What it is:Infrequent or difficult passage of stool, often with straining or a sense you didn't fully empty. Chronic when it's been going on 3 months or more. Chronic idiopathic constipation (CIC) hits about 8-12% of US adults.
The core problem:Either not enough water is staying in the stool (too dry, too hard, too slow through the colon), or the pelvic floor/rectum isn't coordinating the actual act of defecation. Almost every drug class works by pulling more water into the lumen, speeding transit, or both. A small handful work by getting an opioid off the gut's µ-receptors.
What you do about it:Fiber and fluids first, always. Then step up: osmotic laxative → add a stimulant PRN → secretagogue or prokinetic if still stuck. Opioid-induced constipation (OIC) gets its own track once you suspect the opioid itself is the driver.
Almost every laxative class is named for how it moves water, not what it "does" to the colon. Bulk-formers hold water already there. Osmotics drag water in. Secretagogues actively pump chloride and fluid into the lumen. Stimulants irritate the mucosa and speed the muscle wall along. Once you sort a drug into one of those four buckets, the onset, the side effects, and the tier all make sense without memorizing them separately.
Constipation is primary(no identifiable cause, most CIC and IBS-C) or secondary(a drug, a disease, or a lifestyle factor is doing it). Before reaching for a laxative, always ask what's actually causing it, because "add a laxative" is not the answer to hypothyroidism or an anticholinergic med list.
| Category | Examples |
|---|---|
| GI disease | IBS, diverticulitis, hemorrhoids, anal fissure, tumor, Hirschsprung disease |
| Metabolic/endocrine | Hypothyroidism, diabetes with neuropathy, hypercalcemia |
| Neurogenic | Parkinson disease, spinal cord injury, stroke, CNS tumor |
| Pregnancy | Progesterone slows motility, colon reabsorbs more fluid, iron supplements pile on |
| Cardiac | Heart failure (gut hypoperfusion/edema) |
| Psychogenic | Habitually ignoring the urge to go, depression, other psychiatric disease |
Anticholinergics(antihistamines, TCAs, antipsychotics, antispasmodics, antiparkinsonian agents like benztropine) block muscarinic receptors on the gut wall and directly slow peristaltic contractions. This is the same receptor blockade that causes dry mouth and blurred vision elsewhere, so a patient on an anticholinergic med for a completely different reason (overactive bladder, allergies, insomnia) can present with constipation as the "side effect" rather than the chief complaint.
Opioidshit µ-opioid receptors in the enteric nervous system itself, not just the CNS. That's why opioid-induced constipation doesn't respond to typical CNS-sparing tricks and instead needs a drug that blocks the gut receptor specifically (the PAMORAs, below). Oral opioids have a stronger constipating effect than parenteral, because they hit a higher concentration of gut receptors on first pass.
Other frequent offenders: calcium channel blockers(smooth muscle relaxation extends to the gut), iron salts, calcium- or aluminum-containing antacids, NSAIDs, and non-potassium-sparing diuretics(volume contraction pulls more water out of stool).
A patient starts an antihistamine, a bladder anticholinergic, anda TCA for neuropathic pain, then gets a "why is my constipation not responding to Miralax" complaint. The answer isn't a stronger laxative, it's recognizing three overlapping anticholinergic burdens on one gut. Always scan the med list before escalating therapy.
Rome IV criteria require at least 2 of the signs below on ≥25% of bowel movements, for the diagnosis of functional constipation.
| Category | Findings |
|---|---|
| Frequency/form | Fewer than 3 bowel movements per week; hard, small, or dry stools |
| Defecation mechanics | Straining, feeling of incomplete evacuation, sense of anorectal blockage, needing manual maneuvers (digital disimpaction, pelvic pressure) to pass stool |
| What's notably absent | Loose stools essentially never occur without laxative use, if they do, reconsider the diagnosis |
Hematochezia, melena, unintentional weight loss, anorexia, iron-deficiency anemia, family history of colon cancer or IBD, new/worsening constipation in an elderly patient without a clear cause, or symptoms refractory to treatment.Any of these, plus new-onset symptoms after age 50, warrants workup (colonoscopy, labs) before symptomatic therapy, not instead of it.
Exam:a rectal/digital exam checks for fecal impaction, anal stricture, rectal mass, fissures, hemorrhoids, or rectal prolapse, and can catch a mechanical cause a laxative will never fix.
Diagnosis is clinical. There's no routine lab recommendationfor garden-variety constipation, order tests based on clinical suspicion, not reflexively.
Goals:relieve symptoms, reestablish a normal bowel pattern, and do it while minimizing adverse effects, not just achieving any bowel movement by any means.
First, treat what's treatable: correct hypothyroidism, stop or switch a constipating drug if there's a reasonable alternative, or lower its dose if there isn't. If the patient must stay on a constipating drug (opioids especially), build prevention into the regimen from day one rather than waiting for symptoms.
Fiber first → osmotic laxative (preferred first-line pharmacologic agent) → add a stimulant laxative PRN if no relief → secretagogue or prokinetic if still refractory.Stimulants are for intermittent/PRN use, not because they're dangerous long-term, but because osmotics have the better safety and tolerability profile for daily chronic use.
Laxatives are grouped by how fast they work, which is also roughly how aggressive they are. Match the tier to the clinical urgency, don't reach for a same-day agent for routine chronic maintenance.
| Agent | Adult Dose | Onset |
|---|---|---|
| Bulk-Forming Agents (soften stool, 1-3 days) | ||
| Psyllium | Varies by product | 1-3 days |
| Methylcellulose | Varies by product | 1-3 days |
| Polycarbophil | 4-6 g/day | 1-3 days |
| Emollients / Stool Softeners (1-3 days) | ||
| Docusate sodium | 50-360 mg/day | 1-3 days |
| Docusate calcium | 50-360 mg/day | 1-3 days |
| Docusate potassium | 100-300 mg/day | 1-3 days |
| Osmotic Laxatives (soften stool, 1-3 days; preferred first-line) | ||
| Polyethylene glycol 3350 (Miralax) | 17 g/dose in 120-240 mL liquid, once-twice daily (max 34 g/day) | 1-3 days, can take up to 6 mo for durable response |
| Magnesium oxide | 400-500 mg daily | 1-3 days |
| Lactulose | 15-30 mL orally (~15 g/day) | 1-3 days |
| Lactitol | 20 g/day | 1-3 days |
| Sorbitol | 30-50 g/day | 1-3 days |
| Stimulant Laxatives (soft/semifluid stool, 6-12 hr; PRN use) | ||
| Bisacodyl (oral) | 5-15 mg orally | 6-12 hr |
| Senna | 8.6-17.2 mg (dose varies by formulation) | 6-12 hr |
| Magnesium sulfate (low dose) | <10 g orally | 6-12 hr |
| Saline / Watery Evacuation Agents (1-6 hr; bowel prep, not routine use) | ||
| Bisacodyl (rectal) | 10 mg rectally | 1-6 hr |
| Magnesium citrate | 18 g in 300 mL water | 1-6 hr |
| Magnesium hydroxide (milk of magnesia) | 2.4-4.8 g orally | 1-6 hr |
| Magnesium sulfate (high dose) | 10-30 g orally | 1-6 hr |
| PEG-electrolyte lavage solution | 4 L total, 240 mL every 10 min (bowel prep) | 1-6 hr |
| Secretagogues (chronic constipation, third-line) | ||
| Lubiprostone (Amitiza) | 24 mcg BID with food (CIC and OIC) | days |
| Linaclotide (Linzess) | 145 mcg daily, empty stomach ≥30 min before first meal (72-145 mcg for IBS-C) | days |
| Plecanatide (Trulance) | 3 mg daily, any time with regard to food | days |
| Prokinetic | ||
| Prucalopride (Motegrity) | 2 mg daily (1 mg daily if CrCl <30) | days |
| Opioid Receptor Antagonists (OIC specifically) | ||
| Methylnaltrexone | 450 mg orally daily, or 12 mg SC daily | hours |
| Naloxegol | 25 mg daily | hours |
| Naldemedine | 0.2 mg daily | hours |
| Alvimopan | 12 mg preop, then 12 mg BID up to 7 days (max 15 doses); post-op bowel resection only | hours |
Bulk-formers(psyllium, methylcellulose, polycarbophil) work like the fiber they're derived from: they hold water in the stool mass, increasing bulk and softness, which stimulates peristalsis mechanically. They need adequate fluid intake to work and to avoid worsening obstruction in someone with a stricture, so they're a poor choice if a mechanical blockage hasn't been ruled out.
Docusatesare surfactants (detergent-like), increasing water and electrolyte secretion into the small and large bowel so stool stays softer. Key point the handbook is explicit about: docusates prevent constipation, they don't treat it.They're the right call after an MI (avoid straining), after rectal surgery, or with acute perianal disease, where the goal is a soft stool rather than actively driving one out. Don't reach for docusate as monotherapy in someone who's already constipated and needs an active push.
All osmotics pull water into the lumen by osmotic gradient; they differ in cost, taste, and adverse effect profile rather than mechanism.
Polyethylene glycol (PEG 3350)is the workhorse: OTC, tasteless, well-tolerated, and response can be durable for up to 6 months of daily low-dose use. Main complaints are bloating, cramping, and abdominal discomfort, mechanical from the fluid shift, not mucosal irritation.
Magnesium oxideis cheap and effective but needs a renal function check first, magnesium accumulates in renal impairment and can cause clinically significant hypermagnesemia (lethargy, weakness, cardiac conduction changes at high levels). Same caution for any magnesium-based saline cathartic.
Lactuloseis a nonabsorbable disaccharide fermented by colonic bacteria, producing gas along with its osmotic pull, which is exactly why it's notfirst-line: it's costlier than PEG and the flatulence/bloating tradeoff is worse. Reserve it for patients who fail fiber plus a standard osmotic, or for acute constipation where a quick option is needed.
Magnesium and sodium phosphate salts are fine as one-time bowel preps before colonoscopy, but repeated or chronic use risks fluid/electrolyte depletion, and magnesium or sodium accumulation in renal impairment or heart failure. These risks compound with long-term use, this is a bowel-prep tool, not a daily maintenance drug.
Bisacodyl (diphenylmethane class) and senna (anthraquinone class) directly stimulate colonic mucosa and myenteric plexus, triggering a bowel movement in 6-12 hours(oral) or as fast as 1 hour (rectal bisacodyl). They're reserved for intermittent/PRN use, or for patients who've already failed bulk-forming and osmotic agents, both because the evidence base for daily use is thinner and because prolonged use can drive electrolyte imbalance and cramping. Some patients with severe chronic constipation and nonmodifiable risk factors do end up using them regularly, that's a clinical judgment call, not a contraindication.
These three all increase intestinal fluid secretion, but through distinct mechanisms, worth knowing because it explains why one might work when another doesn't.
| Lubiprostone (Amitiza) | Linaclotide (Linzess) | Plecanatide (Trulance) | |
|---|---|---|---|
| Mechanism | Prostaglandin E1 analog, activates ClC-2 chloride channelson the apical enterocyte membrane | Guanylate cyclase-C (GC-C) agonist, raises cGMP, activates CFTR chloride channel | Also a GC-C agonist, same downstream pathway as linaclotide |
| Indications | CIC andOIC | CIC and IBS-C | CIC (not IBS-C) |
| Dose | 24 mcg BID with food | 145 mcg daily, empty stomach | 3 mg daily, any time |
| Age restriction | None specified | Not <18 years | Not <18 years (and avoid in kids <6 due to dehydration risk) |
| Main adverse effect | Nausea (take with food to blunt it), headache, diarrhea | Diarrhea (16.3% vs 2.3% placebo) | Diarrhea (4.3% vs 1.0% placebo, milder than linaclotide) |
All three are reserved for patients who fail conventional first-line therapy (fiber, osmotic laxatives), reflecting both cost and the fact that a cheaper agent should get a fair trial first.
A selective 5-HT4 receptor agonist, it stimulates colonic peristalsis and secretion through enteric neurotransmission rather than an osmotic or secretory mechanism, closer to "making the motor run" than "adding water to the tank." Dose is 2 mg daily, reduced to 1 mg daily if CrCl <30. Common adverse effects are headache, abdominal pain, nausea, and diarrhea. The 2023 AGA/ACG guideline gives it a strong recommendationspecifically for patients who fail OTC agents, it's positioned above the secretagogues in evidence strength even though it often gets reached for later in practice.
OIC happens because opioids agonize µ-opioid receptors directly in the enteric nervous system, not just centrally, slowing motility, reducing secretions, and tightening sphincter tone. That peripheral gut receptor is exactly why standard laxatives often underperform here and why a dedicated drug class exists.
| Agent | Class | Dose | Niche |
|---|---|---|---|
| Methylnaltrexone | PAMORA (peripherally acting µ-opioid receptor antagonist) | 450 mg PO daily or 12 mg SC daily | OIC in advanced illness/palliative care, or when laxatives have failed |
| Naloxegol | PAMORA | 25 mg daily | OIC, chronic noncancer pain |
| Naldemedine | PAMORA | 0.2 mg daily | OIC, chronic noncancer pain |
| Alvimopan | GI-selective µ-antagonist | 12 mg preop, then 12 mg BID up to 7 days/15 doses | Short-term, in-hospital only: accelerates GI recovery after bowel resection |
Why "PAMORA" matters as a concept:these drugs are engineered to not cross the blood-brain barrier well, so they reverse the gut's opioid effect without touching central analgesia. You are not undoing the patient's pain control by giving one.
Contraindicated if the patient has been on therapeutic opioid doses for more than 7 consecutive daysbefore surgery, in that setting it can precipitate opioid withdrawal or GI perforation risk. It's a short-course, inpatient-only drug, never send it home with a patient.
Lubiprostonealso carries an OIC indication (dual approval with CIC), it's a reasonable non-PAMORA option when you want to avoid touching opioid receptors altogether.
IBS-C is constipation plusrecurrent abdominal pain tied to bowel habit, that pain component is what separates it from plain CIC and is why treatment doesn't stop at a laxative.
| Severity | Add for constipation | Add for pain |
|---|---|---|
| Mild | Osmotic laxative (PEG) | Antispasmodics (dicyclomine, hyoscyamine) or peppermint oil |
| Moderate-severe | Secretagogue (linaclotide has the strongest evidence, plecanatide, lubiprostone) or tenapanor | Continue above; consider adding a neuromodulator if pain persists |
| Persistent pain/psych symptoms | - | TCA, SSRI, or gut-directed brain-behavior therapy (CBT, hypnotherapy) |
Antispasmodics(dicyclomine 20 mg up to QID PRN; hyoscyamine IR 0.125-0.25 mg q4-8h PRN, max 1.5 mg/day) are anticholinergics that relax intestinal smooth muscle to cut cramping pain. Widely used clinically despite thin trial data, and worth remembering they carry the same dry mouth/blurred vision/dizziness burden as any anticholinergic, don't stack them on top of a TCA without noticing.
Tenapanor(not covered in the handbook chapter but relevant here) is an NHE3 inhibitor, it blocks sodium absorption in the gut, pulling water into the lumen. Minimally absorbed systemically. Main adverse effect is diarrhea (14.8% vs 2.3% placebo).
| Parameter | When | Watching for |
|---|---|---|
| Bowel movement frequency/consistency | Ongoing, patient-reported | Treatment response, using patient's own baseline as the target, not a fixed number |
| Renal function | Before and during chronic magnesium-based laxative use | Magnesium accumulation, especially in renal impairment or elderly patients |
| Electrolytes | With chronic or high-dose saline cathartic use | Fluid/electrolyte depletion from repeated osmotic pulls |
| Alarm symptoms | Every visit | New hematochezia, weight loss, anemia - reopen the workup, don't just escalate the laxative |
| Adherence to nonpharm measures | Each follow-up | Whether fiber/fluid trial was actually adequate (dose and duration) before calling it a failure |
| Diarrhea on secretagogues | After initiation | Dose-limiting GI adverse effect; may need to hold or reduce |