Table of Contents · 11 sections
In a nutshell. Analgesics are divided into non-opioid (NSAIDs, paracetamol, metamizole) and opioid (weak: tramadol, codeine; strong: morphine, fentanyl, oxycodone). The basis of cancer pain management is the 3-step WHO ladder. For neuropathic pain, first-line treatments are gabapentin, pregabalin, duloxetine, and amitriptyline. Multimodal anesthesia reduces opioid doses and side effects.
1. Classification
| Group | Examples | Mechanism |
|---|---|---|
| Simple non-narcotics | Paracetamol, metamizole | Central action, COX-3 inhibition (partial), effect on serotonergic pathways |
| NSAIDs | Ibuprofen, diclofenac, ketoprofen, naproxen, ketorolac | COX-1/COX-2 inhibition → ↓ prostaglandins |
| Selective COX-2 inhibitors | Celecoxib, etoricoxib | Predominantly COX-2 → fewer GI side effects |
| Weak opioids | Tramadol, codeine | Partial μ-agonists + serotonin/norepinephrine reuptake inhibition |
| Strong opioids | Morphine, fentanyl, oxycodone, hydromorphone, buprenorphine | Full μ-agonists |
| Adjuvants | Gabapentin, pregabalin, TCAs, SNRIs, local anesthetics, corticosteroids | Action on neuropathic and inflammatory pain |
2. WHO Analgesic Ladder (1986, updated 2020)
- Step 1 (mild pain): paracetamol ± NSAIDs ± adjuvants.
- Step 2 (moderate pain): weak opioids (tramadol, codeine) + Step 1.
- Step 3 (severe pain): strong opioids (morphine, fentanyl, oxycodone) + Step 1 and adjuvants.
2020 Update: for severe pain, patients may skip directly to step 3, and for controlled pain after surgery, de-escalation is possible. Step 4 (invasive techniques: neuroablation, infusions) is not part of the classical ladder.
3. Paracetamol
- Analgesic and antipyretic; weak anti-inflammatory effect.
- Dose: 0.5–1 g every 4–6 h (maximum 4 g/day, in patients with CKD/liver disease — 2 g/day).
- Side effects: hepatotoxicity (antidote — N-acetylcysteine in case of overdose).
- Safe for the GI tract and heart — preferred starting option for the elderly and pregnant individuals.
4. NSAIDs
Mechanism
COX blockade → ↓ prostaglandins → analgesia, anti-inflammatory, antipyretic effects.
Side effects
- GI tract: erosions, ulcers, perforation, bleeding (risk ↑ in the elderly, H. pylori infection, anticoagulant use).
- Kidneys: NSAID-induced nephropathy, AKI.
- Cardiovascular: ↑ risk of MI/stroke (especially diclofenac and coxibs except celecoxib).
- "Aspirin-exacerbated respiratory disease": Samter's triad (asthma + nasal polyps + NSAID intolerance).
Tactics
- Minimum effective dose, short course.
- Gastroprotection with PPIs in the presence of GI risk factors.
- Avoid in heart failure, CKD (eGFR < 30), hyperkalemia.
5. Opioids
Weak
- Tramadol — μ-agonist + serotonin/norepinephrine reuptake inhibitor. Risk of serotonin syndrome when combined with SSRIs.
- Codeine — prodrug, metabolized by CYP2D6 into morphine. 10% of Europeans are "poor metabolizers" (no effect), some are "ultrarapid metabolizers" (risk of toxicity). Contraindicated in children < 12 years and after tonsillectomy.
Strong
- Morphine — reference full μ-agonist. Oral bioavailability 30%. Doses: 5–10 mg IV, 10–30 mg orally. Extended-release tablets (MST Continus).
- Fentanyl — 100 times stronger than morphine. Transdermal patches (TTS), transmucosal formulations, IV during mechanical ventilation.
- Oxycodone — oral, long-acting, good bioavailability.
- Hydromorphone, methadone, tapentadol — options for opioid rotation.
- Buprenorphine — partial agonist, ceiling effect; transdermal patch is convenient for elderly patients.
Side effects of opioids
- Sedation, nausea, vomiting.
- Constipation (tolerance does not develop — schedule routine laxatives).
- Respiratory depression — reversed with naloxone.
- Pruritus, urinary retention.
- Hyperalgesia (paradoxical pain amplification at high doses).
- Tolerance and physical dependence; risk of abuse with uncontrolled prescription.
Equianalgesic doses (conversion to oral morphine)
| Drug | Ratio |
|---|---|
| Oral morphine | 1 |
| IV/SC morphine | ×3 (i.e. 10 mg IV = 30 mg PO) |
| Oral oxycodone | ×1,5 |
| Oral tramadol | ÷5 |
| Fentanyl TTS 25 mcg/h | = 60 mg oral morphine/day |
| Buprenorphine TTS 35 mcg/h | = 60–80 mg oral morphine/day |
6. Adjuvants for neuropathic pain
- Gabapentin 900–3600 mg/day, pregabalin 150–600 mg/day — first line.
- Amitriptyline 25–75 mg — TCA, effective in postherpetic neuralgia, diabetic neuropathy.
- Duloxetine 60–120 mg — SNRI, first line in diabetic neuropathy.
- Lidocaine 5% patch — localized neuropathy.
- Capsaicin 8% patch — postherpetic neuralgia.
7. Principles of chronic pain therapy
- Regularly around the clock, rather than "on demand".
- Multimodal — combination of drugs from different classes reduces doses.
- Pain assessment using the NRS scale (0–10), Wong-Baker in children.
- Breakthrough pain — 10–20% of the daily opioid dose in a fast-acting formulation.
- Prevention of constipation and nausea.
- Opioid rotation — in case of tolerance or side effects.
8. Special clinical scenarios
- Postoperative pain — multimodal (paracetamol + NSAID + regional anesthesia + on-demand opioid); PCA (patient-controlled analgesia).
- Cancer pain — WHO analgesic ladder, strong opioids without dose limitation, rotation, adjuvants, palliative sedation.
- Elderly — "start low, go slow"; paracetamol, buprenorphine TTS preferred.
- Pregnancy — paracetamol is safe; NSAIDs — only in the 1st–2nd trimester up to 32 weeks; opioids — for strict indications.
- Renal impairment — avoid morphine (accumulation of M6G), prefer fentanyl, methadone.
9. Non-opioid "novelties"
- Metamizole — available in Russia; risk of agranulocytosis limits use.
- Nefopam — central non-opioid analgesic.
- Cannabinoids (nabiximols) — for chemotherapy-induced nausea/vomiting and neuropathy.
10. Acute opioid overdose
- Triad: miosis + respiratory depression + altered mental status.
- Naloxone 0.04–0.4 mg IV every 2–3 min until respiration is restored.
- Naloxone intranasally (Narcan) — for pre-hospital care.
- Caution in opioid-dependent patients: risk of acute withdrawal syndrome.
11. FAQ
Why is oral morphine restricted in Russia?
Strict accounting of narcotic analgesics; since 2015, the prescription procedure for cancer patients has been simplified (5-year prescription, can be prescribed by a district physician).
NSAIDs — parenteral or oral?
Intramuscular administration offers no advantage in the speed of onset of analgesia, but increases the risk of complications. Tablets/suppositories are preferred.
How to choose the first line for neuropathy?
Diabetic — duloxetine/pregabalin; postherpetic — gabapentin/TCA; trigeminal — carbamazepine; CNS neuropathy — pregabalin.
What is multimodal analgesia?
Combination of drugs from different classes (paracetamol + NSAID + opioid + regional block) — an "opioid-sparing" approach, recommended by ERAS protocols.
When to use a fentanyl patch?
Stable chronic pain requiring a step 3 opioid, with a documented requirement for morphine > 60 mg/day. Not for acute pain!
See also: Local anesthetics · Glucocorticoids · Antidepressants · Epilepsy · Pharmacology catalog