The Physiological Aspects of Effective and Safe Proton Pump Inhibitor Therapy for Acid Suppression in Quetta

This research was designed to analyze the in-appropriate use of proton pump inhibitors (PPI) especially in people who are often affected by syndromes of bones, osteoporosis and taking life long PPIs and multiple medicationsAn increased risk of long-term use of PPI-related adverse outcomes as well as drug-to-drug interactions are discussed in this study. The prescribing proton pump inhibitors for long time use is a common practice now a days. In some cases patiants with peptic ulcers have to take the PPI for whole life. The patients used PPIs and there evolved a distress for the strong antagonistic effect as a result of its continuous therapy. The first reported proton pump inhibitor was omeprazole and then lansoprazole. The French gastroenterologist Jean Paul Galmiche has anticipated that the unprecedented clinical effectiveness of this medicine would have lead (patients and physicians alike) to dependence, and indeed, this is the case. The study aims to document potential disadvantages and benefits of PPI in patients of Quetta. The results of this study showed that the long term use of PPIs results in bone weakness specially vertiberal column and femur. ARTICLE INFORMATION Received: 12.01.2019 Revised: 26.02.2019 Accepted: 29.03.2019 DOI: 10.31580/pjmls.v2i1.986


INTRODUCTION
The therapy of proton pump inhibitor continuousresults in onset of peptic ulcer and hepatic problem (1). Low indications or poor acidity signals their use offers little benefit Patients in hospital often are given on PPIs, often improperly and certainly, inadequate recommendations for PPIs in discharge slip of hospital admitted patients are quite common (2).As the PPIs are now available over any medical store counter (3), patients can have easy access to them and for long phases of time, without seeking medical care (4) and Medication of PPI for long term used by physicians need a care, such as malignancy, that should not be overlooked (5).

Acid Secretion and the Role of the Proton Pump
The proton pump is the final step in the mechanism of gastric acid secretion. When gastric acid secretion is stimulated, there is a morphologic transformation of the membrane of the parietal cell (Helander, 1984). Tubulovesicular membranes, which are prominent in the cytoplasm of the resting cell, diminish in accordance with a 6-10 fold increase in an apical canalicular membrane and the appearance of long apical microvilli. (6), This enzyme is magnesium-dependent and is found on the secretory membranes of the parietal cells. The sequential phosphorylation and dephosphorylation of the proton pump results in H + secretion in exchange for recycled K + . Figure 1.6 represents gastric acid secretion by the parietal cell (3).
Once proton pump inhibitor PPI, used by large number of patients for long-term, the proton pump inhibitors, often , may result in bone weakness and sometimes cardiac distress. especially the mature women. Even though PPIs being the ideal anti-secretory drugs and that innovative longer-acting compounds that developed prolonged acid suppression and they stay, no doubt, the PPIs are prescribing in all age group and give very effective result in all available medications The PPI intitating enzyme is magnesium-dependent and is found on the secretory membranes of the parietal cells. The sequential phosphorylation and dephosphorylation of the proton pump results in H + secretion in exchange for recycled K + . Figure 1 represents gastric acid secretion by the parietal cell (5). Hydrogen ions are secreted against both a parietal cell-tolumen concentration gradient and an electrical gradient. Thus, HC1 secretion by parietal cells is an active energy-dependent process. Parietal cells contain abundant mitochondria to accomplish the active proton transport (7,8).

Methodology of the Study
The random sampling methodwas used to collect data from different hospitals of Quetta, whereas the PPI and drug analysis was done in provincial drug testing laboratory health department, Government of Balochistan, Quetta. Sixteen patients were divided into 4 study groups. Patients included in the study were H. Pylori negative. Qualitative & quantitative analysis of PPIs were performed, acidity sign of relief before and after meals were noted, liver function test (LFT) test for alkaline phosphates was also performed, erythocyes sedementation rate (ESR) and Complete blood picture (CBC) were also performed.

Study Subjects
The drugs were administered to the subjects suffering from gastro-esophageal reflux disease (GERD), patients taking anticoagulant therapy, symptoms of bleeding, anxiety, stress ulcer prophylaxis (SUP), dyspepsia and anti-inflammatory drugs-associated gastrointestinal symptoms .

RESULTS AND DISCUSSION
Our results showed that the long term use of PPIs results in bone weakness specially vertiberal column and femur. On the other hand in some patients it was noted that long term use of PPIs also resulted in renal imparement and in some cases cardiac vessels may also seem to be involved in degeneration of cardiac muscles. The Table. l showing the allergic reactions among the patints suffering from the effects of histamine antagonist and they have a higher degree of non-physiological heat produced through carbohydrate metabolism in the form of higher SGOT or ALT and alkaline phosphate. The frequency of common GERD symptoms in the general population and their percentage of occurrence are given in Table ll. Some evidences showed that PPI use could be associated with development of spontaneous bacterial peritonitis. PPI use in patients with liver cirrhosis must be very cautious since there is no evidence of benefit except for downgrading esophageal ulcers after sclera therapy. The drugs such as omeprazol, lansoprazole, rabeprzole, pantaprazole and esenoprazole were found effective in such conditions of GIT and associated soft tissue infections and lowering in stomach pH. PPIs have become one of the most commonly prescribed drug being the most potent and effective in treating acid related disorders of GIT. Its long lasting acid suppression is due its prolonged duration of action (up to 3 days) which is the leading cause for worldwide use of PPIs. Number of studies on PPIs long term use revealed the appearance of some side effects which effect patient's health adversely by preventing absorption of useful trace elements and vitamin, by providing higher GIT pH which promote the growth of bacterial infection. The FDA and WHO, have approved clinical guidelines under which safe use of PPIs do not harm the patients (12).
The indication of proton pump inhibitors (PPIs) in clinic levels increases the dangers of bones weakness and decrease in muscular strength (9). A comprehensive prolonged treatments, abandoned indications and therapy replacements are recommended in such conditions (10).
Proton pump inhibitor are exclusive drugs in the administration of acidity related condition. However, simple PPI therapy having no big risk of adverse effects (11,12). Longterm PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium or vitamin B12.
Specific PPI formulations should not be selected based on potential risks. The gastric hydrogen potassium ATPase or H + /K + ATPase is the proton pump of the stomach. It exchanges potassium from the intestinal lumen with cytoplasmic hydronium and is the enzyme primarily responsible for the acidification of the stomach contents and the activation of the digestive enzyme pepsin (13).
PPIs,have,become,,one of the,most,commonly.prescribed drug,being.the.most, powerful and,,effective,,in,,treating,,acid related disorders,of,,GIT. Its,long,lasting,,acid,suppression,is due,,its,prolonged,duration,of action,,which,is the,leading,cause for,worldwide,use,of,PPIs.,Number,of,studies,on,PPIs,long,term use,revealed,the,,appearance,of some,side,effects,which.effect patient's,health,,adversely,by,,preventingbabsorptionooffuseful traceeelementssand,vitamin,bby,providing,higher,GIT,pH,which promote,the,growth.of,bacterial,infection. TheeFDAaandkWHO, haveaapprovedcclinicalgguidelines,under,which,safe usesof PPIs do,,notgharmgthe,,patients (12). In July 2005, the State of Tennessee Medicaid Program (TennCare) announced formulary changes for proton pump inhibitors (PPIs) to be implemented in August, 2005. Prior to these changes, pantoprazole was the only preferred PPI, and there were no restrictions to its use. The revised formulary included 3 preferred PPIs (esomeprazole, lansoprazole, and omeprazole OTC), all of which required prior authorization (PA). In order to obtain an approved PA for a PPI, the patient was required to have either (a) a diagnosis of erosive esophagitis, Barrett's esophagus, Schatzki's ring, a pathological hypersecretory condition (e.g., Zollinger-Ellison syndrome, multiple endocrine adenoma), grade III-IV gastroesophageal reflux disease (GERD), non-steroidal anti-inflammatory drug gastropathy, significant gastrointestinal bleed; or (b) another indication for acid suppression therapy (e.g., GERD, hyperacidity in cystic fibrosis, gastric or duodenal ulcer, gastroparesis) with a history of failure of prior therapy with a histamine-2 receptor antagonist (H2-blocker). The internal medicine clinic of a regional medical center implemented an intervention to address these changes in formulary status of PPIs (14) Adenosine triphosphate (ATP) provides the energy required for the active pumping of protons by the H + /K + ATPase (Munson et al, 2000). This enzyme is magnesium-dependent and is found on the secretory membranes of the parietal cells. The sequential phosphorylation and dephosphorylation of the proton pump results in H + secretion in exchange for recycled K + . Figure 1.6 represents gastric acid secretion by the parietal cell.

Conclusion
In Balochistan, specially in Quetta there is a large number of people who are suffering from acidity. They are usually associated with GERD (gastri intestinal reflux disease and IBS irritable bowl syndrom. Ultimately they are suffering with side effects of proton pump inhibitors like bone weakness and habitual PPI intake.