GERD/Peptic Ulcer Disease Flashcards
The physiology of gastric acid secretion is modulated by which pathways?
Paracrine (histmaine)
Neuroendocrine (Ach)
Endocrine (Gastrin)
Which receptors are activated by the pathways in the physiology of gastric acid secretion?
H2, M3, CCK2
What limit the extent of acid secretion in gastric acid secretion?
Somatostatin-secreting D cells and prostaglandins
Is GERD more common in men or women?
Women- common is pregnancy
What are the lifestyles and sx associated with GERD?
High fat meals- increase frequency of sx, calorically dense meals
Tabacco- increases the frequency of sx
Alcohol- no change
Caffeine-no change
What are the four mechanisms associated with GERD?
- Decreased lower esophageal sphincter pressure
- Prolonged esophageal clearance
- Mucosal resistance
- Delayed gastric emptying
What is the normal function of the Lower esophageal sphincter?
tonic, contracted state, relaxing to permit free passage of food into the stomach
What is involved in transient LES relaxations?
Not associated w/ swallowing
Mechanism unclear, possible causes- esophageal distention, vomiting, belching, retching
Responsible for 65% of reflux episodes in GERD pts
What are the medication causes of decreased LES?
Anticholinergics Barbituates Benzodiazepines Caffeine Dihydropyridine Ca2+ channel blockers Dopamine Estrogen Ethanol Isoproterenol Narcotics Nicotine Nitrates Phentolamine Progesterone Theophylline
What are the food causes of decreased LES?
Fatty meals Peppermint/spearmint Chocolate Caffeinated Drinks- coffee, cola, tea Garlic, onions, and chili peppers
What is involved in esophageal clearance?
50% GERD pts have prolonged acid clearance.
Esophagus is normally cleared by peristalsis
Increased salivia provided bicarbonate buffer
What does saliva production decrease with?
Age
Sjogren’s syndrome
Xerostomia
Sleep
What is involved in mucosal resistance?
Mucus secreting glands may function to protect the esophagus
After repeat exposure, H+ ions diffuse into mucosa causing cellular acidification and necrosis
What foods are mucosal irritants?
Spicy foods
Citrus foods
Tomato juice
Coffee
What medications are mucosal irritants?
Aledronate (take w/ full glass water then upright 30 min to avoid ulcerations) Aspirin Iron NSAIDS Quinidine Potassium chloride
What is involved in gastric emptying?
Problem- delayed gastric emptying time. Factors increasing gastric volume/decreasing gastric emptying- smoking and high fat meals
Post-prandial reflux
Infants- defects in antral motility resulting in failure to thrive and pulmonary aspiration
What life style factors are associated with reducing the sx of GERD?
Exercise- weigh lifting, cycling, sit-ups Smoking cessation Obesity Avoid high-fat meals Avoid supine body position Avoid tight fitting clothing Avoid pregnancy Avoid stress
What are typical symptoms of GERD?
Heartburn (pyrosis)
Hypersalivations
Belching
Regurgitation
What are the atypical symptoms of GERD?
Non-allergic astham Chronic cough Hoarseness Pharyngitis Chest Pain Dental Erosion
How is GERD diagnosed?
History
Endoscopy
24 hr ambulatory pH monitoring
Pre-emptively treating with standard or double dose omeprazoel
When is 24 hr ambulatory pH monitoring used to diagnose GERD?
Unusual sx or failure to respond
What are the complications of GERD?
Esophagitis
Esophageal strictures (Complicated by ASA/NSAIDS)
Barretts esophagus
Adenocarcinoma of esophagus
What increases the risk of adenocarcinoma of the esophagus?
30-60x increase if barretts esophagus
Long standing frequent reflux
What are the symptoms of adenocarcinoma esophagus?
Continual pain Dysphagia Odynophagia Bleeding Unexplained weight loss Choking
What are the goals of therapy of GERD?
- Alleviate or eliminate symptoms
- Decrease the frequency or recurrence and duration of the reflux
- Promote healing of the mucosa
- Prevent development of complications
What are the treatments of GERD?
Lifestyle modification
Suppression of Gastric acid production
Promotility therapy
Surgery
What is used for suppression of gastric acid production in the treatment of GERD?
Antacids after meals and at bedtime
H2 histamine receptor antagonist
Covalent inhibitors of the H+, K+ -ATPase of the parietal cell (PPIs)
What is used for promotility therapy in the treatment of GERD?
Metoclopramide (domapine antagonist)
Bethanechol (Cholinergic agent)
What are the lifestyle modifications that can be made to help GERD?
Elevate the head of the bed (increases esophageal clearance)
Make dietary changes
Smoking cessation (decreases spontaneous esophageal sphincter relaxation)
Avoid ETOH
Avoid tight fitting flothing
Discontinue drugs that contribute to reflux
Take medications with plenty of water
What medications contribute to reflux in GERD?
Ca++ channel blockers Beta blockers Nitrates Theophylline Caffeine
What are the dietary changes that should be made to help GERD?
Avoid foods that lower esophageal sphincter pressure (fats, chocolate, ETOH, peppermint & spearmint)
Avoids foods that have instant effect on the esophageal mucosa (spicy foods, OJ, tomato juice, coffee)
Include protein-rich foods, augments lower esophageal sphincter pressure
Eat small meals and avoid eating prior to sleeping-decrease gastric volume.
Loose weight-reduces symptoms.
What are the two therapeutic approaches to GERD?
Patient-directed therapy, progressing to pharmacologic management or interventional therapies
OR
Proton pump inhibitor 1-2x daily then reducing to lowest degree of acid suppression for symptom control
Lifestyle modifications are started initially and continued throughout treatment
What are considered patient directed therapy?
Antacids and OTC acid suppressants
Both shown to be effective in symptom relief induced by heartburn promoting meal
Combination of both superior to antacids alone
OTC H2-blockers considered interchangeable
Antacids- MOA
Neutralize acid to raise intragastric pH Decrease activation of pepsinogen Increased LES pressure Benefit- rapid onset Disadvantage- short duration
Antacid- Side effects
GI- diarrhea or constipiation - diarrhea: magnesium -constipation: aluminum -Gas: calcium, sodium bicarbonate Sodium bicarbonate products can cause fluid overload in pts. with CHF, renal failure, cirrhosis, pregnancy, or any salt-restricted diet; avoid in anyone taking supplemental calcium or with renal dysfunction
Antacid- Drug interactions
alter gastric pH, increase urinary pH, adsorbing medications, physical barrier to absorption, form insoluble complexes
Clinically significant- abx- quinolone, isoniazid, tetracycline, ferrous sulfate, quinidine, sulfonylurea
Antacids- Precautions
Use of med >14 days needs evaluation for barrett’s esophagus and upper GI pathology due to increased risk
Pts excessively using antavids should be treated w/ rx drugs, and is considered more significant disease.
What is involved in antacid counseling?
Dose is product-specific…follow manufacturer’s recommendations
Take at onset of symptoms
If potential for drug interactions, separate dosages by at least 2 hours
Use should not exceed 14 days
Pts should be evaluated if using >2x week
H2 receptor antagonists- MOA
Reversibly inhibit histamine-2 receptors on parietal cells
H2 receptor antagonists- USE
On-demand therapy for intermittent mild to moderate GERD symptoms
Preventive dosing before exercise/meals
Prescription strengths needed for more severe symptoms or for maintenance dosing
Less effective than PPIs in healing erosive esophagitis
What drugs are H2 receptor antagonists?
Ranitidine (Zantac) Cimetidine (tagamet) Nixatidine (Axid) Famotidine (Pepcid) Pepcid Complete These resemble histamines
H2- receptor antagonist- Absorption, fate, and excretion
H2 receptor antagonists are rapidly & well absorbed after oral admin.
Peak conc. 1-2 hours
Oral bioavailability of nizatidine ~ 90%
-Whereas first-pass metabolism limits bioavailability of the other compounds to ~50%,
A large part of these drugs are excreted unchanged in the urine and therefore may need a reduction in dosage w/renal impairment.
H2- receptor antagonist- side effects
Well tolerated
HA, somnolence, fatigue, dizziness, constipation or diarrhea
Thrombocytopenia: rare, reversible
H2- receptor antagonist- Drug interactions
Cimetidine
-Inhibition of metabolism of warfarin, phenytoin, nifedipine, propranolol
Acidic environment required for absorption
-Ketoconazole, itraconazole, ferrous sulfate
Antacids vs H2-receptor antagonist
Combination more effective than antacid therapy alone
What is used in acid suppression?
Proton pump inhibitors (PPIs)- eliminate symptoms and heal esophagitis more frequently and rapidly than other drugs
When should PPIs be given?
Prior to meals
What are the names of the PPIs?
Prototypes- omeprazole (prilosec)
Other agents- Lansoprazole (prevacid), esomeprazole (nexium), pantoprazole (Protonix), rabeprazole (aciphex)
Proton pump inhibitor- MOA
- Inhibit the action of the H+,K+ -ATPase.
- All considered prodrugs in that they need to be activated to be effective. They need the acidic environment (H+) to work.
- Requires 18 hours to synthesize new H+,K+ -ATPase molecules
Proton pump inhibitor- ADRs
Generally uncommon
N/D/C
HA, dizziness, somnolence
May have higher incidence of community-acquired pneumonia
-Clinical significance unclear
-Pts with asthma, COPD, immunocompromised, young or elderly may be at risk
Proton pump inhibitors- Drug interactions
P450s
Omeprazole, lansoprazole, esomeprazole and pantoprazole metabolized by P450 enzymes (rabeprazole metabolized thru nonenzymatic reduction pathway)
Omeprazole and esomeprazole reduce metabolism of: Diazepam, Phenytoin, warfarin
When are promotility agents used?
LES incompetence
Decreased esophageal clearance
Delayed gastric emptying
Promotility agents- Side effects
Limited side effect profile:
CNS effects: drowsiness, irritability, extrapyramidal effects
–Metoclopramide (Reglan): contraindicated in Parkinson’s Dz, mechanical obstruction, concomitant use of other dopamine antagonists, anticholinergics, and pheochromocytoma
–Bethanechol (Urecholine): may increase acid production, not well tolerated due to cholinergic side-effects (usually used for the bladder and not intestines)
–Fatal cardiac dysrhythmia: cisapride
Sulcralfate- MOA
Mucosal protectant
Non-absorbable aluminum salt
Compared to H2-receptor antagonist for mild esophagitis
Less effective in refractory esophagitis
Are mucosal protectants (sucralfate) recommended for use in mild cases of GERD?
Yes
Not recommended for used EXCEPT FOR VERY MILD CASES OF GERD
Sulcralfate (Carafate)- Chemistry and effects
- When the pH is below 4, an extensive polymerization & cross-linking of sucralfate to form a sticky, viscid, yellow-white gel.
- The gel adheres to epithelial cells and adheres very strongly to the base of ulcer craters.
Sulcralfate (Carafate)- Clinical utility
- Effective at promoting healing in PUD
- As a maintenance therapy–more efficacious in duodenal than gastric ulcers.
- Used to prevent stress ulcers
- More effective when administer prior to meals than after since acid is needed for activation.
Sulcralfate (Carafate)- ADRs
Constipation - A3+
Dry mouth
Abdominal discomfort
Sulcralfate (Carafate)- drug interactions
Phenytoin
Tetracycline
Fluroquinolone Antibiotics
Digoxin
Ketocanazole
Better to administer these meds 2 hrs before sucralfate
DO NOT administer w/ agents that decrease acid
What is maintenance therapy?
Improvement of symptoms with full dose PPIs usually reverses with discontinuation of therapy
Effective maintenance therapy controls symptoms and prevents complications
Some pts require chronic PPI therapy
What is ineffective maintenance therapy?
Full dose H2-receptor antagonist once daily not appropriate
Reduced dose PPIs
Alternate day dosing
“Weekend” therapy
Dose needed to control symptoms is appropriate dose for maintenance
What are the effects of therapy on complications in GERD?
Acid suppression decreases recurrence of esophageal strictures
Full dose PPIs lengthen time between symptomatic relapses
No data on prevention of prevention of progression of Barrett’s esophagus
–May be some reappearance of squamous epithelium but significance unclear
What can you give to a phase 1 intermittent, mild heart burn patient?
Lifestyle changes
and antacids
and/or low dose OTC H2 receptor antagonist
Or OTC PPI
What can you give to a Phase 2 patient for symptomatic relief of GERD?
Lifestyle cahnges
And standard doses of H2-receptor antagonist for 6-12 wks
Or PPI for 4-8 weeks
What can you give to a phase 3 patient- healing of erosive esophagitis, moderate to severe symptoms, or complications of GERD?
Lifestyle changes
And PPI for 4-1 weeks (up to BID)
Or high doses of H2-receptor antagonist for 8-12 weeks
What are the phase 3 interventional therapies?
Antireflux surgery
Endoluminal therapy
What is peptic ulcer dz?
Ulcers extending deep into the muscularis mucosa
What are the two most common forms of peptic ulcer disease?
H. Pylori associated
NSAID induced
Stress related mucosal damage (3rd)
What does the incidence vary on for peptic ulcer disease?
Ulcer type-duodenal, gastric
Age
Gender
Societal factors- H. pylori, NSAID use, smoking
What are the two main causes of duodenal ulcers?
H. pylori and NSAIDS
What are the sx of duodenal ulcers?
Epigastric pain, often worse at night
Pain typically 1-3 hrs after meal and may be relieved by eating
Pain can be episodic
What are the two most common causes of gastric ulcers?
NSAID use and h. pylori
What are the sx of gastric ulcers?
Epigastric pain, often worse with food
Associated symptoms: heartburn, belching, bloating, nausea, anorexia
What is involved in the etiology of peptic ulcer dz?
H. Pylor
NSAIDS
Psychological stress
Diet- In high concentrations, alcohol associated with acute gastric mucosal damage, upper GI bleed
Smoking: unclear mechanism, impairs healing, higher death rates
Helicobacter pylori
Gram negative rode that colonized the mucus on the luminal surface of the gastric epithelium
Causes inflammatory gastritis
How is H. pylori transmitted?
Fecal-oral
Oral-oral
Iatrogenic
How do you document an H. pylori infection?
Usually a blood test
Breath test for urea
What are the complications of peptic ulcer dz?
Zollinger-Ellison Syndrome
Upper GI bleed
Perforation
Obstructions
Zollinger-Ellison Syndrome
- -Gastric acid hypersecretion and recurring ulceration from a gastrin-secreting tumor
- -Appox. 1% of patients
- -Can metastasize
- -Treatment: PPIs
Upper GI bleed
- -Erosion of ulcer into artery
- -10-15% pts
- -Presentation: Occult and insidious, Melena or hematemesis
- -Fatal- Uncontrolled bleed, Rebleeding
Perforation
- -Ulceration into a cavity
- -7% of patients
- -Increases with NSAID use
- -Mortality higher in perforated gastric ulcer vs duodenal ulcer
Obstruction
- -2% of patients
- -Typically in chronic PUD
- -Caused by scarring or edema of duodenal bulb or pyloric channel land lead to gastric retention
- -Symptoms:Over several months, Early satiety, bloating, anorexia, nausea, vomiting, weight loss
What is the three drug regimen for peptic ulcer dz?
P= PPI A= Amoxicillin C= Clarithromycin
OR
P=PPI
M==Metronidazole
C=Clarithromycin
what is the drug of choice for PUD?
PPIs
What is the 4 drug regimen for peptic ulcer dz?
P=PPI (or H2 blcoker)
B= Peto bismol
M=Metronidazole
T=tetracycline (or amox, or clarithro)
How do you treat treatment failures?
Retreat with different antibiotics Use Bismuth based regimen Extended treatment duration Assess adverse effects Assess compliance
Bismuth Subsalicylate (pepto-bismol)- beneficial effects
Cytoprotection through enhanced secretion of mucus and HCO3-.
Inhibit pepsin activity.
Accumulate bismuth subcitrate in craters of gastric ulcers.
Antibacterial effects: Reduce bacterial adherence to mucosal cells, Damage bacterial cell walls.
Promote healing of both gastric and duodenal ulcers
Bismuth Subsalicylate (pepto-bismol)- ADRs
- Reaction of bismuth w/bacterial H2S leads to bismuth sulfide causing a black color to the oral cavity and to feces.
- Aspirin ADRs
Prostaglandin Analogs- MOA
- Misoprostol is a synthetic analogue of prostaglandin E.
- Imitates the action of endogenous prostaglandins (PGE2 and PGI2) in maintaining the integrity of the gastroduodenal mucosal barrier.
- Promotes healing.
Prostaglandin analogs- Indications
Ulcer healing
Ulcer prophylaxis w/ NSAID use
Prostaglandin Analog- contraindications
Hypotension
Breastfeeding
Pregnant
Prostaglandin Angalog- ADRs
Diarrhea
Constipation
What is the nonpharmacologic treatment of PUD?
Eliminate or reduce: Psychological stress Cigarette smoking The use of NSAIDs including aspirin -Consider APAP -Lowering the dose -Nonacetylated salicylate (salsalate) -Relatively selective COX-2 inhibitors (nabumetone, etodolac) or highly-selective COX-2 inhibitors (celecoxib) -Co-administration w/H2 antagonist or PPI
What are the diet changes for nonpharmacologic treatment of PUD?
Avoid food and beverages that cause dyspepsia or exacerbate ulcer symptoms: spicy foods, caffeine, ETOH
