Drug review Severe pain

Current treatment options in the

management of severe pain
William Campbell MD, PhD, FRCA, FFARCSI, FFPMRCA

SPL

Opioids are the most frequently used agents lation suffers from persistent pain, which if inade-
quately managed results in poor affect, sleep distur-
for severe nociceptive pain and should not
bance and family unit dysfunction. It also interferes
be withheld in chronic noncancer pain. Our with the ability to carry out gainful employment.1,2
In the acute situation, severe pain requires urgent
Drug review discusses the properties and
attention and the diagnosis is usually obvious. When
efficacy of the opioids in common use, fol- pain persists beyond a few months, despite attempts
at conventional management, it is deemed chronic.
lowed by an analysis of the prescription data
By its very nature and poor response to treatment,
and sources of further information. chronic pain is therefore difficult to manage.
Pain due to tissue damage – the subject of this review

D espite a wide number of treatment options, the

management of pain remains a problem, and
medical education on the subject is frequently very
– is referred to as nociceptive and usually responds to
NSAIDs and opioids. If the pain is due to a disturbance
of the nervous system, such as trigeminal or posther-
poor at both undergraduate and postgraduate levels. petic neuralgia, it is considered neuropathic, and the
It is estimated that 5-10 per cent of the British popu- response to NSAIDs and opioids is often poor.

www.prescriber.co.uk Prescriber 19 March 2010 23

 Severe pain

Principles of prescribing
• establish a treatment plan, with goals
With the exception of certain clearly defined condi-
• regularly review patients for side-effects, sleep and
tions, opioids are the most commonly used agents for
mood changes, in addition to signs of abuse
severe pain. In some conditions where prostaglandins
• the primary outcome should be analgesia – not
play a significant role, such as renal colic, the NSAIDs
anxiolysis or sedation
can be as efficacious as opioids but with a lower inci-
• although psychological co-morbidity or alcohol prob-
dence of side-effects.3
lems do not preclude opioid use, they do indicate the
Where feasible, sustained-release preparations
need for specialist help, such as multidisciplinary pain
should be used on a regular basis to keep pain under
management services or specialised addiction teams
control; this results in more stable plasma concentra-
• avoid injectable opioids
tions of the drug, permitting the patient to function
• evidence of developing tolerance should prompt refer-
in a more normal manner, rather than wondering
ral to multidisciplinary pain management services or
when they should take their next dose of medication.
specialised addiction teams
The steady plasma levels of opioids in particular help
to reduce habit-forming behaviour, since there is no Table 1. British Pain Society recommendations for the use of
‘kick’ after each dose or a rapid withdrawal effect opioids in chronic noncancer pain7
resulting in the sudden need for another dose.
It is often necessary to use multiple therapies but Patients often use less than the prescribed dose of
when adequate relief is attained for a few weeks, one opioids due to side-effects such as sedation, nausea
can establish which drugs are making the largest con- and vomiting. The use of regular cyclizine (Valoid) or
tribution and rationalise therapy to the least required, prochlorperazine during the first week of treatment
in keeping with a realistic reduction in pain. minimises this distressing symptom. Nausea and seda-
A minority of patients have quite unrealistic expec- tion generally become much less problematic after
tations. It is therefore essential to discuss not only the one or two weeks, but constipation usually continues.
diagnosis of their problem and the therapeutic When any opioid is prescribed it is important to
options but also realistic goals. Failing to do so can ensure that patients are aware of these potential prob-
result in regular attendances at the surger y in an lems and that a gut stimulant is routinely prescribed.
attempt to gain a complete return of normality. In Although stool softeners work well with gut stimulants,
these situations the contribution of psychology is they are usually ineffective by themselves.
invaluable, since the psychological component of pain A novel approach, which can be effectively used to
can augment its intensity many fold. manage constipation when potent opioids are needed,
Opioids are commonly used for severe pain and is to employ the combination medication Targinact
are agonists at mu, kappa and delta receptors, which (oxycodone 20mg with naloxone 10mg – and other
are located at many sites within the CNS, in particular strengths of tablet with this 2:1 ratio of opioid to nalox-
the substantia gelatinosa in the spinal cord and the one). This preparation provides a potent sustained-
periaqueductal grey matter of the brain. Opioids may release opioid with naloxone, which has a direct
be pure agonists like morphine, pethidine and fen- opioid antagonist effect on the bowel (avoiding con-
tanyl, or partial agonists such as buprenorphine and stipation), but the vast majority of the naloxone is
pentazocine. metabolised as it passes through the liver and thus
Tramadol is unusual in that most of its activity is does not have a systemic antagonistic effect on the
through the modulation of noradrenaline and sero- central nervous system, where the opioid works.
tonin (descending nociceptive inhibitory pathways), A major concern with repeated dosing of any opi-
with the remaining 20 per cent of its analgesia being oid is psychological dependence. It is important, of
at opioid receptors.4,5 course, to gain rapid control of severe pain when acute.
Although strong opioids have been the prime agents In the chronic situation, if this is not achieved within
used in severe acute and cancer pain, there is a growing a week or so one may consider the withdrawal of the
body of evidence that they should not be withheld in opioid and the use of alternative therapy. Despite this,
chronic noncancer pain.6 Recent high-profile legal cases it is not unreasonable to use an escalating opioid reg-
have debated not only the appropriateness of opioid imen with an agreed plan and goals over several weeks
prescription in chronic pain but the problems of inad- to establish efficacy. The continual need for an esca-
equate analgesia. The British Pain Society (BPS) has lating dosage after the first few weeks indicates that tol-
published recommendations for the appropriate use of erance may be occurring (see Table 2) and that
opioids in chronic noncancer pain (see Table 1).7 specialist support should be sought. Although it is very

www.prescriber.co.uk Prescriber 19 March 2010 25

Severe pain

Tolerance
A reduction in response intensity and duration following
the repeated administration of a drug: this includes the
side-effects as well as the beneficial effects. Analgesic
response generally improves with an increase in dose.
Although this is a normal pharmacological response, the
dose should not have to be increased on multiple occa-
sions.

Physical dependence
This is a normal physiological response. Receptors
become dependent on the presence of exogenous ago-
nist. The sudden withdrawal of an agonist or the use of a
substance with antagonist properties will precipitate a
withdrawal response.

Pseudoaddiction
If inadequate analgesia is provided the patient seeks fur-
ther analgesia. In this situation, despite the patient ask-
ing for increasing doses of analgesia (because of
inadequate pain relief), they tend to use their medication
as prescribed.

Addiction
True drug addiction is the overwhelming desire to con-
tinue to use the same or greater dose of a substance
with psychomimetic properties. The desire is over and
above that for analgesia and involves both psychological
as well as physical factors.

Table 2. Distinguishing between tolerance, dependence,

pseudoaddiction and addiction

uncommon for patients in pain to become truly

addicted to opioids when appropriately managed, it is
preferable that they attend the same healthcare pro-
fessionals for follow-up and repeat prescriptions.6,8,9
A simple protocol such as that shown in Table 3
can be valuable in providing good patient care while
minimising short- and long-term problems.

Opioids in common use

Morphine
The drug most often associated with potent analgesia
within the general population is morphine and it
tends to be the standard against which other anal-
gesics are compared. A naturally occurring substance,
it has been available for many centuries as a con-
stituent of opium. Although associated with side-
effects, it remains a relatively popular analgesic in the
management of severe pain. It can be administered
by the oral (conventional or modified-release prepa-
rations are available), rectal, parenteral (sc, im and

26 Prescriber 19 March 2010 www.prescriber.co.uk

Severe pain

Diamorphine
• an initial assessment, including function and activity
Diamorphine is available as a white powder for recon-
levels, should be performed
stitution. It is approximately twice as potent as mor-
• the reasons for using strong opioids should be
phine. Essentially a prodrug, it is activated by
explained
deacetylation in the plasma to monoacetylmorphine
• it should be made clear that pain will be modified but
and hence to morphine. It is very lipid soluble and
rarely completely controlled
rapidly crosses tissue membranes, with a much more
• side-effects and interactions should be discussed
rapid onset than morphine. However the duration of
• when prescribing, an informal ‘contract’ or opioid trial
action is also shorter, in the region of two hours. This
can be useful
rapid onset and offset, especially when administered
• the oral route of administration should be used, if pos-
by the iv route, greatly increases its addiction potential.
sible
It is possible to achieve extremely high concentra-
• only one opioid should be used at a time
tions of diamorphine in solution for sc administration,
• agents with toxic metabolites, eg pethidine, should be
and hence its value in palliative care of the terminally
avoided
ill, where high doses may be required.
• compound analgesics, eg those containing anti-
emetics, should be avoided
Pethidine
• regular dosing as opposed to ‘as-required’ prescribing
Pethidine was the first totally synthetic opioid. It has
should be used
approximately one-tenth of the potency of morphine,
• long-acting opioids or sustained-release preparations
and like other opioids undergoes extensive first-pass
are preferred
metabolism (47-73 per cent). Convulsions may occur
• changes in dosage should be made quickly to gain
with repeated dosing due to one of the metabolites,
rapid control of pain
norpethidine, which is a proconvulsant. In addition
• regular follow-ups should be arranged
it should not be administered to patients taking
• it should be ensured that documentation is clear and
MAOIs as the combination can cause hypertension,
complete
hyperpyrexia, convulsions and coma.
Table 3. Considerations for prescribing strong opioids in It was favoured in the past as a drug that avoided
severe, chronic pain smooth muscle spasm in conditions such as renal
colic. It is not as popular now and is no longer consid-
iv), spinal and epidural routes. Due to its low lipid sol- ered a first-line analgesic due to concerns over adverse
ubility it cannot be administered by the transdermal reactions, drug interactions (see Table 5) and nor-
route. pethidine neurotoxicity.11
When taken orally or rectally 70 per cent of the
dose undergoes conjugation in the liver to form mor- Oxycodone
phine-3-glucuronide (M3G) and 5-10 per cent mor- This drug is licensed for severe pain and has twice the
phine-6-glucuronide (M6G). The M6G has been potency of morphine. It undergoes first-pass metabo-
shown to be considerably more potent than the parent lism (50 per cent) when taken orally, initially 5mg four
compound. These metabolites depend on renal excre- hourly. It has similar side-effects to morphine but pos-
tion, with important implications for those with renal sibly less sedation. Like morphine, it is available as a
impairment.10 Dosage and response can vary widely, sustained-release preparation (OxyContin), deliver-
regardless of weight, in the adult population. Older ing analgesia for about 12 hours. Also see Targinact,
people may require smaller doses due to receptor sen- mentioned earlier.
sitivity and impaired renal function, whereas the very
anxious individual in pain may require a larger-than- Other opioids
expected dose. Codeine, dihydrocodeine and methadone
Sedation, dizziness and nausea can be problematic Due to its metabolism to morphine varying consider-
as well as constipation. This is especially common in ably between individuals, codeine is not particularly
the frail or elderly, and when using large doses. reliable in treating severe pain. Dihydrocodeine has
Euphoria, dysphoria and itching (see Table 4) may a similar potency to codeine but is available as oral
also occur with morphine, and important drug inter- and parenteral formulations. The typical oral dose is
actions are shown in Table 5. Despite these adverse 30-60mg every four hours, but the sustained-release
effects morphine is a remarkably safe and effective preparation (DHC Continus) can be used at 120mg
analgesic. every 12 hours. When used by the sc or im route the

28 Prescriber 19 March 2010 www.prescriber.co.uk

 Severe pain

dose is up to 50mg every four hours. These drugs have

Side-effects are most common when an opiate dose is being increased
a dose/response ceiling and are of limited value in
rapidly – they should be anticipated, analysed and treated promptly
the management of severe pain.
Methadone has similar potency to morphine but
Respiratory depression
is associated with less sedation and euphoria. It has a
• opioids reduce the sensitivity of the central chemoreceptors to CO2
high oral bioavailability (80 per cent). Due to its long
• pain is a natural antagonist to this effect
half-life (about 24 hours) it should not be adminis-
• if patients are tachypnoeic, opiates reduce the rate but increase the depth
tered more frequently than 12 hourly, yet analgesia
of respiration
may not exceed five to six hours.
• if rate is less than 10 breaths per minute, discontinue administration; nalox-
An unusual property of methadone is its ability to
one if cyanosed, unrousable or rate less than 6 breaths per minute
inhibit N-methyl-D-aspartate (NMDA), which is asso-
ciated with central excitation in some persistent pain
Sedation and euphoria
states.12 Clinical studies in patients with cancer do not,
• usually beneficial in the acute situation
however, support the potential benefits seen from
• if excessive, respiratory obstruction may occur, particularly if the patient is
basic science work.13
lying supine and/or snoring
• dysphoria can occur as well as euphoria
Fentanyl
Fentanyl is 100 times more potent than morphine and
Constipation
the parenteral preparations are generally only used
in areas of close continual monitoring. As fentanyl is
Nausea and vomiting
500 times more lipophilic than morphine, it can be
• opioids stimulate the chemoreceptor trigger zone
administered by the sublingual (Abstral), buccal
(Actiq, Effentora), nasal (Instanyl) and transdermal
Smooth muscle effect
(Durogesic, Fentalis, Matrifen, Mezolar, Osmanil,
• increase in circular smooth muscle tone in bile ducts and ureters
Victanyl; see Figure 1) routes. These latter routes are
valuable in that the transdermal preparation gives up
Cardiovascular effects
to three days of potent analgesia, while the buccal
• peripheral vasodilatation and postural hypotension
preparation works very rapidly to control the onset of
severe breakthrough pain. Since the transdermal
Histamine release
preparation is available in a reservoir or matrix for-
• common with morphine, includes occasional urticaria, vasodilatation and
mulation, it is best to continue with the type initially
bronchoconstriction
used as bioavailability may vary between products.
Transdermal fentanyl is now available as a 12µg
If the patient is very ill they are likely to be sensitive to small changes in
preparation, allowing for greater ease of titration,
opioid dose, especially if opioid naive. Are the signs and symptoms
especially in the patients where side-effects may be
secondary to the opiate or the disease?
problematic.
Instanyl is an intranasal spray of fentanyl available Table 4. Side-effects that may occur when treating severe pain with opioids
in 50-200µg dosage. Since it works like buccal fentanyl
(through mucous membranes) its onset time is fast gually (Temgesic) or as a transdermal preparation
and the same precautions apply. As there is variable (BuTrans, Transtec). Unlike the stronger buprenor-
bioavailability, dosage must be titrated to effect. phine transdermal preparations (Transtec 35, 52.5 or
Table 6 gives approximate equivalent doses of the 70µg per hour delivery over three days), the lower-dose
various opioids available. preparations have a seven-day duration of action and
can be introduced at an earlier stage in pain manage-
Opioids with partial mu receptor activity ment (BuTrans 5, 10 or 20µg per hour delivery).
Buprenorphine Although buprenorphine can also be adminis-
This partial agonist has 30 times the potency of mor- tered parenterally, the rapid rise in drug plasma lev-
phine. Buprenorphine binds intensely to the mu recep- els tends to be associated with more side-effects,
tor, although its intrinsic activity is low.5 It undergoes including respiratory depression that is not reversible
high first-pass liver metabolism if swallowed, but due to by the administration of naloxone, so that other res-
its high lipid solubility (200 times that of morphine) it piratory support measures may be necessary. Sedation
is readily absorbed from the oral mucosa. Due to this and nausea tend to be worse than that seen with mor-
feature it is very effective when administered sublin- phine but euphoria is less common.

www.prescriber.co.uk Prescriber 19 March 2010 31

Severe pain

Pentazocine and meptazinol as pure mu agonists. Since it lowers seizure threshold

These partial agonists are not widely used. Penta- it is best avoided if there is a history of epilepsy.
zocine is available for oral administration (50mg every Tramadol should be used with caution in patients
three to four hours), or parenterally 30-60mg every who concurrently take tricyclic antidepressants, as they
three to four hours. It is associated with particularly have a similar mechanism of action. For the same rea-
unpleasant side-effects such as hallucinations and son, their concurrent use with MAOIs should be
depersonalisation (6-10 per cent).5 avoided.
Meptazinol (Meptid) can be administered par-
enterally or orally, the oral dose being 200mg three to Routes of administration
six hourly, the iv dose 50-100mg two to four hourly. When pain is acute and severe, the iv administration
These drugs have partial mu and kappa receptor activ- of analgesia is preferable since there is a rapid onset
ity, and when given to patients on established mu ago- and the ability to quickly titrate the dose to the
nists may induce withdrawal symptoms. patient’s needs. This should not be a problem in a hos-
pital or hospice situation. Acute severe pain in the
Tramadol community is problematic, in that a clinician is gener-
Tramadol is considerably less potent than morphine ally not immediately available to administer iv analge-
and, although it has some opioid activity, the majority sia. However, the iv route is still preferable for acute
of its efficacy is through noradrenaline and serotonin pain, such as that due to MI.
reuptake inhibition. Parenteral and oral preparations An alternative for those who suffer from acute
are available, the latter as an immediate- or sustained- exacerbations of chronic pain, such as chronic pan-
release product. Typical adult dosing is up to 400mg creatitis, is buccal fentanyl, which has a rapid analgesic
per day. If side-effects such as sedation or nausea are onset.14,15 A 400µg lozenge has similar potency to 4mg
problematic, the compound preparation of paraceta- iv morphine or 12mg oral morphine. However, it is
mol with tramadol (Tramacet) may be better toler- essential that careful selection criteria, goals and lim-
ated. Tramadol has considerably less potential for itations in the availability for individuals are made
abuse than most of the other potent analgesics, such before prescribing rapidly acting opioids to minimise

Opioid Interaction Effect

All domperidone, metoclopramide antagonism of GI effect

CNS depressants enhanced depressant effect
anticonvulsants increased opioid metabolism
cimetidine reduced opioid metabolism

Dextropropoxyphene warfarin, carbamazepine enhanced effect of interacting drug

Methadone phenytoin faster elimination of opioid

rifampicin faster elimination of opioid

Morphine older than 50 years reduced clearance of opioid

clomipramine, amitriptyline increased bioavailability of opioid

Pethidine phenobarbital accumulation of norpethidine

phenytoin faster elimination of opioid
MAOIs CNS excitation, hyperpyrexia and convulsions

Tramadol cardiac glycosides increased risk of digoxin toxicity

SSRIs increased CNS toxicity
MAOIs sympathomimetic pressor response – this can
occur up to 2 weeks after discontinuing
the MAOI

Table 5. Common drug interactions with opioids

32 Prescriber 19 March 2010 www.prescriber.co.uk

Severe pain

tolerance. Buccal fentanyl has been shown to reduce

SPL
the number of calls for primary-care physicians, as well
as calls to accident and emergency departments,
because of pain.16
If pain is chronic the oral route is often preferred,
but to prevent plasma levels rising and falling rapidly
throughout the day, 12- to 24-hourly preparations are
preferred. An alternative is to consider fentanyl or
buprenorphine patches. These release a lipid-solu-
ble opioid through the skin into the subcutaneous
fat from where it is absorbed into the systemic circu-
lation. 17 These preparations are ver y potent but
plasma levels take 6-12 hours to become therapeu-
tic. Likewise when the patch is removed, a depot of
the drug remains in subcutaneous fat continuing to Figure 1. Transdermal fentanyl provides up to three days of
have an effect for a further 12-24 hours. When a new potent analgesia; several preparations are now available, but
patch is applied it should be at a different site to the bioavailability may vary between products
previous one.
Skin temperature affects peripheral blood flow so as driving. This may well be the case on starting opi-
it is important to be aware that a sustained rise in ambi- oids, but when patients in chronic pain use opioid
ent or body temperature can increase drug uptake medication for many weeks, this impression has not
substantially – a rise in body temperature of 3°C will been confirmed. In a structured evidence-based
result in an increased absorption rate of 30 per cent. review, there was no evidence of impairment of psy-
chomotor abilities immediately after being given doses
Practical aspects of opioids, or any consistent evidence for a greater
Respiratory and cardiovascular depression incidence in motor vehicle violations or accidents in
Depression of the CNS due to excessive opioid dosing opioid-dependent or -tolerant individuals.19
can be readily reversed by the iv administration of the Rather than impairing psychomotor tasks, it has
opioid antagonist naloxone. This agent has a duration been illustrated that test scores significantly improved
of action in the region of 20 minutes so that repeated in patients with chronic back pain during the long-
dosing may well be required, since most opioids have term use of oxycodone or transdermal fentanyl.20
a considerably longer action. Dosage is in the range Long-term therapy with opioids does not inevitably
of 0.1-0.4mg, and if given in increments may not nec- impair complex skills such as driving, but the decision
essarily reverse all of the analgesia from the opioid. It to permit driving must be made in individual cases.21
is not a particularly effective antagonist for partial-ago-
nist analgesics, such as buprenorphine, where other Pregnancy
supportive measures may be necessary. The prescription of any medication during concep-
Naloxone will reverse all side-effects seen with mor- tion or pregnancy is best avoided where possible.
phine, including CNS depression, nausea and itch. If Manufactures of NSAIDs recommend avoiding their
given to habitual opioid users it will produce marked use during pregnancy, especially towards term, since
withdrawal symptoms, such as abdominal cramps, they can interfere with closure of the fetal ductus arte-
sweating and agitation. riosus in utero, resulting in persistent fetal pulmonary
hypertension. Babies born to women taking opioids
Addiction have about a 50 per cent chance of showing symptoms
Expert opinion leans towards the view that opioid of drug withdrawal,6 but methadone, buprenorphine
treatment does not carr y a high risk of iatrogenic and morphine have all been used to treat women seek-
addiction in patients suffering chronic pain, publica- ing recovery from opioids without any evidence of
tions on co-morbid chronic pain and addiction being harm to the newborn.22
dominated more by opinion than by evidence.18 Opioids appear to be a safe pharmacological
option for the treatment of pain during pregnancy,
Driving and should be considered if analgesia is needed for
Like all sedative medication, opioids are thought to severe pain as they are amongst the least organ-toxic
worsen the performance of psychomotor tasks such agents.

34 Prescriber 19 March 2010 www.prescriber.co.uk

Severe pain

in renal failure. One of the main metabolites of tra-

Opioid Route Equivalent 24-hr dose
madol, together with the parent drug, accumulates in
Morphine po 30mg renal failure, and methadone and hydromorphone
Codeine po 240mg (Palladone) also depend heavily on renal excretion.
Hydromorphone po 6mg Although the manufacturers of oxycodone advise
Oxycodone po 10-15mg against its use in severe renal failure, its half-life is only
Methadone po 30mg increased by one hour in partial renal impairment.23
Fentanyl td 12µg/hr*
Buprenorphine td 20-35µg/hr* Generic prescribing
Tramadol po 120mg There is a general consensus that it is best not to
switch between differing preparations of potent opi-
Table 6. The approximate potency of various opioids – oral
oids, especially transdermal and sustained prepara-
(po) and transdermal (td). This is only a guide – since there is
tions, as bioavailability may differ to a clinical extent.
considerable interpatient variation in the response to these
drugs it is essential to titrate the dose.27,28 *Transdermal
Some trusts now have specifically listed medications,
medications are continuously released, so equivalent doses including opioids, that are unsuitable for generic
are given as µg per hour prescribing.24

Renal dysfunction Pain Management Programmes

Although the majority of medications used in pain con- Over the past few decades the multidisciplinar y
trol are excreted by the kidney, the initial dose of most approach to managing difficult, and in particularly
medications does not need to be reduced in renal fail- chronic, pain has led to the establishment of Pain
ure: it is the subsequent doses that need to be reduced Management Programmes. The aim is to use cogni-
or the time interval between doses increased. Opioids tive behavioural principles to improve the quality of
such as codeine and morphine are conjugated to glu- life by educating patients about the physiological and
curonides and these are excreted by the kidney. If the psychological aspects of pain, and how self-manage-
active metabolites cannot be excreted due to renal dys- ment can help.
function, side-effects such as sedation, or worse still This multidisciplinary approach tends to be run
respiratory depression, can ensue. in a nonhospital setting with groups of patients work-
A 25 per cent reduction in morphine dosage is rec- ing together led by physiotherapists, psychologists and
ommended if creatinine levels are 150-300mmol per other appropriate healthcare professionals. This can
litre. At levels above 300mmol per litre it is recom- lead to changes in pain beliefs and habits that con-
mended that 25 per cent of the normal dose is used tribute to pain disability.
and at less frequent intervals, but titrated to an appro- Further details can be found in the BPS document
priate response.10 Recommended Guidelines for Pain Management Programmes
Pethidine is normally demethylated to the active for Adults.25
metabolite norpethidine which, although a CNS
depressant, is proconvulsant and tends to accumulate Conclusion
Severe pain requires swift control. Nociceptive pain,
Further reading at www.prescriber.co.uk especially that of visceral origin, responds best to opi-
oids, preferably by the iv route. Renal colic and joint
Effentora: fentanyl buccal tablet for breakthrough cancer and bone pain respond better to opioid medication
pain (New products, 19 April 2009) if used in conjunction with an NSAID due to the high
Opioid use in palliative care: available options and levels of prostaglandin involved in the initial genera-
concerns (Prescribing in practice, 5 June 2008) tion of the nociceptive signal.
Recommended management of cancer pain in the older Potent opioids should not be withheld in cases of
patient (Prescribing in older people, 5 Nov 2008) severe chronic pain but should be used in accordance
Role of transmucosal opioids in managing breakthrough with specialist guidelines mentioned earlier. 7 New
pain (Prescribing in practice, 19 Nov 2009) updated guidelines have recently been published by
Targinact: targets opioid-induced constipation (New the BPS;26 in addition to replacing the previous doc-
products, 5 July 2009) ument, this highlights the limits and hazards in the
Unrecognised opioid toxicity in a patient with cancer long-term use of potent opioids. These include the
pain (Drug points, 19 May 2007) endocrine effect of opioids and their immunosuppres-
sion and hyperalgesic effects.

36 Prescriber 19 March 2010 www.prescriber.co.uk

 Severe pain

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and the Royal College of Psychiatrists. 2004. society.org/book_pmp_main.pdf.
8. Rowbotham MC. The debate over opioids and neuro- 26. British Pain Society. Opioids for persistent pain: good prac-
pathic pain. In: Kalso E, et al, eds. Opioid sensitivity of chronic tice. Januar y 2010. www.britishpainsociety.org/book_
noncancer pain. Progress in pain research and management. opioid_main.pdf.
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11. Beckwith MC, et al. J Pain Palliat Care Pharmacother Dr Campbell is consultant in anaesthesia and pain
2002;16:45-59. medicine at Ulster Hospital, Belfast

Prescription review No. scrips

(000s)
Cost
(£000s)

In 2008, GPs in England wrote 14.8 million pre-

buprenorphine 766 23 761
scriptions for strong opioids at a total cost of £212
codeine phosphate 2 602 8 503
million. This represents an increase in volume of
38 per cent and an increase in costs of 48 per cent diamorphine 98 6 711
since 2005. dihydrocodeine 2 133 11 281
Now comprising 5 per cent of volume and 29 per fentanyl 795 61 496
cent of spending on strong opioids, fentanyl pre- hydromorphone 10 450
scribing (largely transdermal formulations) has dou- meptazinol 83 1 449
bled since 2005 and accounts for over one-third of methadone 82 1 693
cost growth. The market share of buprenorphine has
morphine sulphate 1 919 20 019
more than doubled to 5 per cent and costs have
oxycodone 623 30 584
increased from less than 0.5 per cent to 11 per cent
of the total, again with an increase in the use of trans- pethidine 67 457
dermal products. tramadol 5 621 45 179
For oxycodone, prescribing and spending have
Table 7. Number and cost of prescriptions for strong opioids,
doubled. Spending on codeine phosphate has fallen
England, 2008
by 24 per cent since 2005, but there has been little
change in the use of pethidine, dihydrocodeine and phine has increased by about half over this period,
meptazinol. Prescribing of morphine sulphate but costs have risen by one-third and three-fold
(mainly MST Continus and Oramorph) and diamor- respectively.

www.prescriber.co.uk Prescriber 19 March 2010 37

Severe pain

Resources
Guidelines its associated conditions. Tel: 020 7202 8580; e-mail:
British Pain Society. The assessment of pain in older peo- sarah.griffin@paincoalition.org.uk; website: www.pain
ple. October 2007. www.britishpainsociety.org/ coalition.org.uk.
book_pain_older_people.pdf.
Pain Concern. Information and support for pain suf-
British Pain Society. Opioids for persistent pain: good prac- ferers and those who care for them. Tel: 01875 614537;
tice. Januar y 2010. www.britishpainsociety.org/ Listening Ear helpline: 0844 4994676 (Mon-Fri 10am-
book_opioid_main.pdf. 4pm); e-mail: info@painconcern.org.uk; website:
www.painconcern.org.uk.
British Pain Society. Recommended guidelines for pain
management programmes for adults. April 2007. The Pain Relief Foundation. UK charity which funds
www.britishpainsociety.org/book_pmp_main.pdf. research into the causes and treatment of chronic pain
and is concerned with education of health profession-
als about pain management. Tel: 0151 5295820; e-
Groups and organisations
mail: secretary@painrelieffoundation.org.uk; website:
Action on Pain. National charity providing support for
www.painrelieffoundation.org.uk.
patients and carers. Tel: 01362 820750; PainLine: 0845
6031593 (Mon-Fri 10am-4pm); e-mail: aopisat@btin- Pain Support. Friendly and informative nonprofit
ternet.com; website: www.action-on-pain.co.uk. organisation for those with chronic pain. An inter-
active site with a confidential contact club and lively
British Pain Society. Tel: 020 7631 8870; e-mail: discussion page. Website: www.painsupport.co.uk.
info@britishpainsociety.org; website: www.british
painsociety.org. Websites
International Association for the Study of Pain:
Chronic Pain Policy Coalition. A forum to unite www.iasp-pain.org.
patients, professionals and parliamentarians in a mis-
sion to develop an improved strategy for the preven- Oxford Pain Internet site: www.medicine.ox.ac.uk/
tion, treatment and management of chronic pain and bandolier/booth/painpag/index.html.

38 Prescriber 19 March 2010 www.prescriber.co.uk