Chapter 64: Peptic Ulcer Disease Flashcards
PUD
Group of upper gastrointestinal (GI) disorders
Degrees of erosion of the gut wall
Severe erosion can be complicated by hemorrhage and perforation
PUD causes
Imbalance between mucosal and aggressive factors
Gastric defensive factors
Mucus
Secreted cells of the GI mucosa
Forms a barrier to protect underlying cells from acid and pepsin
Bicarbonate
Secreted by epithelial cells of stomach and duodenum
Most remains trapped in mucus layer to neutralize hydrogen ions that penetrate the mucus
Blood flow
Poor blood flow can lead to ischemia, cell injury, and vulnerability to attack
Prostaglandins
Stimulate the secretion of mucus and bicarbonate
*NSAIDs and H pylori are 2 major agents that weaken defensive mechanism
*mucous and bicarbonate are major defensive mechanisms
Aggressive factors of PUD: H pylori
Helicobacter pylori, also known as H. pylori
Gram-negative bacillus that can colonize the stomach and duodenum
Lives between epithelial cells and the mucus barrier
Escapes destruction by acid
Can remain in the GI tract for decades
Half of the world is infected, but most people do not develop symptomatic peptic ulcer disease (PUD)
60% to 70% of patients with PUD have H. pylori infection
H. pylori may also promote gastric cancer
Duodenal ulcers are much more common among people with H. pylori infection than among people who are not infected
Eradication of the bacterium promotes healing of the PUD and minimized recurrence of PUD
Aggressive factors of PUD : NSAIDs
Inhibit the biosynthesis of prostaglandins
Reduce blood flow, mucus, and bicarbonate
Aggressive factors of PUD: gastric acid
Causes ulcers directly by injuring cells of the GI mucosa and indirectly by activating pepsin
Increased acid alone does not increase ulcers but is a definite factor in PUD
Zollinger-Ellison syndrome
Pathogenesis of PUD: pepsin
Proteolytic enzyme in gastric juice
Pathogenesis of PUD: smoking
Delays ulcer healing and increases risk for recurrence
Summary of ulcer development
Most common cause
Infection with H. pylori is the most common cause of gastric and duodenal ulcers
Additional factors must be involved; 50% harbor H. pylori, but only 10% develop PUD
Second most common cause
NSAIDs
Overview of tx for PUD
Goals of drug therapy
Alleviate symptoms
Promote healing
Prevent complications
Prevent recurrence
Drugs do not alter the disease process; they create conditions conducive to healing
Classes of Antiulcer Drugs
Antibiotics
Antisecretory agents
Mucosal protectants
Antisecretory agents that enhance mucosal defenses
Antacids
Three Ways Antiulcer Drugs Work
- Eradicate H pylori -antibiotics
- Reduce gastric acidity -anti secretory agents, misprostol
- Enhance mucosal defenses -sucralfate, misoprostol
H pylori ulcers drug selection
Antibiotics
Should be given to all patients with gastric/duodenal ulcers and documented H. pylori infection
Antisecretory agents
NSAID-induced ulcer drug selection
Prophylaxis:
Risk factors for ulcer development: Age over 60 years, history of ulcers, high-dose NSAID therapy
Proton pump inhibitors (PPIs) are preferred (e.g., omeprazole)
Misoprostol is also effective but can cause diarrhea
Treatment
Histamine blockers and PPIs (e.g., omeprazole) are preferred
Antacids, sucralfate, and histamine2 receptor blockers are not recommended
Discontinue NSAIDs if possible
Evaluation of treatment
Monitor for relief of pain, endoscopic exams, check for H pylori in stools
Pepsin
Proteolytic enzyme that can contribute to ulcer formation; it promotes ulcers by breaking down protein in the gut wall
Activity of pepsin is pH dependent; drugs that elevate gastric pH (e.g., antacids, histamine2 antagonists, PPIs) can cause peptic activity to increase, thereby enhancing pepsin’s destructive effects
To avoid activation of pepsin, drugs that reduce acidity should be administered in doses sufficient to raise the gastric pH above 5
Non drug ulcer therapy
Diet
Traditional “ulcer diet” does not accelerate healing
No convincing evidence indicates that caffeinated beverages promote ulcers or delay healing
Change in eating pattern to five or six small meals a day reduces pH fluctuations
Avoid smoking, aspirin, other NSAIDs, and alcohol
Stress reduction
Evaluation of Therapy for ulcers
Monitor for relief of pain
Keep in mind: Cessation of pain and disappearance of ulcer rarely coincide
Pain may subside before complete healing or may continue after healing
Radiologic or endoscopic examination of ulcer site
H. pylori tests
H pylori tests
Noninvasive
Breath test
Serologic test
Stool test
Invasive
Endoscopic specimen obtained and evaluated
Stained and viewed under microscope to see if H. pylori is present
Assayed for the presence of urease (a marker enzyme for H. pylori)
Cultured and then assayed for the presence of H. pylori
H pylori tx
Minimum of two antibiotics prescribed (up to three may be used) to reduce risk of resistance developing
Amoxicillin
Clarithromycin
Bismuth compounds
Tetracycline
Metronidazole
Tinidazole
Antibiotic Regimen for h pylori
Clarithromycin (if the area doesn’t have high resistance), amoxicillin, bismuth, metronidazole, and tetracycline
None is effective alone
Want them in combination
If these drugs are used alone, the risk of resistance developing increases
Goal: Minimize emergence of resistance; guidelines recommend using at least two antibiotics, preferably three
Antisecretory agent: PPI or histamine2 receptor antagonist (H2RA) also should be used
Eradication rates are good with a 10-day course and slightly better with a 14-day course
Clarithromycin [Biaxin]
Suppresses the growth of H. pylori by inhibiting protein synthesis
In the absence of resistance, treatment is highly effective
Unfortunately, rate of resistance is rising, exceeding 20% in some areas
Most common side effects
Nausea
Diarrhea
Distortion of taste
Amoxicillin
H. pylori is highly sensitive to amoxicillin
Rate of resistance is low, only about 3%
Amoxicillin kills bacteria by disrupting cell wall
Antibacterial activity is highest at a neutral pH and thus can be enhanced by reducing gastric acidity with an antisecretory agent (e.g., omeprazole)
Most common side effect is diarrhea
Bismuth Compounds
Act topically to disrupt the cell wall of H. pylori, causing lysis and death
Also may inhibit urease activity and may prevent H. pylori from adhering to the gastric surface
Can impart a harmless black coloration to the tongue and stool
Patient teaching
Long-term therapy: Possible risk of neurologic injury
Tetracycline
Inhibitor of bacterial protein synthesis
Highly active against H. pylori
Resistance is rare (less than 1%)
Do not use in pregnant patients and young children because tetracycline can stain developing teeth
Metronidazole [Flagyl]
Very effective against sensitive strains of H. pylori
Over 40% of strains are now resistant
Most common side effects are nausea and headache
Avoid alcohol: Disulfiram-like reaction can occur if metronidazole is used with alcohol
Avoid use during pregnancy
Tinidazole [Tindamax]
Very similar to metronidazole
Has the same adverse effects and interactions
Can cause a disulfiram-like reaction
Do not combine with alcohol
Histamine2 Receptor Antagonists
Cimetidine [Tagamet]
Ranitidine [Zantac]
Famotidine [Pepcid]
Nizatidine [Axid]
All OTC
Typically, when someone presents with PUD, they have tried one, if not many of these before they seek medical tx
First-choice drugs for treating gastric and duodenal ulcers
Promote healing by suppressing secretion of gastric acid
All four are equally effective
Serious side effects are uncommon
Cimetidine [Tagamet] pharmacokinetics
Absorption is slowed if taken with meals
Crosses the blood-brain barrier with difficulty
May cause some CNS side effects
Cimetidine [Tagamet] therapeutic uses
Gastric and duodenal ulcers
Gastroesophageal reflux disease (GERD)
Zollinger-Ellison syndrome
Hypersecretion of gastric secretions lead to PU
Aspiration pneumonitis
Heartburn, acid indigestion, sour stomach
Tagamet ADR
Antiandrogenic effects
CNS effects
Pneumonia
IV bolus: Can cause hypotension and dysrhythmias
Tagamet drug interactions
Warfarin, phenytoin, theophylline, lidocaine
Antacids can reduce absorption of cimetidine
Cimetidine and antacids should be administered at least 1 hour apart
Ranitidine [Zantac]
Has many of the properties of cimetidine
More potent, fewer adverse effects, fewer drug interactions than cimetidine
Zantac ADR
Significant ones are uncommon
Does not bind to androgen receptors
Elevation of gastric pH may increase the risk of pneumonia
Zantac therapeutic uses
Short-term treatment of gastric/duodenal ulcers
Prophylaxis of recurrent duodenal ulcers
Treatment of Zollinger-Ellison syndrome and hypersecretory states
Treatment of GERD
Famotidine [Pepcid]
Actions similar to those of ranitidine
Pepcid uses
Short-term treatment of gastric/duodenal ulcers
Prophylaxis of recurrent duodenal ulcers
Treatment of Zollinger-Ellison syndrome and hypersecretory states
Treatment of GERD
Over-the-counter (OTC): Treatment of heartburn, acid indigestion, sour stomach
Pepcid ADR
No antiandrogenic effects because it does not bind to androgen receptors
Possible increased risk for pneumonia caused by elevation of pH
Nizatidine [Axid]
Actions much like those of ranitidine and famotidine
Therapeutic uses
Duodenal/gastric ulcers
GERD, heartburn, acid indigestion, sour stomach
Proton Pump Inhibitors
Most effective drugs for suppressing secretion of gastric acid
Therapeutic uses: Short term
Gastric/duodenal ulcers
GERD
Well tolerated
Selection of PPI is based on cost and prescriber’s preference
Can increase the risk of serious adverse events, including fracture, pneumonia, acid rebound, and possibly intestinal infection with Clostridium difficile
Omeprazole [Prilosec] actions
First available PPI
Actions and characteristics;
Inhibits gastric secretion
Short half-life
Used for short-term therapy
Ulcer prophylaxis is indicated only for patients in intensive care units, and then only if they have an additional risk factor, such as multiple trauma, spinal cord injury, or prolonged mechanical ventilation (longer than 48 hr)
30 mg dose will decrease acid production by 90-97% in 2 hr
Prilosec ADR
Usually inconsequential with short-term use
Headache
GI effects
Pneumonia
Fractures
Hypomagnesemia
Rebound acid hypersecretion
C. difficile infection
Gastric cancer
Barrett’s esophagitis and that’s precancous
For PUD, when med is d/c, can easily get a reoccurrence of the ulcer
HA an GI SE are minimal
Esomeprazole [Nexium, Nexium I.V.]
Nearly identical to omeprazole [Prilosec]
Uses: Erosive esophagitis, GERD, duodenal ulcers associated with H. pylori infection, prophylaxis of NSAID-induced ulcers
Adverse effects: Headache, diarrhea, nausea, flatulence, abdominal pain, dry mouth, pneumonia, hypomagnesemia, osteoporosis, fractures
Lansoprazole [Prevacid, Prevacid IV, Prevacid 24 HR]
Very similar to omeprazole
Adverse effects: Diarrhea, abdominal pain, nausea, pneumonia, hypomagnesemia, osteoporosis, fracture
Dexlansoprazole [Dexilant]
Reduces gastric acidity by inhibiting gastric H+,K+-ATPase
Uses: Treatment and maintenance of healing of erosive esophagitis; treatment of symptomatic GERD (heartburn)
Adverse effects: Diarrhea, abdominal pain, nausea, vomiting, flatulence, upper respiratory infection, hypomagnesemia, osteoporosis, fractures
Used much less than others
Rabeprazole
Much like omeprazole and lansoprazole in actions, uses, and adverse effects
Uses: H. pylori eradication, duodenal ulcers, GERD, hypersecretory states (e.g., Zollinger-Ellison syndrome)
Mechanism of action: Reduces gastric acidity by inhibiting gastric H+,K+-ATPase
Pantoprazole [Protonix]
Similar to omeprazole and the other PPIs
Uses: Treatment of GERD and hypersecretory states
Adverse effects
Oral: Diarrhea, headache, dizziness
IV: Diarrhea, headache, nausea, dyspepsia, injection-site reactions, including thrombophlebitis and abscess
Long-term use: Hypomagnesemia, osteoporosis, fractures
Other anti ulcer drugs
Sucralfate [Carafate]
Misoprostol [Cytotec]
Antacids
Sucralfate [Carafate]
Creates a protective barrier for up to 6 hours
Therapeutic uses
Acute ulcers and maintenance therapy
Adverse effects
Constipation (only 2% of patients)
Drug interactions
Minimal
Antacids may interfere with effects of sucralfate
Misoprostol [Cytotec]
Therapeutic uses
Only approved GI indication is prevention of gastric ulcers caused by long-term NSAID therapy
Adverse effects
Most common: Dose-related diarrhea and abdominal pain
Contraindicated during pregnancy: Category X
Significant actions need to be taken to ensure that pregnancy does not occur after therapy starts and that patient is not pregnant at therapy initiation
Antacids
React with gastric acid to produce neutral salts or salts of low acidity
Reduce destruction of gut wall by neutralizing acid
May also enhance mucosal protection by stimulating production of prostaglandins
Except for sodium bicarbonate, antacids do not alter systemic pH
Use with caution in patients with renal impairment
Adverse effects
Constipation: Aluminum hydroxide
Diarrhea: Magnesium hydroxide
Sodium loading
Drug interactions
Cimetidine
Ranitidine
Sucralfate
Antacid Families
Aluminum compounds
Magnesium compounds
Calcium compounds
Sodium compounds
Magnesium Hydroxide [Milk of Magnesia]
Rapid-acting, high acid-neutralizing capacity (ANC), produces long-lasting effects
An antacid of choice
Most prominent adverse effect is diarrhea
Usually taken in combination with aluminum hydroxide, an antacid that promotes constipation
Avoided in patients with undiagnosed abdominal pain
Frequently used as a laxative
Use with caution in patients with renal failure
Aluminum Hydroxide
Relatively low ANC, slow acting
Effects have long duration
Rarely used alone
Widely used in combination with magnesium hydroxide
Caution: Significant amounts of sodium
Constipation
Drug interactions: Tetracyclines, warfarin, digoxin
Calcium Carbonate
Rapid-acting, high ANC, effects have long duration
Acid rebound
Principal adverse effect: Constipation, which can be overcome by combining calcium carbonate with a magnesium-containing antacid (e.g., magnesium hydroxide)
Eructation (belching) and flatulence
Low palatability
Sodium Bicarbonate
Useful for treating acidosis and elevating urinary pH to promote excretion of acidic drugs after overdose
Inappropriate for treating PUD: Brief duration, high sodium content, can cause alkalosis
Eructation and flatulence
Can exacerbate hypertension and heart failure
Can cause systemic alkalosis in patients with renal impairment
Combo packs
Helidac
Pylera
Prevpac
