Final Peptic Ulcer PDF

Peptic Ulcer Learning Objectives • Causes of peptic ulcer • Pharmacological approach in the treatment • Drug classifications used to treat peptic ulcer • Mechanism of actions • Pharmacokinetics and side effects • Drug interactions Causes of Peptic Ulcer Disease It is a condition in which painful...

Peptic Ulcer Learning Objectives • Causes of peptic ulcer • Pharmacological approach in the treatment • Drug classifications used to treat peptic ulcer • Mechanism of actions • Pharmacokinetics and side effects • Drug interactions Causes of Peptic Ulcer Disease It is a condition in which painful sores or ulcers develop in the lining of the stomach or the first part of the small intestine (the duodenum). d iiiIiis Causes of Peptic Ulcer Disease Acidic Secretion É iii HI coxecutnnur.name 1-Medical factors: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) 2-Physiological factors: -Increased hydrochloric acid (HCl) secretion te -Inadequate mucosal defense against gastric acid 3-Bacterial factors: Gram-negative Helicobacter pylori aside bbmauinganen.name b.in Iggy 1 rprotenuinase tram y.ygaseareart.be my face prostaglandin release campthiamin Gramps Drug Classifications Pharmacological treatment approaches • H2-Receptor Antagonists 1) Reducing secretion of gastric acid • Proton Pump Inhibitors 2) Providing agents that protect the gastric mucosa from damage • Anti H-Pylori agents µ 1 away haematocase hiniiaieicEm imminent reproach 3) Eradicating the H. pylori infection auean prostaglandins Hisham a histaminreleas • Prostaglandins • Antacids ionisneutralia • Mucosal protective agents H2-receptor antagonists H2-receptor antagonists WE Mt green Mechanism of Actions • They are a competitive blockers of histamine (H2) receptors lead to inactivation of _________which is aan.epu important for _________. Preamp • They are competitive antagonists of histamine and are fully reversible. • Cimetidine, ranitidine, famotidine, and nizatidine potently inhibit (greater than 90%) basal, food-stimulated, and nocturnal secretion of gastric acid. i Npcf Therapeutic uses: a. Peptic ulcer b. Acute stress ulcers c. Gastroesophageal reflux disease (GERD) Pharmacokinetics: I ❖ After oral administration, all agents are rapidly absorbed from the intestine. Eco ❖ They distribute widely throughout the body (including into breast milk and across the placenta) and are excreted mainly in urine. system renal Ema ❖ Cimetidine, ranitidine, and famotidine are also available in intravenous formulations. ❖ The half-life of all agents may be increased in patients with renal dysfunction, and dosage adjustments are needed. Cimetidine, ranitidine, and famotidine undergo first-pass hepatic metabolism resulting in a bioavailability of approximately 50%. Nizatidine has little first-pass metabolism • Diarrhea, headache, fatigue, myalgia, and constipation (occur in less than 3% of patients). and galactorrhea in women • Vitamin B12 deficiency. so increased.se I • Cimetidine when used long-term or in high doses, it may cause gynecomastia or impotence in men t it • Intravenous H 2 antagonists (or proton pump inhibitors) may increase the risk of nosocomial pneumonia in critically • Rapid intravenous infusion of H2 antagonist may cause bradycardia and hypotension through ill patients. • Mental status changes (confusion, hallucinations, agitation) may occur with administration of intravenous H 2 antagonists, especially in patients in the intensive care unit who are elderly or who have renal or hepatic dysfunction. _te blockade of cardiac H 2 receptors; therefore, intravenous injections should be given over 30 minutes. • All H2 antagonists may reduce the efficacy of drugs that require an acidic environment for absorption, such as ketoconazole. E • Cimetidine inhibits several cytochrome P450 isoenzymes and can interfere with the metabolism of many drugs. Proton Pump Inhibitors Proton Pump Inhibitors (PPIs) Mechanism of Action The PPIs bind to the H+/K+-ATPase enzyme system (proton pump) and suppress the secretion of hydrogen ions into the gastric lumen. PPIs forms a covalent disulfide bond with the H + /K + -ATPase, irreversibly inactivating the enzyme. PPIs are: inning Omeprazole Esomeprazole Lansoprazole with used food be can Conbone Dexlansoprazole Rabeprazole All are substituted benzimidazoles in structure Pantoprazole I Therapeutic uses ❖Stress ulcer treatment common most 8 ❖GERD and erosive esophagitis ❖Active peptic and duodenal ulcer ❖Pathologic hypersecretory conditions (for example, Zollinger- Ellison syndrome). e ❖PPIs also reduce the risk of bleeding from ulcers caused by aspirin and other NSAIDs. ❖Used with antimicrobial regimens to eradicate H. pylori. ➢Side effects Pharmacokinetics 8 ❑ Headache and GI effects such as diarrhea and nausea. All these agents are effective orally. • After passing through the stomach into the alkaline intestinal lumen, the enteric coatings dissolve and the pro-drug is absorbed. • For maximum effect, PPIs should be taken 30 to 60 minutes before breakfast or the largest meal of the day. ❑Bone fractures, and dementia have been reported from retrospective observational studies and case reports. i _mm ❑Mental confutation, impotence, gynecomastia and muscle & joint pain have been reported. • Esomeprazole, lansoprazole, and pantoprazole are also available in intravenous formulations. É • The drugs have a short serum half-life of about 1.5 hours, but acid inhibition lasts up to 24 hours owing to the irreversible inactivation of the proton pump. t • Metabolites of these agents are excreted in urine and feces. ❑Hypomagnesaemia and an increased incidence of pneumonia. TIK.am 7 ❑Clostridium difficile colitis may occur in community patients receiving PPIs. ❑Several concerns have been raised about consequences of long-term PPI use. I ➢ Omeprazole and esomeprazole may decrease the effectiveness of clopidogrel because they inhibit CYP2C19 and prevent the conversion of clopidogrel to its active metabolite. ➢ Prolonged acid suppression with PPIs (and H2 antagonists) may result in low vitamin B12 because acid is required for its absorption in a complex with intrinsic factor. I ➢ Elevated gastric pH may also impair the absorption of calcium carbonate. H. Pylori fracture bone H. Pylori at Treatment of H. Pylori aantimicrobial treatment. ❖Patients with peptic ulcer disease (duodenal or gastric ulcers) who are infected with H. pylori require Fine.Ganatra signed Triple therapy e Antimicrobial agents 8 • Triple therapy consisting of a PPI combined with amoxicillin (metronidazole may be used in penicillin-allergic patients) plus clarithromycin is the therapy of choice. ❖Infection with H. pylori is diagnosed via endoscopic biopsy of the gastric mucosa or various noninvasive I methods, including serology and urea breath tests. ❖Eradication of H. pylori results in rapid healing of active ulcers and low recurrence rates (less than 15% compared with 60% to 100% per year for initial ulcers healed with acid-reducing therapy alone). Quadruple therapy • Quadruple therapy of bismuth subsalicylate, metronidazole, and tetracycline plus a PPI is another option. • Quadruple therapy should be considered in areas with high resistance to clarithromycin. This usually results in a 90% or greater eradication rate. ❖Successful eradication of H. pylori (80% to 90%) is possible with various combinations of antimicrobial drugs. a resistance, and is not recommended. Prostaglandins • Treatment with a single antimicrobial drug is much less effective, results in antimicrobial tm ta a 8 • Prostaglandin E, produced by the gastric mucosa, inhibits secretion of acid and stimulates secretion of mucus and bicarbonate. A deficiency of prostaglandins is thought to be involved in the pathogenesis of peptic ulcers. • Substitution of antibiotics is also not recommended (that is, do not substitute ampicillin for amoxicillin or doxycycline for tetracycline). • [Note: GERD (heartburn) is not associated with H. pylori infection and does not respond to antibiotics • Misoprostol, an analog of prostaglandin E1, is approved for the prevention of NSAID-induced gastric ulcers. mut • Prophylactic use of misoprostol should be considered in patients who are taking NSAIDs and are at moderate to high risk of NSAID-induced ulcers, such as elderly patients and those with previous ulcers. Antacids • Misoprostol is contraindicated in pregnancy, since it can stimulate uterine contractions and cause miscarriage. I • Dose-related diarrhea and nausea are the most common adverse effects and limit the use of this agent. • Thus, PPIs are preferred agents for the prevention of NSAID-induced ulcers. Mucosal protective agents E • Also known as cytoprotective compounds, these agents have several actions that enhance mucosal protection mechanisms, thereby preventing mucosal injury, reducing inflammation, and healing existing ulcers. Mucosal protective agents E ▪ Although sucralfate is effective for the treatment of duodenal ulcers and prevention of stress ulcers, its use is limited due to the need 1. Sucralfate: for multiple daily dosing and drug–drug interactions. M This complex of aluminum hydroxide and sulfated sucrose binds to positively charged groups in proteins of both normal and necrotic mucosa. E ▪ Because it requires an acidic pH for activation, sucralfate should not be administered with PPIs, H2 antagonists, or antacids. By forming complex gels with epithelial cells, sucralfate creates a physical barrier that protects the ulcer from pepsin and a ▪ Sucralfate is well tolerated, and the most common side effects is constipation and GIT disturbance acid, allowing the ulcer to heal. later Drug Interaction Drug Interaction Abacavir Sucralfate may decrease the excretion rate of Abacavir which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Sucralfate which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Sucralfate which could result in a higher serum level. Acenocoumarol The therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Sucralfate. Acetaminophen Acetaminophen may decrease the excretion rate of Sucralfate which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Sucralfate which could result in a lower serum level and potentially a reduction in efficacy. Aclidinium Sucralfate may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Sucralfate may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Sucralfate which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Sucralfate which could result in a higher serum level 2. Bismuth subsalicylate This agent is used as a component of quadruple therapy to heal peptic ulcers. In addition to its antimicrobial actions: • it inhibits the activity of pepsin É • increases secretion of mucus • interacts with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer.