CRITICAL FACTS:
(if med school is a Minnesota forest with millions of trees,
these are the red pines)
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Antimicrobials (METRONIDAZOLE, AMOXICILLIN, CLARITHROMYCIN or TETRACYCLINE) are the most effective drugs for preventing and treating peptic ulcer disease because they eradicate H. pylori. Selection of these specific agent(s) is complicated and related to issues of susceptibility, drug distribution, and resistance. Treatment regimens are being tested constantly in clinical trials and will change over time.
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AMOXICILLIN is the penicillin of choice for H. pylori treatment (ampicillin should not be substituted), because it is a broad-spectrum penicillin with good oral bioavailability and acid stability.
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CLARITHROMYCIN is the macrolide antibiotic of choice for H. pylori treatment (AZITHROMYCIN and ERYTHROMYCIN should not be substituted). CLARITHROMYCIN has a substantially lower MIC90, is more acid stable and has fewer side effects.
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TETRACYCLINE can be used to treat H. pylori infections. Co-administration of TETRACYCLINE with antacids (or any substance containing metal ions) significantly decreases antibiotic efficacy due to chelation.
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Proton pump inhibitors (OMEPRAZOLE/ESOMEPROZOLE, RABEPRAZOLE, LANSOPROZOLE and PANTOPROZOLE) are the most effective agents for reducing intragastric acidity because they IRREVERSIBLY block the final common pathway in acid secretion: H+/K+ ATPase.
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H2 receptor blockers (CIMETIDINE, FAMOTIDINE, NIZATIDINE and RANITIDINE) effectively decrease all forms of gastric acid secretion (esp. nocturnal). With the exception of CIMETIDINE, oral administration has few side effects, which is why they have widespread OTC use.
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Weak bases (e.g., ALUMINUM HYDROXIDE and MAGNESIUM HYDROXIDE) are used to buffer stomach acid; antacids differ greatly in efficacy and side effects. These differences can be predicted based on the degree of systemic absorption, the rate of dissolution and reactivity , as well as the effects of cations and/or reaction products.
- To distinguish among agents that decrease intragastric acidity:
ANTACIDS: rapid onset but short duration of action; no prevention of ulcer recurrence à useful for intermittent dyspepsia
H2 BLOCKERS: relatively rapid onset, intermediate duration, some prevention à many uses
PPIs: slow onset of action, very long duration of action, excellent prevention à drugs of choice for Zollinger-Ellison syndrome and GERD, as well as ulcer treatment
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SUCRALFATE and BISMUTH SUBSALICYLATE protect the ulcer surface by different mechanisms .
- Based on mechanism of action, MISOPROSTOL (PGE1) is the drug of choice for treatment of ulcers induced by nonsteroidal anti-inflammatory agents, although side effects and the need for frequent dosing limit its use. It is abortifacient.
- Many drug-drug interactions have been documented for anti-ulcer medications, including: 1) interactions among the drugs within the anti-ulcer regimens (TETRACYCLINE + antacids, for example), and 2) alterations in the pharmacokinetics of other drugs (especially in cases where luminal pH is critical for absorption, as both increases and decreases in bioavailability have been documented). The fact that many of these drugs are available OTC must be considered also.