Do shorter-acting opioids, such as morphine (opioid analgesic) or hydromorphone (opioid analgesic), decrease the risk of opioid-induced constipation?

Shorter-Acting Opioids and Risk of Constipation

Shorter-acting opioids do not significantly decrease the risk of opioid-induced constipation compared to longer-acting formulations, as constipation is primarily related to opioid receptor binding in the gut regardless of duration of action. 1

Mechanism of Opioid-Induced Constipation (OIC)

Opioid-induced constipation occurs when opioids bind to mu receptors in the gastrointestinal tract, resulting in:

• Decreased peristalsis
• Increased water absorption from stool
• Reduced secretion of intestinal fluids
• Increased anal sphincter tone

These effects occur regardless of whether the opioid is short-acting (like immediate-release morphine) or long-acting (like extended-release formulations).

Evidence on Opioid Duration and Constipation

The evidence does not support using shorter-acting opioids to reduce constipation risk:

• According to the ESMO Clinical Practice Guidelines, constipation is a common side effect of all opioids that requires prophylactic management regardless of the opioid's duration of action 1
• The NCCN guidelines emphasize that "constipation can almost always be anticipated with opioid treatment" and recommend prophylactic bowel regimens for all patients on opioids 1

One notable exception is transdermal fentanyl, which may be associated with less constipation than oral morphine according to some evidence, but this is related to its route of administration rather than its duration of action 1.

Management of Opioid-Induced Constipation

Since constipation affects up to 80% of patients taking chronic opioid therapy 1, prophylactic measures should be implemented regardless of which opioid is used:

1. Prophylactic laxative regimen:

   • Stimulant laxatives (senna) with or without stool softeners 1
   • Increase laxative dose when increasing opioid dose 1

2. For persistent constipation:

   • Assess for other causes and rule out obstruction
   • Consider adding osmotic laxatives (polyethylene glycol, lactulose, magnesium citrate)
   • Consider prokinetic agents (metoclopramide)

3. For refractory cases:

   • Consider peripherally acting mu-opioid receptor antagonists (PAMORAs) like methylnaltrexone, naloxegol, or naldemedine 1

Rome IV Criteria for OIC

OIC is defined as new or worsening symptoms when initiating, changing, or increasing opioid therapy, with at least 2 of the following occurring >25% of the time 1:

• Straining
• Lumpy/hard stools
• Sensation of incomplete evacuation
• Sensation of anorectal obstruction
• Manual maneuvers to facilitate defecation
• Fewer than 3 spontaneous bowel movements per week

Clinical Implications and Recommendations

When prescribing opioids for pain management:

1. Do not select opioids based on duration of action to prevent constipation

   • Instead, focus on appropriate pain control and implement prophylactic measures for constipation

2. Implement prophylactic bowel regimens for all patients

   • Stimulant laxatives are recommended as first-line agents 1
   • Maintain adequate fluid intake and dietary fiber when possible

3. Consider opioid rotation if constipation is severe and refractory

   • Some evidence suggests transdermal fentanyl may cause less constipation than oral morphine 1

4. For severe refractory constipation:

   • Consider PAMORAs like naloxegol (strong recommendation, moderate quality evidence) 1
   • Consider naldemedine (strong recommendation, moderate quality evidence) 1

Remember that constipation is the one opioid side effect that typically does not improve over time with continued use 1, making prophylactic management essential regardless of the opioid's duration of action.