Opioid Analgesics
| Drug Class | Schedule | Primary Use | Antidote |
|---|---|---|---|
| Opioid agonists | Mostly DEA Schedule II (tramadol: Schedule IV) | Moderate–severe acute and chronic pain | Naloxone (Narcan) |
Key Points
- Mechanism: Bind to mu, delta, and kappa opioid receptors in the CNS → alter pain perception, raise pain threshold, produce CNS depression
- Primary adverse effect: Respiratory depression — monitor respiratory rate; rate <12/min → withhold and notify provider; keep naloxone at bedside
- Constipation is the most persistent adverse effect — does NOT develop tolerance; requires proactive bowel management
- Morphine is the prototype opioid; no ceiling effect → appropriate for cancer pain and end-of-life care
- In acute coronary syndromes, morphine is a secondary option for persistent pain when optimal nitroglycerin therapy is insufficient.
- Meperidine (Demerol): NOT recommended for routine analgesia — toxic metabolite causes delirium and seizures, especially in elderly and renal-impaired patients
- Avoid opioid-first strategies for chronic noncancer pain when effective alternatives exist, and avoid routine opioid-first use in patients younger than 18 years
- Most full opioid agonists are Schedule II controlled substances, while tramadol is Schedule IV; both require controlled-substance safeguards
- IM opioid onset is slower and more variable than IV; low-perfusion states (for example shock or chilled tissue) can delay absorption and later increase overdose risk as circulation recovers.
- Naloxone reversal can restore ventilation rapidly but also reverses opioid analgesia; reassess pain and respiratory status together after rescue.
- Naloxone duration is short (often around 20-30 minutes), so recurrent sedation/respiratory depression can occur when long-acting opioids are involved.
Mechanism of Action
Opioid agonists bind to opioid receptors (primarily mu receptors) located throughout the CNS and peripheral tissues. Receptor activation:
- Analgesia: Modulates painful signals from peripheral tissues; raises pain threshold
- Euphoria/sedation: CNS depression through limbic and cortical pathways
- Cough suppression: Suppresses cough center in medulla
- Respiratory depression: Decreases responsiveness of brain stem respiratory centers to CO2 — primary life-threatening adverse effect
Key Opioid Agents
| Drug | Route | Typical Adult Dose | Notes |
|---|---|---|---|
| Morphine | IV, PO | IV PCA: 1–2 mg per bolus; PO: 15–30 mg q4h IR | Prototype opioid; no ceiling effect; used for severe pain, cancer/end-of-life care, and selected pulmonary-edema contexts; common in PCA |
| Morphine concentrate (Roxanol) | Sublingual, PO | Concentration often 20 mg/mL; dose individualized | Common in end-of-life care for pain or air hunger when swallowing is limited; reassess comfort-alertness balance |
| Fentanyl (Sublimaze, Duragesic) | IV, transdermal | Acute: 25–50 mcg IV q30–60 min; Patch: 25–100 mcg/hr | Synthetic — safe alternative for morphine allergy; extremely potent; major contributor to opioid overdose deaths |
| Hydromorphone (Dilaudid) | IV, PO | IV: 0.2–1 mg q2–3h; PO: 2–4 mg q4–6h | Semisynthetic; potent; available in both forms for in/out-hospital use |
| Tramadol (Ultram) | PO (IR/ER) | IR: 50 mg; ER: 100/200/300 mg | Schedule IV atypical agent: partial mu agonist + NE/5-HT reuptake inhibition; useful in selected pain contexts but lowers seizure threshold and has misuse risk |
| Oxycodone (OxyContin, Xtampza ER) | PO | IR: 5–15 mg q4–6h; ER: individualized | Less pruritus than morphine; often combined with acetaminophen (monitor total APAP dose ≤4 g/day) |
| Codeine | PO | 15–60 mg q4h; max 360 mg/day | Requires CYP2D6 conversion to morphine; unpredictable response; NOT recommended in children |
| Methadone (Dolophine) | PO, IV | Individualized | Half-life up to 59 hours; used for opioid-use-disorder (opioid use disorder) and chronic pain; neuropathic pain benefit |
| Meperidine (Demerol) | IM, SQ | 50–150 mg q3–4h; max 600 mg/day | NOT for routine analgesia — toxic metabolite (normeperidine) causes CNS excitability, delirium (delirium), seizures; use limited to shivering (rigors) management |
Adverse Effects
| System | Adverse Effect | Clinical Action |
|---|---|---|
| Respiratory | Respiratory depression (RR <12/min) | Withhold opioid; stimulate patient; administer naloxone |
| CNS | Sedation, confusion, dizziness, lightheadedness | Fall precautions; side rails up; assist ambulation |
| Cardiovascular | Hypotension (vasodilation) | Position changes slowly; monitor BP; avoid in hypovolemia |
| GI | constipation (Constipation) (no tolerance develops), nausea, vomiting | Bowel regimen (stool softener + stimulant laxative); anti-emetics |
| Urinary | Urinary retention (higher risk in opioid-naive or spinal-route opioid use) | Monitor urine output; assess for bladder distention; catheterize if needed |
| Dermatologic | Pruritus (especially with spinal-route opioids) | Antihistamines; monitor for added sedation if diphenhydramine is used |
| Neurologic (tramadol risk) | Lowered seizure threshold, especially with overdose/polypharmacy | Use caution in seizure history; escalate promptly for tremor, confusion, or seizure activity |
Respiratory Depression
Respiratory depression is the primary life-threatening risk of opioid use. Risk is highest in:
- Elderly and debilitated patients
- Patients with COPD, sleep apnea, or decreased respiratory reserve
- When combined with other CNS depressants (benzodiazepines, alcohol, sedative-hypnotics)
- When opioid-naive patients receive first doses
Naloxone (Narcan) — Opioid Antidote
Mechanism: Competitive opioid receptor antagonist — rapidly displaces opioids from receptors and reverses CNS/respiratory depression.
Indications: Complete or partial reversal of opioid-induced respiratory depression; suspected opioid overdose.
Administration: IV push (fastest), IM, or intranasal route; repeat every 2–3 minutes until adequate respiratory response. Effect is short (often around 20-30 minutes and generally shorter than many opioids), so re-sedation can occur and repeat doses or infusion may be required.
Naloxone Cautions
- Precipitates acute withdrawal in opioid-dependent patients — signs: sweating, tachycardia, hypertension, vomiting, severe agitation, seizures
- Withdrawal may also present with diarrhea and tremors after abrupt reversal
- Neonates of opioid-dependent mothers: Do NOT administer naloxone — precipitates neonatal withdrawal with convulsions
- Abrupt reversal in postoperative opioid-dependent patients → severe hypertension, ventricular dysrhythmias, pulmonary edema
Nursing Monitoring Priorities
Before Administering:
- Assess pain using validated scale (0–10, FACES, behavioral)
- Prefer oral/IV/subcutaneous/rectal/transdermal routes as appropriate; intramuscular opioid administration is typically avoided when alternatives are available
- If IM opioid dosing is required, monitor closely in low-perfusion states because delayed absorption can lead to later rebound sedation/respiratory depression.
- Assess baseline respiratory rate, LOC, blood pressure
- Review current medications for CNS depressants (benzodiazepines, alcohol history)
- Verify opioid history and tolerance status
- Confirm controlled substance documentation (count, witness)
- Screen high-risk caution contexts before morphine use: head injury/increased ICP, GI obstruction (especially paralytic ileus), biliary/pancreatic disease, severe hepatic/renal impairment, convulsive disorders, and circulatory shock/hypovolemia.
During Therapy:
- Respiratory rate — q1–4h depending on route; RR <12/min → withhold and notify provider
- Level of consciousness — sedation scale assessment
- Pain reassessment — 30–60 min after IV dose; 60 min after PO dose
- In final-hours comfort care, reassess dyspnea relief and ability to interact, and titrate toward the patient-defined comfort-alertness goal.
- After naloxone reversal, monitor for recurrent respiratory depression, hypertension/tachyarrhythmia, and return of severe pain.
- Bowel function — daily; start prophylactic bowel regimen with initial opioid order
- Urinary output — especially with epidural or intrathecal opioids
Safety:
- Fall precautions — bed in lowest position, call light within reach, non-skid footwear
- Side rails elevated when sedated
- Naloxone immediately available at bedside during IV opioid use
Patient Education:
- Do not drive or operate heavy machinery
- Avoid alcohol and CNS depressants
- Never tamper with opioid formulations (for example crushing, chewing, snorting, or injecting) because this sharply increases overdose and death risk.
- Change positions slowly (orthostatic hypotension)
- Report: RR <12/min, extreme drowsiness, inability to be woken
- Take with food to reduce nausea
- Constipation expected — take prescribed laxative/stool softener
Related Concepts
- analgesics — Opioids are Tier 3 (WHO analgesic ladder) for moderate-to-severe pain
- opioid-antagonists — Naloxone, naltrexone, and mixed agonist-antagonist pathways.
- nsaids — Non-opioid analgesics used in multimodal analgesia to reduce opioid requirements
- pain-management — PCA delivery, opioid-sparing strategies, monitoring protocols
- labor-analgesics — Opioid use during labor; all cross placenta; naloxone antidote considerations
- substance-use-disorders — Opioid use disorder, addiction risk, drug diversion
- sedative-hypnotics — Additive CNS/respiratory depression when combined with opioids
Self-Check
- A postoperative patient receiving IV morphine via PCA has a respiratory rate of 10/min and is difficult to arouse. What is the immediate nursing priority?
- A nurse administers naloxone to a patient with suspected opioid overdose. The patient’s respirations improve, but 45 minutes later the nurse reassesses and finds renewed sedation and RR of 11. Why does this occur, and what should the nurse do?
- An elderly patient with COPD and moderate-to-severe cancer pain is prescribed around-the-clock morphine. What special monitoring parameters apply to this patient?