Gastrointestinal and Anti-Emetic Drugs - Pharmacology Lecture Notes PDF

Course Name: Pharmacology Course Code: Teacher Introduction: Dr Nazia Koser Faculty of Allied Health Sciences (FAHS) The University of Lahore  Gastric Drugs Learning Objectives: 1. Classification of gastric drugs. 2. Mechanism of action of gastric drugs. 3. Therape...

Course Name: Pharmacology Course Code: Teacher Introduction: Dr Nazia Koser Faculty of Allied Health Sciences (FAHS) The University of Lahore  Gastric Drugs Learning Objectives: 1. Classification of gastric drugs. 2. Mechanism of action of gastric drugs. 3. Therapeutic uses of gastric drugs.  Gastric Drugs Learning Objectives: 4. Causes of peptic ulcer. 5. Management of peptic ulcer. 6. Adverse Effects of gastric drugs.  Peptic Ulcer The main causes of peptic ulcer disease are: 1. Infection with gram negative Helicobacter pylori. 2. The use of nonsteroidal anti- inflammatory drugs (NSAIDS).  Peptic Ulcer 3. Increased hydrochloric acid (HCl) secretion. 4. Inadequate mucosal defense against gastric acid.  Treatment approaches Treatment approaches include: 1. Eradicating the H. pylori infection. 2. Reducing the secretions of gastric acid. 3. Providing agents that protect the gastric mucosa from damage.  Diagnosis Infection with H. pylori is diagnosed by: 1. Endoscopic biopsy of the gastric mucosa. 2. By using Noninvasive methods i.e. urea breath tests, Blood test.  Urea Breath test 1. Patients are given urea labeled with C 13 orally. 2. H. pylori produce urease, which hydrolyzes labeled urea to 13 CO2 and ammonia.  Urea Breath test 3. 13CO2 is dissolved in the blood and transported to lungs. 4. Exhaled 13 CO2 is analyzed. The presence of H. pylori results in an increased in ratio of CO2 to 13 CO2 in expired breath. 12 Drug therapy  Antimicrobial Agents Patients with peptic ulcer disease who are infected with H. pylori require antimicrobial treatment.  Drug therapy Triple therapy which consists of Proton pump inhibitor (PPIs) combined with amoxicillin plus clarithromycin.  Drug therapy (Continue) In cases which are resistant to clarithromycin the combination of Metronidazole, tetracycline, bismuth subsalicylate plus Proton pump inhibitors (PPIs) should be considered.  Drug therapy (Continue) Treat with Anti-H pylori regimen for 10–14 days. Treatment options: FDA approved Oral Regimens used to eradicate Helicobacter Pylori. Drug combination Dose & Frequency Duration Omeprazole (PPIs) 20 mg b.i.d 1 to 10 days Clarithromycin 500 mg b.i.d 1 to 10 days Amoxicillin 1 g b.i.d 1 to 10 days  Drug therapy (Continue) FDA approved Oral Regimens used to eradicate Helicobacter Pylori. Drug combination Dose & Frequency Duration Bismuth Subsalicylate 525 mg q.i.d 1 to 14 days Metronidazole 250 mg q.i.d 1 to 14 days Tetracycline 500 mg q.i.d 1 to 14 days Proton Pump Inhibitor Orally Twice Daily 1 to 14 days (PPIs)  H2 Receptor blockers Classification: 1. Cimetidine 2. Famotidine 3. Ranitidine 4. Nizatidine  Mechanism of action Gastric acid secretion is stimulated by:  Acetylcholine (Cholinergic receptors).  Histamine (H2 Receptors).  Gastrin (Cholecystokinin (CCK) receptor).  Mechanism of action (Continue) The receptor binding of acetylcholine, histamine or gastrin results in activation of protein kinase, which in turn stimulates H/K-adenosine ATPase proton, pump to secrete hydrogen ions in exchange for K into the lumen of stomach.  Mechanism of action (Continue) The binding of histamine H2 receptor blockers reduce the secretion of gastric acid.  Therapeutic Uses Peptic ulcer. Gastroesophageal reflux disease (GERD).  Administration and Dosage 1. Cimetidine: Patients may receive 400 mg twice daily 0r 800 mg at bed time. 2. Ranitidine: Ranitidine is given orally at a dose of 150 mg twice daily or 300 mg once daily.  Administration and Dosage 3. Famotidine: Famotidine is given orally at a dose of 40 mg once daily for a maximum of 8 weeks. 4. Nizatidine: Nazitidine is given orally at a dose of 300 mg once daily or 150 mg twice daily for up to 8 weeks.  Adverse effects In general, the H2 receptor antagonists are well tolerated. The most common adverse effects reported are: Headache Diarrhea Dizziness Nausea  Adverse effects Cimetidine can have endocrine effects, because it acts as a antiandrogen, such as: Gynecomastia (a condition of overdevelopment or enlargement of the breast tissue in men). Galactorrhea (continuous release/discharge of milk).  Counseling Points All H2 Receptor blockers are contraindicated in individuals < 12 years of age. Antacids impair absorption of cimetidine and ranitidine therefore, should be given 1 hour apart from these drugs.  Drug Interaction Cimetidine binds with the cytochrome P450 of the liver, thus may impair the hepatic metabolism and increases the serum concentrations and pharmacological effects of: Warfarin Phenytoin Clopidogrel.  Drug Interaction (Continue) Imipramine Diazepam Propranolol Phenobarbital Carbamazepine  Proton Pump Inhibitors (PPIs) Classification: 1. Omeprazole 2. Pantoprazole 3. Lansoprazole 4. Esomeprazole 5. Dexlansoprazole  Mechanism of action The PPIs bind to H/K ATPase enzyme system (proton pump) and forms a stable covalent bond with the H/K ATPase. This suppresses the secretion of hydrogen ions into the gastric lumen.  Mechanism of action (Continue) It takes about 18 hours for the enzyme to be resynthesized, and acid secretion is inhibited during this time At standard doses, PPIs inhibit gastric acid secretion by more than 90%.  Therapeutic uses 1. Stomach ulcer. 2. Duodenal ulcer. 3. They are used with antimicrobials drugs to eradicate H. pylori.  Proton Pump Inhibitors (PPIs) Note: Proton Pump Inhibitors (PPIs) are superior to the H2 antagonists in suppressing acid production and healing ulcers.  Dosage Proton Pump Dosage Inhibitors Omeprazole 20 mg Esomeprazole 20 to 40 mg Lansoprazole 30 mg Dexlansoprazole 30 mg Pantoprazole 40 mg Rabeprazole 20 mg  Administration Proton pump inhibitors should be taken in the morning 30 to 60 minutes before eating.  Drug Interactions Omeprazole and esomeprazole may decrease the effectiveness of clopidogrel because they inhibit CYP2C19 and prevent the conversion of clopidogrel to its active metabolite. Concomitant use of these PPIs with clopidogrel is not recommended  Drug Interactions Prolonged acid suppression with PPIs and H2 blockers may result in low vitamin B12 because acid is required for its absorption. PPIs may increase the risk of fractures, particularly if the duration of use is 1 year or greater. Elevated gastric pH may also impair the absorption of calcium carbonate. Calcium citrate is an effective option for calcium supplementation in patients on acid suppressive therapy., since absorption of citrate salt is not affected by gastric pH.  Adverse effects Headache Constipation Abdominal pain Nausea Diarrhea  Prostaglandins Prostaglandin E produced by gastric mucosa inhibit secretion of gastric acid and stimulate the secretion of mucus.  Prostaglandins “Misoprostol” is an analog of prostaglandin E and is approved for prevention of NSAID induced gastric ulcers. Misoprostol has both antisecretory (inhibiting gastric acid secretion) and mucosal protective properties.  Mechanism of Action Misoprostol interacts with prostaglandin receptors on parietal cells within the stomach, reducing gastric acid secretion and stimulating mucus production.  Therapeutic Uses  Misoprostol is approved for the prevention of NSAID-induced gastric ulcer.  Misoprostol is also used off-label in obstetric for labor induction as it increases uterine contractions by interacting with prostaglandin receptors in the uterus.  Administration and Dosage The recommended adult dose of misoprostol is 200 mcg four times daily with food. If this dose is not tolerated then100 mcg four times daily can be used.  Contraindication Misoprostol is contraindicated in pregnancy because of its abortifacient property. It stimulates uterine contraction and cause miscarriage.  Adverse effects The most frequent adverse effects are diarrhea and abdominal pain. Diarrhea is dose related and is often self-limiting. Administration of misoprostol with food minimizes the diarrhea.  Antacids Antacids are “weak bases” that react with the gastric acid and forms salt and water. Commonly used antacids are: i. Aluminum hydroxide ii. Magnesium Hydroxide iii. Calcium carbonate  Therapeutic Uses 1. GERD 2. Promote healing of ulcer. Note: They should be administered after meal for maximum effectiveness.  Adverse Effects 1. Aluminum hydroxide tends to cause constipation. 2. Magnesium hydroxide tends to produce diarrhea.  Mucosal Protective agents Mucosal Protective agents are also known as Cytoprotective agents. Classification: 1. Sucralfate  Sucralfate It is a complex of aluminum hydroxide and sucrose that binds to the protein of both normal and necrotic mucosa. By forming a complex gel with epithelial cells, sucralfate creates a physical barrier that protects the ulcer from pepsin and acid, allowing the ulcer to heal.  Administration and Dosage Sucralfate usually is given in a dosage of 1g four times daily (1 hour before meal) and at bedtime.  Drug Interaction Because sucralfate requires an acidic pH for activation so it should not be administered with Proton Pump Inhibitors (PPIs), H2 antagonists or antacids.  Drug Interaction (Continue) Antacids may reduce the mucosal binding of sucralfate, decreasing its therapeutic efficacy and thus should be given 30 to 60 minutes apart from sucralfate if used in combination ulcer therapy.  Therapeutic uses Adverse Effects: Constipation is the most common adverse effect of sucralfate.  Learning Outcomes: The students will learn about: Classification of gastric drugs. Mechanism of action of these drugs. Therapeutic uses and adverse effects of these drugs.  References  Lippincott, Illustrated Reviews Pharmacology.  Basic and Clinical Pharmacology 12 Edition Katzung.  Comprehensive Pharmacy Review (CPR) for Naplex 8th Edition.