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Management of GERD
1. Management of GERD:
A patient outcome/education-driven
session
Dalia A. Hamdy,
BPSc, MSc, PhD,
RP(ACP), MRSC
Nahla H. Kandil
BPSc, MSc, BCPS
2. Putting issues in perspective: why
are we here?
GERD (DH/NK-April 2015) 2
3. Learning Objectives
• Define GERD and recognize its triggers and pathophysiology
• Identify GERD symptoms and red flags
• Describe the non pharmacological treatment options for your patient
• Choose the most appropriate therapeutic agent for your patient
• Identify the possible drug-drug interactions
• Set the appropriate monitoring plan for your patient
GERD (DH/NK-April 2015) 3
4. Session outline
• GERD pathophysiology, triggers and exacerbating factors
• GERD goals of therapy
• GERD symptoms and red flags
• GERD non pharmacological treatment
• GERD therapy algorithms and drug interactions
GERD (DH/NK-April 2015) 4
5. References
1. Thomson P., Pham Q.D. Patient Self-Care. 2nd Edition. Canadian Pharmacists
Association; 2010. Chapter
2. Shaffer E.A. Therapeutic Choices. 6th Edition. Canadian Pharmacists Association; 2011.
Chapter 60
3. Kinnear M. Clinical Pharmacy and Therapeutics, 5th Edition. Elservier; 2012. Chapter
12.
4. Kaiser T.E. Gastrointestinal disorders. ACCP Updates in Therapeutics; 2014.
5. rxPassport. Antacids, H2RA or PPI? Am I Choosing the Best Option for my Patient?
Heartburn series; 2015
http://www.rxbriefcase.com/passportdefault.aspx
GERD (DH/NK-April 2015) 5
6. GERD: pathopysiology
• Gastroesophageal Reflux Disease
“Refers to troublesome symptoms (heart burn & regurgitation) and/or
complications that result from an excessive reflux of stomach contents into
esophagus”
Therapeutic Choices 2011
GERD (DH/NK-April 2015) 6
7. GERD: pathophysiology , triggers ad Exacerbating factors
1.Physiologic: -Transient relaxation of the lower esophageal sphincter (LES),
-hypotensive LES
-anatomic disruption of the junction; often caused by hiatal hernia
2. Drugs inducing LES relaxation : anticholinergics, aminophyllines, β-adrenergic agonists,
benzodiazepines, and nitroglycerines, B-blockers, -blockers, calcium channel blockers, narcotics,
nicotine, theophylline.
3. Life style: obesity, smoking, diet (fatty food, chocolate, coffee, alcohol, carbonated drinks)
4. Pregnancy
5. Stress and anxiety
6. Age >65 years
GERD (DH/NK-April 2015) 7
8. GERD: goals of therapy
• Relief symptoms & improve quality of life
• Promote healing of esophagitis
• Prevent complications
• Prevent recurrences
GERD (DH/NK-April 2015) 8
9. GERD: Visit your patient
• Mrs Hoda, a 75-year-old woman, showed up in your pharmacy. She is suffering from
heart burn and acidic taste. Two days ago, she had a coffee ground color vomit. Her
past medical history included osteoarthritis, gout, hypertension, and resting tremor
secondary to anxiety. She had no known drug allergies and was taking the following
prescription drugs:
GERD (DH/NK-April 2015) 9
Propranolol 40 mg tid prn
Indometacin 25 mg tid
Diclofenac 50 mg qd
Allopurinol 100 mg qd
Ramipril 10 mg qd
Simvastatin 40 mg qn
10. GERD: Questions for your patient
GERD (DH/NK-April 2015) 10Rxpassport, Heartburn series, 2015
11. GERD: Red Flags!
Alarming symptoms Description
Chest pain Resembling cardiac pain
Chocking Sensation of acid refluxing into the
windpipe causing shortness of breath,
coughing or hoarsness
Dysphagia Difficulty swallowing
GIT bleeding Vomiting blood or having tarry or black
bowl movement
odynophagia Pain upon swallowing
Unintentional weight
loss (>3kg in past 6
months)
Anemia
Persistent vomiting
Severe abdominal pain GERD (DH/NK-April 2015) 11
Therapeutic Choices . 2011
Patient Self-Care, 2010
12. GERD: non-pharmacological treatment
Life style modification:
Avoid foods that ppts events
Avoid lying down right after meals
Obtain ideal body weight
Reduce alcohol intake!
Reduce caffeine intake (2-3 cups/day)
Smaller more frequent meals
GERD (DH/NK-April 2015) 12
13. GERD: non-pharmacological treatment
II. Patient recommendations
Reassure patient about the benign nature of disease
Stress reduction
Avoid exercising or bending on full stomach
Avoid exacerbating foods
Avoid lying down after meals
Avoid tight fitting cloths around the waist
Raise head of bed around 10 cm
Limit nicotine consumption
Obtain ideal body weight
GERD (DH/NK-April 2015) 13
14. GERD: revisit your patient
Patient information:
Question is:
Guidelines and references states…………….
Patient recommendation is………………..
Monitoring plan is……………………
GERD (DH/NK-April 2015) 14
Assessment
Care Plan
Follow-up
evaluation
15. GERD: therapeutic algorithms
The choice of agent should be based on:
• Severity of GERD symptoms
• Impact of symptoms on the patient’s daily life
• Previous experience with GERD pharmacotherapy
• Current medications, adverse effects and potential drug interactions
• Cost
GERD (DH/NK-April 2015) 15
16. GERD: therapeutic algorithms
A 43-year-old man with type 2 diabetes mellitus and hypertension presents with a 6-
week history of intermittent regurgitation occurring about every other day and an
acidic taste in his mouth. He takes metoprolol 100 mg once daily and states that his
diabetes is controlled by diet. He avoids chocolate and spicy foods, sleeps with his head
elevated on a wedge pillow, and uses OTC famotidine 10 mg when symptoms intensify
and when he remembers. He admits that he rarely takes it before eating; instead, he
usually takes it only once the symptoms are present and do not dissipate. The
symptoms have been so significant that he has not slept and has missed 2 days of work
recently. Which is the best course of action to address his symptoms?
A. Administer metoclopramide 10 mg four times daily.
B. Administer esomeprazole 20 mg/day.
C. Continue famotidine 10 mg, but take on a scheduled frequency of three or four times
daily.
D. Continue famotidine, but increase dose to 20 mg, scheduled three or four times daily.
GERD (DH/NK-April 2015) 16
20. GERD: therapeutic algorithms
A 43-year-old man with type 2 diabetes mellitus and hypertension presents with a 6-
week history of intermittent regurgitation occurring about every other day and an
acidic taste in his mouth. He takes metoprolol 100 mg once daily and states that his
diabetes is controlled by diet. He avoids chocolate and spicy foods, sleeps with his head
elevated on a wedge pillow, and uses OTC famotidine 10 mg when symptoms intensify
and when he remembers. He admits that he rarely takes it before eating; instead, he
usually takes it only once the symptoms are present and do not dissipate. The
symptoms have been so significant that he has not slept and has missed 2 days of work
recently. Which is the best course of action to address his symptoms?
A. Administer metoclopramide 10 mg four times daily.
B. Administer esomeprazole 20 mg/day.
C. Continue famotidine 10 mg, but take on a scheduled frequency of three or four times
daily.
D. Continue famotidine, but increase dose to 20 mg, scheduled three or four times daily.
GERD (DH/NK-April 2015) 20
21. GERD: therapeutic algorithms
Prokinetics
• Prokinetics are not widely used to treat GERD because they are not
as effective as other treatments and are associated with numerous
side effects (sedation, anxiety, extrapyramidal symptoms, etc.).
• Prokinetics are reserved for patients who are refractory to other
available treatment options or who have delayed gastric emptying
GERD (DH/NK-April 2015) 21
22. Which of the following is inappropriate monotherapy
for mild, intermittent GERD?
1. Omeprazole
2. Metoclopramide
3. Famotidine
4. Calcium carbonate
GERD (DH/NK-April 2015) 22
GERD: therapeutic algorithms
24. • L.F. is a 48-year-old woman who presents to her primary-care
provider complaining of recurrent heartburn occurring daily
for the past 6 weeks. She states that the heartburn occurs
frequently after meals and often wakens her at night. Lately,
she has been experiencing difficulty swallowing solid foods.
L.F. currently smokes two packs of cigarettes per day and
likes to have two glasses of wine each night with her dinner.
She states that she occasionally uses OTC ranitidine 150 mg
orally up to twice daily, which temporarily relieves her
symptoms. Which medication do you suggest?
GERD (DH/NK-April 2015) 24
GERD: therapeutic algorithms
25. GERD: therapeutic algorithms
a) It should be taken 30 minutes prior to a meal
b) It takes 1-3 days for a clinical response
c) It is associated with a therapeutic effect that last for more than the
14 days of treatment
d) All of the above
GERD (DH/NK-April 2015) 25
Which of the following statements should be used when
counselling a patient taking non-prescription PPI therapy?
26. Maintenance Therapy
L.F.’s symptoms resolved in about 2 weeks after starting PPI therapy, and
she remained asymptomatic after 8 weeks. She then underwent
endoscopy, which revealed that the esophagus had healed completely.
Her primary-care physician then stopped the PPI.
• Now, 2 weeks later, she is experiencing mild heartburn. Is L.F. a
candidate for long-term maintenance therapy?
GERD (DH/NK-April 2015) 26
GERD: therapeutic algorithms
27. Stepping down treatment if patient responds
adequately
It includes:
1- Discontinuing PPI Therapy
2- Switching To Symptom-driven Therapy
3- Reducing dose of daily PPI
GERD (DH/NK-April 2015) 27
GERD: therapeutic algorithms
29. GERD: therapeutic algorithms
Key Points on Non-Prescription PPI
• Most patients will respond to PPI therapy within 1-3 days of treatment. Maximum acid
suppression with PPIs is seen after 3-5 days of treatment.
• Patients should be instructed to take their full course of therapy and to not discontinue it
when the symptoms start to improve.
• This medication is NOT recommended for PRN use like antacids or H2-receptor antagonists.
• It should not be taken more frequently than every 4 months
Bottom Line: A 14-day course of non-prescription omeprazole is the first-line treatment of
choice for patients with heartburn symptoms occurring on 2 or more days per week. This course
will most often resolve the condition.
GERD (DH/NK-April 2015) 29
30. GERD: therapeutic algorithms
Rebound Acid Secretion
• Antacids can be prescribed as “rescue” medication for rebound
acid secretion
• Medicines that contain both an antacid and an anti-foaming agent
are likely to be the most effective treatment for rebound acid
secretion.
GERD (DH/NK-April 2015) 30
31. • Rapidly neutralize esophageal acid within 15-30 minutes and will typically
provide modest relief for up to 90 minutes.
• Alginic acid does not neutralize acid but acts as a physical barrier.
Currently combined with an antacid, as it offers limited benefit when
administered alone.
• Generally well tolerated but can lead to constipation (calcium, aluminum) or
diarrhea (magnesium).
• Interact with many medications
• Caution in older patients and those with renal disease
• Alginic acid contains a large amount of sodium and could be an issue in
patients with congestive heart failure or renal disease
Bottom Line: Inexpensive and rapid relief. The major limitation is the short duration of action. Guidelines
recommend considering it for episodic (≤1 day/week) and/or mild symptoms.GERD (DH/NK-April 2015) 31
GERD: therapeutic algorithms
Key Points on Antacids
32. Which of the following disorders is an adverse
event associated with aluminum hydroxide?
1. Tinnitus
2. Diarrhea
3. Constipation
4. Hyperkalemia
GERD (DH/NK-April 2015) 32
GERD: therapeutic algorithms
33. Antacid component Adverse effects Drug interactions Notes
•Calcium salts
•Magnesium salts
•Aluminum salts
•Magnesium/aluminum
antacids
•Alginic acid
•Aluminum: Constipation
•Accumulation in patients
with renal failure
•Hypophosphatemia
•Calcium: Constipation
•Rebound hyperacidity
•Magnesium: Diarrhea
•Accumulation in patients
with renal impairment
•Magnesium/aluminum
comboMinor changes in
bowel habits
•Alginic AcidFlatulence,
belching
•Allopurinol
•Bisphosphonates
•Iron salts
•Quinolones
•Tetracyclines
•Digoxin
•Rosuvastatin
To minimize the
interaction with these
products patients
should separate
antacid dosing by 1-2
hours
•Dosing should be taken
within 20-60 minutes
and/or after a meal at
bedtime as needed
•Relieves symptoms but
unlikely to heal inflamed
esophagus
•Dosing for
magnesium/aluminum
antacids is 10-30 mL PC
and HS
GERD (DH/NK-April 2015) 33
34. W.J. is a 39-year-old, 130-kg, 170-cm-tall man who presents with
complaints of indigestion. He describes a burning sensation behind his
breastbone and some belching that is often associated with an acid taste
in the back of his mouth. He indicates that his symptoms began a few
months ago, and they only occur a few times a month, especially after
eating large or spicy meals. Also, if he eats too close to his bedtime, the
burning keeps him up at night. He has used liquid antacids in the past for
these symptoms and states they work fairly well, but he has to take
frequent doses, as the symptoms return quickly. He does not take any
other medications. Which medication do you suggest?
GERD (DH/NK-April 2015) 34
GERD: therapeutic algorithms
35. • Mild symptoms and occur infrequently, and no alarm
symptoms.
• To specifically “prevent” meal-related symptoms, he
should take an H2RA 30 to 60 minutes before eating or
drinking.
• If symptoms remain infrequent but are unrelated to meals,
the use of an OTC H2RA as needed for symptoms may be
required.
GERD (DH/NK-April 2015) 35
GERD: therapeutic algorithms
36. a) Famotidine is usually superior to ranitidine at equivalent doses
b) Tachyphylaxis commonly develops with these medications
c) They provide symptom relief in approximately 50% of patients
d) Most drug interactions with these medications are clinically
significant
GERD (DH/NK-April 2015) 36
You start to discuss H2-receptor antagonists with the
patient. Which one of the following statements is TRUE?
GERD: therapeutic algorithms
37. The H2RA associated with the most significant drug
interactions due to inhibition of CYP450 enzymes is
a) ranitidine
b) cimetidine
c) Nizatidine
d) famotidin
GERD (DH/NK-April 2015) 37
GERD: therapeutic algorithms
Drug Metabolism!!
Stay Tuned!
38. • Bind to the H2-receptors on the gastric parietal cells to reduce gastric acid secretion.
• They start to reduce gastric acid within 1 to 2 hours of dosing and the effects last up to 9 hours.
• In equivalent doses, ranitidine and famotidine are equally effective for mild symptoms but are
generally not effective for more frequent or severe symptoms.
• Provide complete symptom relief in only 15% of GERD patients.
• Tachyphylaxis (decrease in acid-lowering response over time) commonly develops and has
been reported within a few doses with these medications; this can limit their use beyond the on-
demand treatment of mild heartburn.
• H2RAs are generally very well tolerated and adverse effects are infrequent.
Bottom Line: Slower onset but longer duration of action compared to antacids. Guidelines recommend their use for mild
and episodic (≤1 episode per week) heartburn or occasional meal-provoked heartburn.GERD (DH/NK-April 2015) 38
GERD: therapeutic algorithms
Key Points on H2 Receptor Antagonists
39. BACK TO PPIs!
The pharmacology of
proton pump inhibitors
GERD (DH/NK-April 2015) 39
GERD: therapeutic algorithms
40. • The gastrointestinal adverse effects of PPIs can be mistaken for
symptoms of GORD, sometimes resulting in increased doses of PPI
being prescribed.
GERD (DH/NK-April 2015) 40
PPIs
Adverse Effects
GERD: therapeutic algorithms
41. Which adverse event can occur in a patient receiving
chronic PPI therapy?
1. Gynecomastia
2. Increased infection risk
3. Extrapyramidal side effects
4. Altered calcium and vitamin D levels
GERD (DH/NK-April 2015) 41
GERD: therapeutic algorithms
42. Adverse effects due to chronic use
• May 2010 - Decreased calcium absorption, leading to increased risk
of fracture
• March 2011- may cause low hypomagnesium if taken for prolonged
periods (in most cases, greater than 1 year).
• Gastric acid suppression with PPIs increases the risk of infection
with gastrointestinal (C.difficile) or respiratory pathogens,
although the absolute risk to most patients remains low.
GERD (DH/NK-April 2015) 42
GERD: therapeutic algorithms
43. GERD: therapeutic algorithms
PPI-Drug interactions
GERD (DH/NK-April 2015) 43
Drug Metabolism
Phase 1: Functionalization reactions
(introduction of a functional group)
Phase 2: Conjugative reactions
(Conjugation with endogenous compounds)
Drug
AND /OR
44. PPI-Drug interactions
Phase 1 metabolism
By introducing or unmasking more polar
a functional group
more readily eliminated
GERD (DH/NK-April 2015) 44
Chemical reactions
Oxidation
Reduction
Hydrolysis
Hydration
Isomerization
Dethioacetylation
GERD: therapeutic algorithms
45. PPI-Drug interactions
Phase 2 metabolism
By conjugation with an more polar and water soluble
endogenous substance
more readily excretable in
urine or bile
GERD (DH/NK-April 2015) 45
Chemical reactions
Glucuronidation/glycosidation
Sulfation
Methylation
Acetylation
Amino acid conjugation
Fatty acid conjugation
GERD: therapeutic algorithms
46. PPI-Drug interactions
PPI’s
Omeprazole
Esomeprazole
Lansoprazole
Pantoprazole (Na or Mg)
Rabeprazole
GERD (DH/NK-April 2015) 46
GERD: therapeutic algorithms
All metabolized by CYP P450, 2C19 and 3A
Possibility of drug-drug interactions
Pantoprazole lower affinity to CYP P450 enzyme
system + mostly sulfation
Rabeprazole metabolized through non enzymatic
pathways
Less drug interactions possibilities
Clinical Pharmacy and Therapeutics 2012
47. PPI-Drug interactions
PPI’s
Omeprazole
Esomeprazole
Lansoprazole
Pantoprazole (Na or Mg)
Rabeprazole
GERD (DH/NK-April 2015) 47
GERD: therapeutic algorithms
Inhibition of CYP2C9 and CYP2C19
D-D interactions possibility with (Monitoring, sp. With >20 mg/day dose)
Phenytoin (2C9) diazepam (2C19)
S-Warfarin (2C9) R-Warfarin (2C19)
Weak Induction of CYP1A2
D-D interactions possibility with (Monitoring) Theophylline
Clinical Pharmacy and Therapeutics 2012
48. Interaction with clopidogrel
• While there was evidence that PPIs may affect clopidogrel activity ex
vivo, the available evidence suggested that this would not translate to
clinically significant adverse outcomes.
• However, if considering prescribing a PPI at the same time as
clopidogrel then pantoprazole is the recommended choice.
Pantoprazole is known to have less of an inhibitory effect on the
CYP2C19 enzyme compared with omeprazole or lansoprazole.
GERD (DH/NK-April 2015) 48
GERD: therapeutic algorithms
49. GERD: Visit your patient
• Mr. Hassan, a 45-year-old man, showed up in your pharmacy. His past medical history
included hypertension and . One week ago, he suffered from heart burn and acidic
taste and was prescribed omeprazole to alleviate this symptom and was asked to
decrease smoking and coffee intake. Yesterday he noticed bruising in his leg and arm.
He is coming to ask for heamoclare and wondering if there is better suggested brand.
He had no known drug allergies and was taking the following prescription drugs:
GERD (DH/NK-April 2015) 49
Omeprazole 40 mg qd
Ibuprofen 400 mg prn
Warfarin
Ramipril 10 mg qd
50. GERD: revisit your patient
Patient information:
Question is:
Guidelines and references states…………….
Patient recommendation is………………..
Monitoring plan is……………………
GERD (DH/NK-April 2015) 50
Assessment
Care Plan
Follow-up
evaluation
54. Calcium carbonate
Aluminium hydroxide
Magnesium hydroxide
Sodium bicarbonate
GERD (DH/NK-April 2015) 54
Which of these antacids is available as a combination
product with a proton pump inhibitor (PPI)?
GERD: therapeutic algorithms
55. Use a combination or not?
GERD (DH/NK-April 2015) 55
GERD: therapeutic algorithms
56. What is the drug of choice for GERD during pregnancy?
• Between 30 – 50% of pregnant women experience symptoms of
GORD and this is considered a normal part of pregnancy
• Antacids > ranitidine >PPIs
GERD (DH/NK-April 2015) 56
GERD: therapeutic algorithms
57. Gastroprotective Therapy
A 67-year-old woman with rheumatoid arthritis is taking naproxen
500 mg by mouth daily, metoprolol 25 mg by mouth twice daily,
aspirin 81 mg by mouth once daily, and alendronate 70 mcg by
mouth weekly.
• Which gastroprotective therapy is best to recommend?
A. Lansoprazole 30 mg daily.
B. No gastroprotective therapy necessary.
C. Misoprostol 200 mcg twice daily.
D. Esomeprazole 40 mg twice daily.
GERD (DH/NK-April 2015) 57
GERD: therapeutic algorithms
59. SUMMARY! Monitoring Plans!
GERD (DH/NK-April 2015) 59
Your symptoms should not require more than 2 weeks of continuous
medication every 6 months
See your doctor if
- Red Flags
- symptoms persist after treatment
- any side effects of the monitored drugs
Fatty food: delays gastric emptying
chocolate, coffee, alcohol : reduce LED tone
Carbonated drink: gastric distention
qn every night
Chocking,
new feeling of shortness of breath or chronic tiredness
1. Answer: B
The patient’s symptoms are consistent with troublesome
GERD; on-demand therapy and lifestyle modifications
have not been effective. Empiric standard-dose PPI
is first-line therapy. Answer A, motility agent, is
incorrect because it is not first line. Answer B is correct;
esomeprazole is a PPI, and 20 mg is the standard dose.
Prescribing frequency is once daily. Answer C is
incorrect; although scheduling famotidine is a better
option than the patient’s current therapy, it is not first
line for troublesome GERD symptoms. Answer D is
incorrect; although increasing and scheduling famotidine
is a better option than the patient’s current therapy, it is
not first line for troublesome GERD symptoms.
Patients that experience the occasional meal-provoked GERD symptoms should avoid the food that causes the symptoms or consider taking an H2RA prior to consuming the food that causes the symptoms
Lifestyle modifications, with or without OTC antacids or H2RAs, are not effective for the management of frequent (≥ 2 times per week) or severe GERD symptoms.3 Prior to the release of BTC proton pump inhibitor (PPI) therapy, patients with more severe GERD symptoms had to be referred to a physician for a prescription PPI.
Omeprazole 20 mg has been approved for the treatment of frequent heartburn.26 Frequent heartburn is heartburn that occurs two or more days per week. Omeprazole is not indicated for patients with infrequent heartburn (≤ 1 episode per week) or for immediate relief of heartburn.
Neither the step-up nor the step-down approach has superior efficacy over the other. The clinician should determine the most appropriate approach for the individual patient. Every attempt should be made to aggressively control symptoms and to prevent relapses early in the course of the patient’s disease in order to prevent the complications. For patients with moderate to severe GERD, especially those with erosive disease, starting with a proton pump inhibitor as initial therapy is advocated because of its superior efficacy over H2-receptor antagonists
1. Answer: B
The patient’s symptoms are consistent with troublesome
GERD; on-demand therapy and lifestyle modifications
have not been effective. Empiric standard-dose PPI
is first-line therapy. Answer A, motility agent, is
incorrect because it is not first line. Answer B is correct;
esomeprazole is a PPI, and 20 mg is the standard dose.
Prescribing frequency is once daily. Answer C is
incorrect; although scheduling famotidine is a better
option than the patient’s current therapy, it is not first
line for troublesome GERD symptoms. Answer D is
incorrect; although increasing and scheduling famotidine
is a better option than the patient’s current therapy, it is
not first line for troublesome GERD symptoms.
Promotility agents are not as effective as acid-suppression agents. Combining promotility agents with acid-suppression drugs offers only modest improvements in symptoms over standard doses of H2-receptor antagonists and should not be routinely recommended. In addition, the availability of a promotility agent that has an acceptable adverse-effect profile is lacking. Mucosal protectants, such as sucralfate, have a limited role in the treatment of GERD
Handbook of non-prescription drugs – 16th edition
A reasonable option for L.F. would be lansoprazole 30 mg daily to be taken 30 to 60 minutes before breakfast each morning for the next 8 weeks; however, if the cost of therapy is an issue, generic omeprazole 40 mg daily would also be an acceptable alternative. L.F. should
also be counseled regarding lifestyle and dietary modifications, including smoking cessation and abstinence from alcohol. She should avoid eating large meals before bedtime and may wish to elevate the head of her bed by 6 to 8 inches with wooden blocks
These potent inhibitors of gastric acid are indicated for use in patients with frequent heartburn (2 or more days a week).
The onset of symptom relief is slower (2 to 3 hours) than with H RAs, and complete relief may require up to 4 days after initiating therapy.
PPIs are superior to HRAs with regard to symptom relief and duration of acid suppression.
Patients should take the OTC PPIs 30 to 60 minutes before a meal (breakfast is preferable) and not take more than one dose daily for up to 2 weeks.
GERD is chronic disease. Up to 80% of patients with severe esophagitis and 15% to 30% with less severe disease have a symptomatic
relapse within 6 months after discontinuing treatment.
The goal of maintenance therapy is to keep the patient symptom free and prevent potentially life-threatening complications. Continuous
maintenance therapy with a daily PPI is more effective than an HRA, with reported relapse rates of 25% and 50%, respectively.
Thus, PPIs are the drugs of choice for maintaining remission in patients with healed esophagitis. An H RA may be considered for patients with mild nonerosive disease. Although one-half of the PPI dose used for esophageal healing has been suggested, guidelines indicate that the recommended maintenance dose should be the dose that is required to render the patient asymptomatic.
Maintenance therapy, to reduce the risk of morbidity associated with chronic, relapsing disease, should be initiated with lansoprazole 15 mg to 30 mg once daily given the severity of L.F.’s esophagitis and symptomatic recurrence after discontinuing the PPI.
PPIs should be used at the lowest effective dose for the shortest possible time. “As needed” use, rather than a regular daily dose, may be appropriate for some patients. Patients should be warned that rebound acid secretion often occurs following withdrawal of treatment, even after periods as short as four weeks. Many patients will be able to manage symptoms during this withdrawal period with alternative medicines, such as antacids.
Many patients will experience reflux symptoms after PPIs are withdrawn, due to rebound acid secretion. This can be indistinguishable from ongoing symptoms of GORD. Patients can be prescribed “rescue” medication to help them manage symptoms that may arise after stopping the PPI. If symptoms are unable to be managed, or continue for longer than one or two weeks, reconsider the decision to withdraw the PPI.
Antacids remain an effective option for treating mild, infrequent heartburn, as they rapidly (within minutes) relieve symptoms, but the duration of symptom relief only lasts about 30 minutes when taken on an empty stomach.
The duration can be extended for several hours if taken within 1 hour after a meal.
Antacids are available in tablet and liquid form and are usually interchangeable when used in recommended dosages.
The dose can be repeated every 1 to 2 hours as needed, but the maximum recommended daily dose should not be exceeded. The addition of alginic acid to the antacid may improve symptom relief for some patients.
Patients requiring frequent or regular antacid use for more than 2 weeks should be reevaluated, as an OTC H2 RA or PPI may be needed.
Another Antacids are most commonly used to temporarily relieve heartburn.10 They work within the esophageal lumen to rapidly elevate esophageal pH and neutralize esophageal acid within 15-30 minutes and will typically provide modest relief for up to 90 minutes.10
Alginic acid does not neutralize gastric acids, but it reacts with sodium bicarbonate in saliva to form sodium alginate.27 This floats on the stomach contents where it acts as a mechanical barrier for the exposure of the esophagus to the gastric contents.27 Alginic acid administered alone will offer limited benefit.12
Although these products are inexpensive and offer rapid relief of individual heartburn episodes, the major drawback is their brief duration of action.10 There are very few well-designed clinical trials that asses the efficacy of antacids.10
Antacid associated adverse effects include diarrhea (magnesium-containing products), constipation (aluminum and calcium-containing products), belching and flatulence.22 Pharmacists should be aware of potential drug interactions with antacids. Many of these drug interactions can be avoided by not taking antacids in close proximity to other medications.22 Antacids should be used with caution in patients with reduced renal function as they could lead to hypermagnesemia or hyperaluminemia.5 Alginic acid containing products commonly contain a significant amount of sodium and this could be an issue in patients on reduced sodium diets (e.g. patients with congestive heart failure or renal dysfunction).
Counsel patients to chew any antacid tablets versus swallowing them whole. Chewing increases saliva which increases their ability to neutralize stomach acid. Refrigeration of liquid antacids may aid in palatability. Chewable tablets may be more effective than liquids because of increased adherence of antacid and saliva to the distal esophagus. Antacids must be taken at least 2 hours apart from tetracyclines, iron, and digoxin. Antacids and quinolones should be taken 4-6 hours apart.
Alginic acid is effective for the relief of GERD symptoms, but no data indicate esophageal healing on endoscopy. Alginic acid is ineffective if the patient is in the supine position and must not be taken at bedtime
Nighttime acid suppression may not be maintained.
W.J. is an appropriate candidate for self-treatment because his symptoms are mild and occur infrequently, and he has no alarm symptoms. Although antacids are an acceptable option for W.J., he has tried these and is unhappy with the frequency of dosing needed to relieve his heartburn. Because W.J. has requested a medication to specifically “prevent” meal-related symptoms, he should take an HRA 30 to 60 minutes before eating or drinking.
If symptoms remain infrequent but are unrelated to meals, the use of an OTC H2RA as needed for symptoms may be required.
He can increase the dose to twice daily if symptom relief is not optimal and may consider an OTC PPI if symptoms occur more 2 than 2 days a week. If he continues to have symptoms beyond 2 weeks, the symptoms become more severe, or they are accompanied by alarm symptoms, he should be referred for further evaluation.
H2-receptor antagonists in divided doses are effective for patients with milder GERD symptoms. Standard H2-receptor antagonist doses may be increased to two to four times the normal dose for patients who do not respond to standard doses. However, if this is necessary, it is more cost-effective and efficacious to switch to a proton pump inhibitor.
The OTC HRAs are indicated for mild to moderate infrequent GERD symptoms.
When compared with antacids their onset of symptom relief occurs within 30 to 45 minutes and they have a longer duration of action (up to 10 hours).
One benefit of the H RAs is that they can be taken before eating a heavy or spicy meal as prophylaxis for postprandial GERD symptoms. They also have a beneficial effect on reducing nocturnal acid secretion.
Tachyphylaxis (tolerance) has been reported with continued use of HRAs, but this effect can be overcome with intermittent or as-needed use.
OTC HRAs arailable in one-half the original prescription low dose and as the full prescription doses. Patients should use the lower OTC
dose twice daily for mild, intermittent symptoms and the higher dose twice daily for moderate symptoms (Table 27-1). The four OTC HRAs (cimetidine, famotidine, ranitidine, nizatidine) are interchangeable when used in recommended dosages.
Patients should avoid cimetidine if the potential for a clinically important drug interaction exists with drugs metabolized by the hepatic
CYP450 enzyme system. When used for self-treatment, the HRA dose should not exceed two doses per day, and the treatment duration should not exceed 2 weeks. Use beyond 2 week should be under the care of a health care provider.
Add-on therapy for those with incomplete PPI therapy response; use as on-demand therapy for intermittent symptoms that may be provoked by food consumption or exercise and/or at bedtime. Effective for these symptoms because of OTC availability and quick onset oaction (peak in 1–2 hours)
Cimetidine
The more recently developed H2RAs are less likely to alter CYP metabolism, with ranitidine being a lesspotent inhibitor than cimetidine and famotidine; therefore, clinically significant problems are seldom encountered.
PPIs are prodrugs, i.e. they are inactive when administered and undergo conversion to an active form in vivo.6 PPIs are acid labile and are therefore formulated with an enteric coating to protect them from degradation in the acidic environment of the stomach. Once they have passed through the stomach and the enteric coating has dissolved in the small intestine, PPIs are absorbed into the blood where they have a relatively short plasma half-life of 1 – 1.5 hours.1 The effect of PPIs extends well beyond this half-life, because the active metabolite binds irreversibly to the H+/K+-ATPase proton pump of parietal cells. This prevents the transport of acidic hydrogen ions into the gut lumen for 10 – 14 hours.6 The acid-suppressing effect of PPIs takes at least five days to reach a maximal effect.1 However, this effect is not absolute; even at high doses approximately one-quarter of proton pumps in each parietal cell will remain active.6
Gastrin is the hormone that stimulates parietal cells to release gastric acid. When PPI inhibition of gastric acid production occurs, gastrin release is increased to compensate for the decreased acidity of the stomach. Recently, several studies have suggested that when PPIs are withdrawn the body will continue to produce gastrin at above pre-treatment levels, causing an effect referred to as rebound acid secretion
Less frequently, PPI use is associated with dry mouth, peripheral oedema, dizziness, sleep disturbances, fatigue, paraesthesia, arthalgia, myalgia, rash, pruritus and interstitial nephritis
Hypomagensemia is very rare, in case reports or case series only, most likely occurs in patients already at risk eg those taking diuretics for heart failure
According to current guidelines, there is insufficient evidence to recommend bone density screening or calcium supplementation for patients on PPI therapy. Osteoporotic patients may remain on PPI therapy.
An increased risk of osteoporosis should be considered in post-menopausal females who are taking PPIs long-term, especially if they have other risk factors, e.g. a family history of osteoporosis or long-term corticosteroid use. Stepping down PPI treatment to the lowest effective dose, or prescribing “as needed” treatment, if appropriate, may reduce this risk
Hypomagnesium: Low magnesium levels, leading to increased risk of hypomagnesia.
March 2011: FDA drug safety communication that prescription PPI drugs may cause low serum magnesium levels (hypomagnesium) if taken for prolonged periods (in most cases, greater than 1 year). According to the report, in about one-fourth of the cases reviewed, supplemental magnesium alone did not correct the hypomagnesium, and the PPI had to be discontinued.
Routine testing of magnesium levels in patients taking PPIs is generally not recommended. However, if a patient has been taking a PPI long-term and they present with unexplained symptoms that are consistent with hypomagnesaemia, consider requesting a serum magnesium level. Increased dietary intake of magnesium rich foods, e.g. nuts, spinach or wheat, or magnesium supplementation may be sufficient to improve serum magnesium levels while continuing the PPI. For some patients the PPI will need to be stopped; if the indication for using the PPI is strong, a re-challenge while monitoring magnesium can be undertaken
Gastric acid suppression with PPIs increases the risk of infection with gastrointestinal or respiratory pathogens, although the absolute risk to most patients remains low. The higher risk is thought to be due to a reduction in the effectiveness of the “acid wall” stomach barrier. This allows viable pathogens to travel up or down the gastrointestinal tract and also colonise the lower airways.
Where possible, consider delaying the initiation of PPIs in patients with an increased risk of infection, e.g. an older patient with a family member who has influenza, patients who are taking antibiotics or travelling to countries where there is a high risk of enteric infection.
Reports show an increased risk of community-acquired pneumonia with short-term PPI
use; however, guidelines recommend that PPI therapy not be withheld because of this
potential risk.
Potential for reduced effectiveness when administered with PPI because of
CYP2C19-mediated inhibition of conversion of clopidogrel to its active metabolite.
Pharmacokinetic and pharmacodynamic data suggest varying degrees of CYP2C19
inhibition among PPIs; to date, there is no evidence that these differences translate
into differences in clinical outcomes.
(2) In 2009, the U.S. Food and Drug Administration (FDA) issued a warning suggesting that
clopidogrel in combination with omeprazole, esomeprazole, or lansoprazole be avoided
because of the potential for increased adverse cardiovascular (CV) events (www.fda.
gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/
ucm190848.ht m).
(3) Findings from studies are inconsistent. Spacing the timing of administering the
two dr ugs to minimize interaction has been proposed; however, further studies are
necessary, and this is not recommended at this time.
(4) Because of the lack of clinical trial data supporting an increased risk of CV events,
the current guidelines do not recommend altering PPI therapy when clopidogrel is
used concomitantly.
qn every night
Traditional, delayed-release PPIs administer 30–60 minutes before the first meal of the
day because the availability of H-K-ATPase (proton pump) is greatest after a prolonged
fast. During a meal, not all parietal cells are active; thus, administering PPIs during
this time correlates with suboptimal outcomes. Exceptions may be dexlansoprazole and
omeprazole-sodium-bicarbonate (see Table 2).
(1) Dexlansoprazole: Dual delayed release; independent of food intake and may be
dosed any time of the day
(2) Omeprazole-sodium-bicarbonate: Immediate release; effective to control
nocturnal symptoms when administered at bedtime
If antacids are being used to control breakthrough symptoms, the dose should be taken no less than 1-2 hours before or after an H2RA is taken. H2RAs may be taken without regard to meals
Combination of a Proton-Pump Inhibitor and Histamine-2 Receptor Antagonists
The addition of an H RA at bedtime to a once or twice daily PPI regimen is sometimes used for patients who continue to have nocturnal symptoms, although the evidence to support this combination remains inconclusive and current guidelines do not endorse this type of antisecretory management strategy at this time.
It has been theorized that one way to possibly avoid this occurrence is to use the H RA on only an as-needed basis when lifestyle and dietary modifications are not effective for preventing nocturnal symptoms.
PPIs may be administered with H2RAs when the time interval between doses is sufficient. Exact interval is unknown but recommended if PPI taken early in the day before first meal; H2RAs may be taken in the evening before bedtime (for nocturnal breakthrough symptoms); however, no evidence supporting efficacy
PPIs are not known to be associated with an increased risk of foetal malformations in humans (Pregnancy Risk Category B3).4 PPIs are therefore considered safe to use during pregnancy, however, other medicines should be used where possible. A reasonable approach for pregnant women who require acid suppressive medication is to trial antacids (e.g. calcium carbonate, alginate formulations) or ranitidine (Pregnancy Risk Category B1) first and if these medicines are not effective, consider prescribing a PPI.
2. Answer: A
Preventive therapy should be selected according to a
combined assessment of GI and CV risk. To calculate the
GI risk, risk factors should be assessed and tabulated. (e.g.,
no risk factors: low risk; one or two risk factors: moderate
risk; three or more risk factors or having a previous
ulcer complication or concomitant use of corticosteroids
or anticoagulants: high risk). For this case, the patient
has two GI risk factors (e.g., age older than 65 years and
aspirin therapy) and is thus categorized as moderate GI
risk. Cardiovascular risk is defined as either low or high.
This patient has high CV risk because of taking low-dose
aspirin. Preventive therapy should be selected for someone
with moderate GI/high CV risk. Therapy options include
naproxen plus PPI (or misoprostol). Answer A is correct;
PPI is a recommended therapy. Answer B is incorrect; from
the GI and CV risk assessment, gastroprotective therapy is
recommended. Answer C is incorrect; although misoprostol
is an approved therapy for moderate GI/high CV risk,
the dose indicated is low, which may reduce misoprostol
adverse events. In addition, it is not dosed often enough. The
recommended dose is 800 mcg four times daily. Answer D
is incorrect; standard-dose PPI is recommended therapy,
which is once daily, not twice daily.