Laxatives

Definition

Laxatives are a pharmacological group of agents used to promote bowel movements or relieve constipation. They act through a variety of mechanisms to soften stools, increase stool bulk, enhance motility, or draw fluid into the bowel. Laxatives are used for therapeutic, diagnostic, and prophylactic purposes in both acute and chronic gastrointestinal conditions.

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Classification of Laxatives (According to Mechanism of Action)

Laxatives are broadly categorized into the following classes:

1. Bulk-forming laxatives

2. Osmotic laxatives

3. Stimulant (contact) laxatives

4. Stool softeners (emollient laxatives)

5. Lubricant laxatives

6. Saline laxatives

7. Prokinetic agents (less commonly classified under laxatives)

8. Peripheral opioid receptor antagonists (for opioid-induced constipation)

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1. Bulk-Forming Laxatives

Mechanism: These agents absorb water in the intestine to form a viscous liquid or gel that promotes peristalsis by increasing fecal bulk.

Common Agents:

• Psyllium (Metamucil)

• Methylcellulose (Citrucel)

• Calcium polycarbophil

Therapeutic Use:

• Chronic constipation

• Irritable bowel syndrome (IBS-C)

• Maintenance of regular bowel habits

Onset of Action: 12–72 hours

Adverse Effects:

• Bloating

• Flatulence

• Risk of obstruction if not taken with adequate fluid

Precautions:

• Contraindicated in fecal impaction or intestinal obstruction

• Caution in patients with swallowing difficulties

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2. Osmotic Laxatives

Mechanism: Retain water in the intestinal lumen via osmotic activity, leading to increased stool liquidity and volume.

Subtypes:

a. Non-absorbable sugars

• Lactulose

• Sorbitol

• Lactitol

b. Polyethylene glycol (PEG)

• PEG 3350 (MiraLAX)

c. Saline osmotic agents

• Magnesium hydroxide (Milk of Magnesia)

• Magnesium citrate

• Sodium phosphate (Fleet enema)

Therapeutic Use:

• Bowel preparation before colonoscopy

• Chronic constipation (PEG, lactulose)

• Hepatic encephalopathy (lactulose)

Onset of Action:

• Oral: 0.5 to 6 hours

• Rectal: 15 minutes to 1 hour

Adverse Effects:

• Electrolyte imbalance

• Abdominal cramps

• Dehydration (with saline agents)

• Hypermagnesemia (especially in renal impairment)

Contraindications:

• Renal failure (avoid Mg-containing agents)

• Congestive heart failure (risk with sodium phosphate)

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3. Stimulant (Contact) Laxatives

Mechanism: Stimulate enteric nerves to increase intestinal motility and alter electrolyte transport to increase fluid in the bowel.

Common Agents:

• Senna (Senokot)

• Bisacodyl (Dulcolax)

• Castor oil (less commonly used)

Therapeutic Use:

• Short-term constipation

• Bowel preparation

• Opioid-induced constipation (as part of combination therapy)

Onset of Action:

• Oral: 6–10 hours

• Rectal: 15–60 minutes

Adverse Effects:

• Abdominal cramping

• Electrolyte disturbances

• Dependency with long-term use

• Melanosis coli (harmless pigmentation of colon)

Precautions:

• Avoid chronic use unless supervised

• Not for routine daily use

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4. Stool Softeners (Emollient Laxatives)

Mechanism: Lower surface tension of stool, allowing water and lipids to penetrate and soften fecal mass.

Common Agents:

• Docusate sodium (Colace)

• Docusate calcium

• Docusate potassium

Therapeutic Use:

• Prevention of straining (post-surgery, postpartum, cardiovascular disease patients)

• Hemorrhoids

• Adjunct in opioid therapy

Onset of Action: 12–72 hours

Adverse Effects:

• Mild GI cramping

• Rare diarrhea

• Hypersensitivity

Limitations:

• Ineffective in severe constipation

• Primarily prophylactic

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5. Lubricant Laxatives

Mechanism: Coat stool surface to reduce water absorption from fecal mass and facilitate easier passage.

Common Agent:

• Mineral oil

Therapeutic Use:

• Short-term treatment of constipation

Onset of Action:

• Oral: 6–8 hours

• Rectal: 2–15 minutes

Adverse Effects:

• Aspiration pneumonitis (especially in elderly or bedridden)

• Impaired absorption of fat-soluble vitamins (A, D, E, K)

• Anal leakage

Contraindications:

• Children under 6 years

• Pregnancy (risk of hemorrhagic disease due to vitamin K malabsorption)

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6. Saline Laxatives

Mechanism: Contain ions (e.g., Mg²⁺, SO₄²⁻, PO₄³⁻) that draw water into the bowel and stimulate intestinal motility.

Examples:

• Magnesium citrate

• Magnesium sulfate (Epsom salt)

• Sodium phosphate (Fleet)

Uses:

• Rapid bowel evacuation

• Bowel cleansing pre-endoscopy

Risks:

• Electrolyte disturbances

• Dehydration

• Nephropathy (particularly with sodium phosphate in elderly or renal disease)

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7. Peripheral Opioid Antagonists

Mechanism: Block peripheral µ-opioid receptors in the gut without affecting central analgesia.

Examples:

• Methylnaltrexone (Relistor)

• Naloxegol (Movantik)

• Naldemedine (Symproic)

Indication:

• Opioid-induced constipation (OIC) in adults with chronic non-cancer or cancer pain

Onset of Action: Typically within 4 hours

Side Effects:

• Abdominal pain

• Diarrhea

• Flatulence

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8. Miscellaneous Agents

• Lubiprostone: Activates Cl⁻ channels (CIC-2) → increases intestinal fluid secretion. Used in chronic idiopathic constipation, IBS-C, and OIC.

• Linaclotide & Plecanatide: Guanylate cyclase-C agonists → increase cGMP → enhanced secretion and motility.

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Indications for Laxative Use

• Acute constipation

• Chronic idiopathic constipation

• Irritable bowel syndrome with constipation (IBS-C)

• Opioid-induced constipation

• Pre-operative bowel evacuation

• Avoidance of straining (e.g., after myocardial infarction, rectal surgery, or in pregnancy)

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Contraindications to Laxative Use

• Bowel obstruction or perforation

• Inflammatory bowel disease (active flare)

• Appendicitis

• Undiagnosed abdominal pain

• Electrolyte imbalance (for osmotic/saline laxatives)

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Risks and Complications of Chronic Use

• Laxative dependence

• Electrolyte imbalances (hypokalemia, hypomagnesemia)

• Dehydration

• Melanosis coli (senna, chronic use)

• Loss of normal bowel function

• Colonic inertia

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Drug Interactions

• Mineral oil: Reduces absorption of fat-soluble vitamins and can interfere with warfarin.

• Stimulants + diuretics: Additive risk for hypokalemia.

• Sodium phosphate: Enhances nephrotoxicity when used with NSAIDs or ACE inhibitors.

• Docusate: Should not be used with mineral oil (increased absorption of mineral oil → toxicity).

• Methylnaltrexone: Should not be used with GI obstruction or perforation.

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Patient Counseling Points

• Encourage adequate fluid intake and dietary fiber to enhance the effect of bulk-forming agents.

• Avoid chronic use of stimulant laxatives unless under medical supervision.

• Review medications causing constipation (e.g., opioids, anticholinergics, iron, calcium).

• Warn patients about the timing of bowel movements post-administration.

• Instruct patients using rectal preparations on proper positioning and retention.

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Pregnancy and Lactation

• Bulk-forming agents and docusate are generally considered safe.

• Avoid stimulants, saline laxatives, and mineral oil unless absolutely necessary.

• PEG is considered relatively safe if hydration is maintained.

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Examples of Common Brand Names

Agent	Brand Name(s)
Psyllium	Metamucil
Polyethylene Glycol	MiraLAX, MoviPrep
Senna	Senokot, Ex-Lax
Bisacodyl	Dulcolax
Docusate	Colace
Lactulose	Enulose, Kristalose
Magnesium citrate	Citroma
Methylnaltrexone	Relistor
Naloxegol	Movantik
Lubiprostone	Amitiza
Linaclotide	Linzess

Emerging Trends and Research

• Novel agents: Development of selective intestinal chloride channel activators and guanylate cyclase-C agonists is expanding.

• Microbiome interaction: Understanding the gut microbiota’s role in constipation has led to research on probiotics and prebiotics.

• Bowel training and digital interventions: Apps and behavioral therapy are being combined with pharmacologic regimens to reduce over-reliance on laxatives.