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The most appropriate therapy for peptic ulcer disease depends on the
cause. The treatment of both gastric and duodenal ulcers involves suppression
of acid secretion and eradication of H pylori (if present). Antisecretory
therapy speeds up the healing process and allows faster relief of symptoms. The
eradication of H pylori in high-risk patients has been shown to greatly
lower the risk of subsequent ulceration and prevent recurrent bleeding in
patients with bleeding peptic ulcers.
It is important to suppress nocturnal acid secretion in patients with
duodenal ulcers. A maintenance antisecretory therapy may be recommended in
patients at high risk for ulceration (ie history of ulcer complications,
frequent recurrences) and for H pylori infection unresponsive to repeat
treatment. Consider primary prophylaxis with antisecretory agents in patients with
a prior history of PUD and on steroids or who are >65 years old, those with
severe physiologic stress, hypoperfusion or extensive burns, patients at high
risk of GI complications from NSAIDs, or those with concomitant high-dose
steroid, antithrombotic or anticoagulant use. Secondary prophylaxis could be
considered for patients with prior complications from PUD (eg bleeding, obstruction
and perforation).
Pharmacological therapy
Antacids
Antacids neutralize gastric acid and lower pepsin activity. This is effective
in relieving symptoms of peptic ulcer disease, promoting healing of ulcers, and
reducing recurrence. It is used for short-term relief of symptoms. Antacids may
be absorbable (eg Sodium bicarbonate, Calcium bicarbonate) or non-absorbable
(eg Aluminum or Magnesium hydroxide). Absorbable antacids may provide fast and
complete neutralization but may cause alkalosis and should only be used for 1-2
days. Non-absorbable antacids are preferred due to lesser systemic side effects.
Peptic Ulcer Disease_Management 1Bismuth Subcitrate
Bismuth subcitrate has high affinity for damaged tissue. This coats the base of the ulcer crater that provides protection against gastric acid, pepsin and bile. Treatment efficacy is comparable with H2RAs and other ulcer-healing agents.
Histamine2-Receptor Antagonists (H2RAs)
Example drugs: Cimetidine, Famotidine, Lafutidine, Nizatidine, Ranitidine, Roxatidine
Histamine2-receptor antagonists decrease gastric secretion by blocking histamine action at the H2-receptors in the parietal cells of the stomach. All H2RAs are equally effective in healing duodenal ulcers. Healing rates were 70-80% after 4 weeks of therapy and 87-95% after 8 weeks.
Double doses of H2RAs are effective in decreasing the risk of NSAID-induced gastric ulcer. H2RAs given with NSAIDs may be a cost-effective way of preventing ulcer bleeding secondary to NSAID use; however, no clinical data is available that proves that this strategy prevents ulcer complications. No study has evaluated the efficacy of H2RAs in chronic NSAID users. This is less effective than PPIs. H2RAs are generally well tolerated but can cause mild central nervous system (CNS) effects due to their ability to cross the blood-brain barrier and react with CNS histamine receptors. Cimetidine and Ranitidine both interact with the hepatic cytochrome P-450 mixed oxidase system and can alter the metabolism of different drugs.
Potassium-Competitive Acid Blockers (PCABs)
Example drugs: Revaprazan, Tegoprazan, Vonoprazan
Potassium-competitive acid blockers reversibly inhibit the activity of H+/K+-ATPase by competing for potassium on the luminal side of the parietal cells. The full effect is achieved with the first dose due to its rapid onset of action and with similar effects seen on succeeding doses. A comparable safety profile and similar efficacy in healing and prevention of NSAID-induced ulcers with PPIs. Tegoprazan and Vonoprazan, in combination with antibiotics, are effective for the eradication of H pylori associated with PUD.
Prostaglandin Analogues
Example drug: Misoprostol
Prostaglandin analogues protect the gastroduodenal mucosa by promoting the secretion of bicarbonate and mucus, and by augmenting mucosal blood flow and cell restoration in the gastric mucosa. These also have an antisecretory effect when given in high doses. These are useful in healing ulcers and preventing ulcer recurrence. These are primarily recommended for the prevention of NSAID-induced gastroduodenal ulceration. Prostaglandin analogues need frequent dosing and are associated with more side effects than H2Ras; hence, these are generally not used for the treatment of PUD. The major drawback is the incidence of diarrhea and its abortifacient property; hence, these are not for use by pregnant women and women of childbearing age.
Proton Pump Inhibitors (PPIs)
Example drugs: Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole
Proton pump inhibitors are the most potent inhibitors of gastric acid secretion. These irreversibly inhibit the activity of the H+/K+-ATPase pump of gastric parietal cells. These have a similar safety profile to H2RAs but heal peptic ulcers faster than H2Ras. These have an 80-100% healing rate after 4 weeks of therapy in patients with duodenal ulcers and 8 weeks for patients with gastric ulcers. Co-medication with PPIs is better than with H2RAs in preventing ulcer bleeding in patients on antiplatelet or anticoagulant therapy.
Proton pump inhibitors are extensively used in combination with NSAIDs to prevent NSAID-induced peptic ulcers. These are associated with significant risk reduction for upper GI bleeding in patients who use NSAIDs. These are the main agent for prophylaxis and treatment of NSAID-related upper GI injury. PPI in combination with COX-2 inhibitors is associated with the highest risk reduction for recurrent complications of ulcers and may be given for primary prophylaxis or if long-term NSAIDs are needed.
In high-risk patients with a non-variceal peptic ulcer bleed, high-dose IV or oral PPIs may be given after endoscopic hemostasis is achieved to decrease the incidence of rebleeding and possible need for surgery. Oral PPIs are recommended to be given for 6-8 weeks after endoscopic treatment of bleeding peptic ulcer for mucosal healing. Refractory PUD may be treated with double-strength PPIs to achieve healing. Long-term PPI therapy may be offered to patients with idiopathic ulcers. These may also be used in patients with gastric outlet obstruction to heal any active ulcers. PPIs may be incorporated with calcium supplements to mitigate increased risk of bone fractures associated with long-term use.
Sucralfate
Sucralfate has been used to treat PUD and has similar healing rates as antacids and H2Ras. This protects the gastroduodenal mucosa by adhering to the base of the ulcer, adsorbing bile acids, inactivating pepsin, and stimulating bicarbonate and mucus secretion without affecting gastric acid secretion. This may also be used in preventing duodenal ulcer relapse. Sucralfate has an excellent safety profile and is generally well tolerated. The treatment duration for PUD is 4 weeks.
Nonpharmacological
Patient Education
Alcohol
Alcohol is a strong promoter of acid secretion. It is an independent
risk factor for peptic ulcer disease. Chronic alcohol drinkers develop
ulceration, while occasional drinkers may only have gastritis. The recurrence
rates of patients who consume alcohol were significantly higher in patients with
gastric ulcer recurrence compared to duodenal ulcer recurrence with ulcers
reappearing at the same or adjacent sites as the previous ulcers. Patients
should be advised to limit their alcohol intake to 1 alcoholic drink/day.
Diet
There
is limited evidence that changing the diet hastens ulcer healing or prevents
recurrence. Patients should be advised to avoid specific foods that may
precipitate dyspepsia, eg coffee, caffeinated soda, fatty and spicy foods. Milk
has been shown to be a potent gastric acid secretion stimulus.
Medication
Use
Aspirin,
NSAIDs and corticosteroids can cause peptic ulceration. Cardiologists should
carefully assess the need for Aspirin in patients with a history of PUD.
Patients should be advised to discontinue NSAID use; if not possible,
alternative agents may be considered to prevent the development of peptic
ulceration and mucosal injury. Prolonged NSAID use should be given with a proton
pump inhibitor (PPI), high-dose (2x) histamine2-receptor antagonists
(H2RAs), or Misoprostol. A selective cyclooxygenase-2 (COX-2)
inhibitor should be substituted for a traditional NSAID. COX-2 inhibitors cause
a significantly lower incidence of ulceration and ulcer complications, but their
use has been decreased due to their association with myocardial infarction and
thrombotic cardiovascular (CV) events. Current studies suggest that both coxibs
and NSAIDs, with the possible exception of full-dose Naproxen, increase CV risk.
Peptic Ulcer Disease_Management 2Smoking
Smoking increases the risk of ulcer recurrence and slows healing. The risk of PUD is correlated with the number of cigarettes smoked per day. The recurrence rates of patients who smoked were significantly higher in patients with gastric ulcer recurrence compared to duodenal ulcer recurrence, with ulcers reappearing at the same or adjacent sites as the previous ulcers. Patients should be advised to stop smoking.
Psychosocial Factors
Inability to tolerate stress and depressive symptoms increases the risk of ulcer development. Work-related stress, social problems, and post-traumatic stress disorder are also predictive of subsequent ulcer disease. Counseling patients regarding stress reduction can be helpful.
Phẫu thuật
Surgery
is recommended in patients with emergent ulcer-related complications (eg
hemorrhage, perforation, gastric outlet obstruction), PUD refractory to medical
and/or endoscopic management, or rare causes of ulcer disease (eg gastrinoma,
Zollinger-Ellison syndrome). The most common indication for surgery is bleeding.
Surgical hemostasis is recommended for patients with bleeding peptic ulcers
after failure of repeated endoscopy or after initial endoscopy in patients with
>2 cm ulcers, hypotension, and/or unstable hemodynamic status. Peritonitis resulting
from perforation is a surgical emergency that needs patient resuscitation,
laparotomy and peritoneal toilette, or omental patch placement.
Definitive
ulcer surgeries include truncal vagotomy, selective vagotomy, highly selective
vagotomy, or partial gastrectomy for duodenal ulcer and partial gastrectomy with
gastroduodenal or gastrojejunal anastomosis for gastric ulcer. Chronic
obstruction may be relieved by vagotomy and pyloroplasty, antrectomy, or
gastroenterostomy. The indications for elective peptic ulcer surgery include
resection of ulcers suspected to be malignant, failure to heal despite maximal
medical therapy (intractability), intolerance or non-compliance with medical
regimen, and relapse while on maximal medical therapy.