Chapter58.pdf

Chapter 58 Drugs Affecting Gastrointestinal Motility Copyright Copyright © 2017 © 2012 Wolters Wolters Kluwer Kluwer All Health Rights Reserved...

Chapter 58 Drugs Affecting Gastrointestinal Motility Copyright Copyright © 2017 © 2012 Wolters Wolters Kluwer Kluwer All Health Rights Reserved | Lippincott Williams & Wilkins Actions of Drugs Used to Affect Motor Activity or Motility of the GI Tract Speed up or improve movement of intestinal contents along GI tract when movement becomes slow or sluggish to allow for proper excretion of wastes (constipation). Increase the tone of the GI tract and stimulate motility throughout the system. Decrease movement along the GI tract when rapid movement decreases the time for absorption of nutrients (diarrhea). Copyright © 2023 Wolters Kluwer All Rights Reserved Sites of Action of Drugs Affecting GI Motility Copyright © 2023 Wolters Kluwer All Rights Reserved Use of Laxative and Antidiarrheal Agents Across the Lifespan Copyright © 2023 Wolters Kluwer All Rights Reserved Laxatives Indicated for short-term relief of constipation, to prevent straining, to evacuate bowel for diagnostic procedures, to remove ingested poisons, and as adjunct for anthelmintic activity Most available as OTC preparations o Have potential for overuse, dependency Copyright © 2023 Wolters Kluwer All Rights Reserved Kinds of Laxatives Stimulants: chemically irritate the lining of the GI tract Bulk-forming agents: cause fecal matter to increase in bulk Osmotic: pull more solute and/or water into GI tract Lubricants: help intestinal contents stay softer, more slippery Newer laxatives available for specific needs; alter sodium absorption or affect opioid receptors in GI tract Copyright © 2023 Wolters Kluwer All Rights Reserved Chemical Stimulants #1 Directly stimulate nerve plexus, causing increased movement and stimulation of local reflexes Drugs o Bisacodyl (Dulcolax) o Castor oil (generic) o Senna (Senokot) Copyright © 2023 Wolters Kluwer All Rights Reserved Chemical Stimulants #2  Therapeutic actions o Begin working at the beginning of the small intestine o Increase motility throughout the rest of the GI tract by stimulating the nerve plexus o Castor oil blocks absorption of fats  Indications o Short-term treatment of constipation  Pharmacokinetics o Most of these agents are only minimally absorbed and exert their therapeutic effects directly in the GI tract Copyright © 2023 Wolters Kluwer All Rights Reserved Chemical Stimulants #3 Contraindications o Allergy o Acute abdominal disorders o Castor oil: pregnancy Caution o Heart block, CAD, debilitation o Acute abdominal pain, nausea, or vomiting o Pregnancy and lactation Copyright © 2023 Wolters Kluwer All Rights Reserved Chemical Stimulants #4 Adverse effects o GI: diarrhea, abdominal cramping, nausea o CNS: dizziness, headache, weakness o Sweating, palpitations, flushing, fainting o Cathartic dependence o Castor oil: blocks absorption of fats (including fat-soluble vitamins) and may lead to malnutrition Drug–drug interactions o Other prescribed medications Copyright © 2023 Wolters Kluwer All Rights Reserved Chemical Stimulant Laxative Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Bulk-Forming Laxatives #1 Cause fecal matter to increase in bulk Increase motility of GI tract by increasing size of fecal matter o Helps pull more fluid in intestinal contents o Stimulates local stretch receptors and activates local activity Drugs o Methylcellulose (Citrucel) o Polycarbophil (FiberCon) o Psyllium (Metamucil) Copyright © 2023 Wolters Kluwer All Rights Reserved Bulk-Forming Laxatives #2 Therapeutic actions o Act in manner similar to dietary fiber Indications o Treatment of constipation o Decrease diarrhea in patients with diverticulosis or IBS Pharmacokinetics o Directly effective within GI tract; not generally absorbed systemically o Can act rapidly Copyright © 2023 Wolters Kluwer All Rights Reserved Bulk-Forming Laxatives #3 Contraindications o Allergy o Acute abdominal disorders o Acute infections o Intestinal obstruction, perforation, rectal bleeding, or healing from acute abdominal surgery Copyright © 2023 Wolters Kluwer All Rights Reserved Bulk-Forming Laxatives #4 Adverse effects o GI effects: diarrhea, abdominal cramping, nausea o CNS effects: dizziness, headache, weakness o Sweating, palpitations, flushing, fainting o Advise patients to take with plenty of water Drug–drug interactions o Other prescribed medications Copyright © 2023 Wolters Kluwer All Rights Reserved Bulk-Forming Laxative Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Osmotic Laxatives #1  Have solutes that increase osmotic pull of fluid into GI tract  Increase pressure in GI tract and stimulate more intestinal motility  Drugs o Magnesium sulfate (Epsom salts) o Magnesium citrate (Citrate of Magnesia) o Magnesium hydroxide (Milk of Magnesia) o Lactulose (Constilac, Cholac) o Lactitol (Pizensy) o Polyethylene glycol (MiraLAX) o Polyethylene glycol electrolyte solution (GoLYTELY) o Sodium picosulfate with magnesium oxide and citric acid (Clenpiq) Copyright © 2023 Wolters Kluwer All Rights Reserved Osmotic Laxatives #2 Therapeutic actions o Draw more water into GI tract and stimulate increased GI motility o Specific actions vary by drug Indications o Treatment of constipation o Other specific indications vary by drug Pharmacokinetics o Rates of action vary based on formulation and route of administration Copyright © 2023 Wolters Kluwer All Rights Reserved Osmotic Laxatives #3 Contraindications o Acute surgical abdomen o Fecal impaction o Intestinal obstruction o Lactulose: appendicitis Cautions o Lactulose: diabetes o Magnesium: renal insufficiency o Polyethylene glycol: history of seizures Copyright © 2023 Wolters Kluwer All Rights Reserved Osmotic Laxatives #4  Adverse effects o GI effects: diarrhea, abdominal cramping, abdominal bloating, nausea o Dehydration: dry mouth, dizziness, light-headedness o CNS effects: dizziness, headache, weakness o Sweating, palpitations, flushing, fainting o Suppositories: rectal irritation  Drug–drug interactions o Other medications o Magnesium salts: neuromuscular junction blockers Copyright © 2023 Wolters Kluwer All Rights Reserved Osmotic Laxative Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #1 Which drug is indicated for treatment of chronic idiopathic constipation? A. Bisacodyl (Dulcolax) B. Senna (Senokot) C. Lactitol (Pizensy) D. Polyethylene glycol (MiraLAX) Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #1 C. Lactitol (Pizensy) Rationale: Lactitol is indicated for treatment of chronic idiopathic constipation. The other listed drugs are indicated for short-term treatment of constipation. Copyright © 2023 Wolters Kluwer All Rights Reserved Lubricants #1  Make defecation easier without stimulating movement of the GI tract  Benefit patients with hemorrhoids, who have had recent rectal surgery, or who could be harmed by straining  Choice depends on condition, speed of relief needed, adverse effects  Drugs o Docusate (Colace) o Glycerin (Sani-Supp) o Mineral Oil (Agoral) Copyright © 2023 Wolters Kluwer All Rights Reserved Lubricants #2 Therapeutic actions o Docusate: Detergent action on surface of intestinal bolus o Glycerin: Hyperosmolar laxative gently evacuates rectum without systemic effects higher in GI tract o Mineral oil: Forms slippery coating on contents of intestinal tract Indications o Short-term treatment of constipation Copyright © 2023 Wolters Kluwer All Rights Reserved Lubricants #3 Pharmacokinetics o Not absorbed systemically o Excreted in feces Contraindications o Allergy Cautions o Abdominal disorders o Pregnancy and lactation Copyright © 2023 Wolters Kluwer All Rights Reserved Lubricants #4 Adverse effects o GI effects: diarrhea, abdominal cramping, nausea o Mineral oil: leakage and staining o CNS effects: dizziness, headache, weakness o Sweating, palpitations, flushing, fainting (less likely with lubricant laxatives than with others) Drug–drug interactions o Frequent use of mineral oil can interfere with absorption of the fat-soluble vitamins A, D, E, and K Copyright © 2023 Wolters Kluwer All Rights Reserved Lubricant Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Opioid Agonists #1 May be used to relieve constipation in specific situations Drugs o Alvimopan (Entereg) o Methylnaltrexone bromide (Relistor) o Naloxegol (Movantik) o Naldemedine (Symproic) Copyright © 2023 Wolters Kluwer All Rights Reserved Opioid Agonists #2 Therapeutic actions o Block effects of opioids on the GI tract by selectively binding to peripheral opioid receptors  Can help maintain normal motility and secretions while patient is on opioid treatment for pain Indications o Treatment of opioid-induced constipation o Alvimopan: Hasten time to gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis Copyright © 2023 Wolters Kluwer All Rights Reserved Opioid Agonists #3  Pharmacokinetics o All but alvimopan: metabolized in liver o Alvimopan: mostly changed to metabolites in GI tract o Eliminated partially by kidneys and partially in feces  Contraindications o Bowel obstruction o More than 15 doses of alvimopan  Cautions o Hepatic or renal impairment o Pregnancy and lactation Copyright © 2023 Wolters Kluwer All Rights Reserved Opioid Agonists #4 Adverse effects o Abdominal pain, diarrhea, nausea, vomiting, dizziness, flatulence, headache o Monitor patients for opioid withdrawal symptoms o Monitor for GI perforation if abdominal pain is severe Drug–drug interactions o Other opioid antagonists o Naloxegol and naldemedine with CYP3A inducers or CYP3A4 inhibitors Copyright © 2023 Wolters Kluwer All Rights Reserved Opioid Agonist Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Gastrointestinal Stimulant #1 More generalized GI stimulation results in overall increase in GI activity and secretions Stimulate parasympathetic activity or make GI tissues more sensitive to parasympathetic activity Metoclopramide (Reglan) Copyright © 2023 Wolters Kluwer All Rights Reserved Gastrointestinal Stimulant #2 Therapeutic actions o Stimulates parasympathetic activity within the GI tract  Increases GI secretions and motility o Blocks dopamine receptors and makes GI cells more sensitive to acetylcholine  Leads to increased GI activity and rapid movement of food through upper GI tract Indications o When rapid movement of GI contents is desirable Copyright © 2023 Wolters Kluwer All Rights Reserved Gastrointestinal Stimulant #3  Pharmacokinetics o Rapidly absorbed o Metabolized in the liver; excreted in feces and urine o Crosses placenta and enters human milk  Contraindications o Allergy o GI obstruction or perforation  Cautions o Pregnancy and lactation o History of tardive dyskinesia, seizures, or depression Copyright © 2023 Wolters Kluwer All Rights Reserved Gastrointestinal Stimulant #4  Adverse effects o Nausea, vomiting, diarrhea, intestinal spasms, cramping o Declining blood pressure and heart rate, weakness, and fatigue o Boxed warning: tardive dyskinesia  Drug–drug interactions o Alcohol or other CNS sedative drugs o Antipsychotic medications o MAOIs o Strong CYP2D6 inhibitors Copyright © 2023 Wolters Kluwer All Rights Reserved Gastrointestinal Stimulant Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Antidiarrheals #1 Block stimulation of GI tract for symptomatic relief from diarrhea Drugs o Bismuth subsalicylate (Pepto-Bismol) o Crofelemer (Mytesi) o Loperamide (Imodium A-D) o Opium derivatives (Paregoric) o Some anticholinergic medications (Chapter 33) o Several available in combination Copyright © 2023 Wolters Kluwer All Rights Reserved Antidiarrheals #2 Therapeutic actions o Slow motility of GI tract  Bismuth subsalicylate: Direct action on the lining of the GI tract  Loperamide: Direct action on muscles of GI tract  Opium derivatives: Action on CNS centers to cause GI spasm and slowing  Crofelemer: Blocks specific chloride channels leading to less water loss as diarrhea Copyright © 2023 Wolters Kluwer All Rights Reserved Antidiarrheals #3  Indications o Relief of symptoms of acute and chronic diarrhea o Reduction of volume of discharge from ileostomies o Prevention and treatment of traveler’s diarrhea o Bismuth subsalicylate: Diarrhea and GI symptoms associated with dietary excess, some viral infections o Crofelemer: Symptomatic relief of noninfectious diarrhea in adult patients on HIV/AIDS antiretrovirals  Pharmacokinetics o Vary depending on agent Copyright © 2023 Wolters Kluwer All Rights Reserved Antidiarrheals #4 Contraindications o Allergy Cautions o Pregnancy and lactation o History of GI obstruction o Acute abdominal conditions o Diarrhea due to poisonings o Hepatic impairment Copyright © 2023 Wolters Kluwer All Rights Reserved Antidiarrheals #5 Adverse effects o Related to effects on GI tract: constipation, distension, abdominal discomfort, nausea, vomiting, dry mouth, toxic megacolon o Other effects: fatigue, weakness, dizziness, skin rash o Opium derivatives: light-headedness, sedation, euphoria, hallucinations, respirator depression Drug–drug interactions o Vary depending on agent Copyright © 2023 Wolters Kluwer All Rights Reserved Antidiarrheal Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #2 Please answer the following statement as true or false. Crofelemer (Mytesi) treats traveler’s diarrhea by killing the bacteria that is the most common cause of the disorder. Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #2 False Rationale: Rifaximin (Xifaxan) was the first antibiotic approved by the U.S. Food and Drug Administration (FDA) specifically for treating traveler’s diarrhea. Rifaximin acts locally in the GI tract against noninvasive strains of Escherichia coli, the most common cause of traveler’s diarrhea. Copyright © 2023 Wolters Kluwer All Rights Reserved IBS and Chronic Constipation Drugs #1  IBS affects three times as  Drugs to treat IBS many females as males o Alosetron (Lotronex)  Reportedly accounts for half o Eluxadoline (Viberzi) of referrals to GI specialists o Linaclotide (Linzess)  Characterized by abdominal distress, bouts of diarrhea or o Lubiprostone (Amitiza) constipation, bloating, o Plecanatide (Trulance) nausea, flatulence, headache, fatigue, o Tegaserod (Zelnorm) depression, anxiety o Hyoscyamine (Chapter  Underlying causes may be 33) stress and/or dysregulation of autonomic nervous  Drug to treat chronic constipation: Prucalopride system (Motegrity) Copyright © 2023 Wolters Kluwer All Rights Reserved IBS and Chronic Constipation Drugs #2  Therapeutic actions and indications o Alosetron  Serotonin 5-HT antagonist  Severe diarrhea-prominent IBS o Eluxadoline  Mu-opioid receptor agonist  Adults with IBS with diarrhea o Lubiprostone  Locally acting chloride channel activator  Chronic, idiopathic constipation, opioid-induced constipation, IBS with constipation in adult females Copyright © 2023 Wolters Kluwer All Rights Reserved IBS and Chronic Constipation Drugs #3 Therapeutic actions and indications (cont.) o Prucalopride and tegaserod  Selective serotonin type 4 receptor agonists  Chronic constipation  Tegaserod: Females younger than 65 who suffer from constipation due to IBS o Linaclotide and plecanatide  Guanylate cyclase-C agonists  Chronic constipation and constipation type IBS Copyright © 2023 Wolters Kluwer All Rights Reserved IBS and Chronic Constipation Drugs #4 Pharmacokinetics o Most are absorbed quickly o Location and extent of metabolism varies Contraindications o Allergy o Mechanical gastrointestinal obstruction o Other contraindications vary by agent Cautions o Pregnancy and lactation Copyright © 2023 Wolters Kluwer All Rights Reserved IBS and Chronic Constipation Drugs #5  Adverse effects o GI symptoms: nausea, abdominal pain, diarrhea, constipation o Alosetron: ischemic colitis o Eluxadoline: pancreatitis o Prucalopride and tegaserod: new onset of depression and self-harm behaviors  Drug–drug interactions o Alosetron or eluxadoline: medications that slow GI motility o Alosetron: CYP1A2 inhibitors; fluvoxamine Copyright © 2023 Wolters Kluwer All Rights Reserved IBS and Chronic Constipation Drug Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #3 Why should laxatives be taken only on a short-term basis? A. To prevent a fluid volume deficit B. To prevent cathartic dependence C. To obtain relief of abdominal distention D. To obtain relief of intestinal cramping Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #3 B. To prevent cathartic dependence Rationale: Cathartic dependence can occur with the chronic use of laxatives, leading to a need for external stimuli for normal functioning of the GI tract. Copyright © 2023 Wolters Kluwer All Rights Reserved