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Author: Paul Abourjaily

1. Objectives: Drugs for Constipation & Diarrhea

  1. Identify drugs commonly used to control symptoms of constipation and diarrhea.

  2. State the mechanisms of action for each of the categories of drugs used for treating symptoms of constipation and diarrhea.

  3. List the most common side effects and drug interactions associated with drugs used to control symptoms of constipation and diarrhea.

2. Medications to manage symptoms of constipation

2.1. Bulk forming agents

  • Plant-derived

    • Psyllium

  • Semi-synthetic

    • Methylcellulose

    • Polycarbophil

The drugs in this category serve as extra sources of fiber and work by increasing stool mass and fluidity. They exhibit little-to-no systemic absorption and thus are considered quite safe.

The most common side effects are GI-related and include bloating and abdominal pain. They should be avoided if obstruction is suspected.

Pharmacokinetic interactions of drug absorption are a common concern.

2.2. Softeners/Surfactants

  • Docusate

  • Mineral oil

The drugs in this category work as emollients to soften the stool and lower surface tension allowing for easier passage. They are not very effective cathartics.

Docusate is usually taken as an oral pill and is generally well tolerated.

Use of mineral oil is unusual given side effects (e.g., foreign body reactions, aspiration, leaking) and drug interaction potential (reduced absorption of fat soluble vitamins).

2.3. Osmotic Agents

  • Saline-based

    • Magnesium salts

    • Phosphate salts

  • Sugar/alcohol-based (non-absorbable)

    • Lactulose, Sorbitol, Mannitol liquids

    • Glycerin suppositories

  • Polyethylene glycol (PEG) solutions

The drugs in this category produce osmotically-mediated water retention which simulates peristalsis.

The main side effects are GI-related and include abdominal pain and distension and flatulence. Saline laxatives need to be used with caution in those with underlying renal or cardiovascular disease and in those with underlying electrolyte disorders or prescribed diuretics.

2.4. Stimulant Agents

  • Diphenylmethanes

    • Bisacodyl

  • Anthraquinones

    • Aloe

    • Cascara

    • Senna

The drugs in this category work to promote migrating colonic contractions.

Role for chronic use is controversial due to concerns of reduced bowel tone and subsequent development of laxative dependency. Pseudomelanosis coli is a relatively benign condition caused by some stimulant laxatives.

Aloe and cascara laxatives removed from U.S. market for failure to prove safety and efficacy.

Phenolphthalein-containing agents removed from OTC market by FDA in 1990s due to controversial carcinogenicity concerns.

2.5. Miscellaneous Agents

  • Lubiprostone

The newest drug approved for treatment of chronic idiopathic constipation.

Available as oral pills that act locally on the apical membranes of the GI tract to activate chloride channels and increase intestinal fluid secretions.

The most common side effect is nausea, which can be minimized by taking with food and reducing the dosing frequency if needed (from twice per day to once per day).

Other common side effects include abdominal pain, flatulence, diarrhea, and headache.

Recommendations are to avoid in pregnancy based on an increased risk of fetal loss associated with use of the drug in animal models.

  • Tegaserod

Use became restricted by FDA in 2007 due to cardiovascular safety concerns.

It is usually dosed twice a day by mouth.

3. Medications to manage symptoms of diarrhea

3.1. Bulk forming and Binding Agents

Includes the bulk forming agents listed above plus

  • Cholestyramine

    • Bile acid bidning resin that was originally indicated for treatment of dyslipidemia (LDL lowering agent)

  • Bismuth subsalsalicylate

    • See section on acid suppressive theriapies for more on this drug

3.2. Antimotility Agents

  • Opioid derivates

    • Loperamide

  • Diphenoxylate + atropine

The drugs in this category work to slow intestinal transit by binding as agonists at opioid receptors throughout the GI tract. Other central opioid effects and side effects are uncommon due to poor CNS penetration.

Loperamide is kept out of the CND via a P-glycoprotein transporter pump and thus has essentially no potential for abuse. It is available without a prescription.

Diphenoxylate will penetrate the blood brain barrier at high doses and thus carries some degree of abuse potential. It requires a prescription and is classified as a schedule V controlled substance.

3.3. Anitsecretory Agents

  • Octreotide

Peptide analog of somatostatin that inhibits secretion of serotonin, gastrin, vasoactive intestinal polypeptide, insulin, and other hormones.

Can be effective for relieving various types of secretory diarrhea.

Also can be useful for treatment of variceal bleeding.

Administration limited to parenteral route.

Most common side effects include nausea, bloating, and injection site reactions.

Chromic use also sometimes associated with impaired glucose control and gallstones.

3.4. Miscellaneous Agents

  • Clonidine

A centrally action alpha-2 receptor agonist that reduces sympathetic outflow.

Side effects include hyptension and rebound hypertension if abruptly discontinued.

Other side effects include sedation and dry mouth.

Available only by prescription, usually as oral tablets or as a pathc for topical administration.

  • Alosetron

Serotonin receptor modulator (5HT3 antagonist) indicated for treatment of irritable bowel syndrome in women when the primary symptom is diarrhea.

Most common side effect is constipation.

Most serious side effect concern is the possible development of ischemic colitis. Use is restricted to registered providers for this reason.

Please refer to the following texts for supplemental reading material on the drugs covered in this lecture:

  • Basic & Clinical Pharmacology, 10th ed. Katzung, Bertram G., ed. Los Altos, Calif.: Lange Medical Publications, 2007. Chapter 63.

  • Goodman & Gilman's the pharmacological basis of therapeutics, 11th ed. Brunton, Laurence L., ed. New York: McGraw-Hill, c2006. Section VI, Chapter 37.