The use of non‐opioid analgesics, such as paracetamol or paracetamol combined with a weak opioid such as codeine, has been shown to decrease acute pain after various surgical procedures (Mahajan et al. [100]). Paracetamol can be given rectally if the oral route is contraindicated. An intravenous preparation of paracetamol offers the ability to achieve therapeutic blood concentrations more readily and more reliably (Chiam et al. [38]). It is more effective and has a faster onset than the same dose given enterally. The use of the intravenous form should be limited to patients in whom the enteral route cannot be used. With regard to dosing schedules for parenteral administration of paracetamol, the dose should be reduced for those who weigh 50 kg or under. For example, patients who weigh between 33 and 50 kg should not exceed a maximum daily dose of 60 mg/kg (up to a limit of 3 g). For patients over 50 kg with an additional risk factor for hepatotoxicity, the maximum daily dose should be 3 g in 24 hours, and for patients over 50 kg with no risk factor then the maximum daily dose can be up to 4 g (Bristol‐Myers Squibb [27]).

Paracetamol taken in the correct dose of not more than 4 g per day is relatively free of side‐effects. When used in combination with codeine preparations, the most frequent side‐effect is constipation.

Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been shown to provide superior pain relief over paracetamol alone (Moore et al. [118]). These drugs can be used alone or in combination with both opioid and non‐opioid analgesics as part of a multimodal approach. Two commonly used NSAIDs are diclofenac, which can be administered by the oral, parenteral, enteral or rectal routes, and ibuprofen, which is available only as an oral or enteral preparation.

Although aspirin confers cardioprotective effects, most other NSAIDs are associated with an increased risk of adverse cardiovascular events, including hypertension, myocardial infarction, cerebrovascular accident (CVA) and heart failure (Brune and Patrignani [32]). A meta‐analysis has suggested that there is little evidence to suggest that any of these drugs are safe in cardiovascular terms (Trelle et al. [180]). Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction and ibuprofen with the highest risk of CVA followed by diclofenac. Diclofenac and lumiracoxib were associated with the highest risk of cardiovascular death. Naproxen is viewed as the least harmful for cardiovascular safety but this advantage should be weighed against gastrointestinal toxicity (Trelle et al. [180]). Newer COX‐2‐specific NSAIDs such as parecoxib, celecoxib and etorocoxib (BNF [14]) have the advantage that they have similar analgesic and anti‐inflammatory effects but also provide a potential reduction in gastrointestinal toxicity. Results of a 2012 meta‐analysis of 28 observational studies by Castellsague et al. ([35]) showed a low risk (relative risk (RR) <2) of upper gastrointestinal complications for aceclofenac, celecoxib and ibuprofen; an intermediate risk (RR 2–4) for diclofenac, meloxicam and ketoprofen, among others; a high risk (RR 4–5) for tenoxicam, naproxen, indomethacin and diflunisal; and the highest risk (RR >5) for piroxicam, ketorolac and azapropazone.

Each patient's clinical background, including gastrointestinal and cardiovascular risk factors, should be taken into account when selecting appropriate NSAIDs (Brune and Patrignani [32]).

Opioids are increasingly being used to treat persistent pain. They have a well‐established role in the management of acute pain and for those with cancer and palliative care needs. There is also evidence from research that opioids can be helpful in the short and medium term in providing symptomatic pain relief from other non‐cancer pain conditions (FPM [60]). Opioids are prescribed to reduce pain intensity. Rarely is pain completely relieved by opioids alone (FPM [60]). In approximately 80% of cases, patients will experience at least one adverse side‐effect from opioids. Opioids should be given careful consideration before they are commenced and patients should be informed that the effects of long‐term use of opioids are unknown in terms of endocrine and immune function (FPM [60]). When opioid therapy is commenced, a plan to review the patient in terms of opioid effects must be in place. From a palliative care perspective, there is guidance available from the National Institute for Health and Care Excellence (NICE) to support safe prescribing of opioids (NICE [126]). There are various opioid analgesics available and they can be given by a variety of routes. Selection is based on a thorough clinical assessment.

Most chronic pain has elements of neuropathic pain. Patients with nociceptive pain are likely to gain some benefit from conventional medications such as NSAIDs but these drugs come with a strong side‐effect profile. Individuals with neuropathic pain are likely to gain some relief from co‐analgesics such as tricyclic antidepressants (e.g. amitriptyline and nortriptyline) and anticonvulsant drugs (e.g. gabapentin and pregabalin). Pregabalin has been shown to have beneficial effects on symptoms of neuropathic pain, but it increases the risk of a number of adverse effects (weight gain, dizziness, somnolence, peripheral oedema, vertigo and euphoria) as well as the risk of subsequent discontinuation due to these adverse effects (Onakpoya et al. [134]).

The WHO analgesic ladder recommends the use of these drugs in combination with non‐opioids for mild to moderate pain and with opioids for moderate to severe pain (see Figure 10.6).

Sometimes it is difficult to attain and maintain adequate pain control without significant side‐effects. In such situations, anaesthetic interventions may be of benefit.

Effective control can be achieved by epidural or intrathecal (spinal) infusions as single injections for simple nerve blocks or as regional nerve blocks that target individual nerves, plexi or ganglia (Hicks and Simpson [78]). An example is the use of a lumbar sympathetic block in the management of inoperable peripheral vascular disease, herpes zoster or diabetic neuropathy (Cherny et al. [37]).

These interventions can be useful but careful consideration and assessment must take place to ensure that any potential side‐effects are discussed with the patient (anaesthetic interventions may severely limit the patient's activities). Additionally, future planning must be addressed with the patient and their family as an epidural or intrathecal infusion may limit discharge options for a patient who is dying.