Pharmacotherapy of Peptic Ulcer Disease and Latest Research

Peptic ulcers have unquestionably been a disease of the twentieth century. Epidemiological data for this disease and its complications have shown striking variation in incidence and prevalence. Various drugs have been used to treat peptic ulcer disease like proton-pump inhibitors, histamine (H2) receptor antagonists, prostaglandin analogues and sucralfate. Because these drugs are complex, expensive and toxic, efforts have been constantly made to find a suitable, palliative and curative agent for the treatment of peptic ulcer disease from natural products of plant and animal origin. Recently, antioxidants are being used to treat peptic ulcer disease. Antioxidants help in scavenging the free radicals and controlling the oxidative stress responsible for the progression of peptic ulcer

Drug therapy in peptic ulcer disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28099/1/0000546.pd

Evaluvation of Anti-Oxidant and Anti Ulcer Activities of Ethanolic Extract of Desmostachya Bipinnata by Using Invivo and Invitro Methods

INTRODUCTION: Peptic Ulcer: Peptic ulcer and other acidic symptom affect up to ten percentages of the humans with sufficient severity to prompt victims to seek medical attention. The more significant disease condition requiring medical focus is ulcer and gastro esophagealdisease1. In the US, approximately 4 million people have peptic ulcer (duodenal and gastric types), and 350 thousand new patient are diagnosed in each year, around 180 thousand peoples are admitted to hospital and treated with drugs yearly, and about five thousand patient from this case die each year as a result of ulcer condition. The lifetime of human being developing a peptic ulcer is about 10 percentages for Americans males and four percentages for female population2. Peptic ulcers is wound in the lesions in the stomach and GIT that are most often affected in younger to older adults population, but this may diagnosed in young adult life. They often appear without obvious sign and symptom, after a period of days to months of active phase of disease, it may heal with or without drug treatment. It also affect because of bacterial infections with H. Pylori. AIM AND OBJECTIVE: GIT disease against few effective drugs available for modern therapy, it produce side effect during the treatment is worse than the condition of rebound acidity. as per the literature review selected plant that cure ulcer diseases so considerable interest has developed in the examination of these numerous plants remedies which are useful for antiulcer activity. So it is necessary to find new drugs of importance in antiulcer effect with fewer side effects. Moreover it is necessary to required scientific validation traditionally using medicinal plants on various systems such as Ayurvedic Siddha Unani systems. In our study Desmostachyabipinnata plant extracts its phytochemical investigation will be a useful tool for the identification and authentication of the plant for industrial and further research purpose, which will be related to the antioxidant activity. Antioxidants, which can scavenge free radicals, have an important role in pharmacological systems. Antioxidants are emerging as prophylactic and therapeutic agents. Hence, antioxidant was also evaluated for the potent extract. And now I have under taken the study of evaluation anti-oxidant and antiulcer activity of Desmostachyabipinnata plant extracts by using invivo and invitro methods To select plant based on their ethnomedical uses and preparation of their extracts. 1. To screen phytochemical profile. 2. To screen the selected extract for antioxidant using various invitro methods 3. To screen the potent plant extract for their invitro antioxidant, 4. To evaluate invivo antiulcer activities by NSAIDs induced animal model. SUMMARY AND CONCLUSION: The present study is evaluated the antioxidant potential and antiulcer effect of AEDB. The results analysed from the present study have indicate that AEDB possesses antioxidant and antiulcer effect on aspirin induced ulcers. The preliminary phytochemical screening of whole plant extracts indicate in presence of flavonoid, alkaloid, proteins,amino acids and terpenoids, fixed oil and glycosides Pre-treatment with AEDB particularly at a dose of 400mg/kg in a single schedule and 400mg/Kg treatment significantly reduce the ulcer index value, total acidity concentration, total volume of acid release and total protein and increase value pH and glutathione content as compared with 100 mg/kg,200mg/kg and control groups. The antioxidant screening shows that it showed reducing power to DPPH radicals. But the efficiency showed that far below from Vitamin C. The concentration of the AEDB needed to scavenge 50% superoxide anion (IC50) equal to that of standard hence the plant extract have the significant antioxidant activity The antiulcer effect is screened in ethanol extract of Desmostachyabipinnata on NSAID induced anti-ulcer study. The results get from these study have been shown that ethanol extract of Desmostachyabipinnata produce antiulcer effect.In aspirin induced model, there is reduction in ulcer index, total acidity, total volume of gastric contents, total protein concentration and higher concentration of glutathione content and pH of gastric secretion they compared with control group. Famotidine used as a standard comparison agents. Famotidine used as H2 receptor blocker, is significantly reduce about 90% of basal, food induced and hormonal mediated gastric acid, which again induced by histamine, gastrin, parasympathomimetic drugs and vagal stimulation. Famotidine mediate its suppression of gastric secretion by inhibiting the histamine mediated c-AMP dependent pathway Famotidine encouraged certain type mucus analogues of gastric mucus for patients with duodenal ulcer. Total acidity responsible quantification acid is present in the gastric secretion. It has a important aggressive factor which induced the ulcer. Gastric release is maintained by vagal control and higher activity of vagus stimulation also contributes to ulcer formation. On ethanol administration, the mucosal mast cells mediate to secretion of vasoactive mediators containing histamine. Histamine is mediated to stimulate the synthesis of cyclic AMP through activation of the enzyme adenylcyclase which mediate the activation of gastric proton pump and secrete of hydrogen ions. The treatment of extracts showed reduce the total acidity of the gastric contents. Serum protein including albumin and globulin. In the peptic ulcer the total protein concentration of serum or gastric secretion are increased. This may be due to leakage of plasma protein in to the gastric secretion or serum with lower mucosal resistance/barrier of the gastric mucosal layer.After treatment with AEDB there was a significant reduction in protein concentration of gastric juice which enhancing leakage of plasma proteins. Acid volume is amount (in ml) of acid release in the gastric content release contain HCl, pepsinogen enzyme, mucus secretion, bicarbonates concentration, intrinsic factor and proteins. Amount of acid release is an important factor responsible for the production of ulcer mediated by exposure of the unprotected lumen of stomach by concentrated acids. AEDB treatment showed decrease in the acid volume of the gastric secretion. Increased pH shows a lower concentration of the hydrogen ion. The hydrogen ion is a major triggering factor responsible for the etiologic factor for ulcer and gastric damage. AEDBtreatment indicate higher concentration of pH of the gastric juices. This values directly shown the AEDB reduce possibility of ulcer and has a protective effect of surface of the gastric mucosa. In gastric ulcer tissues, Glutathione (g-glutamylcysteinylglycine, GSH) levels were found to be decreased112 . aspirin-induced genesis of free radical concentration reduces the cysteine concentration which mediated for GSH released.Values from this study responsible for depletion of gastric GSH is related with induction of gastric lesion in the rats. GSH is a tripeptide and having a superoxide radical scavenger and it protect thiol protein contents essential for release the integrity of tissue against oxidation reaction. In my present study, AEDB treatment showed increase in the glutathione content

The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure

The pharmacokinetics of orally administered ranitidine were studied in 10 patients with endoscopically proved duodenal ulceration after a single 150 mg dose and after 4 weeks 1 ranitidine treatment (150 mg twice daily), at which time there was endoscopic evidence of complete ulcer healing. After a single dose the median elimination half-life was 135 minutes and the median area under the curve (AUC) was l 844 ng/ml.hr. Although the maximum concentration after a single dose (Cmax = 365 ng/ml) was significantly different from that after continuous treatment (Cmax = 562 ng/ml) (p 65 ml/min). There appeared to be no significant differences in absorption rate or amount absorbed but the median elimination rate constant was significantly reduced from 0,31 h⁻¹ in controls to 0,14 h⁻¹ in RF (p <0,002) resulting in a two-fold increase in t½ (312 minutes) after a single dose. Cmax did not differ significantly although Cmin and AUC were significantly larger in RF patients (both p <0,002). It is suggested that the dosage of ranitidine be reduced from 150 mg to 75 mg twice daily in severe renal failure although it was not possible to relate half-life, elimination rate constant or AUC directly to creatinine clearance

Studies of the increased gastrin release associated with Helicobacter pylori infection in duodenal ulcer disease

Duodenal ulcer disease is strongly associated with infection of the gastric antrum by Helicobacter pylori (H. pylori), possibly through the exaggerated plasma gastrin response associated with this organism. The work described in this thesis investigates aspects of both the cause and the effect of this increase in gastrin secretion in duodenal ulcer patients. Chapter 2 provides further evidence that H pylori is responsible for the exaggerated gastrin response since when duodenal ulcers are healed by sucralfate, which does not eradicate H pylori, the gastrin response is unchanged. However, unexpectedly, this treatment decreased basal gastric acid secretion. The results of studies described in chapter 3 suggest that the exaggerated gastrin response occurs by a mechanism independent of luminal pH and with no apparent change in the meal-stimulated secretion of acid or pepsin. Despite the fall in meal-stimulated gastrin the peak acid output also remained unchanged a year after the eradication of H pylori (chapter 4) but the basal acid output appeared to decrease in this small study. The work described in chapter 5 confirms this fact; successful eradication of the organism decreased both basal plasma gastrin concentrations and basal acid secretion, without altering the sensitivity of the parietal cell to circulating gastrin. This may be how the eradication of H pylori prevents ulcer recurrences. The cause of the hypergastrinaemia was addressed in the final chapters. Methods were developed to measure somatostatin mRNA from endoscopic biopsies as a surrogate marker of local somatostatin release. It was then established that the hypergastrinaemia seen in pernicious anaemia is associated with a deficiency of somatostatin mRNA (chapter 6). Finally, an increase in both somatostatin-secreting cells and somatostatin mRNA was found after the eradication of H pylori, implying that this bacterium increases gastrin release by the depletion of somatostatin

A study of the effects of sucralfate in the bile duct litigated pig peptic ulcer model with particular reference to the effects on the physico-chemical properties of gastric mucus and including comparisons with famotidine and misoprostol

Sucralfate is a drug that effectively heals duodenal, gastric and oesophageal ulcers. It is not absorbed systemically and it has been shown to act locally by coating the ulcer base. However when it was also shown to prevent stress ulcers and ethanolinduced gastric mucosa! lesions, it seemed likely that it acted in some way to improve the effectiveness of the gastric mucosa! barrier. Some investigators suggested that it did so by stimulating local prostaglandin release. The Slomiany group, on the basis of in vitro work on the effects of Sucralfate on pig gastric mucus, claimed that Sucralfate acted by altering the physico-chemical properties of mucus to increase the viscosity and retard the back diffusion of H+ ions. The work described in this dissertation set out to verify, in vivo, these claimed effects on mucus, using an experimental porcine model of peptic ulceration, the bile duct ligated pig. In addition, the effects of Sucralfate were compared with those of Famotidine and Misoprostol, and changes in mucous prostaglandins, gastric juice pepsin and gastric flora were sought. By way of introduction, the known and postulated actions of Sucralfate, current understanding of gastric mucus physiology and pathogenesis of peptic ulceration, have been reviewed, as have experimental animal models of peptic ulceration, in order to justify using the bile duct ligated pig model