The GP has an important responsibility not only to relieve patients’ pain skilfully and completely (if possible) but to ensure that the appropriate drugs are prescribed without leading to dependence. This judicious drug use applies to opioids for non-palliative pain, in particular codeine, oxycodone and morphine.
The three categories of pain—nociceptive pain, neuropathic pain and psychogenic pain—each require different therapeutic agents.2 For nociceptive pain the traditional analgesics are used: paracetamol, aspirin, other NSAIDs and opioids. Neuropathic pain is treated with antidepressants, antiepileptics and membrane stabilisers. Agents used to treat muscle pain are muscle relaxants and baclofen.
Medications used to treat pain include:
‘simple’ analgesics (aspirin, paracetamol)
NSAIDS, cyclo-oxygenase-2 (COX-2) specific inhibitors
opioids (weak and strong)
antidepressants, TCAs (e.g. amitriptyline), SNRIs
membrane stabilisers (anticonvulsants, antiarrhythmics)
NMDA blockers (ketamine)
alpha2 agonists (clonidine)
Chronic pain, such as chronic low back pain, represents a challenge but the challenge is to manage acute pain skilfully and prevent chronicity. O'Reilly3 has provided some useful guidelines for the role of the GP in the management of chronic pain:
Emphasise that cure is unlikely.
Encourage the patient to accept responsibility for pain management.
Provide ongoing support and interest.
Promote activity rather than rest.
Educate patients about their condition: review X-rays and discuss drugs, especially the long-term disadvantages of opioids and sedatives.
Encourage time-contingent versus pain-contingent use of medication.
Withdraw unsuitable drugs (e.g. opioids and sedatives).
Consider issue of undiagnosed depression or anxiety as amplifiers of pain perception and treat where necessary.
Promote the use of relaxation, distraction and heat or ice packs rather than increased medication.
Discuss strategy for management of flare-ups in advance.
Refer for psychological support: mindfulness, acceptance–commitment therapy (ACT) and/or cognitive behaviour therapy recommended.
Analgesics in common use1
Paracetamol has minimal anti-inflammatory activity but moderate analgesic (equipotent with aspirin) and antipyretic properties. It is metabolised by the liver and has an excretion half-life of approximately 4 hours. Adverse effects are uncommon but gastrointestinal discomfort such as dyspepsia and nausea can occur occasionally. It is well tolerated by patients with peptic ulcers and has no effect on platelet function. Use of 4 g or more per day over 12 months has been associated with chronic liver disease. It should be administered with caution in patients with kidney or hepatic dysfunction. Although less effective than NSAIDs for pain relief, its excellent safety in therapeutic doses makes it the first-line analgesic for mild to moderate pain.
1 g (o) 4 hourly (max. 4 g/day)
Formulations of paracetamol include:
immediate release tablets and capsules
oral solution and suspension
soluble or effervescent tablets
extended-action formulation—665 mg (may provide up to 8 hours pain relief)
suppositories (125 mg, 250 mg, 500 mg forms)
NSAIDs can be used instead of or in addition to paracetamol.
Aspirin has both analgesic and anti-inflammatory activity and is a very effective drug in adults for mild to moderate acute pain. It has an extremely short half-life and is metabolised to salicylic acid, which shares the above properties. The major problems with aspirin are gastrointestinal discomfort, ulceration and bleeding.
600 mg (o) 4 hourly (max. 4 g/day)
These agents are usually reserved for the treatment of severe pain and are more appropriate for palliative
pain. Commonly used agents are the relatively weaker opioids—codeine, oxycodone, buprenorphine, tramadol—and the stronger ones—morphine, fentanyl, hydromorphone and methadone. Reviews show that opioids are no better than NSAIDs for back pain.5
Adverse effects, which are common, dose dependent and quite variable, include nausea and vomiting, constipation, respiratory depression and dysphoria, oral hygiene problems and hyperalgaesia. Ongoing assessment based on the 5As is recommended. These are: analgesic effect, activity, affect, abnormal behaviour, adverse effects.
Codeine, which is methylmorphine, is metabolised to morphine. Controlled trials have shown codeine 32 mg to be no more effective than aspirin 600 mg.3 Disturbing side effects include nausea and constipation. Its use is best avoided because of its variable metabolism secondary to cytochrome CYP 2D6 genotype polymorphism. This enzyme rapidly metabolises codeine to morphine causing sleepiness and confusion. Breastfed infants of mothers taking codeine require close monitoring.
30–60 mg (o) 4 hourly (max. 240 mg/day)
Oxycodone is a synthetic opioid that is very effective orally. It is useful for moderate pain in bridging the gap between the simple analgesics and strong opioids.2 The oral form has a duration of action of 4 hours.
Adverse side effects include nausea, constipation, confusion and itch. Dependency and abuse is a worldwide problem. It is available as an injection and is equianalgesic to morphine.
10 mg (o) 4 hourly (max. 60 mg/day),
controlled release, (various strengths) 12 hourly
30 mg rectally (8–12 hourly [Prolodone])
Examples: Endone, Oxycontin, OxyNorm, Targin
This controversial drug is structurally related to methadone. Adverse effects include serious cardiac disorders, dysphoria, confusion, lightheadedness and constipation. It has been associated with relatively sudden death when taken in overdose, especially with alcohol.1 Continuous use should be discouraged, particularly in elderly patients and those with cardiac disease.1 Avoid prescribing it for new patients.
Morphine is the most effective and ‘gold standard’ opioid for the relief of moderate to severe pain and cancer pain (see CHAPTER 11). It is worth noting that injections are not more effective than oral administration in achieving pain relief. It should be titrated according to patients’ needs. Dose reduction may need to be made in patients with impaired liver or kidney function and in elderly or debilitated patients.
Note: Dose requirements vary considerably and patient response should be monitored frequently. There may be no upper limit to dosage in cancer patients.
10 mg (o) 4 times daily
SC injection 5–10 mg
IV injection 5–10 mg
equipotent dose: 30 mg (o) = 10 mg parenteral
Tapentadol (Palexia, Nucynta) is a new centrally acting opioid analgesic indicated for chronic moderate to severe pain not responding to non-narcotic analgesics, including palliative care and neuropathic pain. Similar benefits to oxycodone. Adverse effects are common and it should be avoided in severe kidney and liver disease. No known multi-equivalent dose to morphine 30 mg (o). Available as IR 50 mg, 75mg, 100mg ER: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg.
initially ER 50 mg (o) every 12 hours, increasing as necessary (max. dose 500 mg/day).
Methadone is an effective oral analgesic with a long but variable half-life; it is given, preferably, once or at most twice a day. Relatively unsuitable for acute pain, it is valuable for chronic pain, although long-acting morphine preparations have displaced it. It should not be used in elderly patients or those with kidney dysfunction. Its place is in management of opioid dependency but it needs to be used with care because of the risk of respiratory depression and accumulation.
Pethidine is a synthetic opioid with a short duration of action. A problematic adverse effect is accumulation of its toxic metabolite (norpethidine), which can cause myoclonic and general seizures.5 It has no place in the management of chronic pain, whether cancer or non-cancer, and possibly minimal use in acute pain.
Fentanyl is a very potent synthetic opioid which can be administered IV, IM, SC, intranasal (children), transdermal or by the epidural route. Its efficacy is similar to morphine but it has fewer side effects and is the drug of choice in renal failure. The conversion factor is: 10 mg (SC) morphine = 150–200 mcg (SC) fentanyl. Intranasal fetanyl has significant use in paediatric emergency care and also palliative care.
preoperation/postoperation pain, 50–100 mcg
IM or slow IV
patches (various strengths, deliver over 72 hours), initial dose 12–25 mcg/hour
It takes about 8–12 hours before effecting analgesia.
A 25 mcg patch is equivalent to 30–35 mg IV or 100 mg oral morphine daily.
This is structurally similar to morphine but five times more potent. It is available for oral, parenteral and intraspinal use in moderate to severe pain. Like all opioids, the risk of drug dependence is high.
2–4 mg (o) every 4 hours
1–2 mg IM, SC or IV (slow) every 4–6 hours
4–8 mg daily of SR (sustained release) preparation
Tramadol is an atypical analgesic with both opioid and non-opioid features. Its use is suitable for mild to moderate mixed nociceptive and neuropathic pain. Its advantages include analgesia with minimal sedation or respiratory depression and low abuse/dependence potential. Side effects include the serotonin effect, dizziness, vertigo, nausea, vomiting, constipation, headache, somnolence, tremor, confusion and hypersensitivity reactions. Seizures have been reported.6
(as 50 mg caps or SR tabs—100, 150 or 200 mg)
50–100 mg (o) 2–4 times daily or 100–200 mg (SR) twice daily
injection 100 mg/2 mL: 50–100 mg 4–6 hourly IM or slow IV
This is a partial agonist opioid derived from the opium alkaloid thebaine. It is useful in pain management. Sublingual preparations (0.2 mg, 0.4 mg, 2 mg, 8 mg) are used for acute, chronic and cancer pain. It is also available as a transdermal patch (TD), e.g. Norspan and injection formulation. It is used in the treatment of opioid dependence.
The patches are available in 5, 10 and 20 mcg/24 hr patches (equivalent to 3, 6 and 12 mg morphine in a 24-hour period).
Combined analgesics are available for moderately severe pain. They now usually consist of a simple analgesic such as paracetamol combined with the NSAID ibuprofen. Combined analgesics have an additive effect because they act at different receptor sites. The use of combined preparations, especially with codeine, is generally not recommended but if both agents are needed it is advisable to prescribe them separately, thus enabling individual dose adjustments.1 It is worth noting that codeine, either singularly or in combination, is not available over-the-counter (OTC) but only on prescription.
Ketamine (oral or IM use) can be used for induction and maintenance of anaesthesia and for pain relief. It should be used cautiously and by specialists. Neuropsychiatric adverse effects can be very disturbing for affected patients.
This is a volatile anaesthetic agent that is administered as inhalational analgesia with the Penthrox Inhaler in emergency situations such as at the roadside. It can be used with oxygen or air. It provides pain relief after 8–10 breaths and it continues for several minutes. It should only be used if resuscitation facilities are available. Maximum adult dose is 6 ml/24 hours.
Prescribing guidelines for opioids4,6
As a rule, restrict to SR morphine.
SR oxycodone is more ‘likeable’ for patients and should be avoided for conditions such as back pain.
TD buprenorphine is often a good starting agent.
Restrict use of codeine and use with caution.
Tramadol is useful but has a potential serotonin adverse effect and ceiling effect.
Fentanyl is potent and its use questionable.
Do not initiate with hydromorphone or fentanyl.
Hydromorphone is very complex—best for palliative care.
Methadone has complex kinetics so avoid initiating unless well informed.
At least 80% of total daily opioid should be given as an SR formulation.
Use immediate release (IR) as a guide to consolidate SR doses.
Avoid IR-only regimens—use co-analgesics to limit dose and side effects.
Do not use hydromorphone or transdermal fentanyl as first-line opioids in opioid-naive patients with chronic pain.
Ensure that the pain syndrome is opioid sensitive.
Good record keeping is mandatory.
Beware of drug escalation.