What are the potential side effects of morphine (opioid analgesic)?

Morphine Side Effects

The most common side effects of morphine are constipation, nausea, and drowsiness, with constipation being the only side effect that persists throughout treatment and requires prophylactic laxative therapy from initiation. 1

Most Frequent Side Effects (Occur in Majority of Patients)

Constipation (Universal and Persistent)

• Constipation is the only morphine side effect that does NOT resolve with continued use and requires mandatory prophylactic treatment from day one. 1
• Prescribe a laxative at treatment initiation combined with dietary advice and adequate hydration. 1
• Point prevalence reaches 88% of patients, with 62% experiencing moderate to severe intensity. 2

Nausea and Drowsiness (Transient)

• Nausea occurs frequently at initiation but typically resolves within days to weeks. 1
• If nausea persists beyond initial days, exclude other causes first, then prescribe an antiemetic for several days. 1
• Drowsiness occurs primarily during dose titration and usually disappears within a few days. 1
• Point prevalence of sedation is 88%, but period prevalence (persistence) is low as tolerance develops rapidly. 2

Serious but Less Common Side Effects

Respiratory Depression

• Respiratory depression risk is LOW in cancer pain patients who are regularly followed and receive continuous morphine for extended periods. 1
• The FDA label identifies respiratory depression as a serious adverse reaction, particularly with concurrent benzodiazepine use. 3
• Monitor especially during initial titration and dose escalations. 3

Neuroexcitatory Effects (High-Dose Phenomenon)

• Allodynia, myoclonus, hallucinations, and cognitive dysfunction occur particularly at high doses due to accumulation of morphine-3-glucuronide (M3G), a toxic metabolite. 1, 4
• Myoclonus has 83% point prevalence but is usually mild. 2
• Critical pitfall: Increasing morphine dose when these symptoms appear WORSENS the problem rather than improving it. 4
• Management requires opioid rotation to structurally dissimilar opioids (methadone or fentanyl) to allow M3G clearance over hours to days. 1, 4

Cardiovascular Effects

• Severe hypotension, circulatory depression, and rarely cardiac arrest can occur. 3
• These are more common with rapid intravenous administration. 3

Additional Side Effects

Common (>10% incidence)

• Dry mouth (95% point prevalence, most persistent symptom with 20% period prevalence). 2
• Dizziness, lightheadedness, sweating, and vomiting. 3, 5

Endocrine and Metabolic

• Adrenal insufficiency (more common after >1 month of use). 3
• Androgen deficiency with chronic use. 3
• Anti-diuretic effect. 3

Less Common but Clinically Significant

• Pruritus, urticaria. 3
• Urinary retention or hesitancy. 3
• Seizures (particularly with toxic metabolite accumulation). 3, 4
• Delayed gastric emptying. 5
• Hyperalgesia (paradoxical pain increase). 1, 5

Critical Clinical Distinctions

What is NOT a Problem in Cancer Pain Patients

• Psychological dependence (addiction) is RARE in cancer patients. 1
• Tolerance and physical dependence are NOT clinical problems in cancer pain management. 1
• Physical dependence is expected and normal; it is NOT addiction. 3

Important Clinical Pearls

• Miosis (pinpoint pupils) indicates morphine use but is NOT a sign of overdose. 1
• Side effect occurrence shows wide inter- and intra-patient variation and is NOT necessarily dose-related. 1
• Most side effects (except constipation) resolve within the first few days to weeks of treatment. 1

Management Algorithm for Persistent Side Effects

If Drowsiness Persists Beyond Initial Days:

1. First, evaluate for metabolic disorders or drug interactions. 1
2. If morphine is confirmed as the cause, reduce dose if pain is well-controlled. 1
3. If pain control is inadequate, perform opioid rotation. 1

If Resistant Side Effects Develop:

• For very unstable, intense pain: switch to intravenous or subcutaneous patient-controlled analgesia. 1
• For stable or moderate pain: consider opioid rotation to fentanyl, hydromorphone, or oxycodone. 1

Special Populations

Renal Failure/Dialysis Patients

• Morphine must be COMPLETELY AVOIDED in dialysis patients due to accumulation of toxic metabolites (M3G) causing severe neurologic toxicity. 6
• Use buprenorphine or fentanyl instead, which do not accumulate toxic metabolites. 6

Respiratory Disease

• There is NO contraindication for morphine in patients with asthma or respiratory failure when properly monitored. 1