Peptic Ulcer Disease: Causes, Symptoms, Complication, and Treatment (Thesis Sample)

An Introduction to Peptic Ulcer Disease, Causes, Symptoms and Management
by
Name
2022
COLLEGE OF PHARMACY
UNIVERSITY 
An Introduction to peptic ulcer diseases, causes, causes, symptoms and management
This project submitted in accordance with requirements of the University of _______ for the degree of Pharm-D by
2017-2022
I certify that all material in this Project which is not my own work has been mentioned and properly cited
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COLLEGE OF PHARMACY
UNIVERSITY 
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It is certified that the project entitled “An Introduction to peptic ulcer diseases, causes, causes, symptoms and management” has been prepared by _____ under my supervision. He has fulfilled all the requirements and qualifies to submit the project for the degree of Pharm-D.
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Lecturer
College of Pharmacy
University
DECLARATION
This is certified that the Project entitled “An Introduction to peptic ulcer diseases, causes, causes, symptoms and management” submitted by ___________ is accepted in its present form by the faculty of Pharmacy, University of___ as satisfying the partial requirement for award of Pharm D degree from College of Pharmacy, University ______.
Student Name_____________________
Supervised By______________________
Lecturer
College of Pharmacy
University
DEDICATION
This final year Clinical Project is dedicated to my Parents, Teachers and my group fellows, for always believing in me, inspiring me, and encouraging me to reach higher in order to achieve my goals.
Acknowledgment
All glory and Praise are for Allah Almighty who created me and raised me to be at the place where I have done with final year Clinical Project. This work has not been possible without His blessings and guidance in each and every step of the whole process.
I am extremely grateful and honored to work under the supervision of Dr. Hafiz Rashid Hussain who motivated me and inspired me to pursue my career goals and who worked actively to provide me the dedicated academic time to follow these goals. Surely, his guidance and support are most appreciated and cherished by me.
I am grateful for those with whom I have had the pleasure to work during this course of research. Especially, ________ for encouraging me during my research work, my seniors, mentors and technical staff of University College of Pharmacy, University of ____. Their help in scientific research as well as personal guidance made it easy for me to complete this work in due time.
Nobody has been more important to me in the pursuit of this project than the members of my family. I would like to offer special thanks to my parents and as their love and prayers are with me in every step of my life. I owe my life to them. They are my ultimate role models and I strive to make them proud.
1 INTRODUCTION TO PEPTIC ULCERS
6762751193165Peptic ulcer is an acid-induced lesion of the gastrointestinal tract that is usually situated in the stomach or proximal duodenum, and is characterized by damaged mucosa with the defect extending into the submucosa(1).
Figure SEQ Figure \* ARABIC 1: Peptic erosions and ulcers in the stomach and duodenum.(A)small erosions in the gastric antrum(B) Benign peptic ulcer in the body of the stomach(C) Duodenal erosions identified by focal areas of adherent exudate(D)Duodenal ulcer(2).
Most peptic ulcers are caused by over secretion of acid in gastrointestinal tract as well as due to various dietary factors and stress. However, this perception was changed after the discovery of Helicobacter pylori infection and the widespread use of nonsteroidal anti-inflammatorydrugs (NSAIDs) in the mid of 20thcentury. Peptic ulcer disease includes both gastric and duodenal ulcers and has become a major threat to the world’s population over the past two centuries, resulting in high morbidity and mortality rates(2).
Development of ulcer disease and death resulting from it is associated with the birth of urbanization and it was interpreted as a birth-cohort event with the percentage of disease in those born during the late 19th century. Our perception about the disease changed to a great extent after the discovery of Campylobacter pylori(which was renamed as Helicobacter pylori in 1989 due torevision of taxonomic classification) in 1982 by Warren and Marshall(3)
The acid suppressive therapy was replaced with a short-term antibiotic regimen targeting eradication of H pylori infection for treating peptic ulcer disease. Eradication of H. pylori became the primary goal in the treatment of peptic ulcer when Warren and Marshall were awarded with the Nobel Prize for Medicine and Physiology in 2005(4)
This discovery switched the notion from an acid-driven disease to an infectious disease and opened a wide area for intensive research that introduced various mechanisms of pathogenesis of the disease. The present therapeutic principle is based on the fall of the acid dogma in peptic ulcer disease(5)
2 Pathogenesis:
The pathogenesis of peptic ulcer disease may be due to imbalance between defensive factors (mucus-bicarbonate layer, prostaglandins, cellular regeneration, mucosal blood flow) and aggravating factors (hydrochloric acid, pepsin, ethanol, bile salts, drugs).In case of peptic ulcers, there is usually a defect in the mucosa that extends to the muscularis mucosa. Once the mucosal layer is damaged, the inner layers become susceptible to acidity. Further, the ability of the mucosal cells to secrete bicarbonate is also compromised.
H. pylori colonizes the gastric mucosa and causes inflammation.It also impairs the secretion of bicarbonate, and promotes the development of acidity and gastric metaplasia.When H. pylori enters the stomach of host, it utilizes its urease activity to neutralize the acidic conditions at the start of infection. H. pylori needs flagella-mediated movements to move towards gastric epithelium cells of host. After these interactions between bacterial adhesins with host cell receptors takes place, leading to colonization and persistent infection. Finally, H. pylori releases several effector proteins/toxins, including cytotoxin-associated gene A, and vacuolating cytotoxin A (VacA), that will lead to host tissue damage(6)
Figure SEQ Figure \* ARABIC 2: Pathogenesis of H. pylori(6)
3 Risk factors:
1 . H. Pylori infection:
The main risk factor of both gastric and duodenal ulcers is H. Pylori infection.However, only a few people with H. pylori infection or taking NSAIDs or aspirin may develop peptic ulcer disease, which suggests that individual susceptibility to bacterial virulence and drug toxicity is important to the initiation of mucosal damage.
A case study showed that 95% of all ulcer cases in the USA were due to H pylori infection, use of non-steroidal anti-inflammatory drugs (NSAIDs), and tobacco smoking.Some researchers demonstrated that there is a connection between tobacco smoking and H pylori infection, suggesting that tobacco smoking only increases PU risk in those who are already affected by H pylori.
It can be supported by the fact that the prevalence of H pylori infection is low in Denmark, so there are low cases of PU.(7)
2 Misuse of Non-steroidal anti-inflammatory agents (NSAIDs)
Other major risk factors linked to peptic ulcer disease and its complications are the use of NSAIDs and aspirin.A variety of patient characteristics are associated with increased risk for NSAID-related GI complications. Patients with a history of GI injury are at higher risk for GI complications following NSAID use(8)
The elevated risks of GI events have been observed in patients taking high-dose NSAIDs and in patients taking NSAIDs with aspirin even in low dose.The risk of GI injury is also enhanced by certain medications when they are used along with NSAIDs. For example, if oral corticosteroids are administered along with NSAIDs, the rate of GI complications is increased as much as two times compared with patients taking NSAIDs alone(9)
3.2.1. Age
The risk of GI bleeding is also higher in patients with renal failure who are on hemodialysis.Another important factor is age, the risk of bleeding increases with increasing age. As the absolute risk varies by age, a threshold of risk based on age is often suggested to be >60 years old(10)
3.2.2. Drug Induced Peptic Ulcer
If selective serotonin-reuptake inhibitors, corticosteroids or anticoagulants are used along with NSAIDs or aspirin, the risk of upper ulcer disease is increased in some patients(11)
3.2.3. Smoking
Cigarette smoking also appears to be a risk factor for the development, maintenance, and recurrence of peptic ulcer disease(12)
Smoking has an inconsistent effect on gastric acid secretion, but it does have other effects on upper gastrointestinal function that could contribute to the pathogenesis of peptic ulcer disease.
These include:
* Interference with the action of histamine-2 antagonists
* Acceleration of gastric emptying of liquids
* Promotion of duodenogastric reflux
* Inhibition of pancreatic bicarbonate secretion
* Decrease in mucosal blood flow
* Inhibition of mucosal prostaglandin production(13)
Because these effects ar...