Pharmacology of Laxatives and Purgatives

Introduction/Overview

The management of altered bowel function, particularly constipation, represents a common clinical challenge across numerous medical specialties. Laxatives and purgatives constitute a heterogeneous group of therapeutic agents employed to promote defecation by accelerating colonic transit, softening stool, or increasing stool mass. The distinction between these terms, while sometimes used interchangeably in clinical parlance, possesses historical and pharmacological significance. Laxatives generally produce a mild to moderate effect, facilitating the comfortable passage of formed stool. Purgatives, or cathartics, typically induce a more vigorous, fluid evacuation of the bowel, often reserved for specific diagnostic or therapeutic procedures rather than routine constipation.

The clinical relevance of these agents is underscored by the high prevalence of functional constipation, which affects a significant proportion of the general population, with increased incidence in pediatric, pregnant, and geriatric demographics. Beyond functional disorders, laxatives are integral in managing constipation secondary to medications (notably opioids), neurological conditions, and immobility. Furthermore, specific agents are essential for bowel preparation prior to colonoscopy or colorectal surgery, and in the management of certain toxic ingestions to decrease gastrointestinal absorption. The appropriate selection of a laxative requires a thorough understanding of its pharmacological profile, including its mechanism of action, onset and duration of effect, and potential for adverse reactions and drug interactions.

Learning Objectives

• Classify major laxative and purgative agents based on their primary mechanism of action and chemical properties.
• Explain the molecular, cellular, and physiological mechanisms by which different classes of laxatives alter colonic motility, secretion, and stool consistency.
• Analyze the pharmacokinetic profiles of representative agents from each class, correlating these properties with dosing regimens and clinical onset of action.
• Evaluate the therapeutic applications, contraindications, and significant adverse effect profiles for each laxative class in various patient populations.
• Formulate appropriate laxative selection strategies for common clinical scenarios, considering patient-specific factors such as age, comorbidities, and concomitant medications.

Classification

Laxatives and purgatives are systematically classified according to their predominant mechanism of action. This functional classification provides the most clinically useful framework for understanding their effects and guiding therapeutic choice. A secondary chemical classification exists within these groups, particularly for the osmotic and stimulant categories.

Functional Classification

The primary functional classes are as follows:

1. Bulk-Forming Laxatives: These are natural or synthetic polysaccharides and cellulose derivatives that are minimally absorbed. Examples include psyllium (ispaghula husk), methylcellulose, and polycarbophil.
2. Osmotic Laxatives: These agents draw water into the intestinal lumen by establishing an osmotic gradient. This class can be further subdivided:
   • Poorly Absorbed Ions: Magnesium salts (hydroxide, citrate, sulfate), sodium phosphate, sodium sulfate.
   • Poorly Absorbed Sugars and Alcohols: Lactulose, polyethylene glycol (PEG), sorbitol, mannitol.
3. Stimulant (Irritant/Contact) Laxatives: These agents directly stimulate colonic enteric neurons and/or the colonic mucosa to increase propulsive motility and often secretion. Examples include:
   • Diphenylmethane Derivatives: Bisacodyl, sodium picosulfate.
   • Anthraquinone Derivatives (plant glycosides): Senna (sennosides), cascara sagrada, aloe.
   • Castor Oil: Ricinoleic acid.
4. Stool Softeners (Surfactants): These are anionic surfactants that lower the surface tension of the stool, allowing water and lipids to penetrate. The primary example is docusate sodium (or calcium).
5. Lubricant Laxatives: These agents, primarily mineral oil, coat the stool and colonic mucosa to ease passage.
6. Prokinetic Agents (for chronic constipation): While not traditional laxatives, drugs like prucalopride (a selective 5-HT₄ receptor agonist) and lubiprostone (a chloride channel activator) are used for chronic idiopathic constipation and constipation-predominant irritable bowel syndrome.
7. Peripherally Acting μ-Opioid Receptor Antagonists: Agents like methylnaltrexone and naloxegol are used specifically for opioid-induced constipation, blocking opioid receptors in the gut without reversing central analgesia.

Mechanism of Action

The pharmacological actions of laxatives are mediated through diverse pathways affecting colonic physiology, including luminal content, mucosal transport, neuronal activity, and smooth muscle contractility.

Bulk-Forming Laxatives

These hydrophilic colloids resist digestion by human alimentary enzymes and are minimally absorbed in the small intestine. Upon reaching the colon, they absorb significant quantities of water, swelling to form a soft, viscous gel or bulk. This increased luminal volume stimulates stretch receptors in the colonic wall, initiating peristaltic reflex activity via the intrinsic myenteric plexus. The resulting propagated contractions enhance colonic transit. The softened, bulky stool is easier to pass. Their action is essentially physiological, mimicking the effect of a high-fiber diet, and typically requires adequate fluid intake to be effective and safe.

Osmotic Laxatives

Osmotic agents exert their effect by creating an osmotic force that retains water within the intestinal lumen. The specific mechanisms vary slightly between ionic and non-ionic agents.

Poorly Absorbed Ions (Mg²⁺, PO₄^3-, SO₄^2-): These polyvalent ions are poorly absorbed from the gastrointestinal tract. Their presence in the lumen establishes a sustained osmotic gradient that draws water from the plasma into the intestinal contents via paracellular and transcellular pathways. The increased intraluminal water volume not only softens stool but also distends the bowel, stimulating mechanoreceptors and promoting peristalsis. Magnesium ions may also stimulate the release of cholecystokinin, which can increase intestinal motility and secretion.

Poorly Absorbed Sugars and Alcohols (Lactulose, PEG, Sorbitol): These compounds are either non-absorbable (like high-molecular-weight PEG) or poorly absorbed. They remain in the lumen, exerting an osmotic effect. Lactulose, a synthetic disaccharide, undergoes bacterial fermentation in the colon to short-chain fatty acids (acetate, lactate, formate) and gases (H₂, CO₂, CH₄). This fermentation further increases the intraluminal osmotic load and acidifies the colonic contents, which may indirectly stimulate motility. Polyethylene glycol solutions are isotonic or slightly hypotonic and work primarily by osmotic water retention without significant fermentation or electrolyte shifts.

Stimulant Laxatives

This class possesses a more direct and often stronger effect on colonic function, primarily by stimulating enteric nerves.

Diphenylmethane Derivatives (Bisacodyl, Sodium Picosulfate): These are prodrugs activated in the colon. Bisacodyl is hydrolyzed by endogenous esterases in the colonic mucosa to its active metabolite, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM). Sodium picosulfate is activated by colonic sulfatase enzymes. The active metabolites are thought to directly stimulate the submucosal and myenteric plexus (the “gut brain”), leading to increased propulsive peristaltic contractions. They may also enhance mucosal secretion of water and electrolytes, likely through activation of enteric secretomotor neurons and possibly via prostaglandin pathways, contributing to a softer stool consistency.

Anthraquinone Derivatives (Senna, Cascara): These natural glycosides (e.g., sennosides) pass unchanged to the colon, where bacterial glycosidases hydrolyze them to active aglycone forms (e.g., rhein anthrone). The active metabolites have a dual action: they inhibit Na⁺,K⁺-ATPase in the colonic mucosal cells, reducing sodium and water absorption, and they stimulate myenteric plexus neurons to increase colonic motility. Chronic use can lead to melanosis coli, a benign pigmentation of the colonic mucosa due to apoptosis of epithelial cells and phagocytosis of the pigment by macrophages.

Castor Oil: This triglyceride is hydrolyzed in the small intestine by pancreatic lipase to glycerol and ricinoleic acid. Ricinoleic acid, the active component, acts primarily on the small intestine rather than the colon. It stimulates prostaglandin EP₃ receptors and possibly activates enteric neurons and mucosal sensory receptors, leading to a profound increase in intestinal secretion and propulsive motility throughout the small intestine. This results in a rapid, sometimes cramping, evacuation of liquid contents.

Stool Softeners and Lubricants

Stool Softeners (Docusate): Docusate salts are anionic surfactants. They reduce the surface tension of the interfacial barrier between the aqueous colonic contents and the hydrophobic stool mass. This emulsifying action allows water and lipids to penetrate and mix with the fecal matter, resulting in a softer stool consistency. Their effect is primarily on stool texture rather than direct stimulation of motility, though some data suggest very mild inhibitory effects on water absorption.

Lubricant Laxatives (Mineral Oil): Mineral oil is a mixture of liquid hydrocarbons that is not digested or absorbed. It coats the stool surface and the intestinal mucosa, creating a slippery barrier that impedes water absorption from the stool and eases its passage through the colon. Its lubricating effect is mechanical.

Novel Agents for Chronic Constipation

Prucalopride: This is a high-affinity, selective serotonin 5-HT₄ receptor agonist. Stimulation of 5-HT₄ receptors on presynaptic terminals of intrinsic primary afferent neurons in the myenteric plexus enhances the release of acetylcholine and calcitonin gene-related peptide (CGRP). This augments the peristaltic reflex, leading to increased colonic propagating contractions and accelerated transit.

Lubiprostone: This is a bicyclic fatty acid derived from prostaglandin E₁. It selectively activates type 2 chloride channels (CIC-2) on the apical membrane of intestinal epithelial cells. This activation increases chloride-rich fluid secretion into the intestinal lumen, which is followed passively by sodium and water. The increased intraluminal fluid softens stool and stimulates motility.

Linaclotide and Plecanatide: These are guanylate cyclase-C (GC-C) receptor agonists. They bind to and activate GC-C receptors on the luminal surface of intestinal enterocytes. Activation increases intracellular cyclic guanosine monophosphate (cGMP), which in turn stimulates the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, leading to chloride and bicarbonate secretion. The increased luminal fluid accelerates transit. Elevated intracellular cGMP may also reduce visceral hypersensitivity by modulating afferent nerve activity.

Peripherally Acting μ-Opioid Receptor Antagonists (Methylnaltrexone, Naloxegol): These agents are quaternary ammonium derivatives or PEGylated molecules designed to have limited ability to cross the blood-brain barrier. They competitively antagonize μ-opioid receptors within the gastrointestinal tract, reversing opioid-induced inhibition of gastric emptying and colonic propulsion without affecting centrally mediated analgesia.

Pharmacokinetics

The pharmacokinetic profiles of laxatives are crucial determinants of their onset and duration of action, guiding their clinical use for different indications (e.g., chronic management vs. rapid bowel evacuation).

Absorption

Absorption patterns vary dramatically by class. Bulk-forming and osmotic agents (PEG, lactulose, magnesium salts) are minimally absorbed, which is essential for their osmotic activity. Stimulant laxatives like bisacodyl and sodium picosulfate are poorly absorbed as prodrugs but are activated locally in the colon. Anthraquinones are absorbed to a small degree but are largely activated by colonic flora. Docusate is absorbed to a limited extent, while mineral oil is not absorbed. The novel agents have specific absorption profiles: prucalopride is well absorbed orally, whereas lubiprostone and linaclotide act locally within the gut lumen with minimal systemic absorption.

Distribution

For most traditional laxatives, systemic distribution is minimal or irrelevant to their therapeutic effect, which is confined to the gastrointestinal lumen and mucosa. Agents like magnesium or phosphate ions that are absorbed can distribute in extracellular fluid. The novel systemic agents like prucalopride distribute widely. Methylnaltrexone, due to its quaternary structure, is largely confined to the peripheral compartment.

Metabolism

Metabolism is a key factor for several agents. The diphenylmethane and anthraquinone stimulants require bacterial metabolism in the colon for activation. Lactulose is fermented by colonic bacteria. Prucalopride undergoes minimal hepatic metabolism. Lubiprostone is rapidly metabolized within the intestinal mucosa to inactive metabolites. Linaclotide is metabolized proteolytically within the GI tract. Most other agents are not metabolized in a classical hepatic sense.

Excretion

Unabsorbed laxatives are excreted entirely in the feces. Absorbed components, such as a fraction of magnesium or metabolites of senna, are excreted renally or via other routes. The elimination half-life (t_1/2) for locally acting agents is not typically measured or clinically relevant. For systemically absorbed agents like prucalopride, the t_1/2 is approximately 24 hours, supporting once-daily dosing.

Onset of Action and Dosing Considerations

The onset of action is a critical pharmacokinetic-pharmacodynamic correlate.

• Bulk-forming agents: Onset is slow, typically 12 to 72 hours, and requires consistent daily dosing with ample fluids.
• Osmotic agents: Onset varies. Magnesium citrate acts in 30 minutes to 3 hours; lactulose requires 24 to 48 hours for full effect. PEG-based solutions for bowel preparation act within 1-2 hours.
• Stimulant agents: Oral bisacodyl and senna usually act in 6 to 12 hours. Suppository formulations of bisacodyl act within 15 to 60 minutes. Sodium picosulfate, used for bowel prep, acts in approximately 10-14 hours. Castor oil acts within 2 to 6 hours, primarily on the small bowel.
• Stool softeners: Onset is slow, usually 24 to 72 hours.
• Novel agents: Prucalopride and lubiprostone may take several days of regular dosing to achieve full effect for chronic constipation.

Dosing is generally weight- or age-adjusted in pediatric populations. For chronic use, the lowest effective dose should be used. Bowel preparation regimens use specific, often large, doses administered over a short period.

Therapeutic Uses/Clinical Applications

The selection of a laxative is guided by the indication, desired speed of onset, and patient-specific factors.

Approved Indications

Chronic Functional Constipation: First-line therapy often involves lifestyle modifications and bulk-forming agents. Osmotic laxatives like lactulose or PEG are frequently used as second-line or first-line agents. Stimulant laxatives (senna, bisacodyl) are recommended for short-term or intermittent use in patients not responding to bulk or osmotic agents. The novel agents (prucalopride, lubiprostone, linaclotide, plecanatide) are indicated for chronic idiopathic constipation in adults who have had an inadequate response to conventional therapy.

Opioid-Induced Constipation (OIC): This is a common and specific side effect of opioid analgesics. Traditional laxatives are used, but peripherally acting μ-opioid receptor antagonists (PAMORAs) like methylnaltrexone, naloxegol, and naldemedine are specifically approved for OIC when response to laxatives is insufficient.

Irritable Bowel Syndrome with Constipation (IBS-C): Lubiprostone, linaclotide, and plecanatide are FDA-approved for this condition, addressing both stool frequency and abdominal pain symptoms.

Bowel Cleansing for Diagnostic or Surgical Procedures: This is a major indication for purgatives. Osmotic agents are mainstays:

• PEG-based electrolyte solutions (e.g., PEG-3350) are considered first-line due to excellent efficacy and safety profile (minimal fluid/electrolyte shifts).
• Sodium phosphate preparations are effective but carry risks of electrolyte disturbances (hyperphosphatemia, hypocalcemia, hypokalemia) and are contraindicated in patients with renal impairment, heart failure, or ascites.
• Sodium picosulfate/magnesium citrate combinations are also commonly used regimens.

Acute Constipation or Fecal Impaction: High-dose osmotic or stimulant laxatives, often administered rectally (enemas, suppositories), may be used. For disimpaction, a combination of oral and rectal agents is sometimes necessary.

Hepatic Encephalopathy: Lactulose is a cornerstone of therapy. Its colonic acidification traps ammonia (NH₃) as non-absorbable ammonium ion (NH₄⁺), and its cathartic effect reduces the colonic bacterial load and transit time for ammonia production and absorption.

Off-Label and Other Uses

Laxatives are sometimes used off-label in other contexts. Docusate is often prescribed post-operatively or post-myocardial infarction to prevent straining. Mineral oil has been used to treat pinworm infestations. Osmotic laxatives may be part of the management for certain drug overdoses to reduce absorption (whole bowel irrigation with PEG).

Adverse Effects

Adverse effects range from mild, predictable gastrointestinal symptoms to serious electrolyte imbalances and pathological changes, often related to the mechanism of action or dose/duration of use.

Common Side Effects

• Bulk-forming agents: Bloating, flatulence, abdominal distension. Esophageal or intestinal obstruction can occur if taken with insufficient fluid.
• Osmotic laxatives: Cramping, bloating, flatulence, nausea. Excessive doses lead to profuse watery diarrhea, which is the intended effect for bowel prep but a side effect for chronic use. Lactulose and sorbitol can cause significant bloating and flatulence due to bacterial fermentation.
• Stimulant laxatives: Abdominal cramping and pain are common, especially with higher doses. Prolonged use can lead to dependence (laxative abuse syndrome), electrolyte disturbances (hypokalemia), and a condition known as cathartic colon, characterized by colonic atony and dilation.
• Stool softeners: Generally well-tolerated; mild abdominal cramping or diarrhea can occur.
• Lubricant laxatives (Mineral Oil): Leakage and perianal irritation, lipid pneumonia from aspiration (especially in elderly or dysphagic patients), and impaired absorption of fat-soluble vitamins (A, D, E, K) with chronic use.
• Novel Agents:
  • Prucalopride: Headache, nausea, diarrhea, abdominal pain.
  • Lubiprostone: Nausea (often dose-related), diarrhea, headache.
  • Linaclotide/Plecanatide: Diarrhea (can be severe), abdominal pain, flatulence.
  • PAMORAs: Abdominal pain, diarrhea, nausea, hyperhidrosis.

Serious/Rare Adverse Reactions

• Electrolyte and Metabolic Disturbances: Chronic or excessive use of stimulant or osmotic laxatives, particularly magnesium salts, sodium phosphate, and stimulants, can cause hypokalemia, hyponatremia, hypermagnesemia (in renal impairment), hyperphosphatemia, hypocalcemia, and metabolic acidosis or alkalosis. These disturbances can lead to cardiac arrhythmias, neuromuscular irritability, and renal impairment.
• Ischemic Colitis and Severe Cramping: Associated with stimulant use, particularly in high doses or susceptible individuals.
• Melanosis Coli: A benign, reversible pigmentation of the colonic mucosa associated with chronic anthraquinone use.
• Steatorrhea and Vitamin Deficiencies: With chronic mineral oil use.
• Acute Phosphate Nephropathy: A serious renal injury associated with sodium phosphate bowel preparations, characterized by nephrocalcinosis and acute kidney injury, particularly in patients with underlying renal disease, dehydration, or using medications like ACE inhibitors or NSAIDs.
• Allergic Reactions: Rare but possible, particularly to plant-derived agents like psyllium or senna.

No traditional laxative currently carries a FDA Black Box Warning. However, sodium phosphate bowel prep products carry strong contraindications and warnings regarding renal injury and electrolyte disturbances.

Drug Interactions

Laxatives can interact with other medications through pharmacokinetic and pharmacodynamic mechanisms.

Major Drug-Drug Interactions

• Altered Absorption of Oral Medications: This is the most significant and common interaction. By accelerating gastrointestinal transit, stimulant and osmotic laxatives can reduce the time available for absorption of co-administered drugs. Bulk-forming agents can adsorb other drugs, impairing their absorption. It is generally recommended that other oral medications be taken at least 1-2 hours before or after these laxatives. Mineral oil can impair the absorption of fat-soluble vitamins and drugs.
• Electrolyte Imbalances Potentiating Drug Effects: Laxative-induced hypokalemia can potentiate the effects of digoxin (increasing risk of toxicity) and antiarrhythmic drugs. It can also enhance the neuromuscular blocking effects of non-depolarizing muscle relaxants and the toxic effects of drugs like lithium.
• Antacids and Gastric pH: Enteric-coated bisacodyl tablets can be dissolved prematurely in an alkaline stomach environment caused by antacids, milk, or proton pump inhibitors, leading to gastric irritation and cramping.
• Diuretics and Other Drugs Causing Hypokalemia: Concurrent use with loop or thiazide diuretics, corticosteroids, or amphotericin B can have additive effects in causing hypokalemia.
• Opioid Analgesics: Opioids cause constipation, antagonizing the effect of laxatives. This interaction is the rationale for using PAMORAs.

Contraindications

Absolute contraindications are based on the risk of serious adverse events.

• Bowel Obstruction, Ileus, or Acute Abdominal Pain of Unknown Origin: Laxatives of any kind are contraindicated, as they may exacerbate obstruction or cause perforation.
• Severe Inflammatory Bowel Disease (e.g., severe ulcerative colitis, Crohn’s colitis): Stimulant laxatives are contraindicated due to risk of toxic megacolon or exacerbation.
• Specific Agent Contraindications:
  • Sodium Phosphate: Contraindicated in patients with renal impairment (GFR < 30 mL/min), congestive heart failure, ascites, pre-existing electrolyte imbalances, or bowel obstruction.
  • Magnesium Salts: Contraindicated in severe renal impairment (risk of hypermagnesemia).
  • Mineral Oil: Contraindicated in dysphagia, impaired gag reflex, or history of aspiration (risk of lipid pneumonia).
  • Bulk-forming agents: Contraindicated in patients with esophageal or intestinal strictures, or difficulty swallowing.
  • Prucalopride: Contraindicated in patients with severe renal impairment requiring dialysis.

Special Considerations

Pregnancy and Lactation

Constipation is common during pregnancy. The choice of laxative must balance efficacy with fetal safety. Bulk-forming agents (psyllium) and osmotic laxatives (lactulose, PEG) are generally considered first-line due to minimal systemic absorption. Docusate is also widely used and considered safe. Stimulant laxatives (bisacodyl, senna) are sometimes used short-term but are generally recommended as second-line due to theoretical concerns about uterine stimulation (from prostaglandin release or direct irritant effect) and the potential for electrolyte imbalance. Castor oil is contraindicated in pregnancy due to its potent stimulant effect. Mineral oil should be avoided as it may impair maternal absorption of fat-soluble vitamins. Most laxatives are poorly absorbed, so exposure to the infant via breast milk is minimal, but stimulants should be used cautiously.

Pediatric Considerations

Functional constipation is a frequent issue in children. Osmotic laxatives, particularly PEG without electrolytes (PEG-3350), are the mainstay of both disimpaction and maintenance therapy due to their efficacy, safety, and palatability (often flavored). Lactulose is also commonly used. Stimulant laxatives like senna or bisacodyl may be used for short periods or as rescue therapy. Dosing is weight-based. Emphasis is placed on behavioral modifications and dietary fiber. Mineral oil is used cautiously in older children but avoided in infants and those with risk of aspiration.

Geriatric Considerations

The elderly are particularly susceptible to constipation due to polypharmacy, decreased mobility, comorbid conditions, and age-related changes in colonic function. They are also more vulnerable to adverse effects. Bulk-forming agents must be used with caution due to risk of impaction if fluid intake is inadequate and potential swallowing difficulties. Osmotic laxatives like lactulose or PEG are often preferred. Stimulants should be used at low doses and for short durations to avoid electrolyte disturbances, to which the elderly are more prone. Special caution is required with sodium phosphate in elderly patients, who often have decreased renal function. Mineral oil carries a high aspiration risk in this population.

Renal and Hepatic Impairment

Renal Impairment: Magnesium-containing laxatives are contraindicated in severe renal impairment (risk of hypermagnesemia leading to muscle weakness, arrhythmias, and CNS depression). Sodium phosphate preparations are contraindicated due to risk of hyperphosphatemia, hypocalcemia, and acute phosphate nephropathy. Other osmotic agents like lactulose and PEG are generally safe, as they are not absorbed. Docusate and bulk formers are also safe. Dose adjustment for renally excreted systemic agents like prucalopride may be necessary.

Hepatic Impairment: Lactulose is a therapeutic agent in hepatic encephalopathy. Other laxatives should be selected with care in patients with advanced liver disease and portal hypertension, as electrolyte disturbances (particularly hypokalemia) can precipitate or worsen encephalopathy. Bulk-forming agents may theoretically increase the risk of esophageal variceal bleeding in patients with significant portal hypertension and varices, though evidence is limited.

Summary/Key Points

• Laxatives and purgatives are classified by mechanism into bulk-forming, osmotic, stimulant, stool-softening, lubricant, and novel agent classes, each with distinct pharmacodynamic and pharmacokinetic profiles.
• The primary mechanisms involve increasing intraluminal water content (osmotic agents, bulk formers), directly stimulating colonic motility and secretion (stimulants), or altering stool consistency (softeners, lubricants). Novel agents target specific receptors (5-HT₄, GC-C, Cl^– channels) or peripheral opioid receptors.
• Onset of action varies from 15 minutes (bisacodyl suppository) to several days (bulk formers, novel agents), critically informing their selection for acute relief versus chronic management or bowel preparation.
• Therapeutic applications extend from chronic functional and opioid-induced constipation to bowel cleansing and hepatic encephalopathy, with agent selection guided by indication, speed, and safety profile.
• Adverse effects are generally gastrointestinal but can be serious, including electrolyte disturbances (osmotic, stimulants), renal injury (sodium phosphate), aspiration pneumonia (mineral oil), and cathartic colon with chronic stimulant abuse.
• Significant drug interactions primarily involve reduced absorption of concomitant oral medications and additive risks of electrolyte imbalances.
• Special populations require tailored approaches: osmotic/bulk agents are first-line in pregnancy and pediatrics; the elderly are vulnerable to electrolyte shifts and aspiration; magnesium and phosphate salts are contraindicated in renal impairment.

Clinical Pearls

• For chronic constipation, a stepwise approach starting with lifestyle modification, then bulk-forming or osmotic laxatives, is recommended before intermittent stimulant use.
• Polyethylene glycol (PEG) solutions are the preferred agents for bowel preparation due to their favorable safety profile regarding electrolyte balance.
• Stimulant laxatives should generally be reserved for short-term or “rescue” use to avoid tolerance and potential for harm with chronic daily use.
• Always assess for contraindications (obstruction, ileus, severe IBD) before prescribing a laxative.
• In opioid-induced constipation unresponsive to traditional laxatives, consider a peripherally acting μ-opioid receptor antagonist (PAMORA).
• Patient education on adequate fluid intake with bulk-forming agents and realistic expectations regarding onset of action is crucial for adherence and safety.

References

1. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.
2. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
3. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. New York: McGraw-Hill Education; 2021.
4. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill Education; 2023.
5. Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 4th ed. Philadelphia: Wolters Kluwer; 2017.
6. Trevor AJ, Katzung BG, Kruidering-Hall M. Katzung & Trevor's Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill Education; 2022.
7. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
8. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.