DrKhaled Hasan,MD,PhD1 Gastrointestinal Pharmacology Nursery College Dr.Khaled Hasan

DrKhaled Hasan,MD,PhD2 I. OVERVIEW Treatment of common medical conditions involving the gastrointestinal tract: peptic ulcers (PUD) chemotherapy-induced emesis diarrhea and constipation

DrKhaled Hasan,MD,PhD3 Peptic ulceration is a common condition consisting of a distinct break in the gastrointestinal mucosa, usually of the stomach or duodenum. Duodenal ulcers are rarely malignant but gastric ulcers are more commonly associated with malignancy. Peptic ulcer disease usually presents as dyspeptic pain, sometimes associated with nausea, vomiting, anorexia, heartburn, or bloating. Patients may develop complications such as bleeding, obstruction, or perforation. Peptic ulcer Disease (PUD)

DrKhaled Hasan,MD,PhD4 Certain simple measures such as bed rest, dietary modification, and cessation of smoking, may accelerate ulcer healing, but these play an adjuvant role, and the basis of treatment is pharmacological. Treatment is aimed at eradicating H. pylori with antibacterials and neutralising or inhibiting acid activity with antisecretory drugs, and a number of guidelines are available. Surgical treatment is used in patients with acute complications such as perforation, haemorrhage, obstruction, or pyloric stenosis, or in patients with recurrent or intractable ulcer disease, or where there is suspicion of malignancy.

DrKhaled Hasan,MD,PhD5 Pathophysiology The mechanisms of mucosal injury in PUD are thought to be an imbalance of aggressive factors and defensive factors. Defensive factors: mucus production bicarbonate PGs blood flow Defensive factors: mucus production bicarbonate PGs blood flow Aggressive factors: acid production pepsin Helicobacter pylori Ulcerogenic drugs Psychological factors Aggressive factors: acid production pepsin Helicobacter pylori Ulcerogenic drugs Psychological factors

DrKhaled Hasan,MD,PhD6 Treatment approaches include 1) eradicating the H. Pylori. infection, 2) reducing secretion of gastric acid or neutralizing 3) protecting the gastric mucosa from damage. Modifying Secretion Rx of H. pylori Protection mucuosa Histamine H2-blockers Anticholinergic drugs H& K-ATPase Inhibitors Octreotide Antacids Histamine H2-blockers Anticholinergic drugs H& K-ATPase Inhibitors Octreotide Antacids Bismuth Antimicrobials Bismuth Antimicrobials Bismuth Sucarlfate Misoprostol Carnbenoxolone Na Bismuth Sucarlfate Misoprostol Carnbenoxolone Na

DrKhaled Hasan,MD,PhD7 Regulation of gastric acid secretion

DrKhaled Hasan,MD,PhD8 Antimicrobial agents Successful eradication of H. Pylori ( %) is possible with various combinations of antimicrobial drugs. Currently, either triple therapy or quadruple therapy are administered for a two-week course. quadruple therapytriple therapy bismuth subsalicylateproton-pump inhibitor (PPI) metronidazole plus tetracycline plus H2-receptor antagonist plus clarithromycin or proton-pump inhibitor (PPI) metronidazole or amoxicillin

DrKhaled Hasan,MD,PhD9 H2-receptor antagonists Cimetidine, Ranitidine, Famotidine, Nizatidine Cimetidine: (gynecomastia, galactorrhea, and reduced sperm count). Cimetidine inhibits metabolism (potentiate of several drugs (warfarin, phenytoin). Ranitidine: Compared to cimetidine, ranitidine is longer acting, and is 5-10 fold more potent. Ranitidine does not inhibit metabolism of drugs. Famotidine is 3-20 times more potent than ranitidine. Nizatidine: In contrast to cimetidine, ranitidine, and famotidine, which are metabolized by liver, nizatidine is eliminated principally by kidney.

DrKhaled Hasan,MD,PhD10 Cimetidine inhibits CYP450 and can slow metabolism (and, thus, potentiate the action) of several drugs (e.g, warfarin, diazepam, phenytoin).

DrKhaled Hasan,MD,PhD11 D. Inhibitors of the H + /K + ATPase Proton pump Inhibitors (PPIs) Omeprazole is the first of a class of drugs that bind to the H+/K+ATPase enzyme system (proton pump) of the parietal cell, thereby suppressing secretion of hydrogen ions into the gastric lumen. The membrane-bound proton pump is the final step in the secretion of gastric acid. Four additional PPls are available: a)lansoprazole, b)rabeprazole, c)pantoprazole, d)esomeprazole.

DrKhaled Hasan,MD,PhD12

DrKhaled Hasan,MD,PhD13 Antacids Aluminum hydroxide, Magnesium hydroxide, Calcium carbonate and Sodium bicarbonate. Adverse effects: Constipating (Aluminum hydroxide) diarrhea (magnesium hydroxide) Preparations that combine these agents aid in normalizing bowel function. important consideration in patients with hypertension or congestive heart failure (sodium content of antacids)

DrKhaled Hasan,MD,PhD14 PRODUCT Al(OH) 3 a mg/tab or 5 ml Mg(OH) 2 a CaCO 3 a SIMETHICONE a ACID NEUTRALIZING CAPACITY b mEq /tab or /5 ml Tablets Gelusil Maalox Quick Dissolve Mylanta Double Strength Riopan Plus Double Strength Calcium Rich Rolaids Tums EX Liquids Maalox TC Milk of Magnesia Mylanta Maximum Strength Riopan

DrKhaled Hasan,MD,PhD15 Drugs Used To Control Nausea and Vomiting Antiemetic drugs Although nausea and vomiting may occur in a variety of conditions: motion sickness, pregnancy, hepatitis, and are produced by many chemotherapeutic agents. Nearly 70-80% of all patients who undergo chemotherapy experience nausea or vomiting.

DrKhaled Hasan,MD,PhD16 Antiemetic drugs Anticholinergic drugs (scopolamine) H1-receptor antagonists (dimenhydrinate, meclizine, and cyclizine) Ondansetron, granisetron: Seotonin (5-HT3 )-receptor blockers. Benzamides: metoclopramide is highly effective at high doses against the highly emetogenic cisplatin. Butyrophenones: Droperidol, domperidone, and haloperidolprochlorperazine: act by blocking dopamine receptors. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Corticosteroids: Dexamethasone and methylprednisolone, antiemetic mechanism is not known Cannabinoids: Marijuana derivatives, including dronabinol and nabilone.

DrKhaled Hasan,MD,PhD17 Anti-diarrheas A. Antimotility agents: Diphenoxylate and loperamide have opioid-like actions on the gut, activating presynaptic opioid receptors in the enteric nervous system to inhibit Ach release and decrease peristalsis. B. Adsorbents kaolin, pectin, methylcellulose: Substances that adsorb, a solid substance capable with property of attaching other substances to its surface. C. Agents that modify fluid and electrolyte transport Aspirin and indomethacin, are effective in controlling diarrhea. This antidiarrheal action is probably due to inhibition of prostaglandin synthesis.

DrKhaled Hasan,MD,PhD18 Laxatives: Major laxative mechanisms and representative laxative drugs

DrKhaled Hasan,MD,PhD19 Laxatives (Treatment of Constipation) Castor oil is very irritating to the gut, and increases peristalsis. Cascara, senna, and aloe stimulate colonic activity. Bisacodyl is a potent stimulant of colon. Methylcellulose, psyllium seeds, bran: They form gels in large intestine, causing water retention and increasing peristaltic activity. Polyethylene glycol are used as colonic lavage solutions to prepare the gut for radiologic or endoscopic procedures. Lactulose (fructose and galactose). Magnesium sulfate and magnesium hydroxide are nonabsorbable salts that hold water in the intestine by osmosis and distend the bowel, increasing intestinal activity and producing defecation in about one hour Docusate sodium, mineral oil, and glycerin suppositories: Surface- active agents that become emulsified with the stool produce softer feces and ease passage.

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DrKhaled Hasan,MD,PhD21