Peptic Ulcer

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Pharmacotherapy of Peptic Ulcer:

Pharmacotherapy of Peptic Ulcer Dr Maulik Patel Assistant Professor,Pharmacology

What is Peptic Ulcer ?:

What is Peptic Ulcer ? A peptic ulcer disease or PUD is an ulcer (defined as mucosal erosions equal to or greater than 0.5 cm) of an area of the gastrointestinal tract exposed to the acid and pepsin secretion

Because of Imbalance:

Because of Imbalance Imbalance primarily between Aggressive factors and Defensive factors: Aggressive factors, e,g, acid, pepsin, H.pylori, NSAIDs, Alcohol, bile etc. Defensive factors, e.g. mucus, HCO3, PG

Who are they ?:

Who are they ? Barry J Marshall J. Robin Warren Nobel Laureates of Medicine – 2005 Discovery of H. pylori & its role in peptic ulcer

NSAIDS:

NSAIDS Damage to the cytoprotective role of PGs – PGE 2 and PGI 2

PowerPoint Presentation:

Drugs of Ulcer treatment

Physiology of Gastric Secretion:

Physiology of Gastric Secretion

Classification:

Classification Acid Neutralizing agents: (ANTACIDS) Systemic: Sodium Bicarbonate and Sod. Citrate Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium hydroxide gel, Magaldrate 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, enprostil

Classification – contd.:

Classification – contd. Ulcer protectives: Sucralfate, Colloidal Bismuth subcitrate, PG analogue Anti-H. pylori Drugs: Amoxicillin, Clarithromycin, metronidazole, tinidazole and tetracycline

Antacids:

Antacids Duration of action : 30 min when taken in empty stomach and 2 hrs when taken after a meal Side effects : Aluminium antacids – constipation (As they relax gastric smooth muscle & delay gastric emptying) – also hypophosphatemia and osteomalcia Mg2+ antacids – Osmotic diarrhoea

Therapeutic Questions:

Therapeutic Questions Is it rational to combine Aluminium hydroxide and magnesium hydroxide in antacid preparations ?

H2 Antagonists:

H 2 Antagonists MOA: 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)

H2 antagonists - Uses:

H 2 antagonists - Uses 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 Zollinger -Ellison syndrome Prophylaxis of aspiration pneumonia

Proton Pump Inhibitors:

Proton Pump Inhibitors Most effective drugs in antiulcer therapy Prodrugs requiring activation in acid environment Block enzymes responsible for secreting HCl - binds irreversibly to H+K+ATPase Prototype: Omeprazole (Prilosec) Examples: Lansoprazole Pantoprazole Rabeprazole Esomeprazole Omeprazole

Question:

Question Half life of proton pump inhibitors is 1.5 hours only and these drugs are generally given once daily. How this can be justified ? Answer : P.P.I - Irreversible inhibitors of H+K+ATPase (Hit and run drugs)

Adverse Effects:

Adverse Effects The most common are GIT troubles in the form of nausea, abdominal pain, constipation, flatulence, and diarrhea Prolonged use: Gynaecomastia, erectile dysfunction Hypergastrinemia which may predispose to rebound hypersecretion of gastric acid upon discontinuation of therapy and may promote the growth of gastrointestinal tumors (carcinoid tumors )

Prostaglandin analogues - Misoprostol:

Prostaglandin analogues - Misoprostol Actions: Inhibit histamine-stimulated gastric acid secretion Stimulation of mucin and bicarbonate secretion Increase mucosal blood flow (Reinforcing of mucous layer buffered by HCO3 secretion from epithelial cells) Therapeutic uses: Prevent ion of NSAID-induced mucosal injury (rarely used because it needs frequent administration – 4 times daily)

Question:

Question A patient comes to your clinic at midnight complaining of heart burn. You want to relieve his pain immediately. What drug will you choose?

Answer is:

Answer is Antacids Explanation : Antacids neutralize the already secreted acid in the stomach. All other drugs act by stopping acid secretion and so may not relieve symptoms atleast for 45 min

Sucralfate – ulcer protective:

Sucralfate – ulcer protective Salt of sucrose complexed to sulfated aluminium hydroxide (basic aluminium salt) MOA: In acidic pH polymerises to viscous gel that adheres to ulcer crater - more on duodenal ulcer Precipitates protein on surface proteins and acts as physical barrier Dietary proteins get deposited on this layer forming another coat Delays gastric emptying and causes gastric PG synthesis – protective action

PowerPoint Presentation:

Eradication of H.pylori Omeprazole Amoxicillin Clarithromycin Metronidazole

PowerPoint Presentation:

Triple Therapy The 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

H2 Receptor Antagonists:

H2 Receptor Antagonists in stomach at all stages decreases formation of HCl by selective blocking of H2 receptors therapeutic effect after 4 weeks - 60 -80% efficiency, after 8 weeks even 90%, 10-15% resistance Ranitidine, Famotidine /more effective/, Nizatidine: /1- 2x daily/ - good pharmacokinetic /p.o. absorbtion, metabolism in liver/ and safety profile, good tollerance - long-term maintenance therapy after uncomplicated peptic ulcer healing and treatment of some forms of gastric dyspepsias Thank you

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