Chronic diarrhea medical therapy

Chronic diarrhea Microchapters
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Case #1

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2] Anum Ijaz M.B.B.S., M.D.[3]

Overview

Antidiarrheal drugs can be broadly defined as agents that minimize the symptoms of diarrhea by improving stool consistency, reducing stool frequency, or reducing stool weight. Chronic diarrhea is a common symptom of many conditions. In order to appropriately treat chronic diarrhea, the underlying causes must be identified and treated and, in most cases, the chronic diarrhea will resolve.

Medical Therapy

For the treatment of the most common causes of chronic diarrhea, please click below:

• Inflammatory diarrhea
  • Crohn's disease
  • Ulcerative colitis
  • Tuberculosis
  • Strongyloidiasis
  • Ischemic colitis

• Watery diarrhea
  • Celiac sprue
  • Chronic pancreatitis
  • Lactose intolerance
  • Whipple's disease
  • Cholera
  • Giardiasis
  • Hyperthyroidism
  • Addison's disease

• Fatty diarrhea
  • Celiac disease
  • Pancreatic insufficiency
  • Small bowel bacterial overgrowth syndrome

Summary of Treatment Options for Different Etiologies of Chronic Diarrhea

Drug/treatment	Mechanism	Typical target daily dosing range	Efficacy of treatment	Adverse effects (with frequency.a)
Celiac disease
Gluten-free diet	Foods must contain <20 ppm of gluten to be considered gluten-free.	NA	Symptomatic relief typically manifests within days to weeks; however, 22% of patients remain symptomatic after 6 months of therapy.	Constipation Weight gain
Bile acid diarrhea
Bile acid sequestrants (off-label use)	Intraluminal bile acid binders	Starting doses: Cholestyramine: 1 g twice daily Colesevelam: 1250 mg twice daily Colestipol: 1 g twice daily Dose titration based on clinical response.	A systematic review encompassing 7 RCTs (n = 311) demonstrated that 65.2% of patients with bile acid malabsorption experienced diarrhea resolution compared to 18.6% in the placebo group.	Constipation (11%) Dyspepsia (8.3%) Nausea (4.2%) Pharyngitis/rhinitis (3.2%) Myalgia (2.1%)
Microscopic colitis
Budesonide (not FDA approved for this condition)	Anti-inflammatory treatment	9 mg Daily for 6-8 wk	For collagenous colitis, clinical response was observed in 81% of patients (38/47) vs. 17% (8/47) for placebo (RR, 4.56 [95% CI, 2.43-8.55]). In the broader microscopic colitis population, response rates were 88% (50/57) for budesonide vs. 38% (22/57) for placebo (RR, 2.03 [95% CI, 1.25-3.33]).	Gastrointestinal (nausea, dyspepsia, bloating, flatulence) (12%) Arthralgia, myalgia, abdominal pain, leg cramps (6%) Weight gain (6%) Dizziness (4.5%)
Exocrine pancreatic insufficiency
PERT (FDA approved for this use)	Porcine derived, including lipase, amylase, and a mixture of proteases	Initial dose: 40 000-50 000 USP units of lipase with meals and half-dose with snacks. Dose titration based on clinical response Nonenteric-coated enzyme preparations should be given with a proton pump inhibitor	Patients receiving PERT showed superior improvement in the mean coefficient of fat absorption compared to those on placebo (36.7% vs. 12.1%).	Nausea/vomiting (6%) Dizziness (4%) Cough (4%)
SIBO
Rifaximin (off-label use)	Poorly absorbed antibiotic with gram-positive and -negative coverage	Standard dose and duration is 550 mg 3 times daily for 14 d but various regimens have been used, ranging from 600-1000 mg/d for 5-28 d	High-quality evidence for SIBO treatment is currently lacking. However, a meta-analysis of 10 studies (n = 205) indicates that 67.7% (95% CI, 44.7%-86.9%) of patients achieved symptomatic improvement or resolution following successful SIBO eradication.	Nausea (3%) Elevated liver enzymes (2%) 1 Case of Clostridioides difficile infection

Abbreviations: FDA= US Food and Drug Administration; NA = not applicable; PERT= pancreatic enzyme replacement therapy; RCT= randomized clinical trial; RR= relative risk; SIBO= small intestinal bacterial overgrowth; USP = United States Pharmacopeia.

^a If available.

Medical Therapies for Chronic Diarrhea

Medication	Mechanism of action	Recommended dosing	Adverse events (with frequency.a)
Over-the-counter agents
Bismuth subsalicylate	Prostaglandin inhibitor	524 mg Orally as needed, not to exceed 8 doses in 24-h period	Nausea (12.3%) Darkening of tongue and stools (89.5%)
Loperamide	Peripherally acting as μ-opioid receptor agonist	2-16 mg Daily in divided doses	Constipation (5.3%) Nausea (3.2%) Abdominal cramps (3%) Dizziness (1.4%) Overdose leading to central nervous system depression and arrhythmias (<1%)
Prescription agents
Dicyclomine	Antispasmodics	10-20 mg Up to every 6 h as needed	Dry mouth/throat (>5%)
Hyoscyamine		0.125-0.25 mg Up to every 6 h as needed	Blurred vision (>5%)
Diphenoxylate-atropine	Peripherally acting μ-opioid receptor agonists	1-2 Tablets every 6 h, not to exceed 20 mg of diphenoxylate daily	Fatigue (45.5%). Dizziness (36.4%)
Tincture of opium		6 mg Every 4-6 h	Nausea (27.3%) Abdominal pain (27.3%) Overdose and dependence can occur, particularly with tincture of opium
Ondansetron	5-Hydroxytryptamine 3 receptor agonists	4-8 mg Every 6-8 h, not to exceed 24 mg daily	Headache (5%) Constipation (2%)
Granisetron		2-3 mg Daily in single or divided doses	QT prolongation (<2%) Arrhythmias (<1%)
Amitriptyline	Tricyclic antidepressants.b	10-100 mg Once daily	Dry mouth (54%)
Nortriptyline		10-100 mg Once daily	Drowsiness (53%) Difficulty urinating (22%) Blurry vision (17%)
a If available. b The mechanism of action of tricyclic antidepressants in controlling chronic diarrhea is likely through their anticholinergic effects.

Below are some of the drugs that can be used in the symptomatic treatment of chronic diarrhea and their mechanisms of action. Some drugs have numerous mechanisms of action and can thus be found under more than one section. It is important to know that these drugs are used for the symptomatic treatment of chronic diarrhea. In order to appropriately treat chronic diarrhea, the underlying cause of the disease must be identified.

Classification	Category	Examples
Inhibitors of Intestinal Transit Time	Opiates	Loperamide, Eluxadoline, Diphenoxylate, Difenoxin, Codeine, Opium, Paregoric, Morphine
	Enkephalinase Inhibitors	Racecadotril
	5-HT3 Receptor Antagonists	Alosetron
	α2-Adrenergic Agonists	Clonidine
	Somatostatin and Analogs	Octreotide, Lanreotide, Pasireotide
	Calcium Channel Blockers	Nifedipine
Pro-absorptive Agents	Nutrients	Glucose, Amino acids (Oral rehydration solution)
	α2-Adrenergic Agonists	Clonidine
Antisecretory Drugs	Somatostatin and Analogs	Octreotide, Lanreotide, Pasireotide
	Chloride Channel Inhibitors	Crofelemer, Berberine
	Calcium Channel Blockers	Nifedipine
	Calmodulin Inhibitors	Chlorpromazine, Trifluoperazine
	Miscellaneous Antisecretories	Calcium-sensing receptor ligands, Nicotinic acid, Lithium, Zinc, Bismuth, NSAIDs, Corticosteroids, Teduglutide
Intraluminal Agents	Adsorbents	Clays
	Bile Acid-Binding Resins	Cholestyramine, Colestipol, Colesevelam
	Bulk-forming Agents	Fiber

References

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