13 Drugs for PU_PHC561.pdf

Drugs in Peptic Ulcer Diseases Dr Hasseri Halim [email protected] Outcomes At the end of this lecture, students should be able to determine Mechanism of gastric secretion Classification of drugs used in peptic ulcer Mechanism of action, uses and adverse effects...

Drugs in Peptic Ulcer Diseases Dr Hasseri Halim [email protected] Outcomes At the end of this lecture, students should be able to determine Mechanism of gastric secretion Classification of drugs used in peptic ulcer Mechanism of action, uses and adverse effects, drug interactions of ØH2 blockers ØProton pump inhibitors ØAntacids ØUlcer protective New Drugs for peptic ulcer ØPotassium-competitive acid blockers ØCholecyctokinin2 receptor antagonists Drugs for eradication of H-pylori infection  Functional anatomy of the stomach The proximal 80%- makes up the acid secreting oxyntic gland area. The distal 20% - the pyloric gland area and produces the hormone gastrin. 3 Gastric acid secretion Parietal cells (oxyntic glands) Located in body of stomach H+/ K+ ATPase pump Generates ion gradient secrete 1 to 2 liters of 150 to 160 mmol per liter of hydrochloric acid per day as well as intrinsic factor. Influenced by ACh Histamine Gastrin Gastric “Oxyntic” gland 4 Mechanism of Gastric Secretion 5  Acetylcholine, histamine and gastrin directly and indirectly Parietal cell induce acid secretion by parietal cells. Acetylcholine acts through the M3 receptor Gastrin acts through the CKKB receptor Both are Gaq linked to increases in Ca2+ and diacylglycerol through the PLC – IP3 pathway CKKb: cholecystokinin B receptors Gaq: Gq protein alpha subunit PLC - IP3 : Phopholipase C - Inositol trisphosphate 6  Histamine acts through a Gas, activating adenylyl Parietal cell cyclase, increases cAMP and stimulates acid secretion. This pathway has most powerful overall action. Gas : Gs protein alpha subunit 7 cAMP: Cyclic adenosine monophosphate  Parietal Cells Stimulation --> H-K ATPase (proton pump) is inserted into membrane for acid secretion. 8  Mechanism of acid secretion H+ and OH- are generated from H2O OH- bind with CO2 to form H2CO3 through a reaction catalyzed by carbonic anhydrase H2CO3 dissociates into HCO3- & H+ HCO3- extruded from cell base is exchanged for Cl- which diffuses into lumen through Cl- channels. 9  Mechanism of acid secretion K+ ions are counter transported into the parietal cell in exchange for H+ Net resultà production of HCL in the parietal cells and its secretion into the duct of the gastric gland 10 Question If gastric juice is the most acid fluid in the body, what prevents the mucosal lining from being damaged? 11  Protection of the gastric surface epithelium Acid is squirted through mucus layer as a jet A mucus gel layer 50-200 µm thick creates a diffusion barrier for H+ and a pH gradient of 1 to 7.2 Impermeable apical cell membranes and tight junctions limit H+ ion diffusion across the epithelium Vagal stimulation and irritation stimulate gastric mucous cells to secrete mucin, a glycoprotein that is part of the mucosal barrier 12  Protection of the gastric surface epithelium HCO3- accumulates near the cell surface Gastric surface epithelial cells secrete HCO3- when stimulated by acetylcholine, acids, and prostaglandins Mucus protects the gastric surface epithelium by trapping an HCO3- rich fluid near the apical border of these epithelial cells 13 Peptic Ulcer Disease What is an ulcer? What is the primary cause of peptic ulcer disease? What factors put an individual at risk for developing peptic ulcer disease? 14 Peptic Ulcer Definition: Area of tissue destruction that can be caused by increased acid & pepsin OR impaired mucosal defense Inflammation of underlying & surrounding tissues Sites: Stomach: gastric ulcer Duodenum: duodenal ulcer 15 Defensive factors Aggressive factors Mucus Gastric acid Bicarbonate Pepsin PGE2 Prostaglandin deficiency Mucosal normal blood flow H. pylori Mucosal renewal Slow gastric emptying 16 Why Peptic Ulcer Occurs? Imbalance primarily between defensive factors and aggressive factors. uc us, r s e.g. m e fa cto l ow, ns i v od f n Defe PG, Blo eneratio 3, g HCO tion &re tu resti s e. g. to r i v e fac res s b i le, g g , A , p e psin acid i lor H.py Endoscopy of Duodenal Ulcer 18 Endoscopy of Stomach Ulcer in Corpus 19  Epidemiology: 10% of population (mainly asymptomatic) GU: DU = 1:2 GU: more common in ages between 55-65 years, rarely before 40 years Tendency to become malignant Pathophysiology: imbalance between protective mechanism and injurious mechanism Aetiology: multifactorial (increase acid production, h. pylori, dietary factors, stress, NSAIDs etc) 20 Peptic Ulcer: aetiology Helicobacter pylori 85% more commonly associated with DU NSAIDs- 10- 15% Rare causes Zollinger Ellison Syndrome Stress ulcer 21 22 PUD: risk factors Drinking too much alcohol Regular use of aspirin, ibuprofen, naproxen, or other nonsteroidal anti-inflammatory drugs (NSAIDs). Smoking cigarettes or chewing tobacco Being very ill, such as being on a breathing machine Having radiation treatments 23 Gastric Ulcer vs Duodenal Ulcer PUD: complications Haemorrhage Anaemia Malaena Haematemasis Perforationà peritonitis Scarring, stricture & obstruction 25 Diagnostic methods Endoscopy & biopsy of ulcer H. Pylori testing Breath test serology Abdominal x-ray to rule out perforation Blood count to measure haemoglobin 26 Drug treatment Relieve symptoms by neutralising acid & reducing acid secretion Promote healing by enhancing mucosal resistance & eliminating bacterial gastric infection 27 Pharmacotherapy for Peptic Ulcer Disease Four primary classes H2-receptor antagonists Proton pump inhibitors Antibiotics Antacids Miscellaneous drugs Prostaglandin analogues Mucosal protectants i.e. sucralfate, bismuth compounds Anti-muscarinic 28 Treatment Approaches Inhibiting secretion of more acid Neutralizing gastric acid that is already secreted Protecting the ulcer from damaging effects of acid and pepsins Eradicating H. pylori infection Avoidance NSAIDs Classification of Drugs Used in PU 1. Drugs that inhibit gastric acid secretion 2. Drugs that neutralize gastric acid 3. Ulcer protective 4. Anti H. Pylori drugs 1. Drugs that inhibit gastric acid secretion H2 receptor blockers : Ranitidine, Cimetidine, Famotidine, Nizatidine Proton pump inhibitors : Omeprazole, Esomeprazole, Pantoprazole Anticholinergics : Pirenzipine Prostaglandin analogues : Misoprostol New drug: Potassium-competitive acid blockers : Revaprazan, Vonoprazan 2. Drugs that neutralize gastric acid Antacids Systemic antacids : Sodium bicarbonate, Sodium citrate Non-systemic antacids : Magnesium hydroxide, Magnesium trisilicate, Aluminium hydroxide gel 3. Ulcer protectives Ø Sucralfate Ø Colloidal Bismuth Sulfate (CBS) 4. Anti H.pylori Drugs Ø Amoxicillin, Ø Clarithromycin, Ø Metronidazole, Ø Tinidazole, Ø Tetracycline H2 Antagonists Mechanism of action Act selectively on H2 receptors in the stomach, but they have no effect on H1 receptors. They are competitive antagonists of histamine. Suppress secretion of acid in all phases but mainly nocturnal acid secretion. Also reduce acid secretion stimulated by Ach, gastrin, food, etc.. H2 Receptor Antagonist Cimetidine (Tagamet®) Prototype mild temporary diarrhea, dizziness, rash, or headache Long-term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men. interacts with a number of commonly used medications, such as phenytoin, theophylline, and warfarin Ranitidine (Zantac®) provided more pain relief and healed ulcers more quickly than cimetidine common side effect associated with ranitidine is headache Interacts with very few drugs 36 H2 Receptor Antagonist Famotidine (Pepcid®) most potent H2 blocker. Most common side effect is headache Virtually free of drug interactions Use with caution in patients with kidney problems excreted primarily by the kidney. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances. Physicians advised to reduce the dose and increase the time between doses in patients with kidney failure. Nizatidine (Axid®) nearly free of side effects and drug interactions 37 Pharmacokinetics After oral administration, the H2 antagonists distribute widely throughout the body. They are metabolized by liver and excreted mainly in urine. Cimetidine, ranitidine, and famotidine are also available in intravenous formulations. The half-life of all of these agents may be increased in patients with renal dysfunction, and dosage adjustments are needed. Comparison of H2 receptor antagonists Cimetidine Ranitidine Famotidine Nizatidine Bioavailability 80 50 40 >90 Relative Potency 1 5-10 32 5-10 Half life (hrs) 1.5-2.3 1.6-2.4 2.5-4 1.1-1.6 Duration of action (hrs) 6 8 12 8 Inhibition of CYP450 1 0.1 0 0 Dose mg (bd) 400 150 20 150 Therapeutic uses Duodenal ulcer Gastric Ulcer NSAIDs induced ulcers Stress ulcer and gastritis Gastroesophageal reflux disease (GERD)  Adverse Effects l Headache, dizziness, bowel upset, dry mouth l CNS: Confusion, restlessness l Endocrine effects : Cimetidine because it acts as an antiandrogen such as gynecomastia and galactorrhea. Gynecomastia= enlarged breast in men Galactorrhea=Production of breast milk in men or in women who are not breastfeeding Drug Interactions l Cimetidine inhibits several CYP-450 isoenzymes and reduces hepatic blood flow, so inhibits metabolism of many drugs like theophylline, metronidazole, phenytoin, imipramine etc. l All H2 antagonists may reduce the efficacy of drugs that require an acidic environment for absorption, such as ketoconazole.  Clinical Sketch 1 Your friend wants to take a H2 antagonist before he takes alcohol to avoid gastric irritation. He consults you. Which H2 antagonist will you ask him to take ? Ranitidine/Famotidine/Cimetidine ?  Clinical Sketch 1 Your friend wants to take a H2 antagonist before he takes alcohol to avoid gastric irritation. He consults you. Which H2 antagonist will you ask him to take ? Ranitidine/Famotidine/Cimetidine ? ANSWER : Famotidine Explanation; All H2 antagonist except famotidine inhibit gastric first pass metabolism of ethanol and increase its bioavailability  Proton Pump Inhibitors (PPIs) Most effective drugs in antiulcer therapy The PPIs bind to the H+/K+-ATPase enzyme system (proton pump) and suppress the secretion of hydrogen ions into the gastric lumen.  Proton Pump Inhibitors (PPIs) Dexlansoprazole Esomeprazole Available as OTC for the Lansoprazole short term treatment of Omeprazole GERD Pantoprazole and Rabeprazole  Mechanism of action These agents are prodrugs with an acid-resistant enteric coating to protect them from premature degradation by gastric acid. bind to the H+/K+-ATPase enzyme system (proton pump) of the parietal cell, thereby suppressing secretion of hydrogen ions into the gastric lumen. At standard doses, PPIs inhibit stimulated gastric acid secretion by more than 90%. Pharmacokinetics Orally available. For maximum effect, PPIs should be taken 30 to 60 minutes before breakfast or the largest meal of the day. Esomeprazole, lansoprazole, and pantoprazole: IV available Half life is very short and only 1-2 Hrs Still the action persists for 24 Hrs to 48 hrs after a single dose due to covalent bonding with the H+/K+ATPase enzyme. Metabolites of these agents are excreted in urine and feces. Therapeutic uses Gastroesophageal reflux disease (GERD) Zollinger-Ellison syndrome (ZES) Peptic Ulcer - Gastric and duodenal ulcers Bleeding peptic Ulcer Prevention of recurrence of nonsteroidal antiinflammatory drug (NSAID) - associated gastric ulcers in patients who continue NSAID use. Reducing the risk of duodenal ulcer recurrence associated with H. pylori infections Therapeutic uses If a once-daily PPI is only partially effective for GERD symptoms, increasing dosing to twice daily or administering the PPI in the morning and adding an H2 antagonist in the evening may improve symptom control. If an H2-receptor antagonist is needed, it should be taken well after the PPI. H2 antagonists reduce the activity of the proton pump, and PPIs require active pumps to be effective. Finally, they are used with antimicrobial regimens to eradicate H. pylori. Comparative success of therapy with PPI and H2 antagonist  Adverse Effects l May increase the risk of fractures l Prolonged acid suppression with PPIs (and H2 antagonists) may result in low vitamin B12. l 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. l Diarrhea and Clostridium difficile colitis may occur in patients receiving PPIs. Clostridium difficile colitis – infection with the bacteria that can cause mucosal inflammation and damage  Drug Interactions l Omeprazole inhibits the metabolism of warfarin, phenytoin, diazepam, and cyclosporine. l Omeprazole and esomeprazole may decrease the effectiveness of clopidogrel because they inhibit CYP2C19 and prevent the conversion of clopidogrel to its active metabolite. l However, drug interactions are not a problem with the other PPIs. PPI Dosage Schedule  Clinical Sketch 2 Half life of proton pump inhibitors is 1.5 hours only and these drugs are generally given once daily. How this can be justified?  Clinical Sketch 2 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 - causes long duration of action Prostaglandin (PGE1) analogues: Misoprostol l Inhibit gastric acid secretion l Enhance local production of mucus or bicarbonate l Help to maintain mucosal blood flow Therapeutic use: is approved for the prevention of NSAID-induced gastric ulcers Dose : 200 mcg 4 times daily)  Prostaglandin analogues- Misoprostol Adverse Effects l Diarrhoea, nausea and abdominal cramp (Common and dose related) l Uterine bleeding l Abortion l Exacerbation of inflammatory bowel disease Contraindications: l Inflammatory bowel disease l Pregnancy  Antacid A substance which directly neutralize stomach acidity by increasing the pH.  Antacids — Weak bases that react with gastric acid to form water and a salt. — Antacids also reduce pepsin activity. — Composed of calcium, magnesium, potassium, sodium and aluminium salts. Acid-neutralizing ability of antacids Efficacy of an antacid depends on 1. Its capacity to neutralize gastric HCl 2. Full or empty stomach. (food delays stomach emptying allowing more time for the antacid to react).  Commonly used antacids Four major antacid drugs: Salts of aluminium : aluminium hydroxide Salts of magnesium: Magnesium hydroxide Salts of sodium : Sodium bicarbonate Salts of calcium : Calcium carbonate Chemical reactions of antacids with HCl in the stomach  Uses Sympatomatic relief of peptic ulcer (PU) disease and GERD, and they may also promote healing of duodenal ulcer (DU). They should be administered after meals for maximum effectiveness.  Adverse effects 1) Alter gut motility. For e.g., Preparations that combine Aluminium hydroxide can cause constipation. these agents aid in normalizing Magnesium hydroxide can cause diarrhea. bowel function. Note : Absorption of the cations from antacids (Mg2+, Al3+, Ca2+) is usually not a problem in patients with normal renal function; however, accumulation and adverse effects may occur in patients with renal impairment.  Drug Interactions By raising gastric pH & forming insoluble complexes ↓ absorption of many drugs Tetracyclines, iron salts, H2 Blockers, diazepam, phenytoin, isoniazid, ethambutol Non-systemic antacids — Insoluble and poorly absorbed basic compounds — React in stomach to form corresponding chloride salt v Magnesium hydroxide: Milk of magnesia (MOM) v Magnesium trisilicate v Aluminium Hydroxide Duration of action : 30 min when taken in empty stomach and 2 hrs when taken after a meal Aluminium Salts — Widely used. — Aluminium hydroxide is most common. — Classified as non-systemic antacids. — Weak ability to neutralize acid.  Mechanism of action Aluminium salts form a gelatinous mass which adsorbs acid and pepsins. Adverse effects 1. Hypophosphatemia — Aluminium salts significantly adsorb phosphate, reducing phosphate absorption and increasing phosphate loss from the body. — Chronic use : Hypophosphatemia 2. Constipation Adverse effects 2. Bone fractures — Decrease phosphate absorption also causes loss of calcium from bones, making them more brittle and the patient more susceptible to bone fractures. 3. Hypercalcemia Redistribution of calcium from bone into the blood stream can also cause hypercalcemia.  Uses Hyperphosphatemia : Aluminium salts Hypophosphatemia : Aluminium phosphate Implications — Monitor patients taking high doses of aluminium containing antacids chronically for signs of hypercalcemia, hypophosphatemia. — Advise person at risk of phosphate deficiency or osteoporosis. — Since aluminium containing antacids reduce the absorption of many other drugs, advise patients not to take interacting medications orally within two hours of each other.  Magnesium Salts Major magnesium salts: — Magnesium oxide. — Magnesium hydroxide (milk of magnesia) They are potent, rapidly acting but less rapid than sodium bicarbonate or calcium carbonate. Uses Antacids Laxatives Adverse effects 1. Hypermagnesemia 2. Magnesium intoxication 3. Diarrhea Implications Closely monitor patients with poor renal function for neural signs that might cause magnesium intoxication. Have all patients taking any product containing magnesium report severe or prolonged diarrhea, which may lead to dehydration and electrolyte imbalances. Discourage the use of magnesium sulphate (Epson salt) as antacids. Calcium carbonate — Can produce prompt and prolonged effect. — Non-systemic antacid as it is not soluble in water  Uses Antacids Neutralizes gastric acid effectively and stimulates acid secretion. Due to causing constipation and fecal impaction, is rarely used alone. Also used as calcium supplements for the treatment of osteoporosis  Adverse effects 1. Constipation 2. Hypercalcemia 3. Renal calcium stones  Fecal Impaction Retard GI motility à Fecal impaction Overuse 1. Milk-alkali syndrome — Occur when patients take excessive amounts of milk and antacids to control their dyspepsia, leading to overingestion of calcium and base. — Signs and symptoms: hypercalcemia and systemic metabolic alkalosis. — May lead to kidney failure Implications — Persons inquiring about the use of these products should be told to consult with physician first to discuss the potential risks and benefits. — Risks including hypercalcemia and its biologic consequences (including increases risk of renal calcium stones).  Systemic Antacids: ØSodium Bicarbonate ØSodium Citrate Sodium Bicarbonate — One of the most common home remedies for GI upset. — Extremely effective and prompt acid neutralizer. Both sodium and bicarbonate ions are freely absorbed into the blood stream. Uses Antacids PU Mild indigestion or heartburn Adverse effects 1. Hypertension 2. Systemic alkalosis Interactions 1. Patients with GI ulcers should not take sodium bicarbonate. — Sodium bicarbonate reacts with stomach acid to form large amounts of carbon dioxide gas. The gas may stretch the ulcerated stomach wall which may cause further tissue damage and severe bleeding. — Discourage patients from taking sodium bicarbonate for GI disorder and PU disease. Also important for patients with CVS diseases such as hypertension or heart failure.  Clinical Sketch 3 A patient comes to the clinic at midnight complaining of heart burn. GP want to relieve his pain immediately. What drug should be given to the patient?  Clinical Sketch 3 A patient comes to the clinic at midnight complaining of heart burn. GP want to relieve his pain immediately. What drug should be given to the patient? ANSWER : 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 at least for 45 min Mucosal protective (Cytoprotective) Agents Can enhance mucosal protection mechanisms, thereby preventing mucosal injury, reducing inflammation, and healing existing ulcers. Sucralfate, bismuth subsalicylate Sucralfate § A complex of aluminum hydroxide and sulfated sucrose Mechanism of Action: In acidic environment, it polymerises by cross linking molecules to form sticky viscous gel that adheres to ulcer. Astringent action and acts as physical barrier that protects the ulcer from pepsin and acid, allowing the ulcer to heal. § Used for the treatment of duodenal ulcers and prevention of stress ulcers, its use is limited due to the need for multiple daily dosing and drug–drug interactions. Sucralfate Dose: 1 gm 1 Hr before 3 major meals and at bed time for 4- 8 weeks Adverse Effects : Constipation, hypophosphatemia Drug interactions : adsorbs many drugs and interferes with their absorption. Sucralfate interacts with a wide variety of drugs, including warfarin, phenytoin, and tetracycline.  Clinical Sketch 4 A pregnant lady (first trimester) comes to the clinic with peptic ulcer disease. Which drug will the GP prescribe for her?  Clinical Sketch 4 A pregnant lady (first trimester) comes to the clinic with peptic ulcer disease. Which drug will the GP prescribe for her? ANSWER : Antacids or Sucralfate Explanation; H2 antagonists cross placenta and are also secreted in breast milk. Safety of Proton pump inhibitors not established in pregnancy. Misoprostol causes abortion Bismuth Subsalicylate Used as a component of quadruple therapy to heal peptic ulcers. In addition to its antimicrobial actions, it inhibits the activity of pepsin, increases secretion of mucus, and interacts with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer Bismuth Subsalicylate Mechanism of action ↑ secretion of mucous and bicarbonate, through stimulation of mucosal PGE production Detaches H.pylori from surface of mucosa and directly kills them Dose: 120 mg 4 times a day Adverse effects blackening of tongue, stools, dentures Prolonged use may cause osteodystrophy and encephalopathy Diarrhoea, headache, dizziness Osteodystrophy: abnormal changes in the growth and bone formation Encephalopathy: damage that effect the brain function and strcuture  New Drugs for Peptic Ulcer Disease Potassium competitive acid blockers (P-CABs) Cholecystokinin2 receptor antagonists (CCK2) Potassium-competitive acid blockers (P-CABs) New acid suppressant drug (eg: Revaprazan, Vonoprazan) Currently used in Japan, Malaysia (since 2019), Singapore, South Korea, Taiwan, Thailand, Taiwan. Reversibly inhibit the activity of H+/K+-ATPase by competing for potassium on the luminal side of the parietal cell. Rapid onset of action Similar efficacy and comparable safety profile to PPIs May also effective for eradication of H. pylori in combination with antibiotics. Cholecyctokinin2 receptor antagonists (CCK2) Specific type of receptor antagonist which blocks the receptor sites for the peptide hormone cholecystokinin (gastrin), inhibiting acid secretion. Eg: proglumide Best use in combination with PPI’s Treatment of PU — Should consult doctors and other health care professionals for appropriate treatment of peptic ulcers. — In general, the treatment depends on vH. pylori infection vNSAIDs vBoth Treatment of PU — Caused due to H. pylori infection, eradication therapy involves combination of antibiotics and PPI (antisecretory drug). — Caused by use of NSAIDs, NSAIDs should be withdrawn if possible, and a one-to-two month course of PPI or H2 receptor antagonist is recommended. Treatment of PU — Caused by a combination of using NSAIDs and H. pylori infection, two-month course of a PPI and a course of eradication therapy will be given. — Others include antacid and cytoprotective agents. Peptic ulcer healing drugs 1. Antibiotics. — For ulcers, caused by infection, you will be asked to take two or three antibiotics together with a PPI. vAmoxicillin, clarithromycin, metronidazole and tetracycline  Peptic ulcer healing drugs Eradication Therapy Combinations of antimicrobial drugs. Triple therapy consisting of a PPI with either metronidazole or amoxicillin plus clarithromycin Quadruple therapy Consisting of bismuth subsalicylate and metronidazole plus tetracycline plus a PPI Are administered for a 2-week course.  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 General advice on taking PU healing drugs — There are many factors that may affect ulcer healing. Healthy lifestyle and good dietary habits may accelerate healing. — PU healing drugs should be used according to medical directions and patient should adhere to the treatment regimen. — For PU disease caused by H.pylori infection, treatment should be continue for 4 weeks to confirm eradication. General advice on taking PU healing drugs — Be familiar with the name and dosage of the drugs you are taking. — Be cautious about their possible side effects and if persists, ask doctors for advice. — If pain persists despite treatment, discuss with your doctor for other appropriate treatment. Lifestyle advice (non-pharmacological approach) — Lifestyle factors such as diet and stress may worsen PU symptoms. — Healthy lifestyle and good dietary habits may help to accelerate ulcer healing. Lifestyle advice (non-pharmacological approach) — advices such as vTake small but frequent meals and eat at regular time. vAvoid spicy or excessively rich foods that are irritable to the gut vDo not smoke and avoid drinking alcohol and stimulating beverages such as coffee and strong tea vDrink milk and eat milk based food that may help to relieve pain vAvoid situations causing stress and anxiety To think about Why antacid should not be given within two hours of doses of tetracyclines. Why PPI would be more effective than H2 antagonist in patient with ulcers caused by NSAIDs. Differences between H2 antagonist and PPI. Explain two mucosal protective agents and their mechanisms. Explain milk-alkali syndrome. Thank you…..the end