This chapter is to assist candidates preparing for the Pharmacy Examining Board of Canada (PEBC) exams by providing a clear and in-depth understanding of constipation, a common yet multifaceted clinical condition encountered in pharmacy practice. Constipation is broadly defined as unsatisfactory defecation that may manifest through infrequent stools, difficulty in passing stools, or a combination of both.​ Its classification is rooted in pathophysiology and encompasses three primary types:

1. Slow transit constipation,

2. Defecatory disorders (such as pelvic floor dysfunction or dyssynergia), and

3. Normal transit (functional) constipation, which is often the most prevalent form.​

Functional constipation can be further understood through the Rome IV diagnostic criteria, a standardized tool that ensures precise identification and categorization of this condition. 

Notably, irritable bowel syndrome (IBS), particularly the subtype characterized by constipation (IBS-C), closely parallels functional constipation. However, IBS-C is distinguished by an additional hallmark: abdominal pain associated with bowel movements. The detailed discussion of IBS-C in this chapter (refer to the section on Irritable Bowel Syndrome) will highlight its clinical distinctions and overlap with functional constipation.​

It is important to emphasize that constipation is a symptom rather than a disease. This distinction underscores the significance of identifying and addressing its underlying causes, which forms the cornerstone of effective treatment strategies.

This chapter is structured to equip PEBC candidates with not only a theoretical foundation but also practical insights into the clinical aspects of constipation. Through detailed explanations and evidence-based guidance, it aims to enhance the candidate's confidence and competence in addressing this condition in pharmacy practice.

Rome IV Diagnostic Criteria for Functional Constipation

To diagnose functional constipation, patients must meet two or more of the following criteria for at least three months (with symptom onset occurring at least six months before diagnosis):

1. Lumpy or hard stools in more than 25% of defecations.

2. Straining during more than 25% of defecations.

3. Fewer than three spontaneous bowel movements per week.

4. A sensation of incomplete evacuation in more than 25% of defecations.

5. A sensation of anorectal obstruction or blockage during more than 25% of defecations.

6. The need for manual maneuvers (e.g., digital evacuation, pelvic floor support) to facilitate defecations in more than 25% of cases.

Additionally, the diagnosis excludes cases where loose stools (without laxative use) are present and ensures that criteria for irritable bowel syndrome (IBS) are not met.

For PEBC candidates, this table serves as a critical reference for diagnosing functional constipation, emphasizing the importance of distinguishing it from overlapping conditions like IBS.

Goals of Therapy

The overarching aim of therapy is to improve the patient’s quality of life by addressing the underlying causes and preventing complications. The specific goals include:

1. Establishing regular bowel function: Restoring a normal frequency and ease of defecation is the primary objective, especially for patients suffering from chronic symptoms.

2. Abolishing the need to strain and preventing adverse effects of straining: Straining can lead to severe complications such as:

• Hernias

• Gastroesophageal reflux disease (GERD)

• Hemorrhoidal prolapse

• Bladder or uterine prolapse in females

• Increased risk of coronary or cerebrovascular dysfunction, particularly in elderly patients.

3. Preventing complications: Common complications of untreated or poorly managed constipation include:

• Hemorrhoids

• Anal fissures

• Rectal prolapse

• Stercoral ulcers (caused by pressure and irritation in the colon/rectum)

• Fecal impaction and fecal incontinence

4. Treating complications: In cases where complications such as fecal impaction or intestinal obstruction arise, immediate and effective treatment is necessary.

Assessment 

1. Patient History

A thorough patient history is essential and should focus on:

• Definition of normal bowel routine: How often it's normal to poop can vary. Anywhere from three times a day to three times a week can be healthy. But your stools should never be painful or hard to pass. Your diet, your water intake, and your activity can all affect how often you poop. You can try changing your diet and activity or using an OTC medication for mild problems. More severe or sudden changes may require a visit to a healthcare professional. Use tools such as the Bristol Stool Form Scale to objectively evaluate stool characteristics.

• Duration of constipation: Helps differentiate between acute and chronic presentations.

• Symptoms of distress: Include infrequency, straining, hard stool, unusual toilet postures, the need for digital manipulation, or feelings of incomplete evacuation. Additional symptoms like bloating and abdominal pain should also be noted.

• Relevant medical and surgical history: Prior surgeries, structural abnormalities, dietary habits, physical inactivity, and conditions associated with constipation (e.g., hypothyroidism, diabetes mellitus, systemic sclerosis).

• Medication history: Identify constipating drugs (e.g., opioids, anticholinergics, calcium supplements, or iron).

2. Physical Examination

This includes:

• Abdominal and rectal examination: Assess for masses, tenderness, or signs of anorectal abnormalities such as hemorrhoids or fissures.

• Pelvic floor assessment: Identify dysfunctions like dyssynergia.

3. Laboratory Tests

Recommended only if systemic diseases are suspected. Investigations may include:

• Complete blood count (CBC) to rule out anemia.

• Serum electrolytes, calcium levels, and thyroid-stimulating hormone (TSH) to identify metabolic or endocrine causes.

4. Imaging and Endoscopy

Routine lower endoscopy (e.g., colonoscopy) is not typically recommended unless specific conditions are present:

• Alarm symptoms: Such as unexplained weight loss, anemia, rectal bleeding, or recent onset of constipation in patients over 50 years of age.

• Failed first-line management: Symptoms unresponsive to pharmacological treatment.

• Family history of colorectal cancer. Advanced imaging modalities like CT colonography are occasionally considered for further evaluation.

5. Psychological Assessment

In cases where psychological factors such as depression or anxiety are suspected, a mental health evaluation may be warranted.

6. Specialized Diagnostic Tests

These are reserved for chronic refractory constipation:

• Transit studies: Use radiopaque markers to evaluate colonic transit time.

• Defecography: Standard or MR imaging assesses pelvic floor dysfunction or dyssynergic defecation.

• Anorectal manometry: Measures sphincter function and rectal sensory response.

Bristol Stool Form Scale

The Bristol Stool Form Scale is a widely used clinical tool to categorize stool consistency. It aids in identifying the type of constipation or diarrhea based on stool appearance:

Red Flag 

Identifying red flag symptoms is essential in differentiating benign causes of constipation from serious underlying conditions. These symptoms indicate the need for further investigation or specialist referral:

1. GI bleeding: Visible blood in the stool (hematochezia or melena) suggests gastrointestinal pathology such as colorectal cancer or severe hemorrhoidal disease.

2. Unexplained iron-deficiency anemia: Often linked to chronic blood loss, particularly from the gastrointestinal tract.

3. Unintentional weight loss: A significant red flag for malignancies or systemic illnesses.

4. Palpable abdominal mass: May indicate tumors, fecal impaction, or other structural abnormalities.

5. Family history of colon cancer: Raises suspicion for hereditary conditions like Lynch syndrome.

6. Symptom onset at ≥50 years of age: New-onset constipation in older adults requires thorough evaluation for colorectal cancer or other age-associated diseases.

7. Sudden or acute change in bowel habits: Can signal obstruction, ischemia, or other urgent conditions.

Drugs with Constipating Effects

Certain medications are well-known to exacerbate or cause constipation. Pharmacists must be able to recognize these agents and recommend appropriate management strategies.

1. Antacids containing aluminum or calcium: Commonly found in over-the-counter remedies like aluminum hydroxide and calcium carbonate (e.g., Tums).

2. Anticonvulsant agents: Medications like phenytoin and carbamazepine can reduce intestinal motility.

3. Antiparkinsonian agents: Dopaminergic medications, such as levodopa-carbidopa, are associated with slowed gut transit.

4. Antipsychotic agents: Drugs such as olanzapine and clozapine, with anticholinergic properties, often lead to constipation.

5. Antispasmodics: Reduce smooth muscle contractions, contributing to delayed bowel movements.

6. Bismuth preparations: Frequently used for diarrhea and ulcers, e.g., bismuth subsalicylate (Pepto-Bismol).

7. Diuretics causing hypokalemia: Potassium depletion can impair bowel motility, e.g., furosemide, hydrochlorothiazide.

8. Drugs with anticholinergic properties: Common in antihistamines (e.g., diphenhydramine) and tricyclic antidepressants (e.g., amitriptyline).

9. Drugs with neurotoxicity: Examples include checkpoint inhibitors and vincristine, which can impair nerve function in the GI tract.

10. Iron-containing products: Often prescribed for anemia, e.g., ferrous sulfate or ferrous gluconate.

11. Opioids: Potent constipating agents like codeine, morphine, and oxycodone reduce peristalsis by binding to gut opioid receptors.

12. Resins: Such as cholestyramine, used to treat hyperlipidemia or diarrhea, can slow intestinal transit.

13. Serotonin receptor antagonists: Ondansetron, commonly used for nausea, is a frequent cause of constipation.

14. Sucralfate: An anti-ulcer medication that forms a protective barrier, often causing reduced bowel movements.

15. Verapamil: A calcium channel blocker used for hypertension and arrhythmias, known for its constipating side effect.

Nonpharmacologic Choices

Nonpharmacologic approaches focus on lifestyle and dietary modifications, forming the first line of treatment for constipation. These methods should be encouraged alongside pharmacologic therapy when necessary.

1. Dietary Modifications:

• Increase dietary fiber intake to 25–38 g/day through sources such as legumes, whole grains, vegetables, fruits, flaxseeds, and unprocessed bran.

• Recommendation: Gradual increases in fiber are necessary to minimize side effects like bloating, gas, or cramping.

• Suggested fluid intake: 2.2–3 L/day to complement fiber intake.

2. Behavioral Modifications:

• Encourage establishing a regular toilet schedule, e.g., after breakfast.

• Advise against prolonged straining during bowel movements.

• Suggest raising the legs on a footstool while defecating to straighten the anorectal angle and facilitate evacuation.

• Promote regular physical activity to enhance gastrointestinal motility.

3. Discontinuation of Constipating Drugs:

• When feasible, stop medications contributing to constipation or explore alternative therapies.

4. Advanced Nonpharmacologic Therapies:

• For pelvic floor dysfunction or dyssynergic defecation, consider:

• Physiotherapy.

• Biofeedback therapy (neuromuscular retraining for normal defecation).

• Digital stimulation or the use of glycerin suppositories in cases of severe impairment.

Pharmacologic Choices

Pharmacologic interventions are employed when nonpharmacologic measures prove insufficient. Treatment options vary depending on the severity and underlying cause of constipation.

1. Bulk-Forming Agents:

• Example: Psyllium.

• Safe for long-term use but must be taken with adequate hydration.

• Effective for mild constipation and patients with normal colonic transit.

2. Osmotic Laxatives:

• Examples: Polyethylene glycol (PEG), lactulose, and magnesium citrate.

• PEG is preferred due to superior efficacy, especially in geriatric populations, and greater improvements in stool form, frequency, and pain relief.

3. Stimulant Laxatives:

• Examples: Bisacodyl, senna.

• Effective for acute or chronic constipation but may cause cramping or diarrhea.

• Evidence suggests bisacodyl may outperform other secretagogues in increasing bowel movement frequency.

4. Secretagogues:

• Linaclotide: Stimulates fluid secretion into the intestine and increases spontaneous bowel movements. Indicated for chronic idiopathic constipation and IBS-C but associated with diarrhea as a side effect.

• Prucalopride: A serotonin 5-HT4 receptor agonist that improves bowel movements and reduces constipation severity. Should be considered when standard laxatives fail.

5. Rectal Interventions:

• Suppositories (e.g., glycerin) and enemas (e.g., sodium phosphate) are recommended for immediate relief in cases of fecal impaction.

Management of Opioid-Induced Constipation (OIC)

OIC requires a tailored approach due to the mechanism of opioids inhibiting colonic peristalsis.

1. General Measures:

• Dietary fiber and bulk-forming agents are typically insufficient for OIC.

• Consider opioid rotation or dose reduction where possible, as different opioids may vary in their constipating effects.

2. Specific Pharmacologic Interventions:

• Osmotic and stimulant laxatives: Often first-line options.

• Naloxegol: A peripherally acting μ-opioid receptor antagonist. It improves spontaneous bowel movements without affecting analgesia.

• Methylnaltrexone: Another peripheral opioid antagonist used for OIC.

• Linaclotide and prucalopride: May be considered for refractory OIC.

Management of Constipation During Pregnancy

1. Nonpharmacologic Approaches

• Encourage lifestyle modifications such as increased dietary fiber intake, adequate hydration, and regular physical activity. These are first-line measures and form the foundation of safe management.

2. Pharmacologic Options

• Bulk-Forming Agents:
  Psyllium is the preferred first-line agent due to its non-systemic absorption. When taken with sufficient fluids, it improves stool consistency and frequency while softening stools.

• Magnesium-Containing Laxatives:
  Second-line option for persistent constipation. Magnesium-based laxatives, such as magnesium hydroxide, can also alleviate heartburn, a common symptom during late pregnancy.

• Stimulant Laxatives:
  Short-term use of senna or bisacodyl may be recommended for severe cases when other options fail. These agents stimulate bowel motility but should be used cautiously.

• Osmotic Laxatives:
  Polyethylene glycol (PEG) and lactulose may be considered if dietary modifications and bulk-forming agents are insufficient.

3. Medications to Avoid During Pregnancy

• Docusate: Ineffective for relieving constipation.

• Linaclotide: Insufficient data for use in pregnancy.

• Prucalopride: Not recommended due to limited safety data.

• Castor Oil: Known to induce premature uterine contractions.

• Mineral Oil: Can interfere with absorption of fat-soluble vitamins and may cause lipoid pneumonia if aspirated.

Management of Constipation During Breastfeeding

1. Nonpharmacologic Approaches
   Similar to pregnancy, focus on dietary fiber, hydration, and exercise to improve bowel habits.

2. Pharmacologic Options

• Bulk-Forming Agents:
  Psyllium remains the preferred choice as it is safe, cost-effective, and non-systemically absorbed.

• Second-Line Options:
  Magnesium hydroxide can be used if bulk-forming agents are insufficient.

• Stimulant Laxatives:
  Senna and bisacodyl are safe for short-term use in breastfeeding women.

3. Medications to Avoid During Breastfeeding

• Docusate: Ineffective for constipation management.

• Linaclotide: Insufficient safety data for breastfeeding use.

• Prucalopride: Not recommended due to limited data on its safety.

• Other Laxatives: Lack of safety data regarding transfer into breast milk.

Therapeutic Tips for Safe Management

1. Conduct a detailed assessment to identify potential underlying causes of constipation before initiating treatment.

2. Encourage patients to increase dietary fiber intake alongside sufficient fluid consumption and regular physical activity.

3. Advise patients to monitor symptoms and seek medical attention for complications like rectal bleeding or fecal impaction.

4. Use laxatives judiciously to avoid side effects and ensure adherence to the safest options for pregnancy and breastfeeding.

Algorithm for Constipation Management

1. Initial Patient Assessment

• Complaint of Constipation: Begin by obtaining a comprehensive history to understand the patient’s usual bowel habits and their definition of constipation.

• Determine Constipation: If the patient is not constipated:

• Reassure and educate the patient.

• If Constipated: Proceed to evaluate underlying causes.

2. Identify Medical or Drug-Related Causes

• Investigate if an identifiable medical condition (e.g., hypothyroidism, diabetes) or medication (e.g., opioids, anticholinergics) is causing constipation.

• If Yes: Optimize the management of the identified condition or drug.

• If No: Proceed to assess for red flags.

3. Screen for Red Flags

• Evaluate for serious symptoms like GI bleeding, anemia, unintentional weight loss, or a palpable mass (refer to Table 2).

• If Red Flags Present: Further assessment and treatment are required.

• If No Red Flags: Check for IBS-C criteria.

4. Evaluate for IBS-C (Irritable Bowel Syndrome with Constipation)

• Use established criteria (e.g., Rome IV) to determine if IBS-C is the diagnosis.

• If IBS-C: Refer to therapeutic guidelines specific to IBS-C management.

• If Not IBS-C: Focus on general constipation management.

5. Lifestyle Modifications

• Recommend increased fluid intake, dietary fiber, and regular exercise as the first-line intervention.

• Assess response to lifestyle changes:

• If effective, continue these measures.

• If ineffective, evaluate fiber intake.

6. Assess Fiber Intake

• Inadequate Fiber: Introduce a bulk-forming agent like psyllium.

• Adequate Fiber: Proceed with a trial of osmotic laxatives (e.g., lactulose, magnesium citrate, or polyethylene glycol [PEG]) for 4–8 weeks, alongside fiber supplementation.

7. Refractory Cases: Rescue Therapy

• If laxatives are ineffective:

• Consider rescue therapies, such as:

• Glycerin suppositories.

• Stimulant laxatives (e.g., bisacodyl).

• Enemas.

• Alternatively, trial linaclotide or prucalopride for 8–12 weeks.

8. Refer for Further Assessment: If all measures fail, refer the patient for advanced evaluation and treatment.

Definitions:

1. Emollients:

• Function: Soften stool by incorporating water and fats.

• Use: Primarily recommended for patients needing to avoid straining (e.g., post-rectal surgery, myocardial infarction, unstable angina, or perianal disease).

• Notes: Limited evidence supports efficacy; not ideal for acute constipation.

2. Stimulants:

• Function: Enhance peristalsis and increase fluid and electrolyte transport into the colon.

• Use: Typically avoided in chronic use due to the risk of bowel habituation, but short-term use is appropriate for specific conditions (e.g., long-term opioid use, cancer patients).

3. Lubricants:

• Function: Coat the stool to prevent water reabsorption from feces.

• Use: Short-term relief only; avoid bedtime use to reduce aspiration pneumonia risk.

• Notes: May interfere with absorption of fat-soluble vitamins.

4. Bulk-Forming Agents:

• Function: Increase stool weight and consistency, improve transit time, and boost bowel movement frequency.

• Use: Safe for long-term use but requires adequate hydration.

• Notes: Effects may take 2–3 months in cases of chronic functional constipation.

5. Hyperosmotics:

• Function: Draw fluid into the intestines via osmosis to stimulate peristalsis.

• Use: Safe for chronic constipation; preferred options include polyethylene glycol (PEG 3350) for better tolerability compared to lactulose.

• Notes: Avoid in cases where straining must be minimized (e.g., opioid-induced constipation).

6. Saline Laxatives:

• Function: Increase water content in the intestines; stimulate intestinal motility.

• Use: Reserved for specific cases (e.g., pre-surgery bowel evacuation). Avoid in kidney or heart failure patients due to risks of dehydration and electrolyte imbalances.

• Notes: Magnesium hydroxide is an exception for milder cases.