PEPTIC ULCER

PREPARED BY DR. NAITIK D. TRIVEDI, M. PHARM, PH. D LECTURER AT GOVERNMENT AIDED, A. R. COLLEGE OF PHARMACY & G. H. PATEL INSTITUTE OF PHARMACY, VALLABH VIDYANAGAR, ANAND, GUJARAT Mobile: +91 9924567864 E-mail: mastermindnaitik@gmail.com & DR. UPAMA N. TRIVEDI, M. PHARM, PH. D ASSOCIATE PROFESSOR & HoD (Pharm.D), INDUBHAI PATEL COLLEGE OF PHARMACY AND RESEARCH CENTRE, DHARMAJ, GUJARAT E-mail: ups.aasthu@gmail.com PEPTIC ULCER

 Peptic ulcer disease (PUD) is one of the most common diseases affecting the GI tract. It causes inflammatory injuries in either the gastric or duodenal mucosa, with extension beyond the submucosa into the muscularis mucosa.
 A peptic ulcer is a distinct breach in the mucosal lining of the stomach (gastric ulcer) or the first part of the small intestine (duodenal ulcer), [1] a result of corrosive effects of acid and pepsin in the lumen.
 Histologically, peptic ulcer is identified as necrosis of the mucosa which produces lesions equal to or greater than 0.5 cm (1/5").
 The etiologies of this condition are multifactorial and are rarely related simply to excessive acid secretion.
 Helicobacter pylori is one of the most common causes of peptic ulcer. Ulcers can also be caused or worsened by drugs such as aspirin, ibuprofen, and other NSAIDs.
 Even though gastric ulcer is a common disease, a diagnosis can be difficult because it has a wide spectrum of clinical presentations, ranging from asymptomatic to vague epigastric pain, nausea, and iron-deficiency anemia to acute life-threatening hemorrhage. : secrete serotonin and histamine as autocrine regulators.  G-cells : secrete the hormone gastrin into the blood.  In addition to these products, the gastric mucosa (probably the parietal cells) secretes a polypeptide called intrinsic factor, which is required for absorption of vitamin B12 in the small intestine.   HCl, pepsinogen/pepsin, and bile salts. In addition, a steady flow of exogenous substances such as medications, alcohol, and bacteria encounter the gastric mucosa.
 A highly intricate biologic system is in place to provide defense from mucosal injury and to repair any injury that may occur. The mucosal defense system can be envisioned as a three-level barrier, composed of preepithelial, epithelial, and subepithelial elements.
 The first line of defense is a mucus-bicarbonate layer, which serves as a physicochemical barrier to multiple molecules including hydrogen ions.
 Mucus is secreted in a regulated fashion by gastroduodenal surface epithelial cells. It consists primarily of water (95%) and a mixture of lipids and glycoproteins.
 Mucin is the constituent glycoprotein that, in combination with phospholipids (also secreted by gastric mucous cells), forms a hydrophobic surface with fatty acids that extend into the lumen from the cell membrane.
 The mucous gel functions as a nonstirred water layer impeding diffusion of ions and molecules such as pepsin. Bicarbonate, secreted by surface epithelial cells of the gastroduodenal mucosa into the mucous gel, forms a pH gradient ranging from 1 to 2 at the gastric luminal surface and reaching 6 to 7 along the epithelial cell surface. Bicarbonate secretion is stimulated by calcium, prostaglandins, cholinergic input, and luminal acidification.  Prostaglandins are derived from esterified arachidonic acid, which is formed from phospholipids (cell membrane) by the action of phospholipase A2. A key enzyme that controls the rate-limiting step in prostaglandin synthesis is cyclooxygenase (COX), which is present in two isoforms (COX-1, COX-2), each having distinct characteristics regarding structure, tissue distribution, and expression. COX-1 is expressed in a host of tissues including the stomach, platelets, kidneys, and endothelial cells. This isoform is expressed in a constitutive manner and plays an important role in maintaining the integrity of renal function, platelet aggregation, and gastrointestinal mucosal integrity.
 In contrast, the expression of COX-2 is inducible by inflammatory stimuli, and it is expressed in macrophages, leukocytes, fibroblasts, and synovial cells. C) Cigarettes * Cigarette smoking impairs ulcer healing and promotes recurrence * Thought to stimulate gastric acid secretion * May alter blood flow or gastric motility * May cause bile reflux or reduce production of prostaglandins D) Alcohol Acute ingestion may cause gastritis, gastric mucosal damage, and GI bleeding, however not considered a risk factor for PUD E) Caffeine Caffeine acts synergistically with histamine (but not pentagastrin) to stimulate secretion. It also enhances the secretion of pepsin. F) Stress induced ulcer:  psychological stress  physiological stress as in  Shock  SevereTrauma  Septicemia  Extensive burns (Curling's ulcers in the posterior aspect of the first part of the duodenum).  Intracranial lesions (Cushing's ulcers developing from hyperacidity following excessive vagal stimulation).    Major Abdominal Surgery  Vagotomy cuts the vagus nerve and interrupts messages from the brain that stimulate acid secretion in the stomach. This surgery may impair stomach emptying; a recent variation that cuts only parts of the nerve may reduce this complication.
 Antrectomy removes the lower part of the stomach, which manufactures the hormone responsible for stimulation of digestive juices.
 Pyloroplasty enlarges the opening into the small intestine so that stomach contents can pass into it more easily.
 Total gastrectomy:Removing the entire stomach is done only for resistant Zollinger-Ellison syndrome or extensive cancers.

 Billroth I and II
After removing a piece of the stomach, the remainder must be reattached to the rest of the bowel. Simply joining the upper stomach back to the duodenum is called a Billroth I or gastroduodenostomy. It is sometimes better to attach the stomach with another piece of bowel (the jejunum), creating a "y" with the bile drainage and the duodenum forming the second branch of the "y." This part of the procedure is called a gastrojejunostomy. A gastroenterostomy is a more general term for connecting the stomach with any piece of bowel.
A selective vagotomy can be done alone. A complete vagotomy requires either a pyloroplasty or antrectomy. An antrectomy must be reconnected with either a Billroth I or a Billroth II.
 Some of these procedures are now being done through a laparoscope.

ANTACIDS
They neutralize the acid present in stomach by simple acid base reaction.

A) SYSTEMIC ANTACIDS:
 Sodium bicarbonate, Sodium citrate  They are water soluble, act instantly, but the duration is short.
 NaHCO 3 is rapidly cleared from stomach and presents both an alkali and a sodium load.
4. Increases Na ion load: worsen edema and CHF, contraindicated in cardiac disease, HT.

USES:
1. Quick symptomatic relief in heart burn.
2. Alkalization of urine and to treat acidosis.  The most feared complication with amoxicillin is pseudomembranous colitis, but this occurs in <1 to 2% of patients. Amoxicillin can also lead to antibiotic-associated diarrhea, nausea, vomiting, skin rash, and allergic reaction.
 Tetracycline has been reported to cause rashes and very rarely hepatotoxicity and anaphylaxis.  Clarithromycin is a macrolide and is the most expensive of the antibiotics used against H. pylori. It is also very effective, but there is growing bacterial resistance to this drug.  Tetracycline is effective, but tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration. Pregnant women cannot take it.
 Metronidazole was the mainstay in initial combination regimens for H. pylori. As with clarithromycin, however, there continues to be growing bacterial resistance to the drug (about 25% to 35% of H. pylori bacteria). It is a newer proton pump inhibitor. Its advantages over other PPIs are as follows:  It has been shown that rabeprazole achieve more rapid and profound inhibition of acid secretion and they sustain this suppression to provide acid control and symptom relief over 24 hours.
 Faster symptom relief with the first dose and within the first days of treatment.  Daytime and night-time heartburn.
 Rabeprazole may play an important role in restoring a patient's quality of life by providing fast and effective relief from severe heartburn as a major GORD-related symptom.
 Moreover, the balanced hepatic metabolism of rabeprazole, involving both cytochrome P450 (CYP)-mediated reactions in the liver and non-enzymatic reactions, appears to confer an advantage over older PPIs, in that genetic polymorphisms for CYP 2C19 do not significantly influence rabeprazole clearance.