EDITORIAL
SA JOURNAL OF DIABETES & VASCULAR DISEASE
136
VOLUME 7 NUMBER 4 • NOVEMBER 2010
Africa. It is cheap and can be prescribed by primary healthcare
physicians.
Unfortunately, in addition to the precautions noted in their
article, there are several other contraindications to the use of
amitryptilline, e.g. prostatic enlargement (may precipitate urinary
retention) and porphyria, and so there are many diabetic patients
with PDN in whom amitryptilline is contraindicated. The elderly
diabetic patient with co-existent heart disease is also a frequent
problem in this regard. Others find the side effects such as dry
mouth and sleepiness too troublesome.
In these situations, the practitioner will have to use an alternative.
Duloxetine or gabapentin/pregabalin can then be tried, but not
in public healthcare institutions unless the doctor is a specialist/
named specialist (see Table 1). Now, unless there are similar contra-
indications, e.g. cardiac disease, carbamazepine may be the next
drug for the public healthcare doctor to prescribe.
Tesfaye and Selvarajah
2
did not mention using carbamazepine in
their article, despite its efficacy in PDN.
17
This is probably because
of the potentially serious and occasionally fatal side effects of
carbamazepine, and the availability in the UK of safer but more
expensive second-line drugs. During use of carbamazepine,
blood counts and renal and liver function should be monitored.
In addition, the manufacturers of carbamazepine recommend the
prior screening of patients of central Asian origin for the HLA-
B*1502 allele, as this is associated with a fatal Steven-Johnson
reaction.
18
The problem in South Africa is that high-resolution typing of HLA
alleles is not routinely available due to the high cost of the reagents.
As a cheaper alternative, testing can be done for HLA-B15 with an
HLA class 1 serological typing and then if this antigen is present,
an alternative drug to carbamazepine should be considered (pers
commun, Dr Pieter Meyer, National Health Laboratory Services,
Tshwane Academic Division).
In clinical practice, carbamazepine is often successfully used
in South Africa for neuropathic pain of various aetiologies, but
screening and monitoring tests are frequently omitted. While this
could be because the practitioner may not know of their necessity,
in lower levels of public healthcare these tests may not be available
or there may be difficulties in the patient re-attending for test
results. In the private sector, medical aids may not wish to pay for
these tests.
Another particularly South African concern is the diabetic
patient who is also on antiretroviral medication, a not-infrequent
co-morbid condition in this era of an HIV pandemic, as the levels of
antiretroviral agents may be reduced with carbamazepine.
In essence, while carbamazepine can be used when amitryptilline
is contraindicated, particularly if the pain is of the stabbing or
lancinating type, the practitioner must be aware of the contra-
indications, adverse effects and potential for drug interactions with
this drug. Where it is available, oxycarbazepine (structurally related
to carbamazepine) may be a safer and better-tolerated alternative.
19
Second-line treatment
If the above first-line agents fail to control pain adequately, then
Tesfaye and Selvarajah
2
recommend the use of opioid agonists
such as tramadol, morphine and oxycodone, the latter not being
available in South Africa.
Tramadol is referred to as a ‘weak opioid derivative’, but its
action is also due to inhibition of the neuronal re-uptake of
serotonin and norepinephrine, and tramadol should not be used
in conjunction with other drugs which prevent the reuptake of
serotonin, as this can result in the serotonin syndrome.
20
In clinical
practice, amitryptilline is often used in low doses with tramadol,
but there should be a high index of suspicion for signs of the
serotonin syndrome (e.g. flushing, palpitations) and only low doses
of amitryptilline should be used in combination with tramadol.
While tramadol alone or combined with paracetamol as
Tramacet
®
can be effective in the treatment for PDN,
21
there remain
patients in whom stronger analgesics are required and morphine
is the next step. While both morphine syrup and slow-release
morphine tablets should be available for prescription at all levels
of hospitals, slow-release morphine has not been available at most
Free State public hospitals for over a year, for various administrative
reasons, although it remains available in private practice.
Patients with chronic, persistent pain often prefer to use slow-
release morphine as it requires administration only twice a day. This
enables the patient to have a better quality of life with less focus
on pain, compared to when given morphine syrup, as this requires
administration at three- to four-hourly intervals for the same pain
relief.
22
If the patient has pain at irregular intervals, then morphine
syrup with its faster onset and shorter duration of action may be
preferred.
23
When initiating treatment with morphine it should
be emphasised to the patient that the goal is improvement of
function and not solely pain relief. Control of neuropathic pain with
morphine may require relatively high doses and the dose should be
gradually titrated to effect, to minimise adverse events.
24
Unfortunately, South African medical practitioners are often
fearful of prescribing opioids for non-cancer pain, as they areworried
about misuse of opioids by the patient. Indeed, where there is a
history of mental illness or substance abuse, opioids should not be
prescribed. If there is concern that a patient may develop aberrant
drug-related behaviour with opiates, screening tools are available
to help the practitioner decide whether to prescribe opiates.
25
It is
also recommended that all patients who are to be commenced on
opioids are fully counselled regarding the problems of dependence
and an opioids treatment agreement is formulated.
24
Constipation may be a persistent problem and laxatives should
always be prescribed in conjunction with morphine, senna being
cheaper and just as effective as lactulose.
26
In the private sector,
transdermal fentanyl can be used as an alternative to morphine, as
this causes fewer problems with constipation.
27
Other treatments
Topical agents such as capsaicin, as mentioned by Tesfaye and
Selvarajah,
2
and lidocaine (lignocaine) 5% patches are useful
adjuncts to the above treatments,
28
but neither is readily available in
Table 2.
Prescriber restriction categories for Free State public health drugs
Code Prescriber restriction category
10 Registered nurse and higher
12 Specialist nurse and higher (e.g. specialised training in psychiatry)
14 Doctor at primary healthcare level and higher
2 General practitioner at hospital level and higher
4 Specialist designated (e.g. oncology)
5 Named patient (H101 motivation)
