Which opioid causes more sphincter of Oddi contraction?

Which Opioid Causes More Sphincter of Oddi Contraction

Morphine causes significantly more sphincter of Oddi contraction than other opioids, with pethidine (meperidine) demonstrating the least effect and even showing inhibitory properties.

Comparative Effects of Opioids on Sphincter of Oddi

Morphine - Highest Risk

• Morphine produces the most pronounced sphincter of Oddi spasm among commonly used opioids 1, 2, 3
• Morphine increases the frequency of sphincter contractions from 2.4 to 7.9 contractions (P<0.001), representing a more than 3-fold increase 2
• Morphine significantly elevates basal pressure of the sphincter of Oddi (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), and common bile duct pressure (CBDP) 4, 3
• The FDA label explicitly warns that morphine "may cause spasm of the sphincter of Oddi" and recommends monitoring patients with biliary tract disease for worsening symptoms 1

Hydromorphone - High Risk

• Hydromorphone similarly causes sphincter of Oddi spasm, as it acts through the same mu-opioid receptor mechanism as morphine 5
• The FDA label states that hydromorphone "may cause spasm of the sphincter of Oddi" and cautions use in patients with biliary tract disease 5

Fentanyl - Moderate Risk

• Fentanyl can cause sphincter of Oddi spasm, though the FDA label notes this as a precaution rather than a contraindication 6
• Fentanyl "may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease" 6

Pethidine (Meperidine) - Lowest Risk

• Pethidine demonstrates the opposite effect, actually inhibiting sphincter of Oddi contractions 2, 3
• Pethidine decreases contraction frequency from 1.5 to 0.8 contractions (P<0.05), representing a 47% reduction 2
• This inhibitory response is blocked by atropine, suggesting an anticholinergic mechanism 2
• Research shows "no apparent change" or even decreased sphincter activity with pethidine at regular doses 3
• This pharmacological difference provides the rationale for preferring pethidine over morphine in patients with biliary pain 2

Tramadol - Inhibitory Effect

• Tramadol shows an inhibitory effect on sphincter of Oddi motility 3
• Tramadol decreases BPOS from 7.01 mmHg to 2.87 mmHg and reduces amplitude of contractions from 63.34 mmHg to 45.90 mmHg (10 min) and 35.97 mmHg (20 min) 3

Ap-237 - High Risk

• Ap-237 (a synthetic opioid) increases BPOS, SOF, and SOCA similar to morphine 3

Mechanism of Action

• Opioid-induced sphincter of Oddi dysfunction occurs primarily via activation of enteric mu-opioid receptors 7
• Morphine's effect may involve a two-step mechanism: binding to opiate receptors triggers histamine release, which then acts on H1 receptors to produce sphincter contraction 8
• This histamine-mediated mechanism is antagonized by diphenhydramine and naloxone 8

Clinical Implications

High-Risk Scenarios

• Eluxadoline, a mixed mu- and kappa-opioid receptor agonist, is contraindicated in patients with prior sphincter of Oddi problems or post-cholecystectomy due to risk of sphincter spasm and pancreatitis 7
• Serious adverse events including pancreatitis and sphincter of Oddi spasm occurred in 0.5% of patients treated with eluxadoline in clinical trials 7
• Chronic opium addiction can cause sphincter of Oddi dysfunction as a distinct clinical entity, characterized by dilated bile ducts and delayed contrast drainage 9

Practical Recommendations

• For patients with biliary tract disease or acute pancreatitis requiring analgesia, avoid morphine and consider pethidine or tramadol as alternatives 2, 3
• All opioids can increase serum amylase concentrations, requiring monitoring in susceptible patients 1, 6, 5
• Anticholinergic agents (anisodamine, atropine, buscopan) can antagonize morphine-induced sphincter spasm 4