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59 Cards in this Set
- Front
- Back
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Gastroesophageal Reflux Disease (GERD)
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Symptoms or esophageal injury that result from reflux of gastric acid into the esophagus
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GERD:
prev of symptoms impact on QOL Risk factor for _____. |
High prevalence of GERD symptoms1
7% daily, 20% weekly, 60% monthly Negative impact on health-related quality of life2 Risk factor for esophageal adenocarcinoma3 Odds ratio: 7.7 (symptoms at least once/wk, > 5yrs) Odds ratio: 43.5 (longstanding, severe symptoms) **These numbers may be low because GERD that produces extra-esophageal/atypical CP may be unrecognized |
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Etiology of GERD:
Defective ____-________ barrier ↓ esophageal __________ ↑ esophageal _____ __________ Impaired mucosal resistance ______factors _______factors |
Defective anti-reflux barrier
↓ esophageal clearance ↑ esophageal acid exposure Impaired mucosal resistance External factors Gastric factors |
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Etiology of GERD: Defective anti-reflux barrier
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Defective anti-reflux barrier
↓ LES tone Crural diaphragm Hiatal hernia |
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Etiology of GERD: ↑ esophageal acid exposure
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↑ esophageal acid exposure
Peristalsis Body position Saliva |
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Etiology of GERD: External factors
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External factors
Medications: beta agonists, NSAIDs, anticholinergics. Calcium channel blockers, theophylline Dietary fat Smoking |
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Etiology of GERD: Gastric factors
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Gastric factors
Acid Gastric distention Gastric emptying |
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Medications Can Adversely Effect GERD by ____________ or ______________
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Decrease LES Pressure
or injure mucosa |
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Meds that Decrease LES Pressure
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Theophylline promotes reflux
Anticholinergics Antihistamines Tricyclic antidepressants Calcium channel blockers Nitrates |
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Meds that injure mucosa
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Injure mucosa
Tetracyclines Quinidine Aspirin/NSAIDs Potassium tablets Iron pills |
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Helicobacter pylori infection is the primary cause of __________.
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Helicobacter pylori infection is the primary cause of PUD
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Helicobacter pylori:
Associated with 90% of ______and 75% of ______ ulcers Type of bacteria: gram, shape etc. |
Associated with 90% of duodenal and 75% of gastric ulcers
Gram (–), spiral, flagellated rod that colonizes mucus layer of gastric epithelium |
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H pylori:
Helicobacter pylori contain large amounts of ________ that converts _____ to _____and _____. The ______ buffers acid surrounding the bacteria allowing it to _____ in acidic environment. Infection predisposes mucosa to damage by: |
Helicobacter pylori contain large amounts of urease that converts urea to ammonia and CO2
Ammonia buffers acid surrounding the bacteria allowing it to thrive in acidic environment Infection predisposes mucosa to damage by disruption of mucus layer |
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In absence of H. pylori, PUD is most often caused by:
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ASA and NSAIDs
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ASA/NSAIDs enhance mucosal ________and back diffusion of _____. They Inhibit ___________synthesis.
↓ _____ and _____production ↓ _________ |
ASA/NSAIDs
Enhance mucosal permeability and back diffusion of acid Inhibition of prostaglandin synthesis ↓ mucus and bicarb production ↓ blood flow |
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ASA/NSAIDs __(increase/decrease/)____ the risk of PUD complications
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ASA/NSAIDs ↑ the risk of PUD complications
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Aside from H.pylori and ASA/NSAIDs: other causes of PUD
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-Severe physiologic stress; particularly burns, CNS injury and trauma
-Hypersecretory states: Zollinger Ellison syndrome, gastrinoma -Rare causes: viral, radiation, chemotherapy, ischemia, duodenal obstruction -Diseases associated with PUD: cirrhosis, COPD, renal failure, renal transplantation |
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Treatment Goals for GERD/PUD
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Eliminate symptoms
Promote healing Manage or prevent complications Maintain remission/prevent recurrence |
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Lifestyle Modifications are Cornerstone of GERD Therapy, these include:
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-Elevate head of bed while sleeping
-No food 3 hours before bedtime -Stop smoking- decreases muscle tone -Modify diet -Decrease fat and volume -Avoid peppermint, chocolate, alcohol, coffee -Avoid potentially harmful medications -OTC medications prn |
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Medications for GERD/PUD work by: (5)
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-Decrease acid production
-Neutralize activity of acid and pepsin -Enhance Mucosal Protection -Eradicate H. pylori -Increase or lower esophageal sphincter tone |
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Key to Rx –Understanding Acid Secretion
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Neural stimulation via vagus nerve
Endocrine stimulation via gastrin Paracrine stimulation by histamine release from enterochromaffin-like (ECL) cells Acid production by proton pumps on the apical membrane of parietal cells |
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Antacids MOA
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Mechanism of action: chemically inactivates H+
Higher pH decreases activity of pepsin Action lost with gastric emptying (temporary relief) Increases LES tone Bind a large number of medications |
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Antacids- Clinical Uses:
-Main uses: - ___ and ___ used to decrease_________ in CKD. - useful determinant for this -prevention of ______ ______ _____ |
Great for occasional GERD or dyspepsia
Aluminum and calcium antacids used to decrease serum phosphate in CKD Can be useful to determine if chest pain is related to acid reflux Prevention of urinary phosphate stones Replaced by H2RAs and PPIs for treatment of PUD |
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antacids adverse rxns: NaHCO3
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NaHCO3-systemic alkalosis (esp in renal insufficiency)
fluid retention (NA!) |
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antacids adverse rxns: MOM
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Magnesium Hydorxide (MOM®):
diarrhea, hypermagnesemia (in renal insufficiency) |
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antacids adverse rxns: aluminum hydroxide
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Aluminum hydroxide (Amphogel®):
constipation, hypophosphatemia, drug adsorption (↓ bioavailablity) |
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H2RAs MOA
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-tidine
Mechanism of Action: H2RAs prevent histamine induced activation of H+ release |
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H2RAs- Clinical Use
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Heartburn and dyspepsia
Once or twice daily prn Can be added to PPI for nocturnal breakthrough PUD although PPI are better Stress ulcer propylaxis in high risk individuals Zollinger-Ellison although PPIs better Good for HIV, b/c dont interact with antiretrovirals give on empty stomach |
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H2RAs- adverse rxns
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Tagamet rare blood dyscrasia
Confusion HA |
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PPIs MOA
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-azole
Mechanism of action: directly block parietal cell H+-K+ATPase to ↓ H+ secretion into the lumen |
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T/F: in regards to PPI some patients will react to some but not others.
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T; so you may just have to try another one: If one is ineffective, switch to another
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PPI are Best taken when?
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Best taken 30 minutes before a meal
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T/F PPIs are more effective than H2RAs
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true
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PPI clinical indications
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Clinical indication: PUD, GERD, Reflux esophagitis, ZES
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PPI clinical uses:
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IV formulation of PPIs have been shown in Upper GIB to:
Decrease the need for endoscopic intervention Decrease the risk of recurrent UGIB in patients S/P endoscopic intervention Decrease the toxicity of NSAIDs Long term use in ZES |
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PPIs-Adverse Reactions commonones
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Generally well tolerated
Most common SE: HA, abd pain, nausea, diarrhea and flatulence |
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PPI drug interactions
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Metabolized by hepatic P450 system so can have drug interactions:
Neuroactive drugs (BZDs) antiepileptics, antipyschotics, anticoagulants, rifampin Inhibits CYP2C19- Clopidogrel |
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PPI- adverse rxns: more severe, less common
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-Increased risk of GI infections: Bacterial (e.g. Salmonella), Travelers diarrhea, C. difficile infection
-Increased risk of bone fractures -Increased risk of aspiration pneumonia for inpatients -Risk of hypomagnesemia |
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Antacids ___________inactivate _____
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Antacids chemically inactivate H+
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H2 receptor antagonists prevent _____________-induced activation of ____ release
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H2 receptor antagonists prevent histamine-induced activation of H+ release
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PPI’s directly block _________________ to decrease ____________into the _____
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PPI’s directly block parietal H+-K+ ATPase to decrease H+ secretion into the lumen
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Medical approach: Step up
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Step-up (Traditional strategy)
Sequential therapeutic trials beginning with H2RAs followed by PPIs and diagnostic testing for nonresponders |
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Medical approach: Step down
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Step-down
Begin with PPI QD or BID followed by less intensive therapy with sequential diagnostic testing if needed |
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Extraesophageal GERD: Trial of _(high/low)__dose of a __(drug class)___for how long?
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Trial of high dose PPI for a prolonged period of time
PPI BID for 3-6 months |
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Causes of Medical Treatment Failures in GERD
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Incorrect diagnosis
Pill-induced injury Inadequate acid suppression PPI failure Nocturnal Acid Breakthrough (NAB) Poor compliance Cost of medications Delayed gastric emptying Bile reflux (?) |
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T/F: GERD is a Chronic Relapsing Condition
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True: Esophagitis relapses quickly after cessation of therapy
> 50 % relapse within 2 months > 80 % relapse within 6 months Effective maintenance therapy is imperative |
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Nocturnal Acid Breakthrough (NAB)
How is it defined? Prevalence? How do we treat it? |
Recently defined phenomena
Recovery of gastric acid secretion at night (gastric pH < 4 for greater than 1 hour) on a PPI twice a day prior to meals NAB occurs in ~70% of GERD patients or healthy controls NAB is effectively controlled by adding an H2RA at bedtime |
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Prokinetics agents: examples
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Reglan
Domperamide Cisapride |
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Mucosal Protectants- Bismuth Salts
MOA Clinical uses Caution drug interaction |
“Coats” ulcer + inflammed areas, MOA is poorly understood
Clinical Use: gastroenteritis Helps symptoms of nausea, dyspepsia, and diarrhea Traveler’s diarrhea prophylaxis CAUTION: black tongue and feces Interaction with anticoagulants |
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Mucosal Proctectants: Sucralfate
MOA clinical use administration |
Forms a “gel-like” material on ulcers and protects them from actions of acid and digestive enzymes
Clinical Use: Stress ulcer prophylaxis, Bile reflux gastritis and esophageal ulcers Take before meals |
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Mucosal Protectant-Misoprostol
MOA clinical uses not effective in ____. Caution administration side effects |
Misoprostol (Cytotec ®)
Prostoglandin analog: decreases acid secretion, stimulates production of bicarb and mucus Clinical Use: combined with NSAIDs to reduce risk of NSAID induced ulcers Not effective in GERD CAUTION: induces labor, Causes abortion Given 2-4 times daily Side effects: Diarrhea, usually transient |
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PUD treatment
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Eliminate precipitating factors:
Eradication of H. pylori Cure of H. pylori improves healing rate and markedly ↓ recurrence of PUD Avoid NSAIDs Smoking cessation Limit ETOH consumption |
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triple treatment for h.pylori: aka _______
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AKA: Prevpac
Proton Pump Inhibitor BID10-14 days Clarithromycin 500 mg BID 10-14 days Amoxicillin 1 gm BID 10-14 days |
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Triple Therapy for H. pylori with PCN allergy
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Proton Pump Inhibitor BID14 days
Clarithromycin 500 mg BID14 days Metronidazole 500 mg BID 14 days |
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Quadruple Therapy for H. pylori
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Most affordable
Proton Pump Inhibitor BID 14 days Bismuth 525mg QID 14 days Metronidazole 250mg QID 14 days Tetracycline 500mg QID 14 days |
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Prokinetic drugs: Macrolide Abx: (erythromycin)
Use MOA adverse rxns |
Macrolide Abx: (erythromycin)
often used with gastroparesis: delayed emptying and severely symptomatic with N/V Activate motilin receptors on smooth muscle of the antrum and small intestine Used sparingly due to tachyphylaxis and Q-T prolongation |
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Prokinetic drugs: Cholinomimetics
MOA side effects IV use |
Cholinomimetics-activate ACh receptors
Potently increase GI motility Multiple cholinergic and cardiac side-effects limit use IV neostigmine shown to be highly effective in acute colonic pseudo-obstruction (Oglive’s Syndrome |
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Prokinetic drugs: Dopamine Receptor Antagonists:
Metoclopramide, Domperidone clinical use MOA |
Dopamine Receptor Antagonists:
Metoclopramide, Domperidone Clinical use: Gastroparesis Pre and post-synaptic dopamine receptor antagonism promotes gastric intestinal motility through release of Ach work primarily on the stomach Increased gastric tone/pressure Improved antroduodenal coordination Accelerated gastric emptying |
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Metoclopramide: work primarily on _________
side effects common and serious |
#1 drug related cause of malpractice suits for Gastroenterologists!
work primarily on the stomach Multiple side effects: Common and reversible Somolence, feeling jittery, HA, insomnia, diarrhea Serious side effects: Tardive dyskinesia-involuntary, repetitive movements-may be irreversible Dystonia Neuroleptic malignant syndrome |
