Understanding Diarrhea: Causes & Effects

Diarrhea

• Diarrhea is an increased frequency and decreased consistency of fecal discharge compared to a person's normal bowel pattern.
• Frequency and consistency vary between individuals.
• Some people have bowel movements up to 3 times a day while others only 2-3 times a week.
• Diarrhea involves an alteration in normal bowel movements, characterized by increased water content, volume, or frequency (more than three per day) of stool.
• Acute diarrhea lasts less than 72 hours to 14 days.
• Chronic diarrhea lasts more than 14 – 30 days.
• Pathophysiology involves an imbalance in water and electrolyte absorption and secretion.
• Diarrhea can be associated with a specific disease in the gastrointestinal tract or other diseases outside of the gastrointestinal tract.
• Mechanisms include changes in active ion transport, intestinal motility, luminal osmolarity, and tissue hydrostatic pressure.
• Classification includes secretory, osmotic, exudative/inflammatory, and altered motility/motor categories.

Diarrhea - Classification

• Secretory: Secondary to enhanced secretion by intestinal mucosa, often large watery volume with electrolyte loss. Common causes include bacterial/viral/bacterial enteritis, gastric hypersecretion, carcinoid, stimulant laxatives, bile acid malabsorption, celiac disease, IBD (mucosal).
• Osmotic: Secondary to hyperosmolar gradient in intestinal lumen; common causes include osmotic laxatives, carbohydrate malabsorption (e.g., lactase deficiency), fat malabsorption (e.g., pancreatic insufficiency), short bowel syndrome.
• Exudative/inflammatory: Secondary to intestinal mucosa inflammation or infiltration/invasion. Common causes include IBD, invasive infection (e.g., C. difficile toxin, enterotoxigenic Escherichia coli), cytomegalovirus, Shigella, ischemic colitis, radiation enterocolitis, neoplasm.
• Altered motility/motor: Secondary to autonomic nerve dysfunction. Common causes include diabetic neuropathy, post-vagotomy, hyperthyroidism, irritable bowel syndrome (IBS), Addison disease.

Diarrhea - Drug-Induced

• Medications that can cause diarrhea include antibiotics, antineoplastics, laxatives, levothyroxine (overreplacement), metoclopramide, acarbose or miglitol, NSAIDs, digoxin, prostaglandins (misoprostol), colchicine, orlistat, sorbitol (sugar-free products).

Diarrhea - Diagnosis

• Thorough patient history, including disease and drug-induced causes, recent travel history, and temporal relation to food intake.
• Assess fluid and electrolyte status.
• Conduct complete blood count, stool culture, and check for ova/parasites if infection is suspected.
• If infection is suspected, confirm presence of C. difficile toxin and culture, especially if recent antibiotic use or hospitalization.
• Assess stool pH, electrolytes, osmolarity, and fat content if indicated.
• Imaging (e.g., abdominal CT scan) or endoscopy with biopsy might be indicated in severe cases, particularly related to inflammatory diarrhea or suspected neoplasm or celiac disease.

Diarrhea - Pharmacist Role

• Refer to higher level of care if patient is immunocompromised, paediatric, pregnant, has fever, blood in stool, weight loss >5%, or a suspected invasive infection.

Diarrhea - Treatment (General)

• Remove or treat underlying cause.
• Rehydrate, using intravenous fluids for hospitalized patients and oral rehydration for others who haven't vomited. Sodium and glucose are key ingredients in oral rehydration solutions.
• Dietary modifications: avoid dairy products (may have transient lactase deficiency).
• "BRAT" diet for adults (bananas, rice, applesauce, toast).

Diarrhea - Drug Therapy

• Loperamide: µ-receptor agonist for mild to moderate non-invasive diarrhea; adjunctive to other non-opioid therapies. Avoid in suspected invasive infection. Pregnancy category B.
• Diphenoxylate + atropine: µ-receptor agonist for moderate to severe non-invasive diarrhea; used when loperamide is ineffective. CNS effects, respiratory depression, constipation, and anticholinergic effects with atropine are possible adverse effects.
• Bismuth subsalicylate: Anti-secretory, binds toxins; for mild-moderate diarrhea and traveler's diarrhea prevention. Adverse effect: stool discoloration. Avoid in salicylate allergy, pregnancy, or nursing, and in those <12 years old. Use with caution with anticoagulants.
• Octreotide: Antisecretory, hormone release suppression; for tumor-associated diarrhea (e.g., VIPoma, carcinoid, HIV-associated diarrhea). Adverse effects: hyperglycemia, gallstone formation.

Diarrhea - Drug Therapy (Additional)

• Lactase enzymes: For lactase deficiency or intolerance.
• Probiotics (Lactobacilli, Saccharomyces): May help prevent antibiotic-associated diarrhea by competing with pathogens

Constipation

• Constipation is a reduction in frequency of bowel movements compared to normal frequency, characterized by difficulty evacuating, straining, hard, dry stools, abdominal pain/distension, low back pain, and anorexia.

Constipation – Pathophysiology

• Common causes include altered motility (e.g., ileus), neurogenic causes (autonomic neuropathies, Parkinson's disease), endocrine/metabolic disorders (e.g., hypothyroidism, diabetes, hypokalemia, hypercalcemia, uremia), pregnancy, psychogenic causes, structural abnormalities or obstruction, nutritional factors (reduced fiber/water intake), medications.

Constipation – Diagnosis

• Thorough patient history.
• Fluid and electrolyte assessment.
• Thyroid function assessment.
• Imaging (e.g., abdominal CT scan, radiograph) for ileus, obstruction, or dilation.
• Refer for further evaluation for those with symptoms lasting more than 1-2 weeks despite treatment, considerable pain/cramping, pregnancy, fever, blood in stool, reduction in stool caliber, weight loss, paraplegia, or quadriplegia.

Constipation – Treatment (General)

• Treat underlying disease.
• Alter lifestyle factors (particularly diet).
• Prevent further constipations.
• Acute constipation relief with tap-water enema or glycerin suppository, or use oral sorbitol, low-dose bisacodyl or senna, or saline laxatives (e.g., milk of magnesia).
• Address if not due to an underlying disease by treating as an adult, emphasizing high-fiber diet.

Constipation – Treatment – Non-Pharmacological

• Dietary modification: increase fiber intake (20-30 g/day).
• Adequate and increasing fluid intake (6-8 glasses of water daily).
• Exercise (3-5 days/week).
• Adjustment of bowel habits.

Constipation – Treatment – Pharmacotherapy

• Saline osmotic laxatives: Magnesium citrate, magnesium hydroxide, and sodium phosphate. Use for acute or intermittent constipation, preoperative/pre-procedure bowel preparation (fast onset, 15 minutes to 3 hours). Avoid if renal impairment, heart failure (HF), or cirrhosis.
• Other Osmotic Laxatives: Glycerin (management of acute/intermittent constipation; used for pediatric patients as a suppository; fast onset - within 1 hour). Lactulose (management of acute, intermittent, or chronic constipation; preferred in chronic liver disease (onset 1-2 days, multiple doses may be required); associated with gas/bloating; syrup or powder form).
• Stimulant laxatives: Bisacodyl (short-term relief of acute/intermittent constipation). Senna (short-term relief of acute/intermittent constipation and long-term prevention of opioid-induced constipation). Possible side effects: abdominal cramping, electrolyte disturbances, and melanosis coli.
• Bulk-forming laxatives: Psyllium, inulin, wheat dextrin, calcium poly-carbophil, and methylcellulose; used for intermittent/chronic constipation. Onset 12-72 hours and requires adequate water intake; safe for renal/hepatic disease, pregnancy, and senior citizens; may cause gas/bloating).

Constipation – Miscellaneous Agents

• Docusate sodium/potassium: For opioid-induced constipation prevention (combination); used in preventing straining in post-MI, postsurgical, and pregnant patients. Requires adequate water intake for efficacy (onset 1-6 days).
• Methylnaltrexone (Relistor): Opioid-induced constipation; Peripheral opiate antagonist; will not reverse central analgesia; given subcutaneously every other day (onset within 4 hours in ~50% of patients).
• Lubiprostone (Amitiza): For chronic idiopathic constipation and IBS-C; likely in women over 18; increases intestinal fluid secretion by activating Chloride Channel and may decrease bloating and abdominal pain (adverse effect: nausea). Need a negative pregnancy test (only use with a negative pregnancy test).
• Linaclotide (Linzess): For IBS-C and chronic idiopathic constipation. Increases fluid secretion and transit time. Take on an empty stomach 30 minutes prior to meal. Contraindicated in pediatric patients under 6 years old and patients with mechanical obstructions. Do not use in those aged 6-17 years old. Pregnancy category C.

Drug Therapy (General)

• Select drugs based on desired action, patient preference and any potential contraindications.
• Consider special populations.
• Educate patients on alternative forms such as enemas or suppositories.