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 bulk. The distinction between these terms, while sometimes blurred in clinical parlance, traditionally hinges on the intensity of effect: laxatives generally produce a soft-formed stool, whereas purgatives (or cathartics) induce a more forceful, fluid evacuation. The appropriate selection and use of these agents require a thorough understanding of their distinct pharmacological profiles, mechanisms of action, and potential for adverse effects. Their widespread availability as over-the-counter medications often belies the complexity of their actions and the risks associated with misuse, particularly chronic use, which can lead to significant electrolyte disturbances, dependence, and pathological changes in colonic structure and function.

Clinical Relevance and Importance

Constipation is a prevalent symptom with a multifactorial etiology, ranging from functional disorders like irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation to secondary causes such as medication side effects, neurological diseases, and metabolic disorders. The therapeutic goal extends beyond mere evacuation to the restoration of normal, comfortable bowel habits and the improvement of quality of life. Furthermore, these agents are indispensable for bowel preparation prior to diagnostic procedures like colonoscopy or surgical interventions, where efficacy and tolerability are critical. In specific toxicological contexts, certain cathartics are utilized to reduce the absorption of ingested poisons. The pharmacology of these drugs thus intersects with gastroenterology, geriatrics, pediatrics, oncology, and general practice.

Learning Objectives

• Classify major laxative and purgative agents based on their primary mechanism of action and chemical structure.
• Explain the detailed pharmacodynamic mechanisms by which different classes of laxatives alter intestinal fluid dynamics, motility, and stool consistency.
• Analyze the pharmacokinetic properties of key agents, including their absorption, metabolism, and site of action within the gastrointestinal tract.
• Evaluate the appropriate clinical applications for each class, considering factors such as onset of action, indication, and patient-specific variables.
• Identify major adverse effects, drug interactions, and special population considerations to ensure safe and effective prescribing.

Classification

Laxatives and purgatives are systematically classified according to their dominant mechanism of action. This functional classification is most clinically useful for guiding therapeutic selection. A complementary chemical classification exists for agents within these mechanistic groups.

Mechanistic and Chemical Classification

The primary classes include bulk-forming agents, osmotic laxatives, stimulant (contact) laxatives, stool softeners (surfactants), and newer agents with novel mechanisms. The intensity of the laxative effect often increases from bulk-formers to stimulants.

• Bulk-Forming Laxatives: These are natural or synthetic polysaccharides and cellulose derivatives that are poorly absorbed.
  • Psyllium (ispaghula husk)
  • Methylcellulose
  • Polycarbophil
  • Wheat dextrin
• Osmotic Laxatives: These are poorly absorbed solutes that retain water within the intestinal lumen by an osmotic effect. They are subdivided into:
  • Saline Osmotics: Magnesium salts (hydroxide, citrate, sulfate), sodium phosphate, sodium sulfate.
  • Poorly Absorbed Sugars and Alcohols: Lactulose, sorbitol, polyethylene glycol (PEG).
• Stimulant (Contact) Laxatives: These agents directly stimulate colonic enteric neurons and/or smooth muscle to increase propulsive motility and secretion.
  • Diphenylmethane Derivatives: Bisacodyl, sodium picosulfate.
  • Anthraquinones: Senna (sennosides), cascara, aloe.
  • Castor Oil: Ricinoleic acid (a hydroxy fatty acid).
• Stool Softeners (Surfactants): These are anionic detergents that lower surface tension, allowing water and lipids to penetrate the stool.
  • Docusate sodium (dioctyl sodium sulfosuccinate).
• Lubricant Laxatives: These coat the stool and intestinal mucosa to ease passage.
  • Mineral oil (liquid paraffin).
• Chloride Channel Activators and Guanylate Cyclase-C Agonists: These are newer agents with targeted receptor-mediated mechanisms.
  • Lubiprostone (a chloride channel activator).
  • Linaclotide and plecanatide (guanylate cyclase-C agonists).
• Peripherally Acting μ-Opioid Receptor Antagonists: Used specifically for opioid-induced constipation.
  • Methylnaltrexone, naloxegol, naldemedine.

Mechanism of Action

The pharmacological effects of laxatives are mediated through diverse molecular and physiological pathways, primarily within the lumen and wall of the colon. Understanding these mechanisms is fundamental to predicting onset, efficacy, and side effects.

Bulk-Forming Agents

These hydrophilic colloids are neither digested nor absorbed in the small intestine. Upon ingestion with adequate fluid, they dissolve or swell to form a viscous gel or bulk within the intestinal lumen. This increased bulk mechanically distends the bowel wall, which stimulates local stretch receptors and activates the intrinsic myenteric plexus, thereby promoting peristaltic reflex activity. The gel-like consistency also retains water within the stool, softening it and increasing its volume. The effect is physiological, mimicking the action of dietary fiber, and typically results in a formed, soft stool after 12 to 72 hours of consistent use.

Osmotic Laxatives

These agents exert their effect by creating an osmotic gradient that draws water into the intestinal lumen. The increased intraluminal water content softens stool, increases volume, and distends the bowel, stimulating motility.

• Saline Osmotics (Magnesium and Sodium Salts): The divalent (Mg²⁺) or monovalent (Na⁺) cations, along with their anions (e.g., sulfate, phosphate, citrate), are poorly absorbed. Their presence in the lumen establishes a sustained osmotic force, retaining water. Magnesium ions may also stimulate the release of cholecystokinin, which enhances intestinal secretion and motility. Sodium phosphate preparations have a particularly potent osmotic effect and also directly affect colonic epithelial transport.
• Poorly Absorbed Sugars and Alcohols (Lactulose, Sorbitol, PEG): These compounds are neither hydrolyzed nor absorbed in the small intestine. In the colon, colonic bacteria ferment lactulose and sorbitol into short-chain fatty acids (e.g., lactate, acetate) and gases (H₂, CO₂, CH₄). This fermentation process further increases the intraluminal osmotic load and lowers luminal pH. The acidic environment may stimulate colonic peristalsis. Polyethylene glycol (PEG), a large polymer, is non-fermentable and acts as a nearly inert osmotic agent, drawing water into the lumen without significant gas production or electrolyte shifts, making it the gold standard for bowel cleansing.

Stimulant (Contact) Laxatives

This class has a more direct and often more aggressive pharmacological action on colonic function, primarily through interaction with the enteric nervous system and epithelial cells.

• Diphenylmethane Derivatives (Bisacodyl, Sodium Picosulfate): These are prodrugs activated by endogenous enzymes. Bisacodyl is hydrolyzed by intestinal esterases to its active form, BHPM (bis-[p-hydroxyphenyl]-pyridyl-2-methane). Sodium picosulfate is activated by colonic sulfatases. The active metabolites directly stimulate the submucosal and myenteric plexuses of the enteric nervous system, leading to increased colonic peristalsis. They also enhance mucosal secretion of water and electrolytes, likely by stimulating prostaglandin formation and inhibiting Na⁺/K⁺-ATPase activity.
• Anthraquinones (Senna, Cascara): These glycosides (e.g., sennosides) are hydrolyzed by colonic bacteria to active aglycone forms (e.g., rhein anthrone). The active metabolites exert a direct irritant effect on colonic mucosa and stimulate myenteric neurons. They increase colonic motility (mass movements) and inhibit water and electrolyte absorption from the colon, possibly via effects on nitric oxide and prostaglandin pathways. Chronic use can lead to melanosis coli, a benign pigmentation of the colonic mucosa.
• Castor Oil: Hydrolyzed by pancreatic lipase in the small intestine to ricinoleic acid. Ricinoleic acid acts as a direct irritant to the intestinal mucosa and profoundly stimulates intestinal secretion and motility throughout the small and large intestine, leading to a rapid, comprehensive evacuation. Its use is now largely restricted to specific preparations.

Stool Softeners and Lubricants

Docusate Sodium is an anionic surfactant detergent. It lowers the surface tension of the stool-liquid interface, allowing water and lipids to penetrate and soften hard, dry fecal matter. It may also stimulate mild net fluid secretion. Its effect is primarily on stool consistency rather than direct propulsion.
Mineral Oil is a hydrocarbon that is not absorbed or digested. It lubricates the stool and coats the intestinal mucosa, mechanically easing the passage of hard stool. It also impedes colonic water absorption, softening the stool.

Novel Receptor-Targeted Agents

• Lubiprostone: 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 softens stool and stimulates motility. The resulting secretion is isotonic and follows normal physiological secretory pathways.
• Linaclotide and Plecanatide: These are peptide agonists of guanylate cyclase-C (GC-C) receptors on the luminal surface of intestinal enterocytes. Receptor activation increases intracellular cyclic guanosine monophosphate (cGMP), which in turn stimulates the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, leading to increased chloride and bicarbonate secretion and decreased fluid absorption. The increased luminal fluid accelerates transit. Elevated intracellular cGMP may also reduce visceral pain signaling by inhibiting nociceptor activity, providing a dual benefit in IBS-C.
• Peripherally Acting μ-Opioid Receptor Antagonists (PAMORAs): Opioids cause constipation primarily by binding to μ-opioid receptors in the enteric nervous system, inhibiting neurotransmitter release and reducing propulsive motility. PAMORAs such as methylnaltrexone, naloxegol, and naldemedine are designed to antagonize these peripheral receptors without crossing the blood-brain barrier in significant amounts, thereby reversing opioid-induced constipation without compromising central analgesic effects.

Pharmacokinetics

The pharmacokinetic profiles of laxatives are pivotal determinants of their onset of action, duration of effect, and site of activity within the gastrointestinal tract. Most have minimal systemic absorption, confining their actions to the gut lumen.

Absorption

The extent of systemic absorption varies considerably by class. Bulk-forming agents and osmotic laxatives like PEG and lactulose are minimally absorbed, with their actions confined to the gastrointestinal lumen. Saline osmotics (magnesium, phosphate) have low but clinically significant absorption rates; approximately 15-30% of ingested magnesium may be absorbed, which is relevant in renal impairment. Stimulant laxatives like bisacodyl and senna are poorly absorbed as prodrugs but are activated locally within the gut. Their active metabolites may undergo some enterohepatic recirculation. Novel agents like lubiprostone and linaclotide have very low systemic bioavailability (≤0.1% and <0.1%, respectively), as they are designed to act locally on luminal receptors. PAMORAs are absorbed but are engineered to have restricted central nervous system penetration.

Distribution

For the majority of traditional laxatives, distribution is limited to the gastrointestinal tract. Any systemically absorbed component of an osmotic agent (e.g., Mg²⁺, Na⁺, phosphate) distributes in the extracellular fluid. The novel peptide agents like linaclotide are degraded within the gut lumen and are not measurably distributed to tissues.

Metabolism

Metabolism is a key differentiator. Many stimulant laxatives require biotransformation for activation. Bisacodyl is hydrolyzed by endogenous esterases in the small intestine and colon. Sodium picosulfate and anthraquinone glycosides are activated by bacterial sulfatases and glycosidases, respectively, in the colon, explaining their colon-specific action. Lactulose is fermented by colonic flora. Lubiprostone is rapidly metabolized within the intestinal mucosa to inactive metabolites. Linaclotide is metabolized by proteolytic degradation within the GI tract.

Excretion

Unabsorbed portions of all laxatives are excreted in the feces. Systemically absorbed components, such as magnesium ions or metabolites of stimulant laxatives, are primarily eliminated via renal excretion. The elimination half-life (t_1/2) for systemically absorbed components is generally short. For example, the t_1/2 of magnesium is regulated by renal function. The clinically relevant parameter for most laxatives is not plasma t_1/2 but the time to effect, which ranges from 30 minutes to 3 days.

Onset of Action and Dosing Considerations

The onset of action is directly related to the site of activation and mechanism.

• Rapid (0.5 – 3 hours): Saline osmotics, castor oil, stimulant laxatives (when given rectally as suppositories, acting on the distal colon).
• Intermediate (6 – 12 hours): Oral stimulant laxatives (bisacodyl, senna), which require transit to the colon for activation.
• Slow (12 – 72 hours): Bulk-forming agents, stool softeners, lactulose, and oral PEG, which rely on gradual effects on stool consistency and bulk.

Dosing is typically oral, but several agents (bisacodyl, glycerin) are formulated as rectal suppositories or enemas for more rapid, localized effects. Bowel preparation regimens often combine agents (e.g., PEG with bisacodyl or sodium picosulfate) to improve efficacy and palatability.

Therapeutic Uses/Clinical Applications

The selection of a laxative is guided by the indication, desired speed of onset, patient comorbidities, and long-term safety profile.

Chronic Constipation and Functional Bowel Disorders

For chronic idiopathic constipation, bulk-forming agents are considered first-line due to their safety profile and physiological action, but require adequate fluid intake. Osmotic laxatives like PEG and lactulose are effective second-line options for chronic use. Stimulant laxatives are recommended for short-term or intermittent use in chronic constipation due to concerns about tolerance and potential for myenteric nerve damage with chronic daily use. For irritable bowel syndrome with constipation (IBS-C), the GC-C agonists linaclotide and plecanatide are FDA-approved and are preferred due to their dual action on motility and abdominal pain. Lubiprostone is also approved for IBS-C in women and chronic constipation.

Bowel Preparation

Thorough colonic cleansing is essential for colonoscopy and colorectal surgery. High-volume (3-4 L) PEG-based solutions are the most commonly used and are considered safe for most patients due to minimal electrolyte shifts. Low-volume PEG regimens are often combined with stimulant laxatives (bisacodyl or sodium picosulfate) to improve adherence. Sodium phosphate preparations are effective but carry a risk of acute phosphate nephropathy and significant electrolyte disturbances (hyperphosphatemia, hypocalcemia, hypernatremia), limiting their use to patients with normal renal function and hydration status.

Opioid-Induced Constipation (OIC)

This is a specific and common side effect of opioid therapy. Traditional laxatives are often used initially but may be insufficient. PAMORAs (methylnaltrexone, naloxegol, naldemedine) are specifically indicated for OIC when response to conventional laxatives is inadequate. They are highly effective at restoring bowel function without reversing analgesia.

Other Applications

• Fecal Impaction: Often requires a combination of therapies, including high-dose oral osmotic agents (PEG), rectal enemas (mineral oil, phosphate), and manual disimpaction.
• Dietary Supplementation: Bulk-forming agents serve as fiber supplements.
• Hepatic Encephalopathy: Lactulose is a mainstay of treatment. Its fermentation acidifies colonic contents, which traps ammonia (NH₃) as non-absorbable ammonium ions (NH_4⁺), and its cathartic effect reduces the colonic bacterial load that produces ammonia.
• Prophylaxis in Hospitalized Patients: To prevent constipation in bedridden patients or those on constipating medications.

Adverse Effects

While generally safe when used appropriately, laxatives can produce a spectrum of adverse effects, ranging from mild discomfort to life-threatening conditions, particularly with misuse or in vulnerable populations.

Common Side Effects

These are often mechanism-based and dose-dependent.

• Bulk-Forming Agents: Bloating, flatulence, abdominal distension. Esophageal or intestinal obstruction can occur if taken with insufficient water.
• Osmotic Laxatives: Abdominal cramping, nausea, flatulence, and excessive diarrhea leading to perianal irritation. PEG solutions can cause nausea and bloating due to the large volume. Lactulose and sorbitol cause significant flatulence and cramping from bacterial fermentation.
• Stimulant Laxatives: Abdominal cramping and pain, forceful diarrhea, nausea. Prolonged use can lead to electrolyte disturbances (hypokalemia) and dependence.
• Stool Softeners: Generally well-tolerated; mild abdominal cramping reported.
• Lubricants (Mineral Oil): Lipid pneumonia from aspiration, anal leakage, and impaired absorption of fat-soluble vitamins (A, D, E, K).
• Novel Agents: Lubiprostone: nausea, diarrhea. Linaclotide/Plecanatide: diarrhea, which can be severe and necessitate discontinuation.
• PAMORAs: Abdominal pain, diarrhea, nausea, and hyperhidrosis.

Serious/Rare Adverse Reactions

• Electrolyte and Metabolic Disturbances: Chronic or excessive use of stimulant and osmotic laxatives can cause hypokalemia, hyponatremia, hypermagnesemia (with magnesium salts, especially in renal failure), hyperphosphatemia, hypocalcemia, and metabolic acidosis or alkalosis. These disturbances can lead to cardiac arrhythmias, neuromuscular dysfunction, and renal impairment.
• Acute Phosphate Nephropathy: A form of acute kidney injury associated with sodium phosphate bowel preparations, characterized by nephrocalcinosis. Risk factors include advanced age, dehydration, renal insufficiency, and use of medications affecting renal perfusion (ACE inhibitors, NSAIDs).
• Cathartic Colon: A poorly understood but serious condition attributed to chronic, excessive use of stimulant laxatives, particularly anthraquinones. It is characterized by a dilated, atonic colon with loss of haustrations, resembling chronic intestinal pseudo-obstruction.
• Laxative Abuse Syndrome: Seen in eating disorders like bulimia nervosa. Chronic secretagogue laxative abuse leads to chronic diarrhea, severe electrolyte depletion (notably hypokalemia), metabolic acidosis, and secondary hyperaldosteronism. It can cause renal damage and cardiac arrest.
• Allergic Reactions: Rare but possible, particularly with plant-derived bulk-forming agents (psyllium).
• Melanosis Coli: A benign, reversible brownish-black pigmentation of the colonic mucosa associated with chronic anthraquinone use. It has no known malignant potential.

Black Box Warnings

Formal black box warnings are not common for most traditional laxatives. However, sodium phosphate bowel preparations carry a strong FDA warning regarding the risk of acute phosphate nephropathy. The labeling for linaclotide includes a warning regarding the risk of severe diarrhea and its use being contraindicated in pediatric patients under 6 years of age due to deaths in juvenile animal studies. Plecanatide is also contraindicated in children under 6.

Drug Interactions

Laxatives can interact with other medications through pharmacokinetic and pharmacodynamic mechanisms, potentially altering therapeutic efficacy or toxicity.

Major Drug-Drug Interactions

• Altered Absorption of Oral Medications: By accelerating gastrointestinal transit, most laxatives, particularly stimulants and potent osmotics, can reduce the absorption and bioavailability of co-administered drugs. This is a significant concern for medications with a narrow therapeutic index (e.g., digoxin, warfarin, anticonvulsants, antiarrhythmics, oral contraceptives). A minimum separation of 2-3 hours between dosing is typically recommended.
• Electrolyte Imbalance 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 blockade of non-depolarizing muscle relaxants.
• Mineral Oil: Can impair the absorption of fat-soluble vitamins (A, D, E, K) and medications that are lipophilic.
• Antacids and Proton Pump Inhibitors: Enteric-coated bisacodyl tablets may dissolve prematurely in an alkaline stomach environment if taken with antacids or milk, causing gastric irritation and cramping.
• Diuretics and Corticosteroids: Concurrent use with laxatives that cause potassium loss increases the risk of severe hypokalemia.
• Opioid Analgesics: Their constipating effect is antagonized by all laxatives. PAMORAs specifically reverse opioid-induced constipation without affecting central analgesia.

Contraindications

Absolute contraindications are based on the risk of exacerbating underlying conditions.

• Bowel Obstruction or Ileus: All laxatives are contraindicated, as they can precipitate perforation.
• Acute Abdominal Pain of Unknown Origin, Appendicitis, Inflammatory Bowel Disease (severe flare): Laxatives may worsen inflammation or cause perforation.
• Severe Dehydration or Electrolyte Depletion: Osmotic and stimulant laxatives can exacerbate these conditions.
• Specific Agent Contraindications:
  • Sodium Phosphate: Renal impairment (eGFR < 30 mL/min/1.73m²), congestive heart failure, ascites, bowel obstruction, or colitis.
  • Magnesium Salts: Severe renal impairment (risk of hypermagnesemia).
  • Mineral Oil: Dysphagia or risk of aspiration (due to lipid pneumonia).
  • Bulk-Forming Agents: Esophageal or intestinal strictures, fecal impaction (unless used with copious fluids as part of a disimpaction protocol).
  • Linaclotide/Plecanatide: Pediatric patients under 6 years of age.

Special Considerations

The safety and efficacy profile of laxatives must be carefully evaluated in specific patient populations where altered physiology or increased vulnerability exists.

Pregnancy and Lactation

Constipation is common during pregnancy. The general principle is to use agents with minimal systemic absorption. Bulk-forming agents (psyllium) and stool softeners (docusate) are generally considered first-line due to their local action and long safety record. Osmotic laxatives like PEG and lactulose are also commonly used. Stimulant laxatives (bisacodyl, senna) are sometimes used short-term but are generally avoided for chronic daily use due to theoretical concerns about stimulating uterine activity (though evidence is weak) and potential for electrolyte imbalance. Castor oil is contraindicated due to its potent stimulant effect. Mineral oil should be avoided as it can impair maternal absorption of fat-soluble vitamins. Most laxatives are poorly absorbed, so exposure to the nursing infant via breast milk is minimal, but agents with some absorption (like senna) may cause diarrhea in the infant.

Pediatric Considerations

Functional constipation is a frequent issue in children. Treatment often involves a combination of behavioral modification, dietary changes, and pharmacotherapy. PEG without electrolytes is the osmotic laxative of choice for both disimpaction and maintenance therapy in children due to its efficacy and tolerability. Lactulose is also used. Stimulant laxatives like senna or bisacodyl may be used for short periods or as rescue therapy. Mineral oil is sometimes used orally in children but carries aspiration risk. Rectal suppositories (glycerin) are useful for acute relief. The GC-C agonists linaclotide and plecanatide are contraindicated in children under 6 due to animal toxicity data and are used with caution in older children and adolescents.

Geriatric Considerations

Older adults are particularly susceptible to constipation due to polypharmacy, decreased mobility, comorbid diseases, and age-related changes in colonic motility. They are also more vulnerable to adverse effects. Bulk-forming agents must be used with caution due to the risk of impaction if fluid intake is inadequate and potential swallowing difficulties. Osmotic laxatives, particularly PEG, are often preferred for maintenance. Stimulant laxatives should be used intermittently. The risk of electrolyte disturbances, dehydration, and drug interactions is heightened. Sodium phosphate bowel preparations carry a significantly increased risk of acute phosphate nephropathy in the elderly and should be avoided in those with any degree of renal impairment or dehydration.

Renal and Hepatic Impairment

Renal Impairment: Agents that can cause significant electrolyte shifts or are systemically absorbed and renally excreted require dose adjustment or avoidance. Magnesium-containing laxatives are contraindicated in moderate to severe renal impairment due to the risk of hypermagnesemia, which can lead to neuromuscular and cardiac toxicity. Sodium phosphate preparations are contraindicated. PEG and lactulose are safe as they are not absorbed. Stimulant laxatives may be used with caution, monitoring for hypokalemia. Dose adjustment for PAMORAs like methylnaltrexone may be necessary in severe renal impairment.
Hepatic Impairment: Lactulose is a therapeutic agent for hepatic encephalopathy. Other laxatives should be selected with care to avoid precipitating electrolyte imbalances that could worsen encephalopathy. In patients with ascites, sodium-containing laxatives (e.g., sodium phosphate) should be avoided to prevent fluid retention.

Summary/Key Points

• Laxatives and purgatives are classified by mechanism into bulk-forming, osmotic, stimulant, stool-softening, lubricant, and novel receptor-targeted classes.
• Their primary sites of action are the small and large intestine, where they increase stool water content, bulk, and/or propulsive motility through osmotic, neurostimulatory, or secretory mechanisms.
• Pharmacokinetics are characterized by minimal systemic absorption for most agents, with activation often occurring via bacterial or luminal enzymes in the colon, dictating the onset of action from 30 minutes to 3 days.
• First-line therapy for chronic constipation typically involves bulk-forming or osmotic laxatives (PEG). Stimulant laxatives are recommended for short-term or intermittent use.
• Bowel preparation for colonoscopy commonly utilizes high-volume PEG or lower-volume combinations of PEG with stimulant laxatives, with sodium phosphate reserved for select patients with normal renal function.
• Novel agents like linaclotide (GC-C agonist) and lubiprostone (chloride channel activator) are important for IBS-C, while PAMORAs are specific for opioid-induced constipation.
• Adverse effects range from abdominal cramping and bloating to serious electrolyte disturbances, renal injury (with phosphate preparations), and cathartic colon with chronic stimulant abuse.
• Major drug interactions involve reduced absorption of co-administered oral medications and potentiation of drug toxicity (e.g., digoxin) via electrolyte depletion.
• Special caution is required in pediatric, geriatric, pregnant, and renally impaired patients, with agent selection tailored to minimize risks such as aspiration, impaction, electrolyte shifts, and nephrotoxicity.

Clinical Pearls

• Always assess for underlying causes of constipation before initiating long-term laxative therapy.
• Encourage adequate fluid intake with all laxatives, especially bulk-forming agents, to prevent intestinal obstruction.
• For chronic management, osmotic laxatives like PEG often provide the best balance of efficacy and safety.
• Avoid chronic daily use of stimulant laxatives; reserve them for rescue therapy or short-term needs.
• In opioid-induced constipation unresponsive to conventional laxatives, consider a PAMORA.
• Be vigilant for signs of laxative abuse in patients with eating disorders or unexplained chronic diarrhea and hypokalemia.
• For bowel preparation, assess renal function and volume status to guide the choice between PEG and sodium phosphate-based regimens.

References

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