Peptic Ulcer & Antiemetics PDF

PEPTIC ULCER DRUGS BY Dr Reham Ellisy Assistant lecturer of pharmacology Faculty of medicine-SVU  PEPTIC ULCER  An Ulcer is …  Erosion (loss of continuity) in the lining of the stomach (gastric ulcer)or the first part of the small intestine (duodenal ulcer)....

PEPTIC ULCER DRUGS BY Dr Reham Ellisy Assistant lecturer of pharmacology Faculty of medicine-SVU  PEPTIC ULCER  An Ulcer is …  Erosion (loss of continuity) in the lining of the stomach (gastric ulcer)or the first part of the small intestine (duodenal ulcer). Ulcers damage the mucosa of the alimentary tract, which extends through the muscularis mucosa into the sub mucosa or deeper.  WHY ULCERATION OCCURS? Imbalance primarily between Aggressive factors & Defensive factors: GASTRIC DEFENSE MECHANISM PEPTIC ULCER PATHOGENESIS OF PEPTIC ULCER DISEASE IMBALANCE: AGGRESSIVE FACTORS DEFENSIVE FACTORS  Acid  Prostaglandins  Pepsin  Mucosal blood flow  Helicobacter pylori  Mucous gel layer  NSAIDS  HCO3  Epithelial junctions  Epideral growth factors HELICOBACTER PYLORI  1981 - Robin Warren, M.D., an Australian pathologist, discovered numerous bacteria living in tissue taken during a stomach biopsy.  Spiral urease- producing, Gram- negative bacteria always accompanied changes in the stomach lining SYMPTOMS  Burning abdominal pain  Abdominal fullness  Anorexia  Nausea or vomiting  Rhythmicity(meal relation)  Haematemesis  Melena  Unexplained weight loss DIAGNOSIS  Endoscopy: Flexible tube fitted with camera is threaded down the esophagus in to stomach to see the ulcer by physician  Barium meal: Barium liquid is drunk making ulcer visible on X- ray DIAGNOSIS  Test for diagnosing H.pylori Breath test :by measuring the amount of co2 and ammonia in exhaled breath. Blood test: by identifying H.pylori antibodies by ELISA test. Stool test :stool sample tested with H.pylori antigen.  LIFE-STYLE MODIFICATION IN PUD NON DRUG THERAPY OF PEPTIC ULCER  Stop smoking  Stop NSAIDS  ↓Tea,cola,coffee  Diet→ Balanced diet  Frequent small meal  fiber  vitamin E  fat diet  Steroid  Stop Alchol  Stress relieve-rest –good sleep PHYSIOLOGY OF GASTRIC ACID SECRETION  Gastric acid secretion is a complex, continuous process in which multiple central and peripheral factors contribute to a common endpoint secretion of H⁺ by parietal cells.  Neuronal(acetylcholine,Ach onM3receptors)  paracrine(histamine on H2 receptors)  Endocrine (gastrin on CCK2) factors all regulate acid secretion.  The H2 receptor is a GPCR that activates the Gs- adenyl cyclase –cyclic AMP-PKA pathway.  Ach and gastrin signal through GPCRs that couple to the Gq-PLC-IP3-Ca2+ pathway in parietal cells.  In parietal cells , the cyclic AMP and the Ca 2+ dependant pathways activate H+,K+-ATPase (the proton pump), which exchanges hydrogen and potassium ions across the parietal cell membrane  HCl & pepsin Misoprostol Ranitidine Probanthine Pirenzepine PGE2 Histamine Gastrin + _ Proglumide ACh _ Compete Gastrin-R Adenyl cyclase H2 M3 _ PGE + Gastrin + receptor + receptor Ca++ ATP cAMP Ca++ + + + Protein Kinase (Activated) K + H+ K + Parietal cell Proton pump _ Lumen of stomach Omeprazole _ Gastric acid Antacid ANTI ULCER DRUGS 1-REDUCTION OF GASTRIC ACID SECRETION  Histamine antagonist: Cimetidine, ranitidine  Proton pump inhibitors: omeprazole, pantaprazole  Acetyl choline antagonist: pirenzepine, propantheline  Prostaglandin analogue: misoprostol ANTIULCER DRUGS 2-Neutralization of gastric acid(antacids) Systemic : Sodium bicarbonate Nonsystemic : Magnesium hydroxide , Aluminium hydroxides 3-mucosal protectives : Sucralfate,misoprostol 4-Anti helicobacter pylori: amoxicillin, clarithromycin etc  HISTAMINE ANTAGONIST(TIDINES)  Members: 1-Cimetidine(4-6h)duration of action. 2-Ranitidine(6-8). 3-Famotidine(10-12) 4-Nizatidine(12-15) PHARMACOKINETICS  Absorption : rapid-  Bioavailability:50% except 90%nizatidine  Oral and IV  1/3Metabolism in liver – Cimetidine CYP inhibitor  Excreted by kidneys(2/3 unchanged)  Excreted in milk  Cimetidine pass BBB H2-BLOCKERS  Histamine reversible cometitive antagonists inhibit the action of histamine on the parietal cells of the stomach and reduce gastric stomach acid PHARMACOLOGICAL ACTIONS o ↓All phases of gastric acid secretion o Very effective in inhibiting nocturnal acid secretion (as it depends largely on Histamine ) o Modest impact on meal stimulated acid secretion (as it depends on gastrin, acetylcholine and histamine) o Volume of pepsin content and IF are also reduced o Volume reduced by 60 – 70% - anti ulcerogenic effect  H2 BLOCKERS(CONT) SIDE EFFECTS(safe) : - constipation, diarrhea, fatigue, headache, insomnia, muscle pain, and vomiting. - Major side effects(cimetidine) - include confusion and hallucinations, -Anti-androgen→gynacomastia (enlargement of the breasts); impotence -In female→ increase prolactin-galactorrhea-amenorrhea. - CYP inh→diazepam-warfarin-carbmazepine-theoph H2-BLOCKERS USES  it is used in treatment of duodenal ulcer, Gastric ulcer→2tablet daily for 6-8wks followed by one tablet for 6 months - stress ulcer, GERD, zollinger ellison syndrome -Preanesthetic medication ACETYL CHOLINE ANTAGONIST PIRENZEPINE MECHANISM:  It selectively block M1 muscaranic recptors and inhibits gastric secretion.  Because of their relatively poor efficacy, side effects, and risk of blood disorders, they are rarely used today PROTON PUMP INHIBITORS- PRAZOLES  Proton pump inhibitors act by irreversibly blockingthe hydrogen/potassium ATPadenosi ne triphosphatase enzyme system of the gastric parietal cells(rate limiting step).  The proton pump is the terminal stage in gastric acid secretion PPI MECHANISM 0F ACTION PHARMACODYNAMICS PROTON PUMP INHIBITORS OMEPRAZOLE  Omeprazole is inactive at neutral pH, but at pH