Constipation Lecture Notes

Flashcards on Constipation and its Treatment

Constipation

Bowel disorder characterized by difficult, infrequent, or seemingly incomplete defecation that does not meet criteria for irritable bowel syndrome.

Etiology of Constipation

Systemic disorders or drugs; Idiopathic constipation may be associated with normal or slow colonic transit and/or pelvic floor dysfunction.

Chronic Idiopathic Constipation (CIC)

Unsatisfactory defecation and is characterized by infrequent stools, difficult stool passage, or both, present for at least 3 months with symptoms noted for >6 months.

Treatment Principles for Constipation

Dietary modification (increase fiber), exercise, increased fluid intake, correct underlying diseases, address opioid use, and pharmacologic drugs.

Examples of Bulk Forming Laxatives

Psyllium, Polycarbophil, Methylcellulose

How do Bulk Forming Laxatives Work?

Similar to dietary fiber, high-fiber diet should be continued for at least 1 month, with effects noticed in 3 to 5 days.

ADRs of Bulk Forming Laxatives

Abdominal distention and flatus

Example of Emollient Laxatives

Docusate

Uses of Emollient Laxatives

Prevention of constipation, particularly when straining should be avoided.

Adverse effects of Docusate

Mild GI cramping; rashes; throat irritation

Examples of Hyperosmolar Agents

Lactulose, Sorbitol, Glycerin, Polyethylene glycol (PEG), Magnesium salts

MOA of Lactulose

Increases stool frequency and consistency in patients with chronic constipation.

ADRs of Lactulose

flatulence, nausea, and abdominal discomfort or bloating.

MOA of PEG

Causes water retention in the stool, thereby increasing stool frequency.

ADRs of PEG

nausea, vomiting, flatulence, and abdominal cramping.

Examples of Stimulant Laxatives

Senna, Bisacodyl

MOA of Stimulant Laxatives

Stimulate the mucosal nerve plexus of the colon; may also increase intestinal fluid secretion.

ADRs of Stimulant Laxatives

May cause severe abdominal cramping and electrolyte imbalances

Examples of Intestinal Secretagogues

Lubiprostone, Linaclotide, Plecanatide

MOA of Lubiprostone

Chloride channel activator that acts locally in the gut to open chloride channels on the GI luminal epithelium, which, in turn, stimulates chloride-rich fluid secretion into the intestinal lumen.

ADRs of Lubiprostone

Headache, nausea, diarrhea

Uses of Lubiprostone

Chronic idiopathic constipation and opioid induced constipation

Contraindications of Lubiprostone

Known or suspected mechanical gastrointestinal obstruction

Administration Instructions for Linaclotide/Plecanatide

Administer at least 30 minutes before the first meal of the day on an empty stomach.

Contraindications of Linaclotide/Plecanatide

Known or suspected mechanical gastrointestinal obstruction, children <6yrs

1st Line Stimulant Laxatives for OIC

Stimulant Laxatives (ie: Senna or Bisendol) with or without docusate

Examples of Opioids

Morphine, fentanyl, hydrocodone, oxycodone, or hydromorphone

Why do Opioids Cause Constipation?

Opioids bind to specific receptors in the GI tract and central nervous system to reduce peristalsis.

MOA of Prucalopride (Motegrity)

a selective, high affinity 5-HT4 receptor agonist that promotes cholinergic and nonadrenergic, noncholinergic neurotransmission by enteric neurons leading to stimulation of the peristaltic reflex, intestinal secretions, and gastrointestinal motility.

Indication of Prucalopride (Motegrity)

Chronic idiopathic constipation, OIC (off label)

ADRs of Prucalopride (Motegrity)

Abdominal pain, nausea, diarrhea , Headache

Contraindications of Prucalopride (Motegrity)

intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the GI tract (eg, Crohn disease, ulcerative colitis, toxic megacolon/megarectum).

Why should Magnesium Salts not be used on a routine basis?

These agents should not be used on a routine basis as they may cause fluid and electrolyte depletion. Also, magnesium or sodium accumulation may occur in patients with renal dysfunction or congestive heart failure.

MOA of Methylnaltrexone

A mu-receptor antagonist approved for OIC that acts on peripheral mu-receptors to block unwanted opioid side effects such as constipation.

ADRs of Naloxegol

abdominal pain, diarrhea, and nausea.

OIC Treatment Pathway

1. Increase dietary fiber and fluid intake.

2. Initiate a stimulant laxative (e.g., senna or bisacodyl).

3. If response is inadequate, consider a peripherally acting mu-opioid receptor antagonist (PAMORA).

4. Alternative options include lubiprostone or prucalopride, especially if abdominal pain or bloating is prominent.

Examples of PAMORAs

Methylnaltrexone, Naloxegol, Naldemedine

MOA of PAMORAs

Binds to mu-opioid receptors in the GI tract, blocking the constipating effects of opioids without affecting analgesia in the central nervous system.

How to Determine if Constipation is Opioid-Induced

Consider opioid-induced constipation (OIC) if constipation symptoms started or worsened after initiation of opioid therapy. Rule out other causes if possible.

Diagnostic Criteria for Constipation

Rome IV Criteria - Must include two or more of the following:

1. Straining during >25% of defecations
2. Lumpy or hard stools >25% of defecations
3. Sensation of incomplete evacuation >25% of defecations
4. Sensation of anorectal obstruction/blockage >25% of defecations
5. Manual maneuvers to facilitate >25% of defecations (e.g., digital evacuation, support of the pelvic floor)
6. <3 spontaneous bowel movements per week

Loose stools are rarely present without use of laxatives; Insufficient criteria for irritable bowel syndrome

Bristol Stool Chart

Bristol Stool Chart Type 1: Separate hard lumps, like nuts (difficult to pass)

Type 2: Sausage-shaped, but lumpy

Type 3: Like a sausage but with cracks on its surface

Type 4: Like a sausage or snake, smooth and soft

Type 5: Soft blobs with clear-cut edges (passed easily)

Type 6: Fluffy pieces with ragged edges, a mushy stool

Type 7: Watery, no solid pieces. Entirely liquid

Red Flags for Constipation

Alarm features include:

• Rectal bleeding
• Unexplained weight loss
• Anemia
• Family history of colon cancer or inflammatory bowel disease
• Onset of symptoms over age 50

Differential Diagnosis of Constipation

Exclude structural abnormalities (e.g., tumors, strictures) and metabolic disorders (e.g., hypothyroidism, hypercalcemia)

Medication-Induced Constipation

Medications such as opioids, anticholinergics, and certain antihypertensives can contribute to constipation.

MOA of Linaclotide

Guanylate cyclase-C agonist that increases intestinal fluid secretion and motility.

Uses of Linaclotide

Treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C).

ADRs of Linaclotide

Diarrhea, abdominal pain, flatulence, and abdominal distention.

Contraindications of Linaclotide

Known or suspected mechanical gastrointestinal obstruction; avoid use in pediatric patients <6 years of age.

Administration Instructions for Linaclotide/Plecanatide

Administer at least 30 minutes before the first meal of the day on an empty stomach.

Contraindications of Linaclotide/Plecanatide

Known or suspected mechanical gastrointestinal obstruction, children <6yrs

Treatment for OIC

1. Osmotic or stimulant Laxative

2. Lubiprostone or opioid-receptor antagonists

Treatment for Acute Constipation

1. Add osmotic laxative (PEG) if no relief; trial 2-4 weeks

2. Add stimulant laxative if BM in 2 days or no relief

Treatment for Chronic Constipation

Trial of intestinal secretalogue