir antibiotics

Answer 40

c) No single drug is adequate; most effective regimens are combinations of two or three antibiotics + PPI.
i) Antibiotics: amoxicillin, clarithromycin, metronidazole, and tetracycline (see handout titled Overview of Antimicrobial Agents from the RESPII course for pharmacology details of these agents).
(1) Significant side effects reported in 5-20% of patients (mild side effects are very common).
(a) Clarithromycin – gastrointestinal upset, diarrhea, altered taste.
(b) Amoxicillin – gastrointestinal upset, headache, diarrhea.
(c) Metronidazole – metallic taste, dyspepsia, intolerance to alcohol.
(d) Tetracycline – gastrointestinal upset, photosensitivity.
ii) PPIs promote eradication of H. pylori via direct antimicrobial properties (minor) and by lowering the minimum inhibitory concentrations of antibiotics against H. pylori (by raising intragastric pH).

Question 41

recommended initial therapy for h. pylori pts who have NOT received clarithromycin

Answer 41

i) 14-day “triple therapy”
(1) PPI
(2) Clarithromycin
(3) Amoxicillin or metronidazole (for penicillin-allergic individuals)

Question 42

h pylori- e) Recommended therapy for patients previously treated with a macrolide antibiotic or in areas with high rate (≥ 15%) of clarithromycin or metronidazole resistance (also used in patients who have previously failed standard triple therapy)

Answer 42

i) 14-day “bismuth quadruple therapy”
(1) PPI or H2RA
(2) Metronidazole
(3) Tetracycline or doxycycline
(4) Bismuth subsalicylate
(5) Often criticized for being too complex with a high pill count per day

Question 43

h pylori Other treatment options: studied and used in Europe but not validated for use in the U.S.

Answer 43

i) “Sequential therapy” reported an eradication rate of 90% and consisted of a PPI and amoxicillin for 5 days followed by a PPI, clarithromycin, and tinidazole (a cousin of metronidazole) for 5 days.
ii) “Salvage” regimen, used for patients who have failed traditional clarithromycin-based treatments, is a levofloxacin-based triple therapy for 10 days.