Gastroesophageal

Reflux Disease/Peptic Ulcer Disease:

Pharmacological Treatment

高雅慧
2018/09/13
Goals of Treatment
 Alleviate or eliminate acute symptoms
 Decrease frequency of recurrence
 Promote healing if esophageal tissue injury is present
 Prevent complications
Pharmacologic interventions
 Improving defense mechanisms or
decreasing aggressive factors.
(a) decreasing the acidity of the
refluxate,
(b) decreasing the gastric volume
available to be refluxed,
(c) improving gastric emptying,
(d) increasing LES pressure,
(e) enhancing esophageal clearance
(f) protecting the esophageal mucosa

Source: Chapter 19. Gastroesophageal Reflux Disease, Pharmacotherapy: A Pathophysiologic Approach, 9e

Citation: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A Pathophysiologic Approach, 9e; 2014 Available at:
http://accesspharmacy.mhmedical.com/ViewLarge.aspx?figid=45311928&gbosContainerID=0&gbosid=0 Accessed: September 16, 2017
Copyright © 2017 McGraw-Hill Education. All rights reserved
General Treatment Approach

Initial therapy Undergo testing

Seek medical
patient-directed such as an
attention
(self-care) therapy 2 wks endoscopy
• empiric acid
• antacids, OTC
suppression
H2-antagonist,
therapy, eg.
or OTC PPIs
PPI
• lifestyle
modifications
 Nonpharmacologic Therapies
 Lifestyle modifications
• Should be incorporated into the management of GERD regardless of the severity
of disease
• Lifestyle modifications should be tailored to an each individual patient’s needs
 Anti-reflux surgery
• Used as a last resort option in select patients
 When long-term pharmacologic therapy is undesirable
 Who have refractory GERD
 Have complications
 Endoscopic therapies
• Results have been disappointing and hence are not usually recommended
Lifestyle Modifications (I), TABLE 32-4
 Elevate the head end of the bed (increases esophageal clearance).
Use 6- to 8-in. (15-20 cm) blocks under the head side of the bed
 Weight reduction (reduces symptoms) in obese patients
 Avoid foods that may decrease LES pressure or increase transient
lower esophageal sphincter relaxation (TLESR) (fats, chocolate,
alcohol, peppermint, and spearmint)
 Include protein-rich meals in diet (augments lower esophageal
sphincter pressure)
 Avoid foods that have a direct irritant effect on the esophageal
mucosa (spicy foods, orange juice, tomato juice, and coffee)
Lifestyle Modifications (II), TABLE 32-4
 Behaviors that may reduce esophageal acid exposure:
• Eat small meals and avoid sleeping immediately after meals (sleep after 3
hours if possible; decreases gastric volume)
• Stop smoking (decreases spontaneous esophageal sphincter relaxation)
• Avoid alcohol (increases amplitude of the lower esophageal sphincter,
peristaltic waves, and frequency of contraction)
• Avoid tight-fitting clothes
• Always take drugs in the sitting upright or standing position and with plenty
of liquid, especially for those that have a direct irritant effect on the
esophageal mucosa (eg, bisphosphonates, tetracyclines, quinidine,
potassium chloride, iron salts, aspirin, nonsteroidal anti-inflammatory drugs)
Foods and Medications that May Worsen GERD Symptoms
Foods and Medications that May Worsen GERD Symptoms
Pharmacologic Therapy
 Patient directed therapy (Self-care)
• Appropriate for intermittent, mild pyrosis
• Using over-the-counter products such as antacids, OTC H2-receptor
antagonists, and OTC proton pump inhibitors (PPIs)
 Prescription-strength acid-suppression therapy or
promotility medications.
Pharmacologic Agents Used in the
Treatment of GERD – Table 32-3/5
 Antacids and alginic acid products
 H2-receptor antagonists (HRA)
 Proton pump inhibitors (PPIs)
 Promotility agents
PPIs - Drug-drug interaction
 Ketoconazole or itraconazole, which require an acidic
environment to be absorbed
• What happen when taken with PPIs?
 Omeprazole is the strongest inhibitor of CYP2C19
• Clopidogrel, a prodrug, is converted to its active metabolite via
the CYP2C19 and CYP3A4 enzymes
• Has the potential to inhibit the metabolism of warfarin,
diazepam, and phenytoin
 Lansoprazole may decrease theophylline concentration
PPIs - Pharmaceutical concerns
 Degrade in acidic environments: formulated in a delayed-release
capsule or tablet formulation or enteric-coated (pH-sensitive)
granules in a capsule form
 Dexlansoprazole capsule is a dual delayed-release formulation,
with the first release occurring 1 to 2 hours after the dose and the
second release occurring 4 to 5 hours after the dose
• to allow the medication to have a longer lasting benefit, at least 16 to 18
hours
 Patients taking pantoprazole or rabeprazole should be instructed
not to crush, chew, or split the delayed-release tablets
 How to administer to patients who are unable to swallow the
capsules?
PPIs - Patient counseling
 Patients should be instructed to take their proton pump
inhibitor in the morning, 30 to 60 minutes before breakfast
or before their biggest meal of the day, to maximize efficacy,
because these agents inhibit only actively secreting proton
pumps
• Dexlansoprazole can be taken without regards to meals
 If a second dose is needed, take prior to the evening meal
 Onset of relief is 2 to 3 hours and the duration of relief is 12
to 24 hours
Assignment
 Summarize the available pharmaceutical products in Taiwan as
shown in Table 32-3, including promobility agents
  Algorithm. Guidelines for the evaluation and
management of a patient who presents with
dyspeptic or ulcer-like symptoms.
• COX-2, cyclooxygenase-2;
• GERD, gastroesophageal reflux disease;
• H2 RA, H2-receptor antagonist;
• NSAID, nonsteroidal antiinflammatory drug;
• NUD, nonulcer dyspepsia;
• PPI, proton pump inhibitor

Source: Peptic Ulcer Disease and Related Disorders, Pharmacotherapy: A Pathophysiologic Approach, 10e
Citation: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A Pathophysiologic Approach, 10e; 2017 Available at:
http://accesspharmacy.mhmedical.com/ViewLarge.aspx?figid=146058991&gbosContainerID=0&gbosid=0 Accessed: September 14, 2017
Copyright © 2017 McGraw-Hill Education. All rights reserved
Pharmacologic Agents Used to Eradicate
Helicobacter pylori
 First-line therapy: PPI-based three-drug regimen for 14 days
 Second course: different antibiotics or a four-drug regimen with a bismuth
salt, metronidazole, tetracycline, and a PPI should be used
 Patients with NSAIDs induced ulcer - If H. pylori-negative, the NSAID should
be discontinued, and the patient treated with a PPI, H2RA, or sucralfate
 If NSAIDs is continued, co-therapy with a PPI or misoprostol or switching to a
selective COX-2 inhibitor (if available) is recommended for patients at risk of
developing an ulcer-related complication
 Table 33-8, 33-9
Treatment of Helicobacter pylori-Positive Ulcers
 Successful eradication depends on the drug regimen, resistance to
the antibiotics used, duration of therapy, medication adherence,
and genetic polymorphism
 Eradication (cure) rates of at least 80% based on intention-to-treat
analysis or at least 90% based on per-protocol analysis
 Should minimize the potential for antimicrobial resistance
 Antibiotics used in regimens: clarithromycin, amoxicillin,
metronidazole, and tetracycline
Factors that Predict Helicobacter pylori Eradication
Outcomes
 Factors that predict H. pylori eradication outcomes include antibiotic
resistance, poor medication adherence, short duration of therapy,
CagA status, high bacterial load, low intra-gastric pH, and genetic
polymorphism
 Medication adherence decreases with
• multiple medications,
• increased frequency of administration,
• intolerable adverse effects, and
• costly drug regimens
Factors that Predict Helicobacter pylori Eradication
Outcomes
 Common adverse effects
• Metronidazole and clarithromycin: include nausea, vomiting, abdominal pain,
diarrhea, and taste disturbances
• Metronidazole: a disulfiram-like reaction with alcohol
• Tetracycline: photosensitivity and should not be used in children because of
possible tooth discoloration.
• Bismuth salts may cause darkening of the stool and tongue.
• Antibiotic-associated diarrhea and Clostridium difficile–associated disease can
occur. Oral thrush and vaginal candidiasis may also occur
Treatment of Nonsteroidal Anti-Inflammatory
Drug-Induced Ulcers
 If the NSAID is stopped, most uncomplicated ulcers heal with
standard 4-week regimens of an H2RA, PPI, or sucralfate (Table 33-9)
• PPIs are usually preferred because they provide more rapid symptom relief
and ulcer healing
 If the NSAID is continued despite ulceration, consideration should be
given to reducing the NSAID dose, switching to acetaminophen or a
nonacetylated salicylate, or using a more selective COX-2 inhibitor
 PPIs are the drugs of choice when the NSAID is continued, as potent
acid suppression is required to accelerate ulcer healing
Strategies to Reduce the Risk of NSAID Ulcer and
GI Complications
 Medical co-therapy with either a PPI or misoprostol decreases ulcer risk
and GI complications in high-risk patients
 Use of a selective COX-2 inhibitor decreases risk of ulcers and upper GI
events
 The GI benefits must be balanced against the cardiovascular risks
associated with selective COX-2 inhibitor NSAIDs, nonselective NSAIDs,
and concomitant antiplatelet therapy
 Strategies aimed at reducing the topical irritant effects of nonselective
NSAIDs, for example, prodrugs, slow-release formulations, and enteric-
coated products, do not prevent ulcers or GI complications