Flashcards in GERD/Peptic Ulcer Disease Deck (94):
The physiology of gastric acid secretion is modulated by which pathways?
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
What are the four mechanisms associated with GERD?
-Decreased lower esophageal sphincter pressure
-Prolonged esophageal clearance
-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?
Dihydropyridine Ca2+ channel blockers
What are the food causes of decreased LES?
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?
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?
What medications are mucosal irritants?
Aledronate (take w/ full glass water then upright 30 min to avoid ulcerations)
What is involved in gastric emptying?
Problem- delayed gastric emptying time. Factors increasing gastric volume/decreasing gastric emptying- smoking and high fat meals
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
Avoid high-fat meals
Avoid supine body position
Avoid tight fitting clothing
What are typical symptoms of GERD?
What are the atypical symptoms of GERD?
How is GERD diagnosed?
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?
Esophageal strictures (Complicated by ASA/NSAIDS)
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?
Unexplained weight loss
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?
Suppression of Gastric acid production
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 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
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
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
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
-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
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?
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
HA, somnolence, fatigue, dizziness, constipation or diarrhea
Thrombocytopenia: rare, reversible
H2- receptor antagonist- Drug interactions
-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
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
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?
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
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?
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+
Sulcralfate (Carafate)- drug interactions
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
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?
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?
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?
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?
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
Stress related mucosal damage (3rd)
What does the incidence vary on for peptic ulcer disease?
Ulcer type-duodenal, gastric
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?
Diet- In high concentrations, alcohol associated with acute gastric mucosal damage, upper GI bleed
Smoking: unclear mechanism, impairs healing, higher death rates
Gram negative rode that colonized the mucus on the luminal surface of the gastric epithelium
Causes inflammatory gastritis
How is H. pylori transmitted?
How do you document an H. pylori infection?
Usually a blood test
Breath test for urea
What are the complications of peptic ulcer dz?
Upper GI bleed
--Gastric acid hypersecretion and recurring ulceration from a gastrin-secreting tumor
--Appox. 1% of patients
Upper GI bleed
--Erosion of ulcer into artery
--Presentation: Occult and insidious, Melena or hematemesis
--Fatal- Uncontrolled bleed, Rebleeding
--Ulceration into a cavity
--7% of patients
--Increases with NSAID use
--Mortality higher in perforated gastric ulcer vs duodenal ulcer
--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?
what is the drug of choice for PUD?
What is the 4 drug regimen for peptic ulcer dz?
P=PPI (or H2 blcoker)
B= Peto bismol
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
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.
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.
Prostaglandin analogs- Indications
Ulcer prophylaxis w/ NSAID use
Prostaglandin Analog- contraindications
Prostaglandin Angalog- ADRs
What is the nonpharmacologic treatment of PUD?
Eliminate or reduce:
The use of NSAIDs including aspirin
-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