Analgesics

Analgesics are a broad group of medications primarily used to relieve pain without causing loss of consciousness. Pain is a complex physiological and psychological experience, and analgesics act through different mechanisms to reduce or eliminate the sensation of pain. They are among the most widely prescribed and over-the-counter medicines worldwide and are used in the management of acute pain, chronic pain, cancer-related pain, and postoperative pain.

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Classification of Analgesics

Analgesics can be broadly classified into the following groups:

1. Non-opioid analgesics (Non-steroidal and miscellaneous)

   • Non-steroidal anti-inflammatory drugs (NSAIDs)

   • Acetaminophen (Paracetamol)

   • Other non-opioid analgesics (e.g., metamizole)

2. Opioid analgesics

   • Natural opiates (morphine, codeine)

   • Semi-synthetic opioids (oxycodone, hydromorphone, buprenorphine)

   • Synthetic opioids (fentanyl, methadone, tramadol)

3. Adjuvant or co-analgesics

   • Antidepressants (e.g., amitriptyline, duloxetine)

   • Anticonvulsants (e.g., gabapentin, pregabalin)

   • Corticosteroids

   • NMDA receptor antagonists (e.g., ketamine)

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1. Non-Opioid Analgesics

A. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs are the most commonly used class of analgesics. They work by inhibiting the cyclooxygenase (COX) enzymes, COX-1 and COX-2, thereby reducing the synthesis of prostaglandins which mediate pain, fever, and inflammation.

Examples and Typical Doses:

• Ibuprofen: 200–400 mg every 6–8 hours orally (max 3200 mg/day)

• Naproxen: 250–500 mg orally twice daily

• Diclofenac: 50 mg orally two to three times daily; topical formulations also available

• Ketorolac: 10 mg every 4–6 hours orally (short-term use; max 40 mg/day)

• Aspirin (acetylsalicylic acid): 325–650 mg every 4–6 hours orally (analgesic dose)

Uses: Mild to moderate pain, inflammation, dysmenorrhea, headache, musculoskeletal pain, postoperative pain.

Adverse effects: Gastric irritation, ulceration, renal impairment, increased cardiovascular risk (with prolonged use).

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B. Acetaminophen (Paracetamol)

Acetaminophen is an effective analgesic and antipyretic but has minimal anti-inflammatory properties. Its precise mechanism is not fully understood but is believed to involve inhibition of prostaglandin synthesis in the central nervous system.

Typical Dose:

• Adults: 500–1000 mg every 4–6 hours orally (max 4 g/day, but 3 g/day is often recommended to minimize hepatotoxicity)

• Pediatric: 10–15 mg/kg every 4–6 hours (max 75 mg/kg/day)

Uses: Headaches, fever, mild musculoskeletal pain, osteoarthritis.

Adverse effects: Hepatotoxicity in overdose, especially with alcohol use or pre-existing liver disease.

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C. Other Non-Opioid Analgesics

• Metamizole (Dipyrone): Analgesic, antipyretic, and spasmolytic. Dose: 500–1000 mg orally or intravenously. Use is limited in some countries due to risk of agranulocytosis.

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2. Opioid Analgesics

Opioids are the most potent analgesics available and are used in moderate to severe pain. They act primarily on mu (μ), delta (δ), and kappa (κ) opioid receptors in the brain and spinal cord, altering pain perception and response.

A. Natural Opiates

• Morphine: Standard opioid; dose 10–30 mg orally every 4 hours, or 2–5 mg intravenously every 2–4 hours.

• Codeine: Weaker analgesic, often combined with acetaminophen; dose 15–60 mg every 4–6 hours orally.

B. Semi-Synthetic Opioids

• Oxycodone: 5–15 mg orally every 4–6 hours; extended-release forms available.

• Hydromorphone: 2–4 mg orally every 4–6 hours, or 0.2–1 mg intravenously every 2–3 hours.

• Buprenorphine: Partial agonist; 0.3 mg IV/IM every 6–8 hours, or sublingual formulations for chronic pain.

C. Synthetic Opioids

• Fentanyl: Potent opioid; available as IV injection (25–100 mcg every 1–2 hours) or transdermal patches (25–100 mcg/hr changed every 72 hours).

• Methadone: Long-acting; 2.5–10 mg orally every 8–12 hours for pain.

• Tramadol: Weak μ-opioid agonist with serotonin/norepinephrine reuptake inhibition; 50–100 mg every 4–6 hours (max 400 mg/day).

Uses: Severe acute pain (postoperative, trauma), chronic cancer pain, palliative care.

Adverse effects: Respiratory depression, constipation, sedation, nausea, vomiting, dependence and tolerance, risk of overdose.

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3. Adjuvant Analgesics (Co-Analgesics)

Adjuvant medications are not primarily analgesics but are useful in pain management, particularly in neuropathic pain.

• Antidepressants:

  • Amitriptyline (tricyclic): 10–50 mg at bedtime.

  • Duloxetine (SNRI): 60 mg once daily.

• Anticonvulsants:

  • Gabapentin: Start 300 mg daily, titrated up to 1800–3600 mg/day in divided doses.

  • Pregabalin: 75–150 mg twice daily.

• Corticosteroids: Dexamethasone (4–16 mg daily) for cancer-related pain and inflammation.

• NMDA antagonists: Ketamine (0.1–0.5 mg/kg IV infusion) for severe refractory pain.

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Clinical Applications of Analgesics

1. Acute pain: NSAIDs and acetaminophen are first-line; opioids reserved for severe cases.

2. Chronic pain: Requires multimodal approach; opioids may be used cautiously.

3. Cancer pain: Stepwise approach (WHO pain ladder): non-opioids → weak opioids → strong opioids.

4. Neuropathic pain: Often resistant to opioids; adjuvants like gabapentin or duloxetine are preferred.

5. Postoperative pain: Combination therapy using NSAIDs, acetaminophen, and opioids as needed.

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Summary of Common Analgesics and Doses

• Acetaminophen: 500–1000 mg every 6 hours (max 4 g/day)

• Ibuprofen: 200–400 mg every 6 hours (max 3200 mg/day)

• Naproxen: 250–500 mg twice daily

• Diclofenac: 50 mg two to three times daily

• Morphine: 10–30 mg orally every 4 hours

• Oxycodone: 5–15 mg every 4–6 hours

• Fentanyl patch: 25–100 mcg/hr every 72 hours

• Tramadol: 50–100 mg every 4–6 hours (max 400 mg/day)

• Gabapentin: 300–3600 mg/day divided

• Amitriptyline: 10–50 mg at bedtime