Diarrhea & Constipation Lecture Notes (Fall 2024)

Diarrhea & Constipation Dr. Aymen Ali Alqurain Fall 24/25 1  Lecture Learning Outcomes Define diarrhea and constipation Describe the pathophysiology and aetiology Describe the typical clinical presentation Formulate treatment goals and ex...

Diarrhea & Constipation Dr. Aymen Ali Alqurain Fall 24/25 1  Lecture Learning Outcomes Define diarrhea and constipation Describe the pathophysiology and aetiology Describe the typical clinical presentation Formulate treatment goals and expected outcomes Discuss the role of nutritional and surgical interventions Explain the pharmacologic options for remission List the major toxicities associated with pharmacologic agents 2 Diarrhea 3  Clinical Case “PS is a 60-year-old man reported with nausea, vomiting, cramping, and diarrhea. He had been well until 2 days ago, when he began to experience severe nausea that occurred about 6 hours after eating out at a food buffet. No history of milk/dairy products intake. The nausea persisted, and he subsequently vomited “several times” with some relief. In the evening, the problem persisted, and he took Omeprazole. He began to feel achy and warm, and his temperature at the time was 38.2°C. 4  Clinical Case He has continued to have nausea, vomiting, and a mild fever. He has not tolerated solid foods, nor has he been able to keep down small amounts of fluid. He has had 6–8 liquid stools along with crampy abdominal pain. No blood or mucus in stool. His wife brought him to the clinic because he was becoming weak and dizzy when he tried to stand up. No h/o antibiotic use, laxative use, or excessive caffeine intake. What is the best pharmacological option to manage his 5 symptoms?  Definition Diarrhea is an increased frequency and decreased consistency of faecal discharge as compared with an individual's normal bowel pattern. Frequency and consistency are variable within and between individuals.  For example, some individuals defecate as many as 3 times a day, while others defecate only 2 or 3 times per week 6  Definition It involves an alteration in a normal bowel movement characterized by an increase in the water content, volume, or frequency (more than three per day) of stool It can be  Acute is generally considered less than 72 hours to 14 days.  Chronic is generally considered more than 14 – 30 days. 7  Pathophysiology Imbalance in absorption and secretion of water and electrolytes. May be associated with a specific disease of the gastrointestinal tract or with a disease outside the gastrointestinal tract 8  Pathophysiology Mechanisms:  Change in active ion transport by either decreased sodium absorption or increased chloride secretion  Change in intestinal motility  Increase in luminal osmolarity  Increase in tissue hydrostatic pressure 9  Classification Secretory  Secondary to enhanced secretion by intestinal mucosa. Often, large, watery volume with loss of electrolytes  Common causes: Bacterial or viral or bacterial enteritis, gastric hypersecretion, carcinoid, stimulant laxatives, bile acid malabsorption, celiac disease, IBD (mucosal) Osmotic  Secondary to the presence of hyperosmolar gradient in the intestinal lumen  Common causes: Osmotic laxatives, carbohydrate malabsorption (lactase deficiency), fat malabsorption 10 (pancreatic insufficiency), short bowel syndrome  Classification Exudative/inflammatory  Secondary to inflammation or infiltration/invasion of the intestinal mucosa  Common causes: IBD, invasive infection (C. difficile toxin, enterotoxigenic Escherichia coli, cytomegalovirus, Shigella), ischemic colitis, radiation enterocolitis, neoplasm Altered motility/motor  Secondary to autonomic nerve dysfunction  Common causes: Diabetic neuropathy, post vagotomy, hyperthyroidism, irritable bowel syndrome (IBS), Addison disease 11  Drug induced Antibiotics Digoxin Antineoplastics Prostaglandins (misoprostol) Laxatives Colchicine Levothyroxine (overreplacement) Orlistat Metoclopramide Sorbitol (sugar-free products) Acarbose or miglitol NSAIDs 12  Diagnosis Evaluate patient history thoroughly  Disease and drug-induced causes (laxative, recent antibiotic use), recent travel history and temporal relation to food intake.  Assessment of fluid and electrolyte status  Assess CBC and stool culture and evaluate for ova/parasites if infectious cause is suspected. C. difficile toxin and culture if recent antibiotic use or hospitalization  Evaluation of stool pH, electrolytes, osmolarity, or fat content, if indicated  If severe case, imaging (abdominal CT scan) or endoscopy with biopsy may be indicated, particularly for inflammatory 13 diarrhea or suggestion of neoplasm or celiac disease.  Pharmacist role* Refer to higher level of care for further evaluation if  Immunocompromised  Paediatrics  Pregnancy  Presence of fever  Blood in the stool  Weight loss (greater than 5%)  Suspected invasive infection 14  Treatment _ General Removal or treatment of underlying cause Rehydration  Intravenous fluids appropriate for hospitalized patients  Oral rehydration appropriate for all patients if no vomiting is present  Sodium and glucose are key ingredients of oral rehydration solutions because they have active uptake into the intestinal mucosa even during active diarrhea. This results in water being pulled back into circulation. Other formulations (popsicles) are also available.  Gatorade may need to be diluted because it has a large 15 amount of carbohydrates.  Treatment _ General Dietary modifications  Avoid dairy products because transient lactase deficiency may occur.  “BRAT” diet for adults  May need to interrupt feedings for paediatric patients 16  BRAT diet The BRAT diet is one type of bland diet that doctors sometimes recommended for people who are recovering from a gastrointestinal infection. BRAT stands for :  Bananas  Rice  Applesauce  Toast 17  BRAT diet Modified BRAT:  Addition of yogurt, if dairy products are not contraindicated  Addition of Tea. Indications:  Recovery from gastroenteritis or other causes of nausea, vomiting, diarrhea, or stomach upset.  It also helps some women who are suffering from morning sickness during pregnancy.  Avoid fatty and greasy foods, raw fruits and vegetables, alcohol, dairy products, and citrus fruits with BRAT diet 18  Drug therapy for diarrhea Infectious Diseases: next course management of infectious Several different agents available for management of diarrhea Avoid anti-motility agents if invasive infection is suspected 19  Drug therapy for diarrhea Drugs:  Loperamide  Mechanism: μ-Receptor agonist  Indication:  Mild to moderate non-invasive diarrhea  Adjunctive to other non-opiate therapies  Adverse effects and Precautions:  Minimal CNS effects  Avoid if suspected invasive infection 20  Pregnancy category B  Drug therapy for diarrhea Drugs:  Diphenoxylate + atropine  Mechanism: μ-Receptor agonist  Indication:  Moderate to severe non-invasive diarrhea  Suboptimal response to loperamide or bismuth  Refractory diarrhea  Adv Effects and Precautions:  CNS effects, respiratory depression, constipation  Anticholinergic effects with atropine 21  Drug therapy for diarrhea Drugs:  Bismuth subsalicylate  Mechanism: Anti-secretory, Binds toxins  Indication:  Mild-moderate diarrhea  Prevention of traveler’s diarrhea  Adverse Effects and Precautions:  Stool discoloration  Avoid in salicylate allergy, age < 12 years, pregnancy, nursing 22  Caution with anticoagulants, it may bind other drugs  Drug therapy for diarrhea Drugs:  Octreotide  Mechanism: Antisecretory Suppression of hormone release  Indication  Treatment of tumor-associated diarrhea  VIPoma [Verner-Morrison syndrome], carcinoid  HIV-associated diarrhea  Adverse Effects  Hyperglycaemia 23  Gallstone formation VIP: Vasoactive intestinal peptide  Drug therapy for diarrhea Drugs:  Lactase Enzyme  Indication: Lactase deficiency or intolerance  Probiotics (Lactobacilli, Saccharomyces)  Mechanism: Competition with pathogenic organisms, production of antimicrobial substances, enhancement of immune response  Indications:  Prevention of antibiotic-associated diarrhea  Adverse effects & Precautions: 24  Caution if severely immunocompromised Constipation 25  Clinical Case A 75-year-old man with a history of hypertension, type 2 diabetes, and chronic low back pain is admitted to the hospital for abdominal pain lasting 2 days. He denies fever, chills, or sick contacts. His last bowel movement was 3–4 days ago. On examination, he is afebrile and has moderate left upper and lower quadrant tenderness. An abdominal radiograph reveals large amounts of stool in the colon with no signs of obstruction. He currently takes lisinopril 20 mg/day, verapamil 240 mg once daily, acetaminophen 500 mg four times daily, oxycodone sustained release 20 mg twice daily, and oxycodone/acetaminophen 5/325 mg as needed for pain. HisSCr is 1.8 mg/dL (baseline 1.7 mg/dL). 26  Clinical Case Which therapy would best manage this patient’s constipation? A. Sodium phosphate oral solution. B. Bisacodyl suppository. C. Methylcellulose tablets. D. Methylnaltrexone injection. 27  Definition Reduction in frequency of bowel movements relative to a patient’s normal frequency Characterized by difficulty with or incomplete evacuation, straining, or presence of hard, dry stools. Abdominal pain and distention may occur, as well as low back pain and anorexia. 28  Pathophysiology Related to many different factors. Common causes include:  Altered motility (e.g., ileus)  Neurogenic causes (autonomic neuropathies, Parkinson disease)  Endocrine/metabolic disorders (e.g., hypothyroidism, diabetes, hypokalemia, hypercalcemia, uremia)  Pregnancy  Psychogenic  Structural abnormalities or obstruction  Nutritional (e.g., reduced fiber and water intake) 29  Medications  Most common drugs Tricyclic Opioids Antihistamines antidepressants Scopolamine, Bile acid Diuretics benztropine sequestrants Aluminum- Calcium Calcium containing channel supplements/ant drugs (antacids, blockers acids sucralfate) Iron Benzodiazepines Phenothiazines supplements 30  Diagnosis Refer for further evaluation Evaluate patient history for the following patient thoroughly populations. Establish patient Symptoms for more baseline and evaluate than 1–2 weeks for disease and drug- despite treatment induced causes Considerable pain or Assessment of fluid cramping and electrolyte Pregnancy status, thyroid Presence of fever function Blood in the stool Imaging (abdominal Reduction in stool CT scan or caliber radiograph) to assess Weight loss Ileus, obstruction, or Paraplegia, dilatation. 31 quadriplegia  Therapeutic Objectives Prevention of constipation by alteration of lifestyle (particularly diet). Prevent further episodes of constipation. For acute constipation: to relieve symptoms and restore normal bowel function. 32  Treatment: Non-Pharmacological Dietary modification: increase the amount of fiber intake 20–30 g/day consumed daily. Adequate and increasing fluid intake. 6–8 glasses of water per day, if possible Exercise. 3–5 days/week Adjustment of bowel habits to regular 33  Treatment: Non-Pharmacological Treat underlying disease.  GI malignancies  Surgery is necessary with most colonic malignancies and with GI obstruction  Endocrine and metabolic derangements are corrected  Potential drug causes of constipation should be identified: If no reasonable alternatives exist lowering the dose. 34  Dietary modifications Increase amount of fiber consumed: at least 20-30 g of crude fiber, Fruits, vegetables, and cereals High-fiber content should be continued for at least 1 month before effects on bowel function are determined. The patient should be cautioned that abdominal distention and flatus may be troublesome in the first few weeks, particularly with high bran consumption. 35  Drug Therapy Choose drug therapy on the basis of:  Desired onset of action  Patient preference  Presence of potential contraindications Use in special populations. Provide patient education on alternative dose forms (enema, suppository). 36  Pharmacotherapy Saline osmotic laxatives  Magnesium citrate  Magnesium hydroxide  Sodium phosphate Indication & Use:  Acute or intermittent constipation  Preoperative or pre-procedure bowel preparation  Fast onset (15 minutes to 3 hours)  Avoid in renal impairment, HF, cirrhosis  FDA warning regarding oral sodium phosphate and development 37 of acute phosphate nephropathy (avoid use for bowel preparations  Pharmacotherapy Osmotic Laxatives  Glycerin  Management of acute or intermittent constipation  Used in paediatric patients (as suppository)  Fast onset (within 1 hour)  Lactulose  Used in management of acute, intermittent, or chronic constipation, preferred in chronic liver disease  Onset 1–2 days (may require multiple doses)  Associated with gas/bloating 38  Syrup or powder for solution  Pharmacotherapy Stimulant laxatives  Bisacodyl  Used for short-term relief of acute or intermittent constipation or as part of preoperative/colonoscopy bowel preparation  Oral onset 6–12 hours, suppository within 1 hour  Oral tablets are enteric coated  Senna  Used for short-term relief of acute or intermittent constipation  Often used long term for prevention of opioid-induced constipation  Onset 6–12 hours  May cause abdominal cramping, electrolyte disturbances, 39 melanosis coli  Pharmacotherapy Bulk-forming laxatives  Psyllium  Inulin  Wheat dextrin  Calcium poly-carbophil  Methylcellulose  Used for intermittent or chronic constipation  Onset 12–72 hours, and requires adequate water intake to be effective  Several formulations; soluble forms can be incorporated into foods/liquids/recipes  Safe in renal and hepatic disease, pregnancy, geriatrics 40  May cause gas/bloating  Miscellaneous agents Docusate sodium & Docusate potassium  Prevention of opioid-induced constipation in combination with senna  Prevention of straining in post-MI, postsurgical, and pregnant patients  Onset 1–6 days  Requires adequate water intake to be effective Methylnaltrexone (Relistor)  For opioid-induced constipation in palliative care patients  Peripheral opiate antagonist; will not reverse central analgesia  Subcutaneous injection given every other day  Onset within 4 hours in ~50% of patients 41  Miscellaneous agents Lubiprostone (Amitiza)  For chronic idiopathic constipation in adults and for IBS-C in women > 18 years  Chloride channel (ClC-2) activator; results in intestinal fluid secretion  May reduce bloating and abdominal pain  Main adverse effect: Nausea  Need negative pregnancy test before use 42  Miscellaneous agents Linaclotide (Linzess)  For IBS-C and CIC (Chr. Idiop. Constp)  Mechanism: Guanylate cyclase-C agonist: Increases fluid secretion and transit time  Take on empty stomach 30 minutes before meal  Common adverse effects: Diarrhea, abdominal, pain, flatulence and abdominal distension  Contraindicated in paediatric patients < 6 years and in mechanical obstruction. Avoid in patients 6–17 years of age  Pregnancy category C 43  Recommendations The treatment and prevention of constipation:  Bulk-forming agents + dietary modifications.  Acute constipation  Tap-water enema or a glycerin suppository;  If neither is effective,  Use oral sorbitol, low doses of bisacodyl or senna, or saline laxatives (e.g., milk of magnesia )  Treatment of constipation in infants and children  Consider neurologic, metabolic, or anatomic abnormalities when constipation is persistent.  If not related to an underlying disease, treat as adult. 44  High fiber diet should be emphasized Thank you 45