Non-opioid Analgesics

The control of pain is a wide-ranging subject which encompasses many non-drug modalities, as well as a wide spectrum of pharmacological treatments.
This article deals with non-opioids which are used at Step One of the World Health Organisation's analgesic ladder. For more details of this see Pain Control in Terminal Care.

It is difficult to make sweeping statements about effectiveness between members of this group as the picture changes depending on the condition. Differences in individual interactions, contraindications and adverse effects mean that tailoring the medication to the needs of the individual patient is of paramount importance.

Paracetamol is an appropriate first-line drug for many patients, does well in risk vs benefits trials, and in view of recent reports regarding the safety of NSAIDs, is particularly suitable for long-term conditions.

• Similar efficacy to aspirin, no demonstrable anti-inflammatory activity
• Causes less gastric irritation so preferable for elderly
• Overdosage very dangerous, may cause liver damage which may not be apparent for 4-6 days

Significant interactions

• Coumarins (prolonged use may enhance anticoagulant effect)
• Metoclopramide (absorption of paracetamol may be increased)

• Useful where pain is part of inflammatory process and transient musculoskeletal pain, although paracetamol often preferred in elderly.
• NSAIDs are also useful for dysmenorrhoea, secondary bone tumours, peri-operative analgesia.
• Main problems gastro-intestinal side effects, hypersensitivity reactions
• CSM guidance regarding cardiovascular risk recommends using lowest dose of NSAIDs for shortest possible time.

Significant interactions

SSRIs, coumarins, aspirin, ciclosporin and numerous others - see individual drug monographs for full list.

Paracetamol is often used as an adjunct to NSAIDs in clinical practice⁶ although the evidence base to support this is not large. It is thought that NSAIDs may inhibit prostaglandin synthesis in peripheral tissues, and that this may act synergistically with the centrally-acting analgesic properties of paracetamol.⁷ One study showed that paracetamol and NSAID combination was superior to paracetamol alone in the control of post-operative pain, but not to an NSAID used alone.⁷ Other studies have supported the synergistic use of NSAIDs and paracetamol in pain control after tonsillectomy,⁸ orthopaedic surgery⁹ and gynaecological surgery,¹⁰ but further evaluation is required.

• Useful for headache, transient musculoskeletal pain, dysmenorrhoea
• Other NSAIDs preferred for inflammatory conditions as better tolerated and more convenient
• Tablets or dispersible preparation adequate for most purposes and have rapid onset
• A common problem is gastric irritation, reduced by taking after food
• Enteric coated available but less effective for single-dose analgesic use as slower onset of action
• Enteric coated may however be better for night pain

Significant interactions

• Coumarins
• Heparins
• Serum serotonin reuptake inhibitors (SSRIs)
• Phenindione
• Venlafaxine (increased risk of bleeding)
• Methotrexate (increased risk of toxicity)
• NSAIDs (increased adverse effects)

See individual drug monographs for full list.

• May be useful when other non-opiates fail to work.
• Little or no respiratory depression, but causes sympathomimetic and antimuscarinic side-effects (commonly nausea, nervousness, urinary retention, dry mouth, lightheadedness).

Significant interactions

Avoid use with monoamine oxidase inhibitors (MAOIs). Animal studies suggest inhibition of monamine uptake in brain.