Page 6 - 53-Peptic ulcer diseases (Loét dạ dày)

810 PART VI Stomach and Duodenum

According to a joint ACG/Canadian Association of Gastro- patients with PUD not associated with Hp. The role of antisecre-
enterology guidelines, it was recommended that patients with tory drugs in the management of gastrinoma (ZES) is discussed
uninvestigated dyspepsia who are below 60 years of age should in Chapter 34.
have a noninvasive test H and treatment if positive. Those with
a negative test or do not respond to this approach should receive H2Ras
a trial of PPI therapy. Tricyclic antidepressants or prokinetic H2RAs are competitive inhibitors of histamine-stimulated acid
therapies can be tried if they are not responsive to PPI therapy. secretion (see Chapter 51) and markedly suppress basal and meal-
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The incidence of UGI malignancies including gastric cancer stimulated acid secretion. When administered in the evening,
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rises with age and, thus, current nonendoscopic management H2RAs are effective in suppressing nocturnal acid output.
strategies are generally reserved for younger patients with upper H2RAs are well absorbed after oral dosing, and their absorption
abdominal symptoms. The age after which prompt EGD should is not affected by food. Peak blood levels are achieved within 1 to
become routine is debated and, to a substantial degree, depends 3 hours after an oral dose. H2RAs cross the blood-brain barrier
on the epidemiology of UGI cancer in the population under and the placenta. 47,48 After oral administration, several H2RAs
consideration. In Western populations, UGI cancer is uncom- (cimetidine, ranitidine, and famotidine) undergo first-pass hepatic
mon in young individuals, and therefore an age cutoff of 50 or metabolism, which reduces their bioavailability by 35% to 60%.
55 years is often used. Patients older than age 60 presenting In contrast, the H2RA nizatidine does not undergo first-pass
with new-onset upper abdominal symptoms suggestive of PUD metabolism, and its bioavailability approaches 100% with oral
should therefore be referred for EGD. In Asia and Eastern dosing. H2RAs are eliminated by a combination of renal excre-
Europe, where the incidence of gastric cancer is substantially tion and hepatic metabolism. Dose reductions are recommended
higher than in Western nations, a younger age cutoff may be when the creatinine clearance is below 50 mL/min. Dialysis does
reasonable. not remove substantial amounts of H2RAs; thus, dose adjust-
The Joint ACG/Canadian Association of Gastroenterology ments are not necessary for dialysis patients. Dose reductions are
guidelines on dyspepsia in 2017 recommended that patients with generally not required for patients with hepatic failure unless it
uninvestigated dyspepsia who are less than 60 years of age should is accompanied by chronic kidney disease. Tolerance to the anti-
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have a noninvasive Hp test and treatment if positive. 39,41 Those secretory effects of H2RAs develops quickly and frequently,
with a negative Hp test or who do not respond to this approach although the mechanism for tolerance is not clear.
should receive a trial of a PPI therapy. Tricyclic antidepressants H2RAs are safe and well tolerated. One meta-analysis of ran-
or prokinetic therapies can be tried if the patients are not respon- domized clinical trials concluded that the overall rate of adverse
sive to PPI therapy (see Chapter 14 and Fig. 53.3). In areas of effects reported for H2RAs did not differ significantly from pla-
moderate- to- high Hp prevalence, the test-and-treat strategy cebo treatment. Nevertheless, a number of untoward effects
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is preferred. The Maastricht Consensus Conference Report in have been described, primarily in anecdotal reports and uncon-
2017 recommended a test-and-treat strategy for uninvestigated trolled series. Cimetidine has weak antiandrogenic activity that
dyspepsia. This approach is subject to regional Hp prevalence can occasionally cause gynecomastia and impotence. 51
and cost-benefit considerations. 40,42 The test-and-treat strategy Both cimetidine and ranitidine bind to the hepatic cytochrome
is, however, not applicable to patients with alarm symptoms or P-450 (CYP) mixed-function oxidase system. This binding
to older patients. The ability of alarm features (see Box 53.1) to can inhibit the elimination of other drugs that are metabolized
accurately predict malignancy (as opposed to PUD or nonul- through the same system, including warfarin, theophylline, phe-
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cer dyspepsia) has, however, been questioned in a review of 15 nytoin, lidocaine, and quinidine. In contrast, famotidine and
43
studies. The sensitivity of alarm symptoms in the diagnosis of nizatidine have no significant avidity for the CYP system.
malignancy varied from 0% to 83% across studies.
PPIs.
+
MEDICAL THERAPY OF ACTIVE PEPTIC ULCER PPIs decrease gastric acid secretion through inhibition of H ,
K -ATPase, the proton pump of the parietal cell (see Chapter
+
DISEASE 51). These agents are prodrugs that must be activated by acid to
+
+
Several pharmaceutical agents are available to attempt to heal inhibit the H , K -ATPase. Interestingly, prodrug PPIs are also
active DUs and GUs. acid-labile compounds that must be protected from degradation
by gastric acid after oral administration by enteric coating or an
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antacid. Absorption of the enteric-coated PPIs may be erratic,
Pharmaceutical Agents and peak serum concentrations are not achieved until 2 to 5 hours
Antacids after oral administration. Although the plasma half-life of PPIs is
short (≈2 hours), the duration of acid inhibition is long as a result
Antacids neutralize gastric acid but their ability to heal ulcers is of covalent binding of the active metabolite of the prodrug to the
+
+
poor. Most physicians do not use antacids as primary therapy to H , K -ATPase. PPIs undergo significant hepatic metabolism,
heal ulcers but instead recommend their use to relieve dyspeptic but dose adjustments are not required in patients with significant
symptoms. The most common adverse effect of magnesium-con- renal or hepatic impairment. There is genetic polymorphism in
taining antacids is diarrhea. In contrast, aluminum- and calcium- CYP2C19, one of the isoenzymes involved in PPI metabolism.
containing antacids may cause constipation. All antacids must be Approximately 25% of Asians and 3% of white persons have
used with caution, if at all, in patients who have chronic kidney deficient CYP2C19 activity. This polymorphism leads to sub-
disease, in whom magnesium-containing agents can cause hyper- stantially higher plasma levels of omeprazole, lansoprazole, and
magnesemia, calcium-containing antacids hypercalcemia, and pantoprazole, but not rabeprazole. 36,37,54
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aluminum-containing antacid neurotoxicity. PPIs, as a result of their requirement for concentration and
activation in acidic compartments, bind predominantly to those
Antisecretory Agents proton pumps that are actively secreting acid. With meal stimu-
lation, 60% to 70% of the proton pumps actively secrete acid;
Antisecretory therapy is not routinely required for patients with thus, PPIs are most effective if they are administered immediately
uncomplicated Hp ulcers in whom ulcers heal after successful before meals. For once-daily dosing, it is recommended that PPIs
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eradication of Hp even without antisecretory therapy; however, be taken immediately before breakfast. Unlike H2RAs, toler-
antisecretory drugs play an important role in the management of ance to the antisecretory effects of PPI therapy has not been seen.