6.1 Opioid and Non-Opioid Analgesics by Pain Type and Severity
Key Takeaways
- Acetaminophen has a true analgesic ceiling; the labeled adult maximum is 4,000 mg/24 h, many hospice protocols cap at 3,000 mg, and combination opioid tablets can hide a hepatotoxic load.
- NSAIDs help prostaglandin-driven bone and inflammatory pain but carry gastrointestinal, renal, and platelet risks that are magnified in dying, dry, thrombocytopenic, or steroid-treated patients.
- The WHO analgesic ladder is a historical intensity frame; current CHPN-level practice is mechanism-based and starts a strong opioid for moderate-to-severe cancer pain rather than lingering on codeine or tramadol.
- Morphine is typically first-line when GFR is adequate; hydromorphone is a common rotation when morphine metabolites accumulate.
- Avoid meperidine because of normeperidine seizures, avoid mixed agonist-antagonists in patients already on pure mu agonists, treat codeine as CYP2D6-unreliable, and treat tramadol as a seizure and SSRI interaction risk.
6.1 Opioid and Non-Opioid Analgesics by Pain Type and Severity
Pharmacologic pain management is the highest-yield judgment-and-math cluster on CHPN Domain 2 (Patient Care: Pain Management). Exam items almost never ask you to recite a drug class in isolation. They give a pain mechanism, a severity, a creatinine, and a current list, then ask which order you would question or which first-line opioid is appropriate. This section is selection. Titration lives in 6.3. Equianalgesic conversion lives in 6.4.
The WHO ladder is history; mechanism-based selection is current practice
The World Health Organization (WHO) analgesic ladder (1986, later revised) remains a useful intensity frame: mild pain is treated with a non-opioid plus or minus an adjuvant; moderate pain historically moved to a so-called weak opioid; severe pain moved to a strong opioid. Recognize that language. Do not treat the ladder as a mandatory three-week stay on each step.
Current hospice and palliative practice, consistent with NCCN Adult Cancer Pain guidance, is mechanism-based and severity-based:
- Moderate-to-severe cancer pain is treated with a strong opioid. Lingering on codeine or tramadol because Step 2 is unfinished undertreats.
- Bone and inflammatory pain often need an NSAID or corticosteroid in addition to an opioid.
- Neuropathic pain needs an adjuvant (Section 6.2) in addition to an opioid when pain is severe.
- Non-opioids and adjuvants are add-ons. They are not a moral substitute for opioids when pain is severe.
The three WHO administration slogans still apply at the bedside: by the mouth when the gut works, by the clock for continuous pain, and by the individual.
Acetaminophen: ceiling effect and hepatotoxicity
Acetaminophen is a non-opioid analgesic and antipyretic. It has a ceiling: once you are at an effective dose (often 650–1,000 mg), more milligrams do not buy more analgesia. They only buy hepatotoxicity. The labeled adult maximum is 4,000 mg in 24 hours in a well-nourished adult without liver disease. Many hospice protocols cap at 3,000 mg/day. Patients with malnutrition, prolonged fasting, heavy alcohol use, or extensive hepatic metastases often need 2,000 mg/day or less.
Hospice-specific traps:
- Combination tablets (hydrocodone/acetaminophen or oxycodone/acetaminophen) hide acetaminophen. Titrating the opioid by giving more combination tablets can blow past the acetaminophen ceiling while pain remains 7/10. When opioid need rises, switch to a single-entity opioid and keep acetaminophen as a separately counted drug.
- Dying patients are often glutathione-depleted. The toxic metabolite NAPQI is more dangerous in cachexia and poor intake.
- Acetaminophen does not treat prostaglandin-driven bone pain as well as an NSAID. It is a reasonable co-analgesic for mild nociceptive pain or fever, not a complete plan for pathologic fracture pain.
NSAIDs for bone and inflammatory pain
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, ketorolac, and celecoxib inhibit cyclooxygenase and prostaglandin synthesis. Osteolytic bone metastases generate prostaglandins; that is why an NSAID can drop bone pain in a way acetaminophen will not. Short-course parenteral ketorolac is sometimes used for a severe inflammatory flare when the platelet count and glomerular filtration rate (GFR) allow it.
In dying patients the risks are concrete, not theoretical.
| Risk | Why it is worse in hospice | Exam action |
|---|---|---|
| Gastrointestinal bleeding or ulcer | Mucosal prostaglandin loss; worse with corticosteroids, anticoagulants, or prior ulcer | Question the NSAID; do not combine blindly with dexamethasone |
| Renal hypoperfusion | Afferent arteriolar prostaglandin preserves GFR when the patient is dry | Avoid in oliguria, rising creatinine, or diuretic plus ACE-inhibitor stacking |
| Platelet inhibition | COX-1 blockade (less with celecoxib, not zero systemic risk) | Avoid in thrombocytopenia, active bleeding, or an imminent invasive procedure |
If an NSAID is unsafe, dexamethasone may still treat inflammatory and bone pain (Section 6.2). An NSAID is never a reason to withhold a strong opioid for severe cancer pain.
Strong opioids: morphine first when the kidneys are acceptable
Morphine is the CHPN reference strong opioid: inexpensive, available as oral immediate-release (IR), oral extended-release (ER), concentrated oral solution, subcutaneous, intravenous, and rectal. It is typically first-line when renal function is adequate.
Morphine is metabolized to morphine-6-glucuronide (M6G), which is analgesic, and morphine-3-glucuronide (M3G), which is neuroexcitatory. Both accumulate when GFR falls. The exam picture of morphine in renal failure is myoclonus, hyperalgesia, delirium, or seizures, not a cue to give more morphine.
Oxycodone is a strong oral mu agonist when the oral route is intact. It has fewer glucuronide problems than morphine but is not risk-free in severe renal failure.
Hydromorphone is potent, available oral and parenteral, and is a common rotation target when morphine neurotoxicity or renal impairment appears. It still has a 3-glucuronide metabolite. It is better than morphine in moderate renal impairment, not a free pass in anuria.
Hydrocodone in U.S. hospice is often paired with acetaminophen. Treat it as adequate for some moderate pain, then abandon the combination product once acetaminophen milligrams — not pain — become the limiting factor.
Drugs the exam expects you to stop, not start
Meperidine is not a hospice opioid. Its metabolite normeperidine accumulates, especially when kidneys fail, and causes tremor, myoclonus, and seizures. It is the wrong answer for chronic cancer pain, for renal failure, and for using something short-acting solely because the patient is dying.
Mixed agonist-antagonists (nalbuphine, pentazocine, butorphanol) compete at the mu receptor. In a patient already on a pure mu agonist (morphine, oxycodone, hydromorphone, fentanyl), they can precipitate withdrawal and reverse analgesia. Do not stack them as safer breakthrough on a morphine regimen.
Codeine is a prodrug. CYP2D6 poor metabolizers form little morphine and get negligible analgesia; ultra-rapid metabolizers can get unexpected toxicity. Codeine is a poor primary plan for hospice-level cancer pain.
Tramadol is a weak mu agonist plus a serotonin/norepinephrine reuptake inhibitor. It lowers the seizure threshold and can precipitate serotonin syndrome with SSRIs, SNRIs, MAOIs, or other serotonergic drugs. It has a ceiling and is not a substitute for morphine in severe cancer pain.
Selection table
| Clinical picture | Prefer | Avoid or question |
|---|---|---|
| Mild nociceptive pain, organs acceptable | Acetaminophen, with or without an NSAID | Exceeding the acetaminophen ceiling |
| Bone or inflammatory pain; platelets and GFR acceptable | NSAID plus an opioid matched to severity | NSAID plus steroid plus anticoagulant with no plan |
| Moderate-to-severe cancer pain, GFR adequate | Morphine around-the-clock plus IR rescue | Codeine trial, meperidine, tramadol as sole therapy |
| Severe pain, falling GFR, or morphine myoclonus | Hydromorphone (or specialist fentanyl or methadone) | More morphine |
| Already on morphine or oxycodone | Titrate the same pure agonist | Nalbuphine or pentazocine boost |
| Known CYP2D6 poor metabolizer | Morphine or hydromorphone | Codeine; be cautious with tramadol |
Worked selection example
A 72-year-old with metastatic prostate cancer reports 7/10 aching hip pain. Creatinine is 0.9 mg/dL. He takes acetaminophen 1,000 mg four times daily (already 4,000 mg) plus hydrocodone/acetaminophen 5 mg/325 mg, two tablets every 4 hours as needed. If he takes six combination doses, that is another 3,900 mg of acetaminophen. He also takes sertraline.
Stop counting combination tablets. He is over the acetaminophen ceiling. Severe bone pain needs a strong opioid — morphine IR and ER are appropriate because the kidneys are acceptable — plus consideration of an NSAID or dexamethasone for the bone mechanism. Do not add tramadol on sertraline. Do not start meperidine for short action.
Match severity × mechanism × organ function, not a calendar on the WHO ladder.
A hospice patient with osteolytic pelvic metastases has 6/10 aching bone pain, a stable platelet count, and a creatinine of 1.0 mg/dL. Which pharmacologic statement is most accurate?
Which statement about codeine or tramadol is the one the CHPN exam expects you to act on?
How should a CHPN candidate use the WHO analgesic ladder when choosing drugs for moderate-to-severe cancer pain?