What it is:An increase in stool frequency and a drop in stool consistency compared to a person's own normal pattern. Diarrhea isn't a diagnosis, it's a symptom (what the patient reports) and a sign (what you can measure) that something upstream is off with fluid and electrolyte handling in the gut.
The core problem:Every case comes down to an imbalance between how much water and electrolytes the gut secretes versus how much it absorbs. Whatever tips that balance (an infection, a toxin, a malabsorbed sugar, inflamed mucosa, or a motility problem) is the actual disease. The diarrhea itself is downstream.
What you do about it:Most acute diarrhea is infectious and self-limited, so the job is mainly supportive: replace fluid and electrolytes, control symptoms, and know when it's actually something that needs an antibiotic or a workup instead of just loperamide.
Everything in this chapter maps onto four mechanisms: altered ion transport (secretory), too many unabsorbed solutes pulling in water (osmotic), inflamed gut leaking mucus/protein/blood (exudative), and abnormal transit time. Once you know which mechanism is driving a case, the right drug class becomes obvious instead of memorized: opioids slow transit, bismuth and octreotide block secretion, and fasting or fixing the malabsorption fixes osmotic diarrhea.
Two separate axes matter here, and mixing them up is an easy trap.
| Duration label | Cutoff | Typical cause |
|---|---|---|
| Acute | < 14 days | Usually infectious (virus, bacteria, protozoa) and self-limited |
| Persistent | > 14 days | Infection that didn't clear, or an evolving chronic process |
| Chronic | > 30 days | Non-infectious: IBD, malabsorption, secretory tumor, motility disorder, drug-induced, factitious |
The second axis is mechanism, which is really about where in the water/electrolyte balance the problem sits.
| Clinical group | What's actually happening | Classic drivers |
|---|---|---|
| Secretory | A stimulating substance increases secretion or blocks absorption of water and electrolytes | VIP-secreting pancreatic tumors, unabsorbed dietary fat (steatorrhea), laxatives, hormones, bacterial toxins, excess bile salts |
| Osmotic | Unabsorbed solutes in the lumen raise osmolarity and drag water in | Lactose intolerance, malabsorption, osmotic laxatives (PEG, magnesium) |
| Exudative | Inflamed gut wall discharges mucus, protein, or blood directly into the lumen | Inflammatory bowel disease, invasive infection, colitis |
| Altered intestinal transit | Motility itself is disrupted | Reduced small-intestinal contact time, premature colonic emptying, bacterial overgrowth |
Secretoryis a pure fluid/electrolyte problem, the mucosa itself isn't necessarily damaged. Exudativemeans the gut wall is actually inflamed and leaking mucus, protein, or blood into the stool. That's why exudative diarrhea is the one that can present with visible blood or mucus and secretory usually doesn't.
Viruses are the more common cause of acute gastroenteritis overall, but bacteria are responsible for more actual cases of acute diarrhea. The usual bacterial culprits are Shigella, Salmonella, Campylobacter, Staphylococcus,and E. coli. Acute viral disease is mostly the Norwalk group and rotavirus.
Underneath all of that, diarrhea is fundamentally an imbalance in absorption and secretion of water and electrolytes, and it can come from a disease inside the GI tract or a disease entirely outside it (endocrine, neurologic, a drug effect). Four pathophysiologic changes disrupt that balance: altered active ion transport (less sodium absorption or more chloride secretion), altered motility, increased luminal osmolarity, and increased tissue hydrostatic pressure.
If the problem is too much secretion, you block secretion: bismuth subsalicylate has antisecretory activity, and octreotide directly blunts the secretory hormones behind tumor-related diarrhea. If the problem is transit is too fast, you slow it down: opioids (loperamide, diphenoxylate) prolong contact time so more water and electrolytes get reabsorbed. If the problem is net fluid loss regardless of cause, you replace what's lost: oral rehydration solution. None of the standard antidiarrheal drugs fix the underlying infection or inflammation, which is why they're described as palliative, not curative.
Acute diarrhea is usually self-limiting and subsides within about 72 hours. Chronic diarrhea instead shows up as repeated attacks over an extended stretch of time. Infants, young children, the elderly, and debilitated patientsare the ones at real risk for morbidity and mortality from prolonged or high-volume diarrhea, because they tolerate fluid and electrolyte losses far worse.
| Feature | Finding |
|---|---|
| Systemic | Abrupt nausea, vomiting, abdominal pain, headache, fever, chills, malaise |
| Typical acute course | Frequent, non-bloody bowel movements lasting roughly 12-60 hours |
| Small intestinal pattern | Intermittent periumbilical or right-lower-quadrant pain, cramps, audible bowel sounds |
| Large intestinal pattern | Gripping, aching pain with tenesmus (straining, painful, ineffective stooling) |
| Chronic history clues | Prior bouts, weight loss, anorexia, chronic weakness |
| Exam | Hyperperistalsis with borborygmi, generalized or localized tenderness |
Fever, dehydration, hematochezia(bloody stool, suggests lower GI bleeding), or hypotension mark a patient who needs hospitalization, IV fluids and electrolytes, and empiric antibiotics while cultures are pending. This is not a "recommend OTC loperamide" visit.
Most acute, uncomplicated diarrhea doesn't need a workup. When it's indicated:
A long list of medications cause diarrhea, and checking the med list is often faster than ordering a workup.
| Category | Examples |
|---|---|
| Laxatives / antacids | Magnesium-containing antacids |
| Antibiotics | Clindamycin, tetracyclines, sulfonamides, essentially any broad-spectrum antibiotic |
| Cardiac agents | Quinidine, digoxin/digitalis |
| Antihypertensives | Reserpine, guanethidine, methyldopa, guanabenz, guanadrel, ACE inhibitors |
| Cholinergics | Bethanechol, neostigmine |
| GI / acid-suppressive | Misoprostol, proton pump inhibitors, H2-receptor blockers |
| Other | NSAIDs, colchicine, antineoplastics, auranofin (a gold salt) |
Laxative abuse for weight loss is a real and testable cause of "chronic diarrhea of unknown origin." It falls under the factitiouscategory on the chronic-diarrhea differential.
Goals:manage the diet, prevent excessive water/electrolyte/acid-base disturbance, provide symptomatic relief, treat curable causes, and manage whatever secondary condition is driving the diarrhea.
Diarrhea can be the body's own defense mechanism for clearing a pathogen or toxin, the same way a cough clears the airway. The goal isn't automatically to stop it at all costs. If diarrhea is secondary to another illness, treating the primary condition is what actually fixes it.
The differential is wide: intestinal infection (bacterial or protozoal), inflammatory bowel disease (Crohn's or ulcerative colitis), malabsorption (like lactose intolerance), a secretory hormonal tumor (carcinoid or a VIP-secreting tumor), a drug effect or factitious cause (laxative abuse), or a motility disturbance (diabetes, IBS, hyperthyroidism). Work through targeted diagnostics (stool culture/ova/parasites/WBC/RBC/fat, sigmoidoscopy, intestinal biopsy) to land on a cause. If one is found, treat it directly plus symptomatic therapy: rehydrate, stop any inducing drug, adjust diet, and use loperamide or an adsorbent. If no cause is ever identified, you're left treating symptomatically.
Before any drug, diet management is the first priority. Most clinicians recommend stopping solid food for 24 hours and avoiding dairy. Feeding should continue, though, in children with acute bacterial diarrhea. If vomiting can't be controlled with antiemetics, the patient goes NPO; as bowel movements taper off, a bland diet is reintroduced.
Rehydration and electrolyte maintenance are the primary treatmentuntil the episode resolves. If vomiting and dehydration aren't severe, enteral (oral) rehydration is preferred over IV, since it's less invasive and less costly. The WHO's oral rehydration solution (ORS) uses a lower osmolarity, lower sodium, and lower glucose load than older formulations.
| Solution | Osmolality | Carbohydrate | Na⁺ | K⁺ | Cl⁻ |
|---|---|---|---|---|---|
| WHO-ORS(reduced osmolarity) | 245 mOsm/kg | 13.5 g/L | 75 mEq/L | 20 mEq/L | 65 mEq/L |
| Pedialyte | 250 mOsm/kg | 25 g/L | 45 mEq/L | 20 mEq/L | 35 mEq/L |
| CeraLyte | 220 mOsm/kg | 40 g/L (rice syrup) | 50-90 mEq/L | 20 mEq/L | 40-80 mEq/L |
| Enfalyte | 167 mOsm/kg | 30 g/L (rice syrup) | 50 mEq/L | 25 mEq/L | 45 mEq/L |
Oral zinc supplementation, 20 mg daily for 10 days, on top of ORS meaningfully reduces the severity and duration of acute diarrhea. This is strongest evidence in developing-country populations, but it's a legitimate add-on to know, not a throwaway fact.
These drugs are grouped into antimotility agents, adsorbents, antisecretory compounds, antibiotics, enzymes, and intestinal microflora (probiotics). None of them cure the underlying cause; they're palliative.
| Drug | Form | Adult dose |
|---|---|---|
| Antimotility (opioid-based) | ||
| Loperamide | 2 mg capsule | Initially 4 mg, then 2 mg after each loose stool; max 16 mg/day |
| Diphenoxylate (+ atropine) | 2.5 mg tablet or 2.5 mg/5 mL | 5 mg four times daily; do not exceed 20 mg/day |
| Difenoxin (+ atropine) | 1 mg tablet | 2 tablets, then 1 tablet after each loose stool; up to 8 tablets/day |
| Paregoric | 2 mg/5 mL (morphine equivalent) | 5-10 mL, 1-4 times daily |
| Opium tincture | 10 mg/mL (morphine equivalent) | 0.6 mL four times daily |
| Antisecretory | ||
| Bismuth subsalicylate | 262 mg/15 mL, 524 mg/15 mL, 1050 mg/30 mL, 262 mg tablet | 2 tablets or 30 mL every 30-60 min PRN, up to 8 doses/day |
| Octreotide | 0.05, 0.1, 0.5 mg/mL | Initial 50 mcg SC 1-2x/day; titrate up to 600 mcg/day in 2-4 divided doses per indication |
| Enzymes | ||
| Lactase | 1250 neutral lactase units/4 drops; 3300 FCC units/tablet | 3-4 drops with milk/dairy, or 1-2 tablets with the dairy meal |
| Bacterial replacement | ||
| Lactobacillus acidophilus / L. bulgaricus | Tablet or granule packet | 2 tablets or 1 packet, 3-4 times daily with milk, juice, or water |
These delay transit through the gut or increase its holding capacity, which prolongs contact time and lets more water and electrolytes get reabsorbed before the stool leaves. The tradeoffs are real: addiction potential with long-term use, and the possibility of worsening certain infectious diarrheas by keeping pathogens or toxins in contact with the mucosa longer.
Loperamideis the workhorse, recommended for both acute diarrhea (including traveler's diarrhea) and chronic diarrhea. Diarrhea that persists 48 hours past starting loperamide needs medical attention, that's the built-in safety check.
Diphenoxylateand its derivative difenoxinare both combined with atropine (partly to discourage misuse) and share the same indications, precautions, and side effects as each other.
Used for both treatment and prevention of diarrhea, traveler's diarrhea being the classic use case. It works through three separate mechanisms: antisecretory, anti-inflammatory, and antibacterialeffects.
Because it's a multi-component product (bismuth plus salicylate), taking it in excess to try to prevent or treat diarrhea can become toxic. More isn't better here.
Saccharomyces boulardii, Lactobacillus GG,and Lactobacillus acidophilusshorten the duration of both infectious diarrhea and antibiotic-associated diarrhea in adults and children. Dosing varies a lot by brand/product since these aren't standardized like a drug. The main complaint patients report is intestinal flatus, worth mentioning up front so they don't stop it thinking something's wrong.
A synthetic analog of somatostatin, used for symptomatic control of diarrhea from carcinoid tumorsand other peptide-secreting tumors, dumping syndrome, and chemotherapy-induced diarrhea. For carcinoid-related diarrhea specifically, the dose range is 100-600 mcg daily in 2-4 divided doses, subcutaneously, for 2 weeks.
Adverse effects include cholelithiasis, nausea, diarrhea (yes, it can paradoxically cause GI upset), and abdominal pain.
Vaxchorais an oral cholera vaccine licensed in the US. ACIP recommends it for adults aged 18-64 traveling to a cholera-endemic area.
RotaTeqand Rotarixare oral rotavirus vaccines that prevent gastroenteritis from rotavirus infection in infants and children.
Irritable bowel syndrome is a chronic disorder of gut-brain interaction, affecting roughly 4.1-10.1%of the population worldwide. It hits womenand people under age 50disproportionately, and carries real disease burden: worse quality of life, more psychological comorbidity, and high economic cost. It's one of the most common causes you'll actually see behind a "chronic diarrhea" chief complaint, alongside IBD and malabsorption.
Diagnosis is symptom-based: abdominal pain plus a change in stool form and altered bowel habits, with no alarm features(hematochezia, melena, or unintentional weight loss). Before landing on IBS, rule out celiac disease and IBD using fecal calprotectin, fecal lactoferrin, CRP, and ESR.
Subtyping uses the Bristol Stool Form Scale (BSFS)and Rome IV criteria:
| Subtype | Definition |
|---|---|
| IBS-D | >25% of BMs are BSFS 6-7 (loose/watery), <25% are BSFS 1-2 (hard) |
| IBS-C | >25% of BMs are BSFS 1-2, <25% are BSFS 6-7 |
| IBS-M | >25% of BMs are BSFS 1-2 and>25% are BSFS 6-7 |
| IBS-U | Can't be determined; patients can also shift between subtypes over time |
| Severity | Target | First-choice options |
|---|---|---|
| Mild | Diarrhea | Loperamide, bile acid sequestrant (e.g., colestipol) |
| Abdominal pain | Antispasmodics | |
| Moderate | Rifaximin, low-dose TCA, eluxadoline, or alosetron | |
| Persistent pain/psych overlay: low-dose TCA, SSRI, brain-gut behavioral therapy | ||
Loperamide's use in IBS-D is off-labeland carries only a conditional, very-low-certainty AGA recommendation, unlike its solid evidence base in acute infectious diarrhea. It still uses the same dosing logic (4 mg initial, then 2 mg after each loose stool) and is still contraindicated in pseudomembranous colitis, acute dysentery, and children under 2.
| Drug | MOA | Dose | Key caution |
|---|---|---|---|
| Rifaximin (Xifaxan) | Non-absorbed oral antibiotic | 550 mg TID × 14 days | Can retreat up to 2 times if symptoms recur after initial response |
| Eluxadoline (Viberzi) | Mixed μ/κ opioid agonist + δ opioid antagonist, peripherally acting | 100 mg BID (75 mg BID if hepatic impairment or intolerance) | Constipation (usually within first 3 months), nausea, abdominal pain |
| Alosetron | 5-HT3 antagonist, slows intestinal transit | 0.5 mg BID, may increase to 1 mg BID after 4 weeks if inadequate response | REMS-restricted; women with severe IBS-D only |
| Bile acid sequestrants | Bind bile acids in small intestine, eliminated in feces | Colestipol, cholestyramine, colesevelam | May help if bile acid malabsorption is present; testing for BAM in the US is limited |
Absolutely avoid in patients without a gallbladder, with known or suspected biliary duct obstruction or sphincter of Oddi disease, a history of pancreatitis or structural pancreatic disease, severe hepatic impairment (Child-Pugh C), or heavy alcohol use (more than 3 drinks/day). The gallbladder/pancreas contraindications exist because the opioid-receptor activity here can trigger sphincter of Oddi spasm and pancreatitis, which is a very different risk profile from loperamide.
It's restricted to women with severe IBS-D because of an increased risk of ischemic colitisand complications from constipation, including obstruction or perforation. If constipation develops, hold the drug until it resolves, then you can restart; if constipation recurs, discontinue for good. If symptoms haven't improved after 4 weeks at 0.5 mg BID, dose can go to 1 mg BID; if still no response after another 4 weeks, stop it.
Antispasmodics(dicyclomine 20 mg up to 4 times PRN, hyoscyamine IR 0.125-0.25 mg every 4-8 hours PRN up to 1.5 mg/day, or hyoscyamine ER 0.375-0.75 mg every 12 hours up to 1.5 mg/day) are anticholinergics used widely in practice for the abdominal pain component, though the trial evidence behind them is thin. Expect dizziness, dry mouth, nausea, and blurred vision.
TCAs(amitriptyline, nortriptyline, imipramine, desipramine) work as neuromodulators for visceral pain, and their anticholinergic effect doubles as diarrhea control, useful in IBS-D specifically. SSRIs, by contrast, carry an AGA recommendation againstuse for IBS, since evidence is inconsistent and they can worsen symptoms in some patients.
| Parameter | When | Watching for |
|---|---|---|
| Bowel movement frequency & character | Daily during acute illness | Trend toward resolution; constitutional symptoms typically improve within 24-72 hours |
| Vital signs & appetite | Alongside stool tracking | Ongoing dehydration or systemic illness |
| Body weight | Serial during illness | Volume status |
| Serum electrolytes & osmolality | Baseline and as clinically indicated | Correcting fluid/electrolyte disturbance |
| CBC, urinalysis, cultures | When infection or systemic illness is suspected | Source identification, severity |
| Volume status | Continuously in the urgent/emergent setting | This is the single most important outcome to track in a toxic patient |
| Loperamide response | 48 hours after starting | Persistent diarrhea past this point needs medical reevaluation |
| IBS-D drug response | 4 weeks (alosetron dose decision), after rifaximin course | Whether to titrate, retreat, or discontinue |