Pharmacology Seminar 1, Drugs for Constipation and Diarrhea 2024 PDF

Drugs affecting GIT motility Dr/Amira Eladl Lecturer of Clinical Pharmacology Faculty of medicine Mansoura - Horus University  Drugs affecting GIT motility Drugs increase GIT motility Upper GIT: prokinetic drugs Lower GIT: laxatives Drugs decreas...

Drugs affecting GIT motility Dr/Amira Eladl Lecturer of Clinical Pharmacology Faculty of medicine Mansoura - Horus University  Drugs affecting GIT motility Drugs increase GIT motility Upper GIT: prokinetic drugs Lower GIT: laxatives Drugs decrease GIT motility Antispasmodics Antidiarrheal drugs Laxatives  Laxatives 1. Bulk-forming agents: [Dietary fibers – Methylcellulose – Bran] 2. Osmotic laxatives: [Mg sulfate, Lactulose] 3. Irritant (or stimulant) laxatives: [Castor oil , Senna and Bisacodyl] 4. Stool softeners: Docusate sodium 5. Lubricant laxatives: [Liquid paraffin , Glycerin suppositories ] 5. Others 5-HT4 agonists: prucalopride, cisapride Opioid antagonists: methylnaltrexone Chloride channel activator: lubiprostone  1. Bulk-forming agents Mechanism of action They are non-digestible fibers; they retain water in the gut and distend the large intestine → activation of stretch receptors → stimulation of peristalsis. Patient should take large amount of water with them  2. Osmotic laxatives (Mg sulfate, Lactulose) Mechanism of action They are retained in the gut lumen and retain water by their osmotic effect → activation of stretch receptors → stimulation of peristalsis. Lactulose is commonly used during pregnancy  3. Stimulant laxatives (Castor oil , Senna and Bisacodyl) They produce inflammation (irritation) of the intestinal mucosa and inhibit Na+/K+ ATPase enzyme leading to: ▪ Accumulation of water and electrolytes in the gut lumen. ▪ Direct stimulation of peristalsis by their irritant effect. Contraindicated in pregnancy Laxative dependence 4. Stool softeners (Docusate sodium) Mechanism: they are anionic surfactants that enable additional water and fats to be incorporated in the stool, making it easier to move through the GIT.  5-Lubricant laxatives Glycerin has hygroscopic effect. It draws water from rectal mucosa and lubricates the anal canal. It also stimulates reflex rectal contractions and promotes stool evacuation in 15-20 min  Lubiprostone Chloride Channel Activator Lubiprostone is indicated in chronic constipation and irritable bowel syndrome. Contraindicated in pregnancy  Methylnaltrexone Opioids- induced constipation  Antispasmodics ❑Anticholineric drugs Atropine , hyoscine ❑Direct smooth muscle relaxants Drotaverine, mebeverine  Drugs for diarrhea 1. Replacement of fluids 2. Treatment of the cause 3. Symptomatic relief Adsorbants : kaolin, pectin, activated charchol Antimotility drugs Antispasmodics Antimotility drugs  Opioid agonists 1. Diphenoxylate It is given with a small dose of atropine in order to discourage abuse. If taken repeatedly at short intervals, side effects of atropine would appear. In therapeutic doses, CNS effects are not prominent and is used only in diarrheas. In children respiratory depression, paralytic ileus and even toxic megacolon so contrindicated in children below 6 years 2. Loperamide It has selective action on the GI tract with additional antisecretory activity. CNS effects are negligible.  Antimotility drugs Racecadotril Racecadotril, a newly introduced antidiarrhoeal agent is a prodrug. It is converted in the body to the active compound which is a selective inhibitor of enkephalinase, which degrades enkephalins (the endogenous opioids). Enkephalins are neurotransmitters in the gut—they have antisecretory activity on the intestines (act on opioid receptors) Racecadotril correct the hypersecretion of water and electrolytes seen in diarrhoea without reducing intestinal motility  Clinical correlate A 38-year-old businessman is on a trip to Mexico when he develops diarrhea. He has to give a presentation in a few hours and needs rapid relief. He takes an antidiarrheal preparation containing loperamide. Which of the following is a property of loperamide that makes it useful in treating diarrhea? (A) Anticholinergic (B) Broad-spectrum antibiotic (C) Gram-negative antibiotic (D) Inhibitor of myenteric plexus activity (E) Sympathetic nervous system stimulant  MCQ A 45-year-old woman presented to her physician because of a 2-week history of painless diarrhea that was urgent and usually occurred during meals. After physical examination, lab tests, and colonoscopy, a diagnosis of irritable bowel syndrome was made, and the woman was prescribed an appropriate therapy that included loperamide. Direct activation of which of the following receptors most likely mediated the therapeutic effect of the drug in this patient? A. Beta-2 adrenergic B. Nn cholinergic C. 5-HT3 serotonergic D. Alpha-2 adrenergic E. Mu opioid  MCQ A 71-year-old man with terminal metastatic lung cancer had been hospitalized for 3 months. Because of poor food intake, immobility, and requirement for an opioid analgesia, the patient was severely constipated and required daily laxative therapy. Which of the following would be a suitable laxative for this patient? A. Racecadotril B. Ondansetron C. Methylnaltrexone D. Drotavarine E. Loperamide  MCQ 34-year-old hospitalized male patient complained of torticollis, grimacing, and spasm of the ocular muscles 1 day after surgery. The man had received an intravenous drug soon after surgery to treat nausea and vomiting. Which of the following antiemetic drugs most likely caused the patient’s symptoms? A. Ondansetron B. Scopolamine C. Dexamethasone D. Metoclopramide E. Dronabinol  MCQ A 59-year-old woman suffering from chronic constipation routinely self-administered lactulose daily. Which of the following actions most likely mediated the laxative effect of the drug? A. Inhibition of cholecystokinin release B. Retention of water in the gut by osmosis C. Lubrication of fecal material D. Stretching of the intestinal wall E. Formation of a bulky emollient gel  MCQ A 74-year-old patient suffering from chronic constipation complained of very loose stools after a treatment with bisacodyl, one tablet daily for 1 week. Which of the following would be the best advice to give to this patient? A. There is no cause for alarm the situation is self -limiting. B. Continue bisacodyl, but take the medication with a small snack. C. Continue bisacodyl, and add lactulose. D. Discontinue bisacodyl, and increase fiber and fluid intake. E. Discontinue bisacodyl, and switch to castor oil. Peptic ulcer discussion  MCQ As a gastroenterologist, you recommend the use of H2-blocker for a patient who has a history of atrial fibrillation, for which he takes warfarin. Your office receives a call from his primary physician, who has admitted the patient for warfarin toxicity. Which of the following H2-blockers has the patient likely been taking? a. Cimetidine b. Ranitidine c. Scopolamine d. Famotidine e. Nizatidine  MCQ A 63-year-old man with long-standing, poorly controlled diabetes complains of regurgitation of food following even small meals. You suspect the development of diabetic gastropathy, a consequence of his autonomic neuropathy. Which of the following might help his condition? a. Sucralfate b. Metoclopramide c. Scopolamine d. Misoprostol e. Bismuth subsalicylate  Case A 64-year-old man complained to his physician of burning and substernal pain for about 3 weeks. The pain usually occurred after dinner when he was lying on the couch watching television and was sometimes accompanied by regurgitation of foul-tasting fluid into his mouth. The man had been suffering from Parkinson disease for 1 year and was currently receiving dopamine increasing drugs. Which drugs would be most appropriate to treat the patient’s symptoms?  MCQ A 78-year-old woman sees her primary care physician with complaints of “heartburn.” Her history includes only hypertension. Her doctor recommends over-the-counter antacids to be used regularly. Which of the following would be a good choice and why? a. Sodium bicarbonate because it is good for long-term use b. Calcium carbonate because it is good for long-term use and she could use the calcium c. Magnesium hydroxide for short-term use only because of her hypertension d. A combined agent to balance the constipation associated with magnesium hydroxide and the diarrhea associated with aluminum hydroxide e. A combined agent to balance the diarrhea associated with magnesium hydroxide and the constipation associated with aluminum hydroxide Drug Regimens Used to Eradicate Helicobacter pylori Peptic ulcer drugs and pregnancy Drug Category Omeprazole Pregnancy Category C Other PPIs Pregnancy Category B Rabeprazole,lansoprazole, esompeprazole, pantoprazole H2 blockers: ranitidine famotidine, Pregnancy Category B cimetidine , nizatidine Sucralfate Pregnancy Category B Misopristol Pregnancy Category X