for Patients
Therapy of Hp + PUD
The commonly used fi rst-line standard triple ther- apy includes two antibiotics, such as clarithromy- cin or metronidazole, and amoxicillin along with a PPI, such as omeprazole, lansoprazole, panto- prazole, rabeprazole, or esomeprazole, and is given for 7–14 days. Sequential therapy, which shows signifi cantly higher eradication rates [ 27 ], generally consists of PPI and amoxicillin for the fi rst 5 days, followed by PPI along with clarithro- mycin and metronidazole for 5 days.
Second-line treatment adds bismuth salts or a fl uoroquinolone-based antibiotic (e.g., levofl oxa- cin or moxifl oxacin) to PPI and the other antibiot- ics. If second-line therapy fails, further eradication depends on the antibiotic susceptibility [ 28 ].
In patients with antrum-predominant gastritis, eradication of Hp restores impaired gastrin- somatostatin link, decreases basal and stimulated acid secretion in the stomach, and restores acid load in the duodenum. However, the atrophy of gastric mucosa does not reverse after successful eradication of Hp [ 29 ].
Therapy of Hp − PUD
Most antacids are inorganic salts (magnesium and/
or aluminum hydroxide and/or bicarbonate, and calcium carbonate), which neutralize gastric acid
directly. Aluminum additionally increases synthe- sis of PGE 2 and gastric mucosal microcirculation, yet it may cause constipation. Magnesium can cause diarrhea. Due to their adsorptive capacity, these antacids may hinder intestinal absorption of concurrent medication. Moreover, antacids con- taining sodium bicarbonate, magnesium hydrox- ide, and calcium carbonate are contraindicated in patients with renal insuffi ciency [ 30 ].
Anticholinergics (e.g., pirenzepine or telenze- pine) speed up the healing of peptic ulcers due to their inhibitory effect on gastric acid secretion.
However, side effects include visual disturbances, photophobia, and dryness of the mouth, limiting their use, especially in patients with glaucoma (see chapter “ Glaucoma ”), enlarged prostate, or stenosis of the pylorus sphincter [ 31 ].
H2RAs (e.g., cimetidine, ranitidine, famoti- dine, nazatidine, roxatidine) competitively and reversibly block the H2R on the basolateral membrane of the parietal cells inhibiting mainly basal and partially meal-stimulated gastric acid secretion. Possible side effects of H2RAs include the development of tolerance and rebound acid hypersecretion (a temporary increase in gastric acid secretion after the abrupt withdrawal of H2RA) [ 32 ].
PPIs (e.g., omeprazole, lansoprazole, panto- prazole, and rabeprazole) inhibit acid secretion by the parietal cell [ 33 ]. Although gastric acid inhibition is very effective, prolonged suppres- sion favors small intestinal bacterial overgrowth and concomitant malabsorption and facilitates enteric infections (especially with Clostridium diffi cile ), as bacteria are no longer effectively eliminated in the stomach [ 34 ]. Additionally, osteoporosis (due to parathyroid hyperplasia, see chapter “ Osteoporosis ”) and hyperplasia of enterochromaffi n cells (due to chronic hypergas- trinemia) can develop (Fig. 2 ) [ 35 ].
To enhance mucosal defense, initially, miso- prostol, a prostaglandin E1 analogue, was used.
Unfortunately, its use was limited by abdominal pain and diarrhea due to its stimulatory effect on intestinal motility [ 36 ]. Sucralfate exerts protec- tive action by increasing the synthesis of muco- sal growth factors, mucosal microcirculation, and by angiogenic actions [ 37 ]. Colloidal bis- muth subcitrate accelerates ulcer healing by the
Peptic Ulcer Disease
134
formation of occlusive complexes and the accu- mulation of epidermal growth factor (EGF) in the ulcer crater [ 38 ].
Rebamipide is cytoprotective and enhances gastric mucus production, stimulates the release of endogenous prostaglandins, and inhibits the generation of ROS [ 39 ].
Perspectives
Thanks to a declining prevalence of Hp infection and introduction of effective anti-Hp therapies, PUD frequency is decreasing [ 40 ], and NSAIDs- induced ulcers now emerge as the most important cause of PUD.
With regard to the increasing resistance rate of Hp and rising frequency of Hp − ulcers, novel therapies to strengthen the mucosal defense are urgently needed. New candidates to reinforce the mucosal defense include melatonin, probiot- ics, H 2 S, NO, and CO [ 41 ]. Melatonin enhances gastric microcirculation and exerts antioxidative effects on the gastric mucosa, independently of prostaglandin synthesis [ 42 ]. Some probiot- ics increase production of mucosal growth fac- tors and reduce proinfl ammatory cytokines [ 43 ].
Finally, H 2 S, NO, and CO were shown to increase protective prostaglandins in gastroduodenal mucosa and inhibit the generation of proinfl am- matory cytokines [ 44 ].
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E. Lammert, M. Zeeb (eds.), Metabolism of Human Diseases, 137 DOI 10.1007/978-3-7091-0715-7_22, © Springer-Verlag Wien 2014