constipation

Identify the secondary causes of constipation 

• IBS, diverticulitis

• Hemorrhoids

• CNS disabilities like brain/spinal cord trauma

• Metabolic disorders

  • Diabetes

  • Hypothyroidism 

• Immobility 

• Poor diet 

• Pregnancy 

• Medications

  • Calcium channel blockers

  • Tricyclic antidepressants

  • Opiates

  • Aluminum or calcium containing antacids

  • Iron supplements

Approach to Treatment 

• Self-care, non-pharm first - if appropriate 

• Typically try bulk-forming agents first for treatment 

• Next try other laxatives types based on patient factors

  • Osmotic laxatives

  • Saline osmotic laxatives

  • Stimulant laxatives

• Add on stool softer as needed based on stool consistency 

• May need to be evaluated for food intolerances if no other cause identified

When to seek medical attention

• Patient has alarm symptoms

  • Worsening constipation 

  • Blood in stool 

  • Weight loss

  •  Fever 

  • Anorexia

  • nausea/vomiting

• Symptoms are severe

•  Symptoms last > 3 weeks

• Symptoms are disabling 

• There are significant change in usual bowel habits

Treatment approach 

• If a patient is experiencing slight irregularity (for example, patient usually has a BM every day and now has a BM every few days), start with lifestyle/dietary modifications

  • If effective, these should be continued

  • If slightly effective, but not enough, try a bulk-forming laxative

• If patient has significant constipation (for example, hasn’t had a bowel movement in one week or more), recommend applicable lifestyle/dietary modifications, but for immediate relief, start/choose an appropriate laxative agent

  • Choose laxative based on patient preference (dosage form), taste, indication, desired time of onset, age, etc. 

  • If stool is hard, add a stool softener

Rx indication 

prescribed only after failing lifestyle/dietary modifications and OTC treatments. Some have dangerous side effects and very specific indications, and most are quite costly.

Opioid-induced constipation → Treatment approach

• Prevention is best: start laxative with or without stool softener when beginning opioid therapy (don’t wait for constipation to start)

• Take daily – not PRN – unless diarrhea results

• *Most common agent for opioid-induced constipation = MiraLax (available OTC and generic)

• If OTC agents are ineffective, Rx agent will likely be prescribed

  • Discontinue maintenance laxatives prior to treatment; may reintroduce laxatives as needed if suboptimal response to new agent

  • Discontinue treatment if opioid pain medication is discontinued

Special populations →pediatrics 

• Many products are available with dosing for 6 – 11-year-olds

• Seek evaluation by physician before using products in < 6 years of age

• Assess diet, fluid intake, level of physical activity

  • May need to recommend dietary/lifestyle modifications

• MiraLax commonly used in kids with acute or chronic constipation

  • Can be mixed with drink mix to flavor (like Crystal Light or flavored electrolyte packet) 

  • Better tasting when served cold

• Bisacodyl use is limited in kids due to unpleasant side effect of cramping

Non–pharm 

• Increase fiber intake to 20-35g /day 

• Avoid highly processed low-fiber foods

• Adequate fluid intake 

  • 6-8 glasses per day 

  • Avoid dehydration (alcohol, caffeine)

• Regular walking - increase frequency of walks  

• Counsel on not avoiding the urge to have VM

• Discontinue constipation meds if possible

• Use squatty potty 

Bulk-forming laxatives - OTC

1st line after or with lifestyle modifications

• Indication:

  • Intermittent or chronic constipation

  • Constipation in pregnancy 

• MOA: soluble fibers that absorb water in intestines

  • Forms viscous liquid which promotes peristalsis and reduces transit time 

• Agents:

  • Wheat dextrin (Benefiber)

  • Psyllium (Metamucil)

  • Calcium polycarbophil (FiberCon)

  • Methylcellulose

  • Psyllium husk 

    • Can be found in health food stores 

  • Dosing often in g/day

• Counseling points

  • AEs: flatulence, abdominal cramping, bloating 

  • Take with plenty of water (8oz)

  • Onset of action 12-72 hours (usually 2-3 days)

  • Continue to dose until effect = BM

  • Give one month trial before deciding if success/failure

  • Separate doses by at least 2 hours from other drugs 

Osmotic Laxatives - OTC

MOA: draws water into intestinal lumen → distension → peristalsis

• Lactulose (Enulose, Generlac) 

  • Liquid form 

  • Prescription only 

  • Indication: acute, intermittent, or chronic constipation

    • Also indicated for use in chronic liver disease 

  • Onset: 24-48 hours to produce normal bowel movement 

• Sorbitol 

  • Rectal enema or oral form 

  • Oral not recommended - monitor glucose levels if taken orally 

  • Onset (rectal): 15 minutes to 1 hours 

• Glycerin 

  • Suppository (pedia-Lax) or enema (Fleet)

  • Onset: 15-30 minutes 

• Adult indication: constipation; considered acceptable use in pregnancy 

• Pediatric indications

  • Fecal impaction (used for rapid disimpaction)

  • Constipation 

  • Used in neonatal population as ‘chips’ (chaves pieces from whole suppository)

• Polyethylene glycol (PEG) 3350 (Miralax) - OTC

  • Fine, white powder that must be mixed with liquid 

  • Dosed in grams (17 g per capsule); take daily until effect then taper down

  • Onset: 24-96 hr

  • Indication: 

    • Bowel prep

    • occasional/acute constipation

    • Refractory constipation 

    • Chronic constipation/ opioid-induced constipation 

    • recommended/safe for use in kid and pregnancy 

Counseling points

• AEs: flatulence, abdominal cramping, bloating

• Know expected onset of action to judge effectiveness

• Glycerin and PEG 3350 are not absorbed so systemic side effects not expected

Saline osmotic laxatives - OTC

MOA: electrolytes pull water into lumen of intestines → distension of colon → peristalsis

• Magnesium Citrate (Citroma)

  • Clear liquid/oral solution 

  • Indications: occasional constipation; also used for bowel prep

• Magnesium Hydroxide (Milk of Magnesia, Phillips)

  • Milky, thick suspension is most common form; available as chewable tablets

  • Can be used in children 2 and older

  • Give at bedtime or in divided doses

  • Indications:

    • Occasional constipation 

    • Also has indication as antacid

• Sodium phosphate (Fleet Enema)

  • Clear liquid for rectal enema

  • Warning: hypocalcemia, hypokalemia → QT prolongation 

  • Indication: bowel prep prior to colonoscopy 

  • There is not oral product, but it is NOT recommended due to warning for acute phosphate nephropathy  

Counseling points 

• AEs: accumulation of Mg, Phos in patients with renal dysfunction; abdominal pain; diarrhea; avoid use in heart failure, cirrhosis, and renal impairment 

• Remind patient about onset (0.5 hours to 6 hours)

• To increase palatability, chill oral solution prior to drinking

• Drink full dose – follow with glass of water

Stimulant Laxatives - OTC

MOA: direct irritant to nerve plexus of smooth muscle in intestine → altered water/electrolyte secretion → fluid accumulation → peristalsis

• Bisacodyl (Dulcolax, Correctol)

  • Delayed release oral tablet 

  • Rectal suppository or rectal enema

  • Onset: 6-12 hours (oral); 15 minutes - 1 hr (rectal)

  • Indications:

    • Constipation (acute, intermittent); short-term use

    • Bowel cleansing with enema (commonly used in hospital setting for pre-op bowel prep)

  • Doing available for children down to 3 years old (limited data available)

Counseling points: Bisacodyl

• AEs: cramping, diarrhea

• Bisacodyl (oral)

  • Administer on an empty stomach with glass of water for rapid effect

  • Swallow tablet whole; do not break, chew, or crush

  • Do not administer within 1 hour of antacids, milk, or dairy products

• Bisacodyl (rectal enema)

  • Shake well; remove protective shield, insert tip into rectum gently; squeeze bottle until nearly all liquid expelled. Gently remove and maintain position until the urge to evacuate is strong (usually 5 – 20 minutes).

• Senna (ex-lax, Senokot)

  • Comes in tablets, oral syrup or liquid, chewable tablet, gummies, chocolated form

    • Combination product with docusate = Senokot-S

  • Indications:

    • Constipation (acute, intermittent); short-term use

    • Long-term use for prevention of opioid-induced constipation 

    • Often given with saline laxative for bowel prep regimen

  • Can be used in children 2 and up 

  • Often given at bedtime; administer 2 hours before or after other medications

• Castor oil

  • Oil form 

  • Indications:

    • Bowel evacuation

    • Constipation

  • Onset: 6 – 12 hours

  • Warnings: Do not use in pregnancy for treatment of constipation

  • Take on empty stomach with juice or carbonated beverage

  • Not routinely used due to availability of other products that do not cause electrolyte disturbances; do not use longer than 1 week unless directed by provider

Stool Softener - OTC

MOA: reduces surface tension of oil - water interface → increased incorporation of fat/water → softening of stool; easier to pass

• Docusate

  • Docusate calcium or docusate sodium (Colace, Dulcolax)

  • Oral capsule form most common; rectal enema available; oral liquid can be used for kids

  • Indication:

    • Stool softener

  • Onset: 12 – 72 hours for oral

Counseling points: take with full glass of water; due to potential electrolyte imbalance, should not use long term; unnecessary to use if stool is well hydrated or “mushy” and soft

• Part of “mush” in Mush-and-Push (push = stimulant laxative)

Lubricant - OTC

MOA: coats stool; decrease water reabsorption by colon 

• Mineral oil

  • Indication 

    • Constipation

  • Take oil orally (15 – 45 mL qhs or DD)

  • Caution in elderly and young patients due to aspiration risk

  • Available as enema

  • Prolonged use may decrease absorption of fat-soluble vitamins

Lubiprostone (Amitiza)

MOA: chloride channel activator → increased intestinal fluid secretion and motility 

• Indications: 

  • Chronic idiopathic (unknown cause) constipation

  • IBS-C

• AE: headache, nausea (may decrease nausea by taking with food), diarrhea

• Not safe in pregnancy 

Linaclotide (Linzess)

MOA: results in chloride and bicarbonate secretion in the intestinal lumen → increases fluid in lumen and GI transit increased

• Oral capsule

• Indications:

  • Chronic idiopathic constipation

  • Opioid-induced constipation

• Contraindications: < 2 years of age

• AEs: diarrhea, severe diarrhea; abdominal distension/pain, dyspepsia, flatulence 

Methylnaltrexone bromide (Relistor)

MOA: peripheral acting opioid receptor antagonist in GI tract → inhibits opioid-induced decreased GI motility

• Indication: 

  • Opioid-induced constipation with advanced illness 

  • Opioid-induced constipation with chronic non-cancer pain

• Subcutaneous (SC) injection or oral tablet

• Reduce dose when CrCl < 60 mL/min

• AEs: abdominal pain, flatulence, nausea

Plecanatide (Trulance)

MOA: binds and agonizes guanylate cylase-C in the intestine → increases cGMP  → chloride and bicarbonate secreted into intestinal lumen →  increased intestinal fluid → GI transit time accelerated

• Oral tablet 

• Indications:

  • Chronic idiopathic constipation

  • [Also has indication for IBS-C]

• Contraindicated in patients < 6 years old due to serious (fatal) dehydration; safety not established in patients younger than 18 years old

• AEs: severe diarrhea is most common

Prucalopride (Motegrity)

MOA: 5-HT4 receptor agonist that leads to stimulation of peristaltic reflex → gastrointestinal motility

• Oral tablet Indications:

  • Chronic idiopathic constipation

  • Opioid-induced constipation

• Contraindications: intestinal perforation or obstruction, severe inflammatory conditions of the GI tract

• AEs: abdominal pain, diarrhea, headache

Naldemedine (Symproic)

MOA: peripheral-acting mu-opioid antagonist 

• Oral tablet

• Indication: 

  • Opioid-induced constipation

• AEs: abdominal pain, nausea, gastroenteritis, diarrhea

• Efficacy established in patients taking opioids for > 4 weeks

Naloxegol (Movantik)

MOA: mu-opioid receptor antagonist; limited ability to cross BBB, functions peripherally in GI tract

• Oral tablet

• Indication:

  • Opioid-induced constipation

• AEs: abdominal pain, severe abdominal pain, diarrhea, flatulence, nausea, vomiting, headache

Vibrant Capsule

• MOA: micro-vibrations through colon

• Dosage form: mechanical pill; take 5 days per week

• Indications:

  • Chronic idiopathic constipation

• Contraindicated: bowel obstruction; diverticular disease; gastroparesis, IBD, etc. 

• AEs: abdominal pain/distension/discomfort, N/V, blood in stool, diarrhea, flatulence

• FDA-cleared; drug-free

• Dispensed through specialty pharmacy