Constipation: Pathophysiology & Treatment

• Michael A. Zappone, Pharm.D., Assistant Professor, Department of Pharmacy Practice, presented these notes on February 4, 2025.

Learning Objectives

• Recognize the definition, pathophysiology, and causes of constipation.
• Recall exclusions for self-treatment of constipation.
• Review indications, dosing, and potential drug interactions for nonprescription medications that treat constipation.
• Evaluate a patient with constipation symptoms and determine if a medical referral is needed.
• Design patient-specific self-care plans using both nonpharmacologic and pharmacologic therapies for constipation concerns.

Constipation Overview

• General definition: Fewer than three bowel movements per week with straining or difficult passage of hard, dry stools.
• Common symptoms include straining, hard stools, small stools, incomplete bowel evacuation and decreased stool frequency.
• Most likely to experience constipation: persons >65 (5 times more likely than younger adults), women (3 times more likely than men), late-term pregnancy, postpartum and nonwhite ancestry.
• Constipation treatment goals include relieving constipation, restoring normal bowel function within one week and establishing dietary and exercise habits to prevent recurrence
• Promote the safe and effective use of laxative products if indicated.

Pathophysiology of Constipation

• Food ingested passes:
  • First into the stomach, where it remains for ~3 hours (partially digested.)
  • Through peristaltic waves into the duodenum.
  • Then into the small intestine, where it remains for ~3 hours.
  • Next into the large intestine (nondigestible material).
  • Into the sigmoid colon where fecal matter is stored until defecation.
  • Finally into the rectum (internal anal sphincter relaxation, where fecal matter is propelled).
• Voluntary tightening of muscles and relaxation of external anal sphincter allows stool to passes.

Causes of Constipation

• Primary causes: slower than normal GI transit time and defecatory disorders (e.g., pelvic floor dysfunction).
• Secondary causes include structural abnormalities; systemic, neurologic, and psychological conditions; inadequate fluid / dietary fiber intake; failing to empty at appropriate times; lack of exercise and medications.

Clinical Presentation of Constipation

• Self-reported decreased frequency or difficulty passing stools.
• Other symptoms include anorexia, headache, lethargy, low back pain, abdominal discomfort, bloating, flatulence, and psychosocial distress.

Constipation Treatment

• Occasional, temporary constipation can usually be managed with self-care measures.
• Continuing constipation or concurrent conditions require sustained therapy.
• Long-standing or untreated constipation can lead to hemorrhoids, anal fissures, rectal prolapse, fecal impaction, rectal ulcers, and blood pressure/cardiac rhythm disturbances.
• General treatment approach: Lifestyle changes, increased fiber/fluid intake, regular exercise and consider medication for more immediate relief .
• The FDA limits nonprescription products use to short-term (<7 days) treatment.
• Medical evaluation should be sought if rectal bleeding occurs or if constipation persists despite appropriate laxative use.

Exclusions for Self-Treatment of Constipation

• Marked abdominal pain, distention, cramping, flatulence, fever, nausea, and/or vomiting.
• Chronic medical conditions that may preclude self-care laxative treatment (e.g., paraplegia, quadriplegia, inflammatory bowel disease, colostomy).
• Daily laxative use (excluding fiber-based therapies).
• Unexplained changes in bowel habits with weight loss.
• Blood in stool or dark, tarry stool.
• Marked change in stool character (e.g., pencil-thin stool).
• Any bowel symptoms persisting >2 weeks or recurring over 3 months.
• Symptoms recurring after dietary/lifestyle changes or laxative use, inflammatory bowel disease, anorexia, and age <2 years.

Nonpharmacologic Therapy

• Balanced diet (fruits, vegetables, and whole grains)
• Exercise
• "Bowel Training"
• Daily dietary fiber intake recommendations: 25 g for adult women, 38 g for adult men
• Drink eight 8-ounce glasses of fluids per day; pregnant and lactating women should drink an additional 300-1000 mL of fluid, respectively.
• If dietary modifications are ineffective, consider commercial fiber supplements.

Types of Fiber Supplements

• Classified as bulk-forming laxatives: Methylcellulose (Citrucel), Calcium polycarbophil (FiberCon), and Psyllium (Metamucil).
• Classified as dietary supplements: Inulin (FiberChoice, Metamucil Clear & Natural), Partially hydrolyzed guar gum (Sunfiber), Powdered cellulose (Unifiber), and Wheat dextrin (Benefiber).

Pharmacologic Therapy

• Bulk-Forming: Calcium polycarbophil, methylcellulose, psyllium
• Hyperosmotic: PEG 3350, glycerin
• Emollient: Docusate sodium, docusate calcium
• Lubricant: Mineral oil
• Saline: Magnesium citrate, magnesium hydroxide, dibasic sodium phosphate, monobasic sodium phosphate, magnesium sulfate
• Stimulant: Sennosides, bisacodyl

Bulk-Forming Laxatives

• This class includes methylcellulose, psyllium, and calcium polycarbophil.
• Mechanism of action is similar to the natural process of producing a bowel movement.
• these are agents most often recommended for constipation.
• Useful for patients who should avoid straining or have low-fiber diets.
• Onset of action is 12-24 hours and can take up to 72 hours.
• Separate administration by 2 hours from other medications (can interfere with drug absorption).
• Adverse effects are minimal when used as directed; abdominal cramping and flatulence are most common.
• Cautions: Take with at least 8 oz. of fluid or swelling/choking in the throat can occur.
• Avoid in patients with swallowing difficulties.
• Patients with intestinal ulcerations, stenosis, or disabling adhesions should not take these.
• Use with caution in patients with fluid restrictions.
• Calcium polycarbophil can contain up to 150 mg (7.6 mEq) calcium per tablet.

Hyperosmotic Laxatives

• Includes Polyethylene glycol 3350 (PEG 3350)
  • Recommended dose is 17 g of powder mixed into 4-8 ounces of water, once daily as needed.
  • Onset of action is 12-72 hours and may take as long as 96 hours.
  • No clinical drug interactions.
  • Few adverse effects, but can include abdominal discomfort, cramping, bloating, and flatulence.
  • Patients with renal disease or irritable bowel syndrome should seek primary care provider approval before use.
  • Self-care use in patients 17 years of age or older.
• Glycerin
  • Available as a suppository for lower bowel evacuation.
  • Onset of action is 15-30 minutes to stimulate a bowel movement.
  • Safe for use in patients 2 years of age and older, with different adult and pediatric doses.
  • Adverse effects limited, but can include rectal irritation; avoid in patients with preexisting rectal irritation.

Emollient Laxatives

• Also known as "Stool Softeners."
• Includes docusate sodium and docusate calcium, with no clinical difference between the two.
• Can be used to prevent straining/painful defecation with anorectal disorders.
• Onset of action is 12-72 hours but can take 3-5 days to see effect.
• Not absorbed and does not hamper absorption of nutrients.
• Rare adverse effects (unless larger-than-recommended doses are taken).
• More often used in combination with a stimulant laxative.
• Do not take with mineral oil.

Lubricant Laxatives

• Mineral Oil (liquid petrolatum) is the only nonprescription lubricant
• Onset of action is 6-8 hours (oral administration) and 5-15 minutes (rectal administration).
• Adverse effects include impaired absorption of fat-soluble vitamins (ADEK), oil leakage through anal sphincter, anal pruritus and cryptitis.
• A drug interaction can occur with docusate.
• After oral administration, patients should not lie down because of the risk of lipid pneumonia from aspiration.
• Not for use in patients less than 6 years old, pregnant women, bedridden patients, older adults, and individuals with swallowing difficulties.
• Repeated use may elicit a typical foreign body reaction
• Should avoided if possible (risks generally outweigh benefits of use)

Saline Laxatives

• Include magnesium citrate, magnesium hydroxide, dibasic sodium phosphate, monobasic sodium phosphate, and magnesium sulfate.
• Oral magnesium hydroxide is appropriate for occasional constipation in otherwise healthy patients as it promotes a bowel movement within 30 minutes-6 hours.
• Other products (e.g., magnesium citrate) can be used for colonoscopy prep, promoting a bowel movement within 30 minutes-3 hours for oral doses and 2-15 minutes for rectal doses.
• Drug-drug interactions can occur with magnesium-containing laxatives.
• Patients who are not on fluid restriction should follow oral doses of magnesium salts with at least 8 ounces of water (to prevent dehydration.)
• No more than one nonprescription sodium phosphate product should be used in a 24-hour period.
• Adverse effects include abdominal cramping, nausea, vomiting, and dehydration; with long-term or at high doses, electrolyte imbalances can occur. Cautions
• Magnesium sulfate (Epsom salt) should be avoided.
• Magnesium-containing laxatives should be avoided in patients on restricted diets and in persons at increased risk for magnesium toxicity.
• Sodium phosphate-containing products should be used cautiously in patients with renal impairment/restricted diets and those taking medications affecting electrolyte levels
• Sodium phosphate products are contraindicated in patients with congestive heart failure.
• Rectally-administered sodium phosphate products should be avoided in patients with megacolon, GI obstruction, imperforate anus, or colostomy.

Stimulant Laxatives

• Includes sennosides, bisacodyl, and castor oil*.
• Combination products, including docusate (stool softener), are used synergistically.
• Onset of action for oral products is generally 6-10 hours but may take up to 24 hours; bisacodyl suppositories usually produce a bowel movement within 15-60 minutes.
• Adverse effects include electrolyte/fluid deficiencies, loss of protein, malabsorption, severe cramping, and hypokalemia.
• Bisacodyl can also be a component of a colonoscopy bowel preparation regimen.
• Senna may color urine pink to red, red to violet, or red to brown.
• Overdoses require prompt medical attention; symptoms include nausea, diarrhea, sudden vomiting, and abdominal cramping
• High dosages can cause cramping, increased mucus secretion, and excessive evacuation of fluid.

Clinically Important Drug-Drug Interactions With Nonprescription Laxative Agents

• Bulk-forming laxatives (e.g., psyllium): Separate dosing of prescription oral medications by at least 2 hrs due to interference with drug absorption with digoxin, anticoagulants, salicylates, and potentially other oral drugs.
• Docusate salts: Avoid concurrent use with mineral oil due to increased absorption of mineral oil.
• Magnesium citrate: Avoid oral magnesium citrate within 1-3 hours with fluoroquinolone and tetracycline antibiotics to decreased drug absorption with fluoroquinolone and tetracycline antibiotics.
• Magnesium hydroxide: Separate dosing by at least 2 hours (for most agents) due to decreased oral bioavailability and/or rate or extent of drug absorption with captopril, cefdinir, some oral bisphosphonates, gabapentin, iron salts, nitrofurantoin, phenothiazines, phenytoin, and rosuvastatin.
• Magnesium hydroxide: Avoid magnesium hydroxide for at least 4 hours before or up to 3 hours after due to decreased drug absorption with ketoconazole, itraconazole, fluoroquinolone, tetracycline antibiotics, and levothyroxine the interacting agent.
• Bisacodyl: Avoid milk products or interacting drugs within 1 hour before or after. Premature dissolution of the bisacodyl enteric coating which leads to gastric irritation or dyspepsia with Milk products or drugs that raise gastric pH (e.g., proton pump inhibitors).

Product Selection Guidelines

• Bulk-Forming Laxatives are often recommended as the initial treatment choice (most closely duplicates the normal process). They may take up to 72 hours or longer for onset of effect.
• PEG 3350 also is considered a first-line agent, especially if a bulk-forming agent is ineffective or inappropriate.
• If PEG 3350 is unable to produce a satisfactory response, a stimulant (e.g., bisacodyl) should be considered.
• Patients who fail to achieve a therapeutic response after 7 days of self-treatment require medical referral.

Complementary Therapy

• Dietary supplements used to treat constipation include flaxseed, aloe, cascara, and probiotics.
• The safety and effectiveness of these products varies.
• Aloe and cascara in nonprescription stimulant laxative products are banned by the FDA.
• If a stimulant laxative is indicated, FDA-approved products should be chosen.

Special Populations: Pregnancy

• Constipation is common in pregnancy, and dietary measures are first-line.
• Laxatives should be added only after nondrug approaches have been tried.
• Bulk-forming laxatives are recommended initially with additional fluid intake. Alternatively, some health care providers recommend PEG 3350 first-line due to its low systemic absorption.
• Docusate can be used for patients with primarily dry, hard stools.
• Short-term bisacodyl or sennosides use is considered low-risk. Some health care providers prefer these agents because of greater availability of data for use in pregnancy.
• Castor oil, mineral oil, and saline laxatives should be avoided because of other risks. Castor oil leads to uterine contraction and rupture.

Special Populations: Breastfeeding

• Laxatives can be used postpartum to reestablish normal bowel function and docusate can be used immediately following delivery to minimize straining.
• Sennosides, bisacodyl, PEG 3350, and docusate are considered compatible with breastfeeding, as they are negligibly absorbed or do not accumulate in significant concentration in breast milk.
• Castor oil and mineral oil should be avoided.

Special Populations: Pediatric Patients

• Before recommending a laxative product, identify and address potential causes. Common ones include unavailability of toilet facilities, chronic medical conditions, emotional distress, febrile illness, fear of defecation, pain, family conflict and change in routine.
• Mild constipation can often be relieved with dietary or behavioral modifications.
• Nonprescription laxatives approved in children ages 2 to <6 include docusate sodium, magnesium hydroxide, and sennosides. Rectal use of glycerin, mineral oil, and sodium phosphate products.
• Oral docusate (or magnesium hydroxide) are first-line if occasional relief is needed in this age group.
• Pediatric glycerin suppositories can be recommended for faster relief.
• Nonprescription products approved for children ages 6-12 include methylcellulose, calcium polycarbophil, psyllium powder, docusate sodium, mineral oil, magnesium citrate, magnesium hydroxide, magnesium sulfate, sennosides, bisacodyl, and castor oil.
• PEG 3350 is not approved for use in those younger than 17 years old. Rectal use of glycerin suppositories, mineral oil, sodium phosphate, and bisacodyl are also approved.
• In Children ages 6-12: bulk-forming agents, docusate, or magnesium hydroxide should be used first-line; oral stimulants are reserved for when these fail.
• Magnesium sulfate and castor oil safety haven't been demonstrated so should be avoided in this age group.

Special Populations: Geriatric Patients

• Older adult patients are at a greater risk of constipation.
• Lifestyle modifications are first-line therapy, but are considered in the context of comorbid conditions.
• If interventions are shown to be ineffective, bulk-forming laxatives are appropriate as a first-line.
• If this is not possible, doesn't provide enough relief, or if a faster onset of action is desired, PEG 3350 works as a first-line.
• Mineral oil should be avoided because of aspiration pneumonia risk, and saline laxatives should be avoided from risk of electrolyte imbalance.
• Rectal enemas may be appropriate for fecal impaction is suspected, used sodium phosphate products need to be used with caution.

Patient Education

• Include a balanced diet with fruits, vegetables, and whole grains.
• Increase insoluble fiber (e.g., fruits, vegetables, wheat bran, whole grains) to minimize GI irritation.
• The goal is 25-38 grams of fiber per day.
• Patients should increase fluid intake by 2 L/day when taking dietary fiber.
• Encourage dietary fiber supplements can be used to increase fiber intake if dietary modifications are not sufficient.
• Schedule bowel training (strongest 30 minutes of day and after a meal). Low physical levels have been associated with constipation.
• Bowel habit frequency and patterns vary.
• Advise that Daily bowel movements are not a physical necessity. Limiting the use of unnecessary laxatives.
• When taking bulk forming laxatives mix with at least 8oz of fluid for each dose to avoid intestinal blockage while consuming quickly after mixing. -Advise patients with diabetes to choose sugar-free formulations options when choosing a laxative if applicable.
• PEG 3350 should be mixed in 4-8 oz. of cold to room temperature liquids.
• When taking Saline laxatives take an additional 8oz of water to prevent dehydration.
• Don't chew or break apart or give with substances that increase gastric pH with medications like a Enteric Saline to help prevent gastric irritation.
• Soft gel versions should not be mixed with antacids due to risk erosions and the need to decrease effectiveness.
• Suggest medical referral if rectal bleeding occurs, constipation persists despite therapy (>7 days), bowel habits abruptly change (>2 weeks), an individual with abdominal cramping, distention occur that may lead to appendicitis.

Assessing a Pharmacy Patient

• A patient asking for assistance from the pharmacy counter.
• Determine decreased stool frequency or passing stool more frequently.
• Obtain more information subjectively from assessment and encourage for individual to evaluate against their normal baseline.
• What stool and consistencies are normal?
• What are the patient's current bowel movement status, color consistency ect?
• How long has this occurred for, the length of time impacts treat-ability.
• Therapy is indicated for several weeks and months for concomitan and conditions therapy is indicate.
• Are there any Exclusion for self-Treatment being displayed, a review of what to do and not to do for the patient.
• Medications being administered , if a patient uses laxative daily they need primary care immediately.
• Is there anything causing the condition or an alternative being used to help with the current medical care.
• Review the different medications and a possibility of potential therapies depending on care.
• If paraplegia or quadriplegia are occurring this needs to be addressed more by their care provider. -Children under 2 years of age should be administered to a pediatrician.

Clinical Pearls:

• Don't give laxatives when exclusions are being display.
• Specific situation should be addressed, as well as age that may impact needed care . Diet,exercise and the correct fluid help will promote simple constipation needs.
• 3350 PEG are great choices but can take 72 hours depending on working and providing faster relief.
• Avoid most laxatives with an excess of 2 hours.
• Laxative treatment should be administered to any individual.