ULCER: PATHOGENESIS, PREVALENCE, AND MANAGEMENTHTML Full Text
ULCER: PATHOGENESIS, PREVALENCE, AND MANAGEMENT
Majaz A. Quazi * 1 and Khurshid I. Molvi 2
Ali-Allana College of Pharmacy 1, Akkalkuwa, Nandurbar - 425415, Maharashtra, India.
Ibn. Sina National College for Medical Studies 2, Jeddah, Kingdom of Saudia Arabia.
ABSTRACT: Ulcers are a breach in the mucosa of the alimentary tract that extends through the muscularis mucosae into the submucosa or deeper. They can occur in any portion of the gastrointestinal tract exposed to the excessive amount of acid-peptic juices. Prevalence of peptic ulcer is approximately 11% to 14% for men and 8% to 11% for women during the age of 30 to 50 years. The occurrence of peptic ulcer is very rare above 60 years but produce death in 80% of cases. This review gives an overview of the symptoms, diagnosis, treatment, prevalence, and management of ulcers.
INTRODUCTION: Ulcers are defined histologically as a breach in the mucosa of the alimentary tract that extends through the muscularis mucosae into the submucosa or deeper. They can occur in any portion of the gastrointestinal tract exposed to the excessive amount of acid-peptic juices 1. The gastric ulcer is classified aphthous ulcers, esophageal ulcers, and a peptic ulcer by their occurrence in the gastrointestinal tract in mouth, esophagus, and stomach or the duodenum respectively 2.
Aphthous Ulcers: Aphthous ulcers are typically recurrent round or oval sores or ulcers with yellow-greyish pseudomembrane surrounded by raised margins and the erythematous hole inside the mouth on areas where the skin is not tightly bound to the underlying bone, such as on the inside of the lips and cheeks or underneath the tongue.
They are also known as aphthae, aphthosis, aphthous stomatitis and canker sores 3, 4. Mouth ulcers commonly have a family history (up to 40%) and are usually due to trauma (because of not proper fitting of dentures, fractured teeth, or fillings), anaemia, measles, viral infection, oral candidiasis, chronic infections, throat cancer, mouth cancer, and vitamin B deficiency. It is estimated that 15-20% of the population worldwide and 50-66% in North America suffers from aphthous ulcers 2. They are classified as a minor ulcer (5-10 mm in size, 10-14 days duration and 75-80% prevalence) , major ulcer (above 10 mm in size, more than two week duration, and 10-15% prevalence) and herpetiform ulcer (below 5 mm in size, 10-14 days duration and 5-10 % prevalence) 4.
Esophageal Ulcers: Esophageal ulcers are lesions that occur at the end of the esophagus due to gastro-esophageal reflux disease (GERD) with 2-7% prevalence. They can produce pain right below the breastbone. The etiology of esophageal ulcers is not well defined; it is considered as it occurs due to peptic ulcer, carcinoma, corrosive substances, prolonged use of drugs like NSAIDs, and smoking. Esophageal ulcers also reported due to cytomegalovirus, herpes simplex virus, and human immune deficiency virus 2, 5.
Peptic Ulcer: Peptic ulcers are chronic, most often solitary, lesions that occur in any portion of the gastrointestinal tract exposed to the aggressive action of acid-peptic juices. At least 98% of peptic ulcers are either in the first portion of the duodenum or in the stomach, in a ratio of about 4:1. 1 The infection caused by the bacteria H. pylori and acid-pepsin secretion is mostly responsible for the generation of peptic ulcer while non-steroidal anti-inflammatory drugs (NSAIDs), shock, severe trauma, septicemia, intracranial lesions, local irritant like alcohol, smoking, and spiced food are also responsible for the production of peptic ulcers 7. Symptoms of peptic ulcers include abdominal discomfort, pain, weight loss, poor appetite, bloating, nausea, and vomiting commonly and blood in stool and vomit rarely 2.
Based onthe site of occurrence, peptic ulcers are categorized as gastric ulcer and duodenal ulcer, they occur in stomach and duodenum respectively. However, they can also classify as an acute and chronic ulcer based on their severity. Acute peptic ulcers arise in the form of single or multiple lesions with depth up to the submucosa of all parts of the stomach and in the first few centimeters of the duodenum. Chronic peptic ulcers occur singly in the pyloric antrum of the stomach and in the duodenum which may extend up to adjacent pancreas or liver by penetrating through the epithelial and muscle layers of stomach or duodenum wall 6. They may produce complication like obstruction, haemorrhage, perforation, and malignant transformation 7.
Pathogenesis: Peptic ulcers occur because of an imbalance between aggressive factors (gastric acid and pepsin secretion, H. pylori infection, NSAIDs, alcohol, etc.) and defensive factors (elaboration of prostaglandins, epithelial regenerative capacity, apical surface membrane transport, surface mucus secretion, and bicarbonate secretion). Among the "aggressive forces," H. pylori is very important because of involvement in 90% of duodenal ulcers and 70% of gastric ulcers. H. pylori stimulate an intense inflammatory and immune response with increased production of proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF) which activate neutrophils and activation of T cells and B cells respectively. The organism also responsible for the increased gastric acid secretion and impairs duodenal bicarbonate production result in alteration of gastric pH Fig. 1. 1
FIG. 1: PATHOGENESIS OF ULCER
Diagnosis: Diagnosis of the ulcer by symptoms is most common and depends on ulcer location and patient age. Gastric ulcer characterized by pain typically starts with an empty stomach and generally relieved by antacids or food but provoked by alcohol and caffeine. However, weight loss and gastrointestinal bleeding occur more frequently with gastric ulcers. Duodenal ulcers tend to produce more consistent pain generally in midmorning which relieved by food only and at night after a few hours sleep. Hemorrhage, repeated vomiting or evidence of abdominal pain is important in the diagnosis of duodenal ulcers 8. A peptic ulcer can be diagnosed specifically by direct visualization by endoscopy or radiology and by detection of H. pylori by various endoscopic and nonendoscopic tests. Endoscopic tests involve histology, culture of biopsy, rapid urease detection with ammonia, while non endoscopic tests consist of detection of antibodies to H. pylori in serum, urea breathe test (H. pylori urease breaks down ingested labeled C urea, patient exhales labeled CO2) and stool antigen test (presence of antigen against H. pylori in stool changes its color which can be detected visually or by spectrophotometer) 9.
Treatment: The management of peptic ulcers includes pain relief, ulcer-heal, prevention of complication such as bleeding, perforation - the drugs used in the treatment of ulcer classified as follows 10.
- Drugs Reducing Gastric Acid Secretion:
- Antihistamines like cimetidine, ranitidine, famotidine, roxatidine.
- Proton pump inhibitors like omeprazole, lanso-prazole, pantoprazole, rabeprazole, esomeprazole,
- Anticholinergic drugs like pirenzepine, propantheline, oxyphenonium.
- Prostaglandin analogue like misoprostol.
- Systemic antacids like sodium bicarbonate, sodium citrate.
- Non-systemic antacids like magnesium hydroxide, magnesium trisilicates, aluminum hydroxide, calcium carbonate and magaldrate.
- Ulcer protective like sucralfate, colloidal bismuth subcitrate.
- Antimicrobial agent against pylori infection like amoxicillin, clarithromycin, metronidazole tinidazole, tetracycline.
Prevalence: Prevalence of peptic ulcer is approximately 11% to 14% for men and 8% to 11% for women during the age of 30 to 50 years. The occurrence of peptic ulcer is very rare above 60 years but produce death in 80% of cases 8.
Methods for Evaluation of Anti-Ulcer Activity: Peptic ulcers generally induced in rodents by physiological, pharmacological or surgical treatments which have etiological importance for the induction of peptic ulcers. Some models are mentioned in following which used experimentally for testing or evaluating anti-peptic ulcer activity of drugs 11, 12.
- Stress ulcer through immobilization stress.
- Ethanol-induced mucosal damage in rats (cytoprotective activity).
- Sub-acute gastric ulcer in rats.
- Gastric ischemia-reperfusion injury in rats.
- Water-immersion stress or cold-water-restraint
- NSAIDs- (indomethacin, aspirin, & ibuprofen) induced gastric ulcers.
- Acetic acid-induced gastric ulcers.
- Histamine-induced gastric ulcers.
- Reserpine-induced gastric ulcers.
- Serotonin-induced gastric ulcers.
- Pylorus-ligated-induced peptic ulcers.
- Diethyldithiocarbamate (DDC)-induced peptic ulcers.
- Methylene blue-induced ulcers.
- Ischemia-reperfusion induced gastric ulcers.
- Cysteamine-induced duodenal ulcers.
- Indomethacin- histamine-induced duodenal ulcers.
- Ferrous iron-ascorbic acid-induced gastric ulcers.
- Acetic acid- pylori-induced ulcers.
Plants having Anti-ulcer Activity: Herbal medicines have been used to treat human gastric ulcers since ancient time. Several controlled clinical studies have shown that more than 90% of patient cures of peptic ulcer with herbal treatment 13.
TABLE 1: LIST OF PLANTS HAVING ANTI-ULCER ACTIVITY
|S. no.||Botanical name||Common name||Parts of plant||Active phytochemical|
|1||Acacia nilotica Fabaceae||Kikar||Aerial portion||Phenolic cumpounds, flavonoids, tannins|
|2||Ageratum conyzoides Asteraceae||Goatweed||Leaf||flavonoids|
|Indian saris||Leaves, bark, flower||Phenolic compounds, flavonoids,
|4||Alove vera Liliaceae||Gritkumari||leaves||Barbaolion, iso-barbaloin, saponins|
|5||Azadirachta indica Meliaceae||Neem||leaves||Phenolic compound, saponin, flavonoids|
|6||Basella rubra Apocynaceae||Indian spinach||Leaf||flavonoids, saponin|
|7||Curcuma longa Zingiberaceae||Haldi||Rhizome||Phenolic compound, tannins, flavonoids|
|8||Falcaria vulgaris Umbelliferae||Ghazzyaghi||Seeds||Tannins and saponin|
|9||Ficus arnottiana Moraceae||Paras papal||Leaf||β-sitosterol, glunol acetate, sterol, alkaloids|
|Licorice||Root & rhizomes||Glycyrrhizinic
|11||Jatropa curcas Euphorbiaceae||Rattanjot||Leaves||Phenolic compound, flavonoids, saponin|
|Milk tree||Bark||Phenolic compound, flavonoids, saponin, protein|
|13||Nerium indicum Apocynaceae||Kaner||Leaf, root||Phenolic compounds, flavonoids|
|Kalonji||Seed||Alkaloids, nigellicin, nigellidin, quinazoilin, tannins|
|Polysaccharides, flavonoids, amino acids triterpenoids|
|16||Panax japonicas Araliaceae||Japanese ginseng||Rhizomes||Phenolic cumpounds, flavonoids, saponin|
|17||Terminalia billerica Combertaceae||Baheda||Seed||Tannins, gallic acid, ellagic acid|
|18||Terminalia chebula Combertaceae||Harida||Seed||Tannins, gallic acid, chebulic acid, sorbitol|
|19||Vetiveria ziziinoides Graminae||Benachar||Root||Phenolic compound, flavonoids, saponin|
|20||Zingiber officinale Zingiberaceae||Ginger||Root||Phenolic compounds, flavonoids|
Flavonoids, terpenoids, and tannins are most important in the antiulcer activity of plant because they consist of poly phenolic structure which can act as an antioxidant. Some potent medicinal plants used in the treatment of ulcer are given in Table 1. 14
CONCLUSION: The review might be useful to supplement the information regarding symptoms identification, diagnosis, treatment, prevalence, management, and herbs used in the treatment of ulcers. This article also motivates researchers and helps them during a screening of medicinal plants.
ACKNOWLEDGEMENT: Authors are thankful to Dr. G. J. Khan and Maulana G. M. Vastanvi for valuable guidance, motivation, and direction which helped us all the times while writing this article.
CONFLICT OF INTEREST: Authors declares that there is no conflict of interest.
- Kumar V, Abbas AK and Fausto N: Robbins and Cotran Pathologic basis of disease. Elsevier India Private Limited; New Delhi, Edition 7th, 2006.
- Kumar A, Singh R, Sharma R and Kumar S: Peptic ulcer: a review on etiology and pathogenesis. International Research Journal of Pharmacy 2012; 3(6): 34-38.
- Subiksha PS: Various remedies for recurrent Aphthous ulcer: a review. J of Pharm Sci & Res 2014; 6(6): 251-53.
- Scully C, Gorsky M, and Lozada-Nur F: The Diagnosis and management of recurrent aphthous stomatitis. The J of the American Dental Association 2003; 134(2): 200-07.
- Higuchi D, Sugawa C, Shah SS, Tokioka S and Charles EL: Etiology, treatment and outcome of esophageal ulcers: A 10-year experience in an urban emergency hospital. Etiology & Outcome of Esophagus Ulcer 2003; 7(7): 836-42.
- Pahwa R, Neeta, Kumar V and Kohli K: Clinical manifestations, causes and management strategies of peptic ulcer disease. International Journal of Pharma-ceutical Sciences and Drug Research 2010; 2(2): 99-106.
- Mohan H: a Text book of Pathology. Jaypee brother’s medical publisher (P) Ltd.; New Delhi, Edition 6th, 2013.
- Truter I: Evidence-based pharmacy practice (EBPP): peptic ulcer disease. South African Pharmaceutical Journal 2009; 76(1): 10-20.
- Gulia Y and Choudhary M: Peptic ulcer disease: a review. Pharmacologyonline 2011; 3: 48-70.
- Tripathi KD: Essential of medical pharmacology. Jaypee Brother’s Medical Publisher (P) Ltd., New Delhi, Edition 7th, 2013.
- Adinortey MB, Ansah C, Galyuon I and Nyarko A: In-vivo models used for evaluation of potential anti-gastro-duodenal ulcer agents. Ulcers 2013: 1-12.
- Vogel HG: Discovery and evaluation, Pharmacological assays. Berlin Springer Publication, Edition 2nd, 2002.
- Bi WP, Man HB, and Man MQ: Efficacy and safety of herbal medicines in treating gastric ulcer: A review. World Journal Gastroenterology 2014; 20(45): 17020-17028.
- Gadekar R, Singour PK, Chaurasiya PK, Pawar RS, and Patil UK: A potential of some medicinal plants as an anti-ulcer agent. Pharmacognosy Review 2010; 4(8): 136-46.
How to cite this article:
Quazi MA and Molvi KI: Ulcer: pathogenesis, prevalence and management. Int J Pharmacognosy 2018; 5(12): 756-59. doi link: http:// dx.doi.org/10.13040/IJPSR.0975-8232.IJP.5(12).756-59.
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