Pharmacologic Management of Upper GI Bleeding

In the past few decades we have witnessed major changes in the pharmacologic management of PUD, upper GI bleeding, and GERD. The advent of PPIs has transformed our ability to manage acid secretory conditions. Although there is still a role for H2RAs for the occasional heartburn sufferer and in pregnancy, there is really no place for this therapy for PUD (Ruigomez et al, 1999). Historically, the treatment of excess gastric acid secretion relied upon the use of antacids and H2RAs. Currently, there are the following four US Food and Drug Administration (FDA)-approved H2RAs (see Table 251): (1) cimetidine (Tagamet), (2) ranitidine (Zantac), (3) famotidine (Pepcid), and (4) nizatadine(Axid). None of these agents have an indication for the prevention of re-bleeding secondary to PUD, and therefore, their efficacy is limited in PUD. H2RAs have been used for the past several decades and they have a long track record for safety. They are available in both oral and parenteral forms (Levine et al, 2002). With continued usage H2RAs result in tachyphylaxis, with diminished efficacy over time. With IV treatment this generally occurs after approximately 24 hours of use. To date, there are no controlled studies that have shown efficacy for their use in the prevention of PUD re-bleeding. This is probably accounted for by the tachy-phylaxis, which occurs with continued usage. Another limiting factor with the use of the H2RAs in the prevention of re-bleeding following ulcer hemostasis is their inability to raise the intragastric pH above a threshold level of approximately 6 (Pisegna, 2002).

Unlike the H2RAs, PPIs as a group have a different mechanism of action, which permits a greater amount of inacti-vation of parietal cell secretory function. PPIs have now been used for over two decades and have been used in a multitude of clinical investigations, which have demonstrated their safety and efficacy. PPIs currently approved by the FDA include (1) omeprazole (Prilosec), (2) lansoprazole (Prevacid), (3) pan-toprazole (Protonix), (4) rabeprazole (Aciphex), and (5)

esomeprazole (Nexium). Each has a similar mechanism of action although they are formulated differently. Only panto-prazole is available in both oral and IV formulations, although clinical studies are underway in the United States for the development of IV lanosprazole and esomeprazole formulations. Pantoprazole has been approved by the FDA for the inpatient management of erosive esophagitis, as well as conditions associated with gastric acid hypersecretion, including ZE syndrome (Metz et al, 2001). Each of these agents can be administered orally as slurry by suspending the tablet or capsule with sodium bicarbonate to permit NG infusion. Although this approach may have some merits in the chronic suppression of PUD they have major limitations because of absorption in the acute PUD setting, in which case an IV administration would be a preferable route ofadministration.

As a group, the PPIs act by inhibiting H+/K+-ATPase, the final step in the synthesis of gastric acid. Studies have shown that to achieve the optimal reduction in ulcer rebleeding rate, the intragastric pH should be suppressed to a pH value 5 6 or greater. Given that PPIs act by blocking the final step in the synthesis of gastric acid they are as a group more effective than H2RAs. Therefore, they are the preferred method of managing the patient with PUD except perhaps in pregnancy (Li et al, 2000; Yacyshyn and Thomson, 2000).

In the setting of a patient with upper GI bleeding, the goal of antisecretory therapy is to increase the intragastric pH above 6 during the period preceding and following endoscopic hemostasis. The rationale for achieving this intragastric pH is to improve platelet function and the coagulation cascade to stabilize the clot formation (Barkun et al, 1999). This is facilitated with the development of IV formulations of PPIs, such as pantoprazole, omeprazole, and lansoprazole. The use of IV PPIs reduces the rate of ulcer rebleeding (Lau et al, 2000). The dose of IV omepra-zole (Prilosec) that was shown to effectively reduce rebleeding was an 80 mg loading dose followed by a continual infusion of 8 mg/h (Lau et al, 2000). Furthermore, the use of IV PPIs in the setting of acute PUD bleeding was shown to be cost effective for the more serious ulcer bleeds (Spiegel et al, 2003). In another study, IV pantoprazole

(Protonix) was able to dose-dependently (Figure 25-3) inhibit gastric acid secretion in a pentagastrin-stimulated model of ZE syndrome as well as in a cohort of ZE syndrome patients. The optimal dose of pantoprazole in each study was 80 mg administered twice daily. Gastric acid was inhibited rapidly (ie, within 1 hour) and the duration of effect was nearly 20 hours.*

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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