Management of dyspepsia, GERD and PUD

Antacids - MOA

• direct chemical interaction with H+ to raise pH

• available as aluminum < magnesium < calcium salt

  • sodium bicarbonate is option but LOTS of sodium ions meaning lots of fluid movement

• can be combined with alginic acid

  • when given with glass of water, forms a gel layer when in contact with stomach acid

  • superior vs. antacid alone

Antacid - AEs

• Al3+ and Ca2+ cause constipation

• Mg2+ cause diarrhea

  • can be combined to offset each other

  • generally, more diarrhea because Mg2+ very effective

• Ca2+ causes bloating and gas

• Al3+ and Mg2+ caution when renal dysfunction because can accumulate a lot

• need to be separated 2h from certain medications

  • FQ, tetracycline - physically stick together to divalent cations

Antacid - dosing

• suspensions more potent than tablets

  • less palatable

• taken PRN

  • 30 minutes after meals or HS

• fast onset but limited duration

  • limited based on gastric emptying

H2 Receptor Antagonists (H2RAs) - MOA

• block H2 receptor on parietal cell

  • decreases acid production

• more potent and longer lasting than antacids

• all equally effective

H2 Receptor Antagonists (H2RAs) - AEs

• generally well-tolerated

• headache most common

• dizziness, drowsiness, diarrhea

• long-term, high-dose of cimetidine associated with gynecomastia (enlargement of breast tissue) and erectile dysfunction

• ranitidine recall - has a potentially carcinogenic byproduct (not sure if clinically insignificant)

H2 Receptor Antagonists (H2RAs) - dosing

• slower onset (gives 15-30 minutes before meals)

• meal-stimulated acid inhibited for 3-5h and nocturnal for 8-13h

• tachyphylaxis (loss of effectiveness) can occur with daily use > 2-6 weeks

Proton pump inhibitors (PPIs) - MOA

• block proton pump on parietal cell

  • decreasing acid production

• more potent and longer lasting than H2RAs

• slower onset- can take up to 4 days

  • PRN use is NOT appropriate

Proton pump inhibitors (PPIs) - AEs

• well tolerated short term

• common - diarrhea, nausea, headache

  • is NOT a class effect so can try another PPI and may not have side effects

• long-term based on observational studies:

  • fractures

  • B12 deficiency (not acidic enough)

  • pneumonia

  • C. diff infection

  • hypomagnesemia

  • CKD

  • dementia

  • withdrawal can lead to rebound hypersecretion

• use lowest effective dose as short as possible

• interaction with drugs that require acidity

• esomeprazole most likely to inhibit CYP2C19

Non-pharm management for dyspepsia (regardless of type)

• small, more frequent meals

• food diary to identify triggers

  • fatty and acidic foods

  • fruit juices

  • coffee

  • alcohol

  • **caution with patients with functional dyspepsia and consider referral to dietician because can get into unhealthy food patterns

• smoking cessation

• weight loss

Medications that may cause or exacerbate dyspepsia (regardless of type)

• nitrates

• tricyclic antidepressants

• calcium channel blockers

• Aspirin, NSAIDs

• **look for alternatives or use lowest effective dose

  • only consider changing if non-pharm not working

Approach to patient presenting with undiagnosed dyspepsia

1. rule out need for immediate referral (VBAD, age)

2. recommend non-pharm

3. perform medication review and adjust if appropriate

4. if needed, trial non-rx antacid, H2RA or PPI

   • choice depends on severity and pattern (nocturnal or tied to meals)

5. refer if:

   • continues to experience symptoms even with therapy

     ….OR….

   • medication is needed daily > 2 weeks

     ….OR….

   • requires medication > 3 times/year (episodes)

What is the algorithm for referred patients with uninvestigated dyspepsia?

• if there are any of the red flags - endoscopy

• if there is >20% prevalence of local H. pylori - test and treat

• if there is no local prevalence or the test is negative - treat with daily PPI for 4-8 weeks

• if symptoms resolve - try step down or stopping

• if still ongoing symptoms - endoscopy and if not tested for H. pylori at this point test

• if there is an absence of findings on endoscopy - reassure, retreat H. pylori - diagnose as functional dyspepsia

Importance of empathy with functional dyspepsia patients

• medication often unsuccessful

• impaired QoL

• higher risk for anxiety and depression

• reassure dyspepsia is benign

  • even though symptoms, not awful underlying cause

• stress reduction

Management of functional dyspepsia

• non-pharm

• **trying things to just see what happens because very little evidence of what works

• on-demand H2RAs or PPIs

• aggressive H. pylori test and treat

• metoclopramide or domperidone

• tricyclic antidepressant, mirtazapine, buspirone

Urgent red flags for referral of heartburn or GERD

• frequent vomiting >7 days

• hematemesis, ground coffee emesis, dark tarry stools

• possible chest pain

  • shoulder, neck or arm pain

  • shortness of breath

  • nausea

  • sweating

Non-urgent reg fags for referral of heartburn or GERD

• < 18 years

• epigastric mass

• symptoms of anemia (lightheaded, pale, cold)
  unexplained weight loss ( > 5%)

• dysphagia or odynophagia

• > 50 years with new or worsening heartburn (increase cancer risk)

• recurrence within 90 days of previous episode (ensure not something worse)

• GI cancer in first-degree relative

• nocturnal symptoms (increase risk of EE)

• severe symptoms (interfere with daily activity)

• extra-esophageal symptoms (recurrent cough, wheeze, hoarseness)

Non-pharm management heartburn and GERD

• smoking cessation

• avoid restrictive clothing

• smaller meals more frequently

• reduce alcohol and caffeine

• avoid food triggers

• avoid eating within 2-3h bedtime

• weight loss (if needed)

• avoid bending over or lying down shortly after eating

• elevate head of the bed (best to use blocks or foam wedge)

Medications that exacerbate heartburn and GERD

• nitrates

• aspirin and NSAODs

• tricyclic antidepressants

• calcium channel blockers

Approach to patient presenting with heartburn or GERD

1. rule out need for referral

2. recommend non-pharm

3. perform med review and adjust if needed

4. recommend medication (non-rx or rx) as appropriate

Medication for heartburn (mild symptoms <2x/week)

step-up approach - increase potency until symptoms resolved

• start with non-rx agent PRN for 2 weeks

  • antacid ± alginate or H2RA

• if does not work, Rx H2RA BID for 2 weeks

• if does not work, Rx PPI daily for 4 weeks

• if does not work, refer

if one of the regimens works, stop or step down

Medication for mild-to-moderate GERD (mild symptoms >2x/week or moderate symptoms)

step-down approach - gain symptoms control quickly, then deescalate

• start Rx PPI once daily for 4 weeks

• if works, continue for another 4 weeks then d/c and use non-rx PRN

• if does not work, refer

Management of patients with severe symptoms or GERD complications

• require assessment and careful monitoring by physician

• MD will prescribe 4-8 week trial PPI once daily

  • faster healing esophageal erosions

  • will not reverse histological changes

• if does not work, increase to 4-8 week trial PPI BID

• if works, d/c or reduce to lowest effective dose

• if does not work, other investigations needed and considered refractory GERD

Management of GERD in pregnant patients

• generally resolves quickly post-partum

• same algorithm as non-pregnant adults

• avoid sodium bicarbonate because retention of even more fluid

Management of GERD in infants

• diagnosis based on esophagitis, nutritional compromise or respiratory complications

• avoid second hard smoke

• continue breastfeeding (normally not able to over feed)

• thickening agent, if bottle fed

• avoid overfeeding

• keep infant upright 30 minutes after a feed

• 2 week removal of allergens (cow’s milk or soy protein)

• 2-4 week trial H2RA or PPI

  • if severe symptoms where conservative measures have failed

Risk factors of PUD and mitigation strategies for NSAID use

• choice of NSAID - use lowest risk agent

• high dose NSAID - use lowest effective dose

• prolonged use NSAID - use shortest effective duration

• smoking/excessive alcohol - lifestyle modification

• combined NSAID therapy - avoid whenever possible

• concomitant therapy with glucocorticoids, anticoagulants/clopidogrel, SSRIs - ensure indication

High-risk patients and preventative strategies to decrease risk of PUD

Risk Factors

• age > 65 years

• high-dose NSAID

• concurrent use of aspirin, corticosteroids or anticoagulants

Risk and strategies

• Low risk (no factors) - lowest dose, lowest ulcerogenic

• Moderate risk (1-2 factors) - NSAID + PPI or misoprostol

• High risk (> 2 factors) - alternative therapy or COX2 + PPI or misoprostol

*some clinicians will screen for H. pylori because do not want both NSAID and H. pylori

Preventative medications for moderate-high risk patients

• PPI once daily

  • decreases PUD risk

• misoprostol 200mcg QID

  • decreases gastric ulcer risk only

• H2RA double dose

  • only for patients who cannot tolerate PPI or misoprostol

  • does not decrease gastric ulcers

Primary prevention of critical illness - stress-induced ulcer

• incidence of stress ulcer is high, only small chance of clinically significant bleeding

• will only prophylactically treat for patients with high risk of bleed risk

• will be given once daily PPI (IV or PO)

• will need to re-evaluate bleed risk daily, and d/c when necessary

Management of bleeding PUD

1. stabilize patient (IV fluids, blood products)

2. hold NSAIDs, anticoagulants/antiplatelets

3. give pantoprazole 80mg IV (bolus, twice the amount)

   • don’t want them to consume anything because aspiration concern

   • stomach full of blood and oral meds not well absorbed

4. perform endoscopy

   • diagnostic - where exactly is bleeding coming from

   • risk assessment - what is the chance of rebleed

   • therapeutic - clip, elastic band, cauterize, epinephrine

5. acid suppression for healing of ulcer

6. address the underlying cause to prevent a recurrence

Types of endoscopy findings and risk of rebleeding if ONLY medical management

risk too high for rebleeding, need treatment during endoscopy

• active bleeding

• non-bleeding vessel

• adherent clot

low risk for rebleeding can be treated only with medical management

• flat spot

• clean ulcer

Acid suppression treatment for bleeding PUD

• if high risk of rebleeding

  • high-dose PPI x 72 h (8mg/h or 40mg q12h)

  • then oral BID x 14d if no further evidence or bleeding

  • then standard-dose PPI once daily

• if low risk of rebleeding

  • standard-dose PPI once daily

**once daily dosing is continued for: (± repeat endoscopy)

• 4-8 weeks duodenal (b/c less acidic, less heal time)

• 8-12 weeks gastric

Steps when addressing underlying cause to prevent recurrence of bleeding PUD

• bleeding PUD significant risk of morbidity and mortality so aggressive so to not happen again

• test-and-treat for H. pylori

  • even if believe something else

• manage NSAID use

  • d/c if possible

  • or switch to COX2 + PPI or misoprostol if using for pain

• decide if necessary to restart anticoagulants/antiplatelet

  • depends on risk of clot vs risk of rebleed

Management of non-bleeding PUD

1. acid suppression for ulcer to heal

   • standard-dose PPI once daily

   • NSAID -induced: 4-8weeks, depending on size

   • non-H. pylori, non-NSAID: usually long term

2. test-and-treat for H. pylori

3. discontinue NSAIDs, if possible

   • if not possible, add PPI or misoprostol

   • decide if necessary to restart anticoagulants/antiplatelet

**PPIs superior to H2RAs for speed and likelihood of ulcer healing

Indications for test-and-treat

• different than other infections, because actively go looking for it

• part of the algorithm for the management of dyspepsia

• for diagnosis of PUD in symptom management <60 years

• to identify the cause of anyone diagnosed with PUD endoscopically even if they use NSAIDs

• others:

  • first-degree relative with gastric malignancy

  • first-generation immigrant from Asia, Africa, and Central/South America (higher H. pylori incidence)

Types of H. pylori testing

• serology

• stool antigen assay (SAA)

• Urea breath test (UBT)

• Biopsy

several causes of false negatives - MUST be off PPI for > 2 weeks and not using bismuth/antimicrobials > 4weeks (difficult because a lot of patient discomfort)

H. pylori serology test

• blood sample and look for antibodies

• cannot differentiate past resolved infection or active current infection

• cannot be used to prove if therapy has worked

• no risk of false negatives

H. pylori urea breath test

• most common

• rapid response - result in 20 minutes

steps:

1. drink radio labeled urea

2. H. pylori will metabolize and convert to radio labelled CO2

3. exhale and analyze breath for radio labelled CO2

H. pylori tissue biopsy

• requires biopsy - so not going to do unless already doing an endoscopy

• allows for culture and antibiotic sensitivity

Treatment of H. pylori infection

• antimicrobial resistance is common - quadruple therapy is needed (PPI + 3 antimicrobials with different MOAs)

• First line:

  • PBMT x 14d (PPI + Bismuth + Metronidazole + Tetracycline) …OR…

  • PAMC x14d (PPI + Amoxicillin + Metronidazole + Clarithromycin)

• confirm eradication via UBT or SAA at least 4 weeks post-rx and off PPI at least 2 weeks

Treatment for H. pylori infection - if amoxicillin allergy

• PBMT

• or PMC - not as effective

Treatment for H. pylori infection - if local clarithromycin resistance <15%

• use triple therapy

  • most testing to diagnose is non-invasive so resistance is not going to be known

• PAC x14d

• PAM x14d

• PMC x14d

  
  

• also account patient-specific recent antimicrobial use

Steps if failure of first choice therapy

**common due to resistance and non-adherence - help by administer in blister pack and communication of importance

• if fails clarithromycin or levoflocacin - don’t use aginst

• PBMT x14d (if was initial, higher PPI or metronidazole)

• PAL x14d

• PAR x14d (last line) - used if at least three treatment failures

PPI deprescribing importance

• second most prescribed class in Canadian seniors

• 20-70% are inappropriate

• common source:

  • continued at hospital discharge

  • not reassessed after initiation

• attempt to stop/reduce PPI at least once per year

When to initiate deprescribing?

• no need to recommend deprescribing:

  • Barrett’s esophagus

  • chronic NSAID users with bleeding risk

  • severe esophagitis

  • documented history of bleeding GI ulcer

• recommend deprescribing:

  • indication unknown

  • mild-moderate esophagitis

  • GERD after treatment of 4-8 weeks

  • treatment after ulcer and never d/c

How to recommend deprescribing?

• decrease to lower dose - can potentially taper

• discontinue (if used to treat ulcer)

• use on-demand

• once change made - monitor at 4 and 12 weeks:

  • add non-pharm options

  • manage occasional symptoms with OTC

• if symptoms relapse:

  • test-and-treat H. pylori

  • continue returning to previous dose

Tapering when deprescribing PPIs

• no evidence that one tapering approach is better than other

• no evidence that tapering helps patient not require going back onto PPI

On-demand dosing when deprescribing PPIs

• daily intake until achieve resolution

• following resolution, discontinue medication

• if symptoms recur, restart medication until symptoms resolve

• repeat cycle