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AN OVERVIEW OF TREATMENT MODALITIES FOR PEPTIC ULCER
PRESENTED BY: DIPTESH T. PATILROLL NO. 18FIRST YEAR M. PHARMGUIDED BY: MRS. VAISHALI MISTRY
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Definition
• A peptic ulcer is a mucosal break, 3 mm or greater in size with depth, that can involve mainly the stomach or duodenum.
• It has to be deep enough to penetrate the muscularis mucosa.
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REASON• The gastroduodenal mucosal integrity is determined by
protective (defensive) & damaging (aggressive) factors
• When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to ulcerations
Aggressive factors, e.g, acid, pepsin, bile etc.
Defensive factors, e.g. mucus, HCO3, PG
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TYPES1. ESOPHAGAEL ULCER
2. GASTRIC ULCER
3. DUODENAL ULCER
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CAUSES• Helicobacter pylori• NSAIDs• Ethanol• Tobacco• Severe physiologic stress (Burns, CNS trauma,Surgery, Severe medical illness)• Steroids
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Ulcers associated with H. pylori
Ulcers associated with NSAIDs
• More often in duodenum • More often in stomach
• Often superficial • Often deep
• Less severe GI bleeding • More severe GI bleeding
• Usually pain with dyspepsia • Sometimes asymptomatic
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CLASSIFICATION1. Acid Neutralizing agents: (ANTACIDS)
• Systemic: Sodium Bicarbonate and Sod. Citrate• Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium hydroxide gel
2. Reduction in Gastric acid secretion:• H2 antihistamines: Cimetidine, Ranitidine, Famotidine, Nizatidine and Roxatidine• Proton pump inhibitors: Omeprazole, Lansoprazole Pantoprazole, Rabeprazole and
Esomeprazole• Anticholinergics: Pirenzepine, Propantheline and Oxyphenonium• Prostaglandin analogue: Misoprostol
3. Ulcer protectives: Sucralfate, Colloidal Bismuth subcitrate
4. Anti-H. pylori Drugs: Amoxicillin, Clarithromycin, metronidazole, tinidazole and tetracycline
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ACID NEUTRALIZING AGENTS:(ANTACIDS)
• OVER THE COUNTER and are taken by mouth for quick relief.
• Treatment with antacids alone is symptomatic and only justified for minor symptoms.
• Antacids are distinct from acid-reducing drugs like H2-receptor antagonists or proton pump inhibitors and they do not kill the bacteria Helicobacter pylori, which causes most ulcers.
• Fast onset of action makes them first choice for serious PUD for all patients and for every condition of PUD.
• Antacids contain alkaline ions that chemically neutralize stomach gastric acid, reducing damage and relieving pain.
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1. Systemic• Sodium bicarbonate is a systemic alkalizer, which increases plasma bicarbonate, buffers
excess hydrogen ion concentration, and raises blood pH• thereby reversing the clinical manifestations of acidosis. • Sodium bicarbonate acts as an antacid and reacts chemically to neutralize or buffer
existing quantities of stomach acid but has no direct effect on its output. This action results in increased pH value of stomach contents, thus providing relief of hyperacidity symptoms.
2. Non-Systemic• Aluminum hydroxide, Calcium carbonate, Magnesium hydroxide are a basic inorganic salts • Acts by neutralizing hydrochloric acid in gastric secretions. • Aluminum hydroxide is slowly solubilized in the stomach and reacts with hydrochloric acid
to form aluminium chloride and water. • It also inhibits the action of pepsin by increasing the pH and via adsorption. Cytoprotective
effects may occur through increases in bicarbonate ion (HCO3-)and prostaglandins
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• EXAMPLESa) Aluminium hydroxide b) Magnesium hydroxide c) Aluminum hydroxide with magnesium hydroxided) Aluminum carbonate gel e) Calcium carbonate f) Sodium bicarbonate g) Hydrotalcite [Mg6Al2(CO3)(OH)16 · 4(H2O)] h) Bismuth subsalicylate
• Simethicone: (polydimethylsiloxane and hydrated silica gel)Decrease surface tension thereby reduce bubble formation - added to prevent reflux.
• Alginates: Form a layer of foam on top of gastric contents & reduce reflux
• Oxethazaine/Oxetacain: Surface anaesthetic
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REDUCTION IN GASTRIC ACID SECRETION:H2 ANTIHISTAMINES
1. Extremely safe drugs and well tolerated
2. Promote the healing of gastric and duodenal ulcers• Duodenal ulcer – 70 to 90%• Gastric Ulcer – 50 to 75% (NSAID ulcers))• Stress ulcer and gastritis• GERD
EXAMPLES: Cimetidine, Ranitidine, Famotidine, Roxatidine, Nizatidine
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Mechanism Of Action
• Reversible competitive inhibitors of H2 receptor• Highly selective, no action on H1 or H3 receptors• All phases of gastric acid secretion• Very effective in inhibiting nocturnal acid secretion (as it
depends largely on Histamine )• Modest impact on meal stimulated acid secretion (as it
depends on gastrin, acetylcholine and histamine)• Volume of pepsin content also reduced• Volume reduced by 60 – 70% - anti ulcerogenic effect• No effect on motility
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Main ADRs are related to Cimetidine:• Antiandrogenic effects• Increases prolactin secretion and inhibits degradation of
estradiol by liver• Cytochrome P450 inhibition – theophylline, metronidazole,
phenytoin, imipramine etc.• Antacids
Others:• Headache, dizziness, bowel upset, dry mouth• Bolus IV – release histamine – bradycardia, arrhythmia, cardiac
arrest• Elderly - precaution
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PROTON PUMP INHIBITORS
• Most effective drugs in antiulcer therapy• Prodrugs requiring activation in acid environment• Prototype: Omeprazole (Prilosec) • Examples:
• Lansoprazole • Pantoprazole• Rabeprazole • Esomeprazole
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MECHANISM OF ACTION• Acts by irreversibly blocking the hydrogen/potassium adenosine
triphosphatase enzyme system (the H+/K+ ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells.
• Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, results in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.
• Decreasing the acid in the stomach can aid the healing of duodenal ulcers and reduce the pain from indigestion and heartburn.
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ANTICHOLINERGICS• Unpopular as a first choice because of high incidence of
anticholinergic side effects (dry mouth and blurred vision)
(receptors on parietal cells are M3)• Atropine:
• Block the M1 class receptors• Reduce acid production• Abolish gastrointestinal spasm
• Pirenzepine and Telenzepine:• Reduce meal stimulated HCl secretion by reversible blockade of
muscarinic (M1) receptors on the cell bodies of the intramural cholinergic ganglia
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PROSTAGLANDIN ANALOGUE• Inhibit gastric acid secretion• Exhibit ‘cytoprotective’ activity• Enhance local production of mucus or bicarbonate• Promote local cell regeneration• Help to maintain mucosal blood• ONLY ONE DRUG IS IN MARKET MISOPROSTOL
(Reinforcing of mucous layer buffered by HCO3 secretion from epithelial cells)
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Mechanism Of Action:Inhibit histamine-stimulated gastric acid secretionStimulation of mucin and bicarbonate secretionIncrease mucosal blood flow
Therapeutic uses:Prevent ion of NSAID-induced mucosal injury (rarely used
because it needs frequent administration – 4 times daily)Misoprostol is contraindicated in Pregnacy.
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ULCER PROTECTIVES• Example:- Bismuth subsalicylate
• Pharmacological actions:• Undergoes rapid dissolution in the stomach into bismuth and salicylates• Salicylates are absorbed • Bismuth coats ulcers and erosions protecting them from acid and
pepsin and increases prostaglandin and bicarbonate production
• Uses:• Treatment of dyspepsia and acute diarrhoea
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ANTI-H. PYLORI DRUGS• It was identified in 1982 by Australian
scientists Barry Marshall and Robin Warren, In recognition of their discovery, Marshall and Warren were awarded the 2005 Nobel Prize in Physiology or Medicine.
• To avoid the acidic environment of the interior of the stomach (lumen), H. pylori uses its flagella to burrow into the mucus lining of the stomach to reach the epithelial cells underneath, where it is less acidic.
• It also neutralizes the acid in its environment by producing UREASE, which breaks down the urea present in the stomach to carbon dioxide and ammonia. These react with the strong acids in the environment to produce a neutralized area around H. pylori.
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When H. pylori infection is present, the most effective treatments are combinations of 2 antibiotics and a proton-pump inhibitor (PPI), sometimes together with a bismuth compound. In complicated, treatment-resistant cases.
• Amoxicillin acts by inhibiting the synthesis of bacterial cell walls.• Clarithromycin prevents bacteria from growing by interfering with their protein
synthesis.• Metronidazole and Tinidazole inhibits nucleic acid synthesis by disrupting the
DNA of microbial cells.• Tetracycline inhibits protein synthesis by blocking the attachment of charged
aminoacyl-tRNA to the A site on the ribosome. Tetracycline binds to the 30S subunit of microbial ribosomes.
• Thus, it prevents introduction of new amino acids to the nascent peptide chain.
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Triple TherapyThe BEST among all the Triple therapy regimen is:
Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd
Given for 14 days followed by P.P.I for 4 – 6 weeks
Short regimens for 7 – 10 days not very effective
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Bismuth subsalicylate – 2 tab qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid
Some other Triple Therapy Regimens are
Ranitidine Bismuth citrate - 400 mg bd
Tetracycline - 500 mg bd
Clarithromycin / Metronidazole - 500 mg bd
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NON PHARMACOLOGICAL TREATMENT
• DO’s and DON’Ts• Spicy and fatty foods should be avoided as those generally irritate the
stomach lining.• Smoking and drink should be stopped in moderation.• OTC pain relievers such as aspirin and NSAIDS should be avoided
•Acupuncture
•Homeopathy•Argentum nitricum•Arsenicum album•Kali bichromicum
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• Herbs• Cranberry (Vaccinium macrocarpon)• Mastic (Pistacia lentiscus)• Licorice (Glycyrrhiza glabra)
•Probiotics
•SURGERY•Truncalvagotomy or Pyloroplasty•Gastrojejunostomy•Billroth I and II Gastrectomy•Antrectomy
•AYURVEDIC TREATMENT
•VACCINATION
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REFERENCE• “AN OVERVIEW OF TREATMENT MODALITIES FOR PEPTIC ULCER”
Diptesh T. Patil, Pratiksha V. Doke, Dr. Vanita Kanase, Dr. Pramila YadavWorld Journal of Pharmaceutical Research, Volume 4, Issue 8, 2302-
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• Najm, WI. "Peptic ulcer disease" Primary care, September 2011; 38(3): 383–94, vii.
• Milosavljevic, T; Kostić-Milosavljević, M; Jovanović, I; Krstić, M. "Complications of peptic ulcer disease“ Digestive diseases (Basel, Switzerland), 2011; 29(5): 491–3.
• "Ulcer Disease Facts and Myths". BY http://ulcerdisease.net/
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