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PHAR 255 > Dypepsia and GERD > Flashcards

Dypepsia and GERD Flashcards

1
Q

What is dyspepsia (3)

A
  1. Epigastric pain or discomfort originating from upper GI tract
  2. An umbrella term to describe many possible symptoms and causes
  3. Termed functional dyspepsia if no abnormalities found
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2
Q

What is GERD? (2)

A
  1. Reflux of gastric contents into the esophagus
  2. Described as heartburn
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3
Q

What is PUD? (2)

A
  1. An ulcer formed in the gastric or duodenal mucosa
  2. May have symptoms similar to dyspepsia / GERD
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4
Q

Functional dyspepsia has many potential mechanisms. List them (6)

A
  1. Gastric motility and compliance
  2. Visceral hypersensitivity
  3. Helicobacter pylori infection
  4. Altered gut microbiome
  5. Duodenal inflammation
  6. Psychosocial dysfunction
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5
Q

What are some risk factors for dyspepsia? (7)

A
  1. No strong association with sex, age, socioeconomic status
  2. Dietary indiscretion
  3. Medications
  4. H. pylori infection
  5. Anxiety
  6. Irritable bowel syndrome
  7. ?Smoking or alcohol use
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6
Q

There are many drugs that can induce dyspepsia. What are the 4 most important ones to know?

A
  1. Bisphosphonates
  2. Iron
  3. NSAIDs
  4. Potassium
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7
Q

There are many symptoms that qualify as dyspepsia. What are the 2 most important ones to know?

A
  1. Epigastric pain or discomfort
  2. Fullness or early satiety
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8
Q

How long do dyspepsia symptoms typically last. How do they present?

A
  1. > 1 month duration of symptoms
  2. Often follows relapsing - remitting course
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9
Q

The main alarming symptoms (red flags) of dyspepsia are? (Remember VBAD!)

A

Vomiting
Bleeding/anemia
Abdominal mass or unexplained weight loss
Dysphagia (difficulty swallowing) or odynophagia (painful swallowing)

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10
Q

Should know the steps of the systematic approach in patients with dyspepsia (6)

A
  1. Other possible causes?
    - Abdominal or pancreatic cancer, for example
  2. Upper GI location?
  3. New onset symptoms (other than reflux/heartburn) > 50 (++ > 60) or red flag symptoms?
  4. NSAID use?
  5. Reflux or regurgitation as main symptom?
  6. H. pylori present?
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11
Q

What are 6 potential causes of GERD?

A
  1. Defective lower esophageal sphincter
  2. Increased intra-abdominal pressure
  3. Hiatal hernia
  4. Impaired esophageal peristalsis
  5. Delayed gastric emptying
  6. Excessive gastric acid production
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12
Q

Risk factors for developing GERD include: (9)

A
  1. Obesity
  2. Pregnancy
  3. Family history
  4. Smoking
  5. Increased age (>65)
  6. Hiatal hernia
  7. Stress and anxiety
  8. Medications
  9. Diet
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13
Q

There are many drugs that can induce GERD. What are the 3 most important ones to know?

A
  1. Anticholinergics
  2. Benzodiazepines
  3. Opioids
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14
Q

Dietary contributors to GERD include: (7)

A
  1. Over-eating*
  2. Fatty foods
  3. Chocolate
  4. Coffee
  5. Alcohol
  6. Carbonated drinks
  7. Acidic juices
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15
Q

The primary symptoms of GERD are heartburn and regurgitation, but what are some other findings? (3)

A
  1. Belching
  2. Hypersalivation (water brash)
  3. Non-cardiac chest pain
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16
Q

What are some atypical extra-esophageal symptoms that may be present with GERD? (6)

A
  1. Chronic cough
  2. Throat clearing
  3. Shortness of breath or wheezing
  4. Laryngitis
  5. Oropharyngeal symptoms
  6. Dental erosions
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17
Q

Classification of GERD:
Mild vs. Moderate to Severe
What is the difference in terms of intensity?

A

Mild = low
Moderate to severe = high

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18
Q

Classification of GERD:
Mild vs. Moderate to Severe
Interference with daily activities?

A

Mild = no
Moderate to severe = yes

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19
Q

Classification of GERD:
Mild vs. Moderate to Severe
Frequency?

A

Mild < 3/week
Moderate to severe ≥ 3/week

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20
Q

Classification of GERD:
Mild vs. Moderate to Severe
Duration?

A

Mild = < 6 months
Moderate to severe = ≥ 6 months

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21
Q

Classification of GERD:
Mild vs. Moderate to Severe
Nocturnal symptoms?

A

Mild = no
Moderate to severe = yes

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22
Q

Classification of GERD:
Mild vs. Moderate to Severe
Complications?

A

Mild = no
Moderate to severe = yes

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23
Q

GERD can be further classified into what 2 types?

A
  1. Non-erosive reflux disease - less severe
  2. Erosive esophagitis - more severe, mucosal damage
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24
Q

Potential complications of GERD inlcude: (5)

A
  1. Esophagitis
  2. Esophageal stricture
  3. Esophageal erosions
  4. Barrett’s esophagus
  5. Esophageal cancer
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25
Q

Red flags for physician referral for GERD includes: (VBAD +2)

A
  1. Vomiting
  2. Bleeding/anemia
  3. Abdominal mass or unexplained weight loss
  4. Dysphagia (difficulty swallowing) or odynophagia (painful swallowing)
  5. Choking
  6. Constant pain
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26
Q

How is GERD typically diagnosed? (3)

A
  1. Diagnosis made based on symptoms after ruling out other causes
  2. Those with typical symptoms do not require invasive testing
  3. Trial course of pharmacologic therapy is a useful diagnostic tool
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27
Q

When diagnosing GERD, upper endoscopy is not typically required. Who are some candidates who would require it though? (4)

A
  1. New onset symptoms (other than reflux/heartburn) >50 (>60) or red flag symptoms
  2. Any alarm features
  3. Refractory GERD
  4. At risk for Barrett’s esophagus
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28
Q

Other diagnostic tests for GERD include: (3)

A
  1. Barium swallow
  2. Esophageal manometry
  3. Ambulatory esophageal pH monitoring
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29
Q

What are the goals of therapy for GERD? (5)

A
  1. Relieve symptoms
  2. Promote healing of injured mucosa
  3. Prevent and treat complications
  4. Prevent recurrence
  5. Avoid issues with long-term use of pharmacotherapy
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30
Q

Non-pharmacologic treatment should be considered in all GERD patients. What are the 3 most important lifestyle changes that may demonstrate benefit?

A
  1. Lose and maintain ideal weight
  2. Stop smoking
  3. Elevate head of bed
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31
Q

As-needed or on-demand pharmacologic treatment of GERD includes what 4 drug classes?

A
  1. Alginates
  2. Antacids
  3. Histamine 2 Receptor Antagonists (H2RAs)
  4. Proton-pump inhibitors (PPIs)
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32
Q

What are 2 pharmacologic adjunct treatments of GERD?

A
  1. Domperidone
  2. Metoclopramide
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33
Q

What is THE alginate medication used for GERD?

A

Sodium alginate

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34
Q

What is the indication for sodium alginate use?
How about CIs?
Side effects (3)?

A
  1. Mild, intermittent, post-prandial GERD
  2. No CIs
  3. Bloating, flatulence, belching
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35
Q

What is the MOA of sodium alginate?

A

Forms a viscous “raft” that floats within the stomach (not proven)

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36
Q

What is the administration of sodium alginate?
What is the onset and duration of action?

A
  1. Taken ~1 hour after eating
  2. Rapid onset and short duration < 1 hour
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37
Q

What are the 6 antacid medications?

A
  1. Aluminum hydroxide
  2. Magnesium hydroxide
  3. Magnesium trisilicate
  4. Calcium carbonate
  5. Sodium bicarbonate
  6. Combination of above
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38
Q

What is the indication for antacids?

A

Mild, infrequent, post-prandial GERD

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39
Q

What is the CI for antacids?

A

Avoid in severe renal impairment
- Unless dialysis - Ca carbonate for phosphate binding

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40
Q

What is the MOA of antacids? (3)

A
  1. Neutralizes stomach acid
  2. Inhibits pepsin generation
  3. Binds to bile acids
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41
Q

What is the onset and duration of action of antacids? (i.e., how fast until they work and for how long?)

A
  1. Rapid acting
  2. Short duration of action
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42
Q

What is the dosing and administration of antacids? (2)

A
  1. Chew 2-4 tablets up to QID (max 8-16 tablets)
  2. 30-60 minutes after a meal and/or at bedtime
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43
Q

What is the total dose of a calcium carbonate tablet? How much of that is elemental?

A

Total dose = 400-1000mg
Elemental = 160-400mg

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44
Q

What is the total dose of an aluminum hydroxide tablet? How much of that is elemental?

A

Total dose = 80-200mg
Elemental = 28-70mg

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45
Q

What is the total dose of a magnesium hydroxide tablet? How much of that is elemental?

A

Total dose = 100-300mg
Elemental = 40-120mg

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46
Q

What are the common side effects of the following antacids:
Aluminum
Magnesium
Calcium

A

Aluminum - constipating
Magnesium - laxative effect
Calcium - well tolerated

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47
Q

What are the serious side effects of the following antacids:
Aluminum (3)
Magnesium
Calcium (2)

A

Aluminum - bone demineralization, neurotoxicity, hypophosphatemia
Magnesium - hypermagnesemia
Calcium - hypercalcemia, alkalosis

48
Q

Antacids have many DIs resulting in chelation. List a few of these drugs (8)

A
  1. Tetracyclines
  2. Fluoroquinolones
  3. Iron
  4. Bisphosphonates
  5. Digoxin
  6. Phenytoin
  7. Levothyroxine
  8. Sotalol
49
Q

Antacids have a few drug interactions in which the antacid impairs absorption of pH sensitive drugs. What are some examples? (5)

A
  1. Dabigatran
  2. Many HIV meds
  3. Fosinopril
  4. Ketoconazole
  5. 5-ASA products
50
Q

What does data show about efficacy of antacids in GERD? (4)

A
  1. Limited evidence
  2. Slight reduction in symptom severity and frequency
  3. Better than placebo, inferior to other agents
  4. Possible role of add-on therapy in severe cases
51
Q

What are the 4 H2RA medications?

A
  1. Cimetidine
  2. Famotidine (OTC and Rx)
  3. Ranitidine (OTC unavailable; Rx still available)
  4. Nizatidine
52
Q

What are the Health Canada indications for H2RAs? (2)

A
  1. All: GERD treatment and duodenal / gastric ulcer treatment and prevention
  2. Famotidine: GERD maintenance of remission
53
Q

What are some off-label indications for H2RAs? (4)

A
  1. Functional dyspepsia
  2. Prophylaxis of NSAID-related ulcers
  3. Nocturnal GERD
  4. H. pylori infection
54
Q

What are the CIs of H2RAs?

A

None

55
Q

What is the MOA of H2RAs? (3)

A
  1. Parietal cells in stomach pump hydrogen ions into gastric lumen
  2. Blocking the histamine 2 receptors prevents pump activation
  3. Reduction in basal and stimulated gastric acid secretion
56
Q

What is the onset and duration of H2RAs? (3)

A
  1. Acid secretion inhibitions begins within 1-3 hours
  2. Meal stimulated secretion inhibited for 3-5 hours
  3. Nocturnal suppression lasts 8-13 hours
57
Q

What is the prescription dosage of cimetidine?
How many times per day?
What is the max/day?

A

800mg BID
Max = 2400 mg/day

58
Q

What is the prescription dosage of famotidine?
How many times per day?
What is the max/day?

A

20-40mg BID
Max = 80 mg/day

59
Q

What is the prescription dosage of ranitidine?
How many times per day?
What is the max/day?

A

75-150mg BID
Max = 300 mg/day

60
Q

Although they are extremely well tolerated, what are the common side effects of H2RAs? (4)

A
  1. Headache
  2. Vomiting
  3. Diarrhea
  4. Drowsiness
61
Q

H2RAs are typically well tolerated except for __________ which is poorly tolerated, with its notable side effect being ____________

A

cimetidine; gynecomastia

62
Q

What is the DI seen with all of the H2RAs?

A

Decrease absorption of drugs requiring acidity

63
Q

What is the efficacy of H2RAs? (2)

A
  1. Effective for mild or food-triggered GERD
  2. More effective than antacids, less effective than PPIs
64
Q

When are H2RAs mostly used? (2)

A
  1. Safe, cheap option to consider in mild GERD
  2. Additional role as step-down therapy
65
Q

The main drawback of H2RAs is that they demonstrate significant _____________

A

tachyphylaxis (tolerance)

66
Q

What are all of the PPI medications? (-prazoles) (ROPDLE)

A
  1. Rabeprazole
  2. Omeprazole
  3. Pantoprazole sodium and magnesium
  4. Dexlansoprazole
  5. Lansoprazole
  6. Esomeprazole
67
Q

What are the indications for using PPIs? (6)

A
  1. Treatment of GERD symptoms
  2. Symptomatic relief and healing of erosive esophagitis
  3. Symptomatic relief and healing of duodenal and gastric ulcers
  4. Prevention of NSAID-induced ulcers
  5. Use in H. pylori eradication regimens
  6. Treatment of Zollinger-Ellison syndrome
68
Q

What are the CIs of PPIs?

A

None

69
Q

What is the MOA of PPIs? (4)

A
  1. Directly inhibits proton pump to prevent gastric acid secretion
  2. Prodrugs designed to become activated in duodenum
  3. Absorbed and concentrated in the parietal cell
  4. Only works on actively secreting proton pumps
70
Q

What is the onset and duration of action of PPIs? (3)

A
  1. Initial doses will result in suboptimal gastric acid inhibition
  2. Daily use for at least 3-5 days results in maximal inhibition
  3. Proton pump recovery takes 24-48 hours after discontinuation
71
Q

Don’t need to know the numbers in terms of dosing PPIs, but in general, everyone should be started on what dosage regimen?

A

The standard dosage of PPI once daily

72
Q

When might hypersecretory doses of PPIs be used?

A

In Zollinger-Ellison patients

73
Q

PPIs in renal impairment and dialysis. Yay or nay?

A

Yay - no adjustments needed for any degree of renal impairment and can be used safely in dialysis

74
Q

The best time to administer PPIs is when?

A

30 minutes before breakfast.
If experiencing nocturnal symptoms then 30 minutes before dinner would be acceptable too.

75
Q

Indications for double dose PPIs include: (4)

A
  1. If standard dose not effective after adequate trial (~4-8 weeks)
  2. Initial presentation of erosive esophagitis
  3. Ulcers or GI bleed indications
  4. H. pylori eradication
76
Q

What is the duration of therapy for PPIs?

A

Standard or double-dose for 4-8 weeks, then ds/c or step-down

77
Q

What are the common side effects of PPIs? (8)

A
  1. Well tolerated
  2. Dysgeusia (altered taste)
  3. Nausea
  4. Headache
  5. Dizziness
  6. Diarrhea
  7. Constipation
  8. Rash/pruritis
78
Q

What are the serious side effects of PPIs to keep in mind? (9)

A
  1. C. diff infection
  2. Microscopic colitis
  3. Hypomagnesemia
  4. Fractures
  5. Fundic Gland Polyps
  6. B12 deficiency
  7. Pneumonia
  8. Gastric cancer
  9. Mortality increase
79
Q

It appears that PPIs potentially have a lot of serious side effects to worry about, but what should we note when it comes to these findings? (5)

A
  1. All concerns based off low quality evidence with significant confounding
  2. Understand there are potential risks
  3. Understand that PPIs tend to be overused
  4. Periodically reassess dose and need for ongoing therapy
  5. Do not withhold PPIs when benefit demonstrated
80
Q

What drug interaction is seen with all the PPIs?

A

Reduces absorption of drugs requiring acidity, substrates of CYP

81
Q

Lansoprazole has a DI that causes a mild reduction in what 2 drugs?

A
  1. Theophylline
  2. Mycophenolate
82
Q

Omeprazole and esomeprazole have DIs which modifies levels of: (4)

A
  1. Increases carbamazepine
  2. Increases phenytoin
  3. Increases warfarin
  4. Decreases clopidogrel*
83
Q

True or False? Not all of the PPIs are equally effective in terms of efficacy?

A

False - all PPIs equally effective

84
Q

What are the 2 prokinetic agents used in GERD?

A
  1. Domperidone
  2. Metoclopramide
85
Q

What is the MOA of domperidone and metoclopramide?

A

Dopamine antagonists stimulate gastric motility

86
Q

What is the dosing and administration of domperidone and metoclopramide? (3)

A
  1. Domperidone = 10mg TID
  2. Metoclopramide = 5-10mg TID-QID
  3. Give 15-30 mins before meals and bedtime
87
Q

What is the onset and duration of domperidone and metoclopramide?

A
  1. Works within 30 minutes
  2. Lasts 1-2 hours
88
Q

What are the CIs of metoclopramide? (4)

A
  1. GI obstruction, perforation, or hemorrhage
  2. Seizure disorder
  3. Extra-pyramidal symptoms
  4. Parkinsons
89
Q

What are the CIs of domperidone? (4)

A
  1. GI obstruction, perforation, or hemorrhage
  2. Long QT interval
  3. Electrolyte disorders
  4. Use with potent 3A4 inhibitors
90
Q

What are the common side effects of metoclopramide? (5)

A
  1. Drowsiness (~50%)
  2. Muscle weakness
  3. Headache
  4. Dizziness
  5. Confusion
91
Q

What are the serious side effects of metoclopramide? (5)

A
  1. Pseudoparkinsonism
  2. EPS symptoms
  3. Tardive dyskinesia
  4. Gynecomastia
  5. Hyperprolactinemia
92
Q

What are the common side effects of domperidone? (2)

A
  1. Dry mouth
  2. Mild headache
93
Q

What are the serious side effects of domperidone? (2)

A
  1. QT prolongation
  2. Gynecomastia
94
Q

What are the DIs seen with metoclopramide? (3)

A
  1. 2D6 substrate, watch for strong inhibition
  2. Opposes effect of anti-Parkinson agents
  3. Enhances effect/toxicity of antipsychotic agents, SSRIs, or TCAs
95
Q

What are the DIs seen with domperidone? (2)

A
  1. 3A4 substrate, watch for strong inhibitors
  2. QT prolonging agents
96
Q

There are 2 approaches to pharmacologic treatment of GERD. Step up and step down. What is step up? (4)

A
  1. Lifestyle modification
  2. PRN therapy
  3. Scheduled H2RA
  4. Scheduled PPI
97
Q

There are 2 approaches to pharmacologic treatment of GERD. Step up and step down. What is step down? (2)

A
  1. Scheduled course of PPI for specific duration
  2. Then find the lowest strength option to control symptoms (lower dose or on-demand PPI; H2RA PRN or scheduled; no therapy)
98
Q

There are 2 approaches to pharmacologic treatment of GERD. Step up and step down. Which is preferred?

A

Step down. PPIs are very well tolerated and efficacious. Step up simply delays symptom control

99
Q

PPIs users should reassess symptoms at 4-8 weeks. What are the two possibilities that can occur at this point?

A
  1. If symptoms resolved, trial discontinuation appropriate
    - If symptoms recur ≥ 3 months after ds/c, begin another 4-8 weeks course
    - If symptoms recur < 3 months after ds/c, treat again, but investigate more
  2. If symptoms improved, but not resolved, continue for another 4-8 weeks
    - Consider dose increase or switch to another PPI
100
Q

GERD is considered refractory when: (2)

A
  1. Failure on 2 month course of once daily PPI
  2. Symptoms recur within 3 months of PPI discontinuation
    (About 25% of patients will be refractory)
101
Q

What are some possible causes of treatment failure in GERD (refractory)? (5)

A
  1. Medication timing and adherence
  2. Differences in PPI metabolism
  3. Weakly acidic or alkaline reflux
  4. Reflux hypersensitivity
  5. Alternative diagnoses
102
Q

What are the 8 steps in refractory GERD management?

A
  1. Reassess for any alarm symptoms
  2. Ensure adequate duration attempted
  3. Ensure proper adherence and administration
  4. Reinforce lifestyle and dietary modification
  5. Optimize OR switch current PPI
  6. Advanced diagnostics
  7. Add adjunct treatments
  8. Surgery
103
Q

Candidates to recommend deprescribing PPIs include: (4)

A
  1. Mild-moderate GERD who responded to therapy
  2. Peptic ulcer disease treated for proper duration
  3. Asymptomatic for 3 consecutive days
  4. H. pylori eradication successful
104
Q

Majority of PPI patients can successfully discontinue. Tapering is a more successsful approach than abrupt discontinuation. So, how then would we taper? (3)

A
  1. Decrease dose each week as step-wise as possible
  2. May dose every-other-day to help with taper
  3. Initiating H2RA may help with taper
105
Q

In which patients/situations would we actually not deprescribe a PPI and instead advise continued use? (4)

A
  1. Barrett’s esophagus
  2. Chronic NSAID users with bleeding risk
  3. Severe esophagitis
  4. Documented history of bleeding GI ulcer
106
Q

How can functional dyspepsia be managed? (4)

A
  1. PPIs once daily for 4-8 weeks
  2. H. pylori testing/eradication
  3. Switch/add-on TCA
  4. Switch/add-on prokinetic agent (domperidone/metoclopramide)
107
Q

GERD treatments in infants should only be considered if complications, such as: (3)

A
  1. Poor weight gain
  2. Blood in stool or vomitus
  3. Intense irritability temporally related to food intake
108
Q

Warning signs of more serious pathology of GERD in infants includes: (4)

A
  1. Forceful vomiting
  2. Abdominal tenderness or distension
  3. Fever
  4. Systemic signs
109
Q

What are the safety concerns of acid suppression in pediatrics? (3)

A
  1. Acid rebound
  2. Diarrhea
  3. Pneumonia
110
Q

What are the 5 steps in GERD management in pediatrics?

A
  1. If no warning signs, parent reassurance
  2. Assess lifestyle as a trigger
  3. Trial of acid suppression for two weeks
  4. If improvement, continue therapy for 2-3 months
  5. If no improvement, begin more intensive diagnostics
111
Q

What GERD meds should be avoided in pregnancy/lactation?

A

Antacids with bicarbonate and magnesium trisilicate

112
Q

H2RAs and PPIs in pregnancy. Yay or nay?

A

No harm indicated with H2RAs and PPIs
- Prefer lansoprazole, omeprazole, and pantoprazole
So, yay

113
Q

Which PPI is preferred in lactation?

A

Pantoprazole

114
Q

What is drug-induced esophagitis?

A

Pills can become lodged in esophagus

115
Q

The common culprits of drug-induced esophagitis are: (5)

A
  1. Doxy/tetracycline
  2. Potassium tablets
  3. ASA and NSAIDs
  4. Bisphosphonates
  5. Clindamycin
116
Q

Go through the process of minor ailment prescribing for GERD. (5 things to be aware of essentially)

A
  1. Pharmacist initiated treatment appropriate for mild to moderate symptoms AND no red flags
  2. Predominate symptoms must be heartburn and regurgitation
  3. If mild and infrequent, must use step-up approach
  4. If frequent or moderate, can initiate on a PPI for 4 weeks + 1 refill
  5. If a recurrence occurs within 3 months or ds/c, considered refractory –> refer
117
Q

Risk of drug-induced esophagitis is increased by: (8)

A
  1. Lying down after taking medications
  2. Swallowing pills with saliva only
  3. Inadequate water intake
  4. Esophageal dysmotility
  5. Hiatal hernia
  6. Esophageal strictures
  7. Large pills
  8. Bed-ridden

PHAR 255 (14 decks)

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