GI Conditions Flashcards
What is dyspepsia?
Epigastic pain or discomfort originating from upper GI tract
It is an umbrella term to describe many possible symptoms and causes
What is GERD?
Gastroesophageal reflux disease
It is reflux of gastric contents into the esophagus
What is peptic ulcer disease?
An ulcer formed in the gastric or duodenal mucosa
Similar symptoms as dyspepsia or GERD
What is the most common diagnosis of dyspepsia?
Uninvestigated dyspepsia (only after endoscopy are patients organized between functional dyspepsia or GERD)
What are some mechanisms by which functional dyspepsia can develop?
- Gastric motility and compliance
- Visceral hypersensitivity (linked to pH and motility)
- H. Pylori
- Altered gut microbiome
- Duodenal inflammation
- Psychosocial dysfunction
What are some non-functional causses of dyspepsia?
- GERD (most common)
- Gastric ulcer
- Gastric erosions
- Gastro-esophageal malignancy (rare)
What are some risk factors associated for developing risk factors for dyspepsia?
- No strong association with sex, age, socioeconomic status
- Dietary indiscretion
- Medications
- H. Pylori infection
- IBS
- Smoking or alcohol use (can worsen existing dyspepsia)
What are some drugs that can cause drug-induced dyspepsia?
- Bisphosphonates
- Iron
- NSAIDs
- Potassium
What are some symptoms of dyspepsia?
Any of the following for more than 1 year
- Epigastric pain or discomfort
- Fullness or early satiety
- Nausea
- Upper abdominal bloating
What are the main “red flag” symptoms for dyspepsia?
- Vomitting
- Bleeding
- Abdominal mass or unexplained weight loss
- Dysphagia or odynophagia
How many Canadians have dyspepsia?
About 30% of Canadians have some degree of dyspepsia
All ages impacted equally
What happens in GERD?
Reflux of stomach acid contents into esophagus, possibly leading to reflux (non-erosive) esophagitis or erosive esophagitis
How many GERD patients have reflux esophagitis (non-erosive)?
About 70% of GERD patients have less severe presentation
How many GERD patients have erosive esophagits?
About 30% of patients have the more severe presentation of GERD
What are some causes of GERD specifically?
- Defective lower esophageal sphincter
- Increased intra-abdominal pressure
- Hiatal hernia
- Impaired esophageal peristalsis
- Delayed gastric emptying
- Excessive gastric acid production
What are some risk factors for developing GERD?
- Obesity
- Pregnancy
- Family history
- Smoking
- Increased age (more than 65)
- Hiatal hernia
- Stress and anxiety
- Drugs
What are the most common drugs that cause GERD?
- Anticholinergics
- Benzodiazepines
- Opioids
These drugs slow esophageal peristalsis or relaxation of upper esophageal sphincter
What are some dietary contributors to GERD?
Over-eating in general
Specific foods:
- Fatty foods
- Chocolate
- Coffee
- Alcohol
- Carbonated drinks
- Acidic juices
Review slide 22 for classifying the severity of GERD symptoms
What are some potential complications associated with GERD?
- Esophagitis
- Esophageal stricture
- Esophageal erosions
- Barrett’s esophagus (squamous cells in esophagus are replaced by hardier columnar cells, but 40-60x higher cancer risk)
What are some red flags for physician referral?
- VBAD symptoms
- Choking
- Constant pain
How can a trial of pharmacological therapy use used as a diagnostic tool for GERD?
PPI treatment will resolve GERD, if issue not resolved then other causes may be present
Who are some people that qualify for a upper endoscopy for GERD diagnosis?
New onset of symptoms after the age of 50
- VBAD symptoms
- Refractory GERD
- At risk for Barrett’s esophagus (endoscopy is indicated)
What patient groups are at risk for Barrett’s esophagus?
Male, chronic GERD (longer than 5 years or frequent episodes) and 2 more of the following:
- Older than 50
- Caucasian
- Central obesity
- Current or past history of smoking
- Family history of Barrett’s esophagus
Besides upper endoscopy, what are some other diagnostic tests for GERD?
- Barium swallow
- Esophageal manometry
- Ambulatory esophageal pH monitoring
Where is GERD the most prevalent?
10-20% of people living in the West report having GERD or GERD like symptoms
What are some goals of treatment for GERD?
- Relieve symptoms
- Promote healing of injured mucosa
- Prevent and treat complications
- Prevent recurrence
- Avoid issues with long-term use of pharmacotherapy
What are some lifestyle changes that can demonstrate benefit in GERD treatment?
- Lose and maintain ideal weight
- Stop smoking
- Elevate head of bed
What are some commonly used drugs in GERD treatment?
- Alginates and Antacids (used at the onset of symptoms and more for PRN Use)
- H2RAs and PPIs (prevent symptoms from occuring in the first place)
What is the mechanism of action for alginates?
Forms a viscous “raft” that floats within the stomach
Starts working in less than an hour
What is the mechanism of action for antacids?
- Neutralizes stomach acid
- Inhibits pepsin generation
- Rapid acting, but short duration of action
Take after a meal for the best effect
What are some contraindications for antacids?
- Avoid in severe renal impairment (unless the patient is on dialysis and calcium carbonate can be also used as a phosphate binder)
How are antacids taken?
- Chew 2-4 tables up to QID
- 30-60 minutes after a meal and/or bedtime
What are some common side effects associated with antacids?
Depends on the metal ion:
Aluminium - constipating
Magnesium - laxative effect
Calcium - well tolerated
What are some serious side effects associated with antacids?
Depends on the metal ion:
Aluminium - bone demineralization, neurotoxicity, hypophosphatemia
Magnesium - hypermagnesemia
Calcium - Hypercalcemia, alkalosis
What are the main types of drug interactions with antacids?
- Chelation with many drugs (antibiotics, iron, bisphosphonates, etc.)
- Impaired absorption of pH sensitive drugs (dabigatran, HIV meds)
What is the efficacy of antacids in GERD treatment?
- Limited evidence
- Slight reduction in symptom severity and frequency
- Better than placebo, inferior to other agents (good for mild, infrequent dyspepsia/GERD)
What are some examples of antacids?
- Aluminium hydroxide
- Magnesium hydroxide
- Magnesium trisilicate
- Calcium carbonate
- Sodium bicarbonate
What are some examples of H2RAs?
- Cimetidine
- Famotidine
- Ranitidine
- Nizatidine
What is the mechanism of action for H2RAs?
- Parietal cells in stomach pump hydrogen ions into gastric lumen
- Blocking the H2 receptors prevents pump activation
- Reduction in basal and stimulated gastric acid activation
What are some common side effects associated with H2RAs?
- Extremely well tolerated (except cimetidine)
- Headache, vomiting, diarrhea, drowsiness (just as potent as other options, but more side effects)
What are some drug interactions associated with H2RAs?
- All drugs that need higher stomach acidity for optimal absorption (Dabigatran and HIV drugs are particularly concering)
- Cimetidine
What is the efficacy of H2RAs?
They are more effective than antacids, less effective than PPIs (tend to be the mainstay of self-care therapy)
Can H2RAs be used long-term?
No, patients rapidly develop tolerance against H2RAs (usually within 8 weeks of continuous use)
Are H2RAs combined with PPI to get more benefit?
No, the combo is not any more effective
What are some examples of PPIs?
- Rabeprazole
- Omeprazole
- Esomeprazole
- Pantoprazole
- Lansoprazole
- Dexlansoprazole
What are the two formulations of pantoprazole, and are they interchangable?
Panto sodium and panto magnesium (they are not interchangable)
sodium (older formulation)
magnesium (newer formulation, longer duration of action)
What are the main indications for PPIs?
- Treatment of GERD symptoms
- Symptomatic relief and healing of duodenal and gastric ulcers
- Use in H. Pylori eradication regimens
What are some contraindications associated with PPI treatment?
None
What is the mechanism of action for PPIs?
- Directly inhibits proton pumps (only if they are actively secreting H+) to prevent gastric acid secretion
When is the best time to administer a PPI?
30 min before breakfast or the first meal of the day (PPIs work best when preceded by a fast)
What is the onset of action for PPIs?
Daily use for at least 3-5 days results in maximal inhibition (scheduled use is more beneficial)
What is the duration of action for PPIs?
PPI recovery takes 24-48 hours after discontinuation
What are some indications for double-dose PPIs?
- Standard dose is not effective after adequate trial (4-8 weeks)
- Initial presentation of erosive esophagitis
- Ulcers or GI bleed indications
- H. Pylori eradication
What are some common side effects associated with PPI use?
Overall well tolerated
- Dysgeusia (altered taste, bitter or metallic)
- Nausea
- Headache
- Dizziness
What are some serious side effects of PPIs?
- C. diff infection (rare in healthy patients)
- Microscopic colitis
- Hypomagnesemia
- Fractures (reduced absorption of calcium carbonate due to higher pH)
- Fundic Gland Polyps
- B12 deficiency
- Pneumonia
- Gastric Cancer (low risk)
- Increased Mortality (confounding variable, people on PPIs have other conditions)
How can the risk associated with PPI use be managed?
Understand PPIs tend to be overused (periodically reassess dose and and need for on-going therapy)
What are some drug interactions associated with PPI use?
Any drug that depends on stomach acidity for absorption (reduced absorption when concurrently administered)
What are some drug interactions that are specific to Lansoprazole?
Theophylline (rarely used) and mycophenolate
What are some drug interactions that are specific to Omeprazole and Esomeprazole?
Reduce Clopidogrel
Increase:
- Warfarin
- Phenytoin
- Citalopram
What is the relative efficacy of PPIs ?
They are equally effective
More effective than H2RAs and antacids
What are some pro-kinetic drugs used in GI conditions?
Domperidone and Metoclopramide (dopamine antagonists stimulate GI motility)
Used for GI motility disorder, limited use in GERD
When should pro-kinetic drugs administered for GI conditions?
Give 15-30 minutes before meals and bedtime
What are some contraindications associated with Metoclopramide?
GI obstruction, perforation, or hemorrhage
Crosses the BBB and can cause CNS effects (seizures, extra-pyramidal symptoms, pseudo-Parkinson’s)
What are some contraindications associated with Domperidone?
- GI obstruction, perforation, or hemorrhage
- Long QT prolongations (with high doses)
- Electrolyte disorders
What is the preferred treatment strategy for GERD?
Step down
1. Scheduled course of PPI for specific duration
2. Then find lowest strength options to control symptoms (lower dose on-demand PPI, H2RA prn or scheduled, no therapy)
What are some factors that confirm refractory GERD?
- Failure on 2 month course of once daily PPI
- Symptoms recur within 3 months of PPI discontinuation
- About 25% of patients will be refractory
What are some causes of PPI treatment failure?
- Medication timing and adherence (30 min before meal and take everyday)
- CYP polymorphisms
- Weakly acidic or alkaline reflux (acidity is not issue in this patient)
- Reflux hypersensitivity
- alternative diagnosis
Review slide 73 for management of refractory GERD
When should PPIs be deprescribed?
Should attempt to deprescribe after 4-8 week trial (ensure they do not have chronic needs)
If long-term therapy, attempt deprescribing once per year
Who are some ideal candidates for PPI deprescribing?
- Mild-moderate GERD who responded to therapy
- Peptic ulcer disease treated for proper duration
- Asymptomatic for 3 consecutive days
- H. Pylori eradication successful
What is the process of PPI deprescribing?
Tapering PPI is more successful than abrupt discontinuation
- Decrease dose every other day
- Initiate H2RA may help with taper
- On-demand PPI (used for GERD symptom recurrence)
What is the main indication for chronic PPI therapy?
Chronic NSAID users can use PPIs to help reduce GI bleed risk
Review slide 76 for more details on PPI deprescribing
What is the treatment strategy for functional dyspepsia?
- PPIs once daily for 4-8 weeks
- H. Pylori testing/eradication
- Switch/add-on TCA
- Switch/add-on prokinetic agent (domperidone and metoclopramide)
When should GERD treatment be considered in infants?
Only in the case of complications
- Poor weight gain (failure to thrive)
- Blood in stool or vomitus
- Intense irritability temporally related to food intake
What are some red flag associated with GERD in pediatrics?
- Forceful vomiting
- Abdominal tenderness or distension
- Fever
- Systemic signs
Review slide 79 for treatment strategy for GERD in pediatrics
Are PPIs safe in pregnant women?
No harm indicated with PPIs and H2RAs
Lansoprazole, Omeprazole, and Pantoprazole are preferred
Panto is preferred in lactating women
When can pharmacists prescribe PPIs for GERD?
Appropriate for mild-moderate symptoms and no red flags
- Predominate symptom must be heartburn and regurgitation
- If mild and infrequent, must be step-up approach
- If infrequent or moderate, can initiate on a PPI for 4 weeks + 1 refill
- If a recurrence occurs within 3 months of d/c, considered refractory (then refer)
What are some drugs that can cause drug-induced esophagitis?
Pills can become lodged in esophagus (take drugs with water and do not lie down for at least 30 minutes)
Common culprits:
- Doxy/tetra
- K+ tablets
- ASA and NSAIDs
- Bisphosphonates
- Clindamycin
What patient groups with GI issues qualify for endoscopy?
- New onset symptoms (over 50)
- Any alarm symptoms (VBAD)
- Refractory symptoms
- At risk for Barrett’s esophagus
What is the definition of peptic ulcer disease (PUD)?
A broad term that encapsulates any breach in the mucosa of the digestive tract
Majority of PUD are gastric or duodenal ulcers (esophaus ulcers are rare)
What are gastric erosions?
They are less severe forms of ulcers because they do not affect deeper tissues
What are some causes of PUD?
- H. Pylori
- NSAIDs
- Pepsin (stomach enzymes)
- Physiologic stress
- Acid
- Alcohol
What are some protective factors for PUD?
- Gastric mucous
- HCO3
- Prostaglandins
- Mucosal blood flow
- Epithelial cell regeneration
What are the lowest risk NSAIDs for developing PUD?
Celecoxib (COX-2 selective)
Ibuprofen
What is the risk level of Naproxen to cause PUD?
Average risk
What is the highest risk NSAID for developing PUD?
Ketorolac
What patient groups are at elevated risk for developing PUD?
- History of an uncomplicated ulcer
- Age over 60
- High dose or multiple NSAID use
- Concomitant ASA, glucocorticoids, anticoagulants, SSRI
- History of CVD
High risk (complicated ulcer history to 3 of the above factors)
Moderate risk (1 or 2 risk factors)
Low risk (none)
What are some characteristics of H. Pylori?
Gram negative rod spread via fecal-oral route (exclusively colonizers gastric epithelium)
Risk factors for colonization:
- Crowded living conditions
- Unclean water
- Raw vegetables
H. Pylori produces phospholipase and catalase (inhibit immune system reaction)
What are the pathogenic mechanisms for H. Pylori induced PUD?
- Direct cytotoxic effect
- Renders underlying mucosa more vulnerable to acid damage
- High levels of ammonia (prevents detection of acidity, more acid is released, causes more damage)
- Promotion of cytokines and inflammation
What is the primary cause of PUD?
H. Pylori is responsible for 80-90% of all PUDs, the remainder are largely caused by NSAIDs
What are the clinical symptoms of PUD?
70% of peptic ulcers are asymptomatic (especially in elderly and NSAID induced PUD), a GI bleed is often the first sign
Dyspeptic symptoms
Symptoms in relating to food (can provide information about location before endoscopy)
What are some complications associated with PUD?
- Quality of life decrease
- GI bleeds
- Perforations or fistulations
- Gastric outlet obstructions
- Mortality increase
What are some signs of PUD related bleeding?
- Nausea and vomitting (coffee ground emesis)
- Melena (dark, tarry stool)
- Orthostatic hypotension
- Red blood in stool if massive bleed (considered emergency if source of bleed is upper GI = lots of undigested blood)
What are some signs of PUD related obstruction?
- Nausea and vomiting
- Early satiety
- Bloating
- Indigestion
- Anorexia and weight loss
What are some symptoms of a perforation of a GI ulcer?
- Sudden change in symptom pattern
- Halitosis
- Post-prandial diarrhea
- Weight loss
Review slide 110 to 112 for PUD diagnosis
What is the most common H. Pylori test?
Urea Breath Testing (H. Pylori causes more ammonia to develop in the stomach)
What are some risk factors for PUD recurrence?
- NSAIDs
- H. Pylori suboptimal eradication or reinfection
- Smoking
- Alcohol use
- Long-standing PUD
What are the goals of therapy for PUD?
- Relieve dyspepsia
- Heal the ulcer
- Prevent complications
- Prevent recurrence
- Implement lifestyle changes (avoid foods that trigger symptoms, eliminate alcohol, smoking cessation)
What is the treatment strategy for NSAID-induced ulcers?
- d/c the NSAID if possible, consider alternatives
- Begin ulcer healing therapy (PPI standard dose, gastic ulcer=8 to 12 weeks, duodenal ulcer=4 to 8 weeks)
- H. Pylori testing should be done
- Consider on-going secondary prevention for some patients
What are some options for secondary prevention of NSAID-induced PUD?
- Lower NSAID dose
- Switch to Celecoxib
- Add long-term PPI
- Add misoprostol
What is the mechanism of action of misoprostol in PUD?
It is a prostaglandin analogue leading to an increase in:
- Gastric mucous
- Bicarbonate secretion
- Inhibition of basal and nocturnal gastric acid secretion
What is the preferred treatment option for H. Pylori induced ulcers?
Quadruple therapy (PBMT and PAMC)
PBMT (PPI, Bismuth, Metronidazole, Tetracycline)
PAMC (PPI, Bismuth, Metronidazole, Clarithromycin)
What are some second line treatment options for H. Pylori induced ulcers?
PAL (PPI, Amox, Levoflox) or PABL (PPI, Amox, Bismuth, Levoflox)
PBMT if not tried already
What are some characteristics of PBMT treatment of H. Pylori induced ulcer management?
Advantages:
- Highly effective
- Overcomes resistance
- Preferred if penicillin allergy
Disadvantages:
- High pill burden (QID treatment)
- Metronidazole interacts with alcohol
What are some characteristics of PAMC treatment of H. Pylori induced ulcer management?
Advantages:
- Highly effective (less than PBMT)
- Simplified regimen (BID instead of QID)
Disadvantages:
- More GI ADRs
- Clarithromycin resistance
- Pencillin allergy
- Metronidazole interacts with alcohol
Why are triple therapy regimens not recommended for H. pylori-induced ulcer management?
They are restricted in use due to high resistance rates, which leads to higher failure rates
What is the utility of PAL or PABL treatments in H. Pylori induced ulcers?
Used in treatment failure with PMBT or PAMC treatment
What are some characteristics of PAL/PABL treatment for H. Pylori induced ulcers?
Advantages:
- Important option for previous failure
Disadvantages:
- Lower eradication rates vs. first line
- Penicillin allergy
- Increased risk of increasing resistance to levofloxacin
What is the role of PAR treatment in H. Pylori induced ulcers?
It is a last-line option if all other regimens have failed
What patient factors should be considered when choosing a treatment regimen for H. Pylori induced ulcers?
- Allergy history
- Recent antibiotic use (esp. metro/clarithro)
- Alcohol use (avoid metronidazole)
- DI potential (especially with clarithro)
- Adherence/pill burden (difficulty especially if patient is already on polypharmacy)
- Anticoagulant or antiplatelet use if considering bismuth
Review slide 135 for H. Pylori induced ulcer treatment algorithm
What are some common reasons for H. Pylori induced ulcer treatment failure?
- Poor adherence (can help with compliance packaging)
- Incorrect regimen used (use evidence based treatment combinations only)
- High local resistance rates
How is treatment success for H. Pylori induced ulcers assessed?
Fecal stool antigen test four weeks after completion of therapy is optimal
What is the role of PPI maintenance therapy after successful H. Pylori eradication?
Duodenal ulcer: generally not indicated (possiblity 2 weeks after stopping combo therapy)
Gastric ulcer: continue PPI for 8 weeks
What is the utility of probiotics in H. Pylori induced ulcer management?
Improves efficacy and tolerability (not harmful to try)
For ulcers that are not caused by H. Pylori or NSAID use, what is the treatment strategy?
- Poor prognosis
- PPI for 4-8 weeks is the only treatment option
- Increase dose and duration if initial trial fails
- Reassess and consider alternate diagnosis if little improvement
- Consider long-term PPI
