NMT150 PHARM Wk 10 Drugs that Affect GI Motility (1).pdf

DRUGS THAT AFFECT GI MOTILITY Dr. Adam Gratton NMT150 MSc ND March 9, 2023 LECTURE COMPETENCIES Compare and contrast the mechanisms of action and indications of bulk-forming, osmotic, and stimulant laxatives Describe the adverse effects associated with bulk-forming, osmotic, and...

DRUGS THAT AFFECT GI MOTILITY Dr. Adam Gratton NMT150 MSc ND March 9, 2023 LECTURE COMPETENCIES Compare and contrast the mechanisms of action and indications of bulk-forming, osmotic, and stimulant laxatives Describe the adverse effects associated with bulk-forming, osmotic, and stimulant laxatives Describe the antidiarrheal mechanism and indication of opioid agonists Describe the adverse effects of opioid agonists Describe the intestinal motility effects of tricyclic antidepressants and selective serotonin receptor inhibitors INTESTINAL TRANSIT TIME How long it takes for food to move through the GI tract Average transit time is 30 – 40 hours Increased transit time can lead to constipation Reduced transit time can result in diarrhea BULK-FORMING LAXATIVES Agents that retain fluid in the stool itself Increase stool weight and improve consistency Generally soluble fibers that gel when mixed with water Do not alter peristalsis PSYLLIUM Most commonly discussed bulk-forming laxative Generally a first-line recommendation when dietary fiber intake is inadequate (25 – 30 g/d) Indicated for both constipation and diarrhea PSYLLIUM Commercial psyllium products are powdered preparations of the mucilaginous portion (psyllium hydrophilic mucilloid) Recommended dose: 3.4 g once daily to TID PO Time to onset: 12 – 72 hours PSYLLIUM Adverse effects: bloating, flatulence, abdominal discomfort In rare instances: allergic reactions and esophageal and colonic obstruction Must be taken with a minimum of 250 mL water Do not take within 2 h of other medications OSMOTIC LAXATIVES Poorly absorbed agents that draw water into the intestines Hydrates and softens stool Increase colonic peristalsis MAGNESIUM Citrate, hydroxide, and sulfate salts all have osmotic laxative effects Use with caution in patients with renal dysfunction as they can result in hypermagnesemia Mild: Weakness, nausea, dizziness and confusion Moderate: hyporeflexia, worsening confusion and sedation, bladder paralysis, flushing, headache, constipation MAGNESIUM CITRATE Dose: 3.75 – 7.5 g daily PO for acute purgative effect (preoperatively) Time to effect: 30 min – 6 h More commonly used in much smaller doses and tailored to patient tolerance STIMULANT LAXATIVES Stimulate the myenteric plexus and Auerbach plexus Increase intestinal secretions and motility Decrease absorption of water from the bowel lumen SENNA Generally only recommended for short-term treatment of constipation May be necessary to use long-term, particularly with opioid therapy SENNA Can cause abdominal pain and cramps Can cause benign, reversible pigmentation of the colonic mucosa called pseudomelanosis coli SENNA Most commercial preparations are 8 mg per tablet Dose: 16.2 – 32.4 mg (2 – 4 tablets) at bedtime PO Maximum 64.8 mg (8 tablets) per day Time to effect: 6 – 12 h OPIOID AGONISTS Opioids typically cause constipation as an adverse effect when used for their analgesic effect Tolerance to constipation does not develop, unlike many of the other adverse effects Interacts with intestinal mu-opioid receptors which reduces intestinal motility, increases transit time and water and electrolyte reabsorption LOPERAMIDE Indicated for diarrhea Some caution when used for microbial etiologies as use may enhance infection LOPERAMIDE Adverse effects include sedation, nausea, and abdominal cramps. Lowest addiction potential of all opioids Reports of loperamide being abused as an opioid substitute In high doses can cause cardiac dysrhythmia and death Not to be used in children under 2 years of age due to increased risk of respiratory depression and serious cardiac adverse effects LOPERAMIDE Usually formulated in 2 mg doses (tablets, wafers, etc.) Dose: 4 mg PO followed by 2 mg after each unformed stool Maximum 16 mg per day ANTIDEPRESSANTS Often used within the context of irritable bowel syndrome Effect for IBS seems to be independent of their effect on mood May alter pain perception and reduce visceral hypersensitivity Alter GI transit TRICYCLIC ANTIDEPRESSANTS More robust evidence for TCAs vs SSRIs Increase colonic transit time and may be more effective for diarrhea-dominant IBS (IBS-D) and concomitant depression Used in much lower doses than for treating psychiatric conditions AMITRYPTALINE Dose: 25 – 100 mg QHS PO May cause drowsiness, dry mouth and headache Recommended to start with low doses and increase gradually SSRI Mechanism similar to that of TCAs Decrease colonic transit time and may be more effective for constipation-dominant IBS (IBS-C) and concomitant depression CITALOPRAM Dose: 20 mg daily PO Adverse effects include: nausea, dry mouth, sleep disturbance, somnolence, sweating, sexual dysfunction, increased risk of GI bleeding Recommendation to start with lower doses and titrate based on response SAMPLE QUESTION Which of the following drug pairs increase intestinal transit time? A. Loperamide and citalopram B. Citalopram and amitryptaline C. Amitryptaline and senna D. Senna and loperamide