10/7- Drugs in Acid Peptic Disease and GERD Flashcards
T/F: Some degree of gastro esophageal reflux occurs normally in most individuals.
True
What is the basic underlying mechanism of GERD?
Some causes?
Factors potentially harmful to the esophagus overwhelm protective mechanisms
- Decreased salivation
- Impaired esophageal acid clearance
- Impaired tissue resistance
- Transient LES relaxation
- Decreased resting tone of LES
- Delayed gastric emptying
What are the symptoms of GERD? What is causing them?
Heartburn (and others) from mucosal damage
What are TLESRs? How long do they last?
Brief episodes of LES relaxation unrelated to swallowing or peristalsis
- Last ~10-35s
What is the most common cause of symptomatic GERD?
Excessive acid reflux due to TLESRs
Decreased ____ is more common among pts with GERD, especially those with ______ or ______
Decreased LES tone is more common among pts with GERD, especially those with esophageal strictures or Barrett’s esophagus
What are some substances that increase/decrease LESP: hormones?
Increase:
- Gastrin
- Motilin
- Substance P
Decrease:
- Secretin
- Cholecystokinin
- Glucagon
- Gastric inhibitory peptide (GIP)
- Vasoactive intestinal polypeptide
- Progesterone
What are some substances that increase/decrease LESP: Neural agents?
Increase:
- a-adrenergic agonists
- B-adrenergic antagonists
- Cholinergic agonists
Decrease:
- a-adrenergic antagonists
- B-adrenergic agonists
- Cholinergic antagonists
- Serotonin
What are some substances that increase/decrease LESP: medications?
Increase:
- Metoclopramide
- Domperidone
- Prostaglandin F2a
- CIsapride
Decrease:
- Nitrates
- CCBs
- Theophylline
- Morphine
- Meperidone
- Diazepam
- Barbiturates
What are some substances that increase/decrease LESP: foods?
Increase:
- Protein
Decrease:
- Fat
- Chocolate
- Ethanol
- Peppermint
What do you expect to hear in the history of someone with GERD (symptoms)?
Esophageal
- Heartburn
- Regurgitation
- Chest pain
Extra-esophageal
- Cough
- Laryngitis
- Asthma
- Dental erosions
What nerve is responsible for innervating sensation of the stomach? Other connections?
Vagal afferents provide the brain with feedback from the stomach (neural reflex mechanism)
- Vagal efferents drive the lungs
- GERD can cause direct mucosal injury of the lungs
Pros/Cons of Therapeutic trial?
When should an endoscopy be performed?
What can be diagnosed with it?
- Essential if there are alarm symptoms
- Will diagnose erosive esophagitis
- 2/3 of pts have normal endoscopy
- Enables ID of Barrett’s esophagus
What are some components of reflux monitoring?
Ambulatory pH
- Measure acid reflux
Ambulatory MII + pH
- Measure both acid and non-acid reflux
How does reflux testing via pH monitoring work?
Answers 2 questions:
- Is there an abnormal amount (pathological) of reflux?
- Is there an association between reflux episodes andsymptoms
Sensor lies 5 cm above LES
What is MII? How is it monitored?
Multichannel Intraluminal Impedance
- Multiple sensors along the catheter; internal reference with 1-2 pH channels and 7-8 rings
- Sense fluid (drop in impedance) pH sensed simultaneously
- pH under 4 is considered acidic and distinguishes between acid and non-acid reflux
What is impedance?
Electrical resistance measured with an alternating current
- Inverse of conductance
- Measured in Ohms Low impedance means many ions are moving (high impedance means only a few are moving)
Analyze this impedance graph- what is happening at each stage?
What conditions are seen here?
Left: swallow
Right: reflux
How does ambulatory pH testing work?
Tubeless method: Bravo system
- Radio telemetry capsule to be attached to the esophageal mucosa
- Minimizes discomfort of transnasal catheters
Benefit of joint impedance-pH monitoring?
Detects reflux regardless of acidity (can measure acid and non-acid reflux)
May increase sensitivity of study, especially when gastric acid secretion is suppressed
- Treatment with proton pump inhibitors
- Atrophic gastritis
What are the benefits of doing Barium swallow for diagnosis?
Sensitivity for esophagitis: 80% if severe, 25% if mild
Reflux of barium during exam:
- Positive in 25-75% of symptomatic patients
- Positive in 20% of normal controls
NOT useful for GERD diagnosis
- Only potential role = pre-op eval (hiatus hernia, foreshortening)
What are some pharmacological strategies for acid peptic disorders?
- Neutralize gastric acid
- Protect the mucosa from acid-peptic damage
- Control gastric acid secretion
What are some things that can be used to neutralize gastric acid? Adverse effects?
Antacids: neutralize secreted gastric acid
- Aluminum hydroxide (adverse effect: constipation)
- Magnesium hydroxide (adverse effect: loose stools)
- Aluminum + Magnesium hydroxide (Maalox, Mylanta)
**Avoid Mg preparation in chronic renal failure due to possible hypermagnesemia
- Calcium carbonate, sodium bicarbonate
What are some cytoprotective agents that can be used to protect the mucosa from acid-peptic damage?
- Sucralfate
- Prostaglandin analogues (misoprostol)
What is sucralfate? How does it work? Adverse effects?
- Complex sucrose salt, insoluble in water, binds to ulcerated sites
- Physicochemical barrier, may enhance mucosal defense / repair
- May interfere with absorption of other medications
How do prostaglandin analogues work? Ex?
Adverse side effects?
Ex) Misoprostol
- Enhance mucosal defense and repair, much of which is PG-dependent (why NSAIDs and the blocking of COX can cause mucosal damage)
- Diarrhea and abdominal cramps are frequent side effects
- Contraindicated in pregnancy
What are the mechanisms of acid suppression?
- PPI (proton pump inhibitor) blocks H-K pump that normally secretes H/protons and reabsorbs K
- H2 blocker: prevents translocation of pump to the surface
- Gastrin blocker?
- ACh blocker?
How should NSAID ulcers be treated?
Stop NSAID if possible
- More rapid healing if NSAID stopped
Test and treat H. pylori Anti-secretory therapy in non-H. pylori ulcers
- 4-6 weeks of acid suppression
- PPI more effective than H2RAs
- Long-term PPI recommended when NSAIDS must be continued
What lifestyle modifications may be involved in the treatment of GERD/peptic acid disease?
- Weight loss
- Avoid recumbency for 3 hours postprandial
- Elevate head of bed
- Decrease fat intake
- Smoking cessation
Recommend to all pts
- Unlikely to control symptoms in most
Results of treatment (H2 blockers vs. PPIs) for healing erosive esophagitis?
If true mucosal changes have occurred, H2 blocker won’t cut it; want pt on a PPI
Which is better for symptom relief: H2 blockers or PPIs?
PPIs
What is the generic ending of a PPI?
–azole
Examples:
- Omeprazole (Prilosec)
- Lanzoprazole (Prevacid)
- Pantoprazole (Protonix)
- Rabeprazole (Aciphex)
- Esomeprazole (Nexium)
- Omeprazole + Sodium Bicarbonate (Zegerid)
- Dexlansoprazole (Dexilant )
What is the best PPI for healing of erosive esophagitis?
Esomeprazole (Nexium)
- Practically/clinically, there is only a modest (if any) benefit in using this one over others
- For practical purposes, all PPIs are about the same (although may have statistical significance in larger groups)
What is the best PPI for symptom relief?
Esomeprazole (Nexium)
- Again, there is a benefit, but not a huge one (especially clinically)
How long do you generally want a pt on a PPI?
4-8 weeks (rarely 8-12 wks)
What are some safety concerns of long-term acid suppression? ASEs? At risk for what?
- How should these safety concerns be managed?
- Generally well tolerated
- 1-3%: diarrhea, headache, nausea, abdominal cramps
In retrospective data, there is possible risk of:
- C. difficile
- Osteoporosis
- Pneumonia(?)
To mange:
- Use PPIs only when indicated
- Use lowest effective dose
What are possible surgical therapies for peptic ulcer disease?
When should it be considered?
Fundoplication
- Modulate anti-reflux barrier at LES
- Fundus is wrapped (totally or partially) around the stomach/LEJ underneath the diaphragm
Fundoplication should only be considered:
- In pts with no contraindications to surgery
- By a skilled laparoscopic surgeon with experience in fundoplication
How does fundoplication compare to pharmacological treatment?
Efficacy similar to PPIs
What are adverse effects of fundoplication?
- Perioperative morbidity/mortality
- Dysphagia
- Bloating (even inability to burp)
Summary: Management of GERD
- Weight loss for GERD patients who are overweight or have had recent weight gain
- Head of bed elevation and avoidance of meals 2 – 3 hrs before bedtime (nocturnal GERD).
- An 8-week course of PPIs is the therapy of choice for symptom relief and healing of erosive esophagitis. There are no major differences in efficacy between the different PPIs.
- Traditional delayed release PPIs should be administered 30 – 60 min before meal for maximal pH control.
- PPI therapy should be initiated at once a day dosing, before the first meal of the day .
When should PPIs be taken in regard to meals?
30-60 min BEFORE the meal
