CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 6, July 2012
AFRICA
351
fact that warfarin is an excellent cardio-
protectant.’
‘For years we were told that warfarin
was insufficient protection for the heart,
despite some evidence to the contrary (the
ASPECTS study group trial in the UK),
and that antiplatelets were required in AF
patients with coronary artery disease’, he
said. ‘I only add aspirin (81 mg) in those
patients with coronary heart disease,
unstable angina or stents’, Dr Butcher
said, noting that dual use did increase the
bleeding risk.
Referring to clinical practice, Dr
Butcher noted that after a TIA he provides
dabigatran immediately, while with a
large stroke it is customary to wait about
a week, rescan and then put the patient
on dabigatran, provided spontaneous
haemorrhagic transformation has not
occurred. He stressed that this practice
is off-label, as the trial evidence of
RE-LY was based on 14 days’ post-stroke
administration of dabigatran.
With regard to patients on dabigatran
undergoing surgery, Dr Butcher
encouraged physicians to stay involved
with the patient and not to stop the
drug too early. ‘Bridging the patient with
low-molecular weight heparin is not
required, but may be useful in situations
where surgeons are uncomfortable
with the newer agents. Guidelines for
dabigatran usage in this situation are
currently being developed.’
Julia Aalbers, Glenda Hardy
1.
Connolly SJ,
et al
. Dabigatran versus warfa-
rin in patients with atrial fibrillation.
N Engl
J Med
2009;
361
: 1139–1151.
2.
Dawlatshahi D, Butcher KS, Asdaghi N,
et al
. Poor prognosis in warfarin-associat-
ed intracranial haemorrhage despite anti-
coagulation reversal.
Stroke
2012; May 3
(e-published).
3.
Kaatz S, Kouides PA, Garcia DA,
et al.
Guidance on the emergent reversal of oral
thrombin and factor Xa inhibitors.
Am J
Hematol
2012;
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(Supp1): S141–145.
Managing neuropathic pain: first expert recommendation for South Africa places emphasis on
stepwise pharmacological intervention
Neuropathic pain, initiated or caused by a
primary lesion or disease in the peripheral
or central nervous system, is best treated by
first defining the aetiology, then treating
the primary cause such as diabetes or
rheumatoid arthritis, and thirdly, initiating
appropriate and adequate doses of pain-
relieving medication. ‘Frequently, patients
are referred to us at the Pain Clinic with
appropriate pain-relieving therapy, but
at very timid doses’, Dr Milton Raff,
Christiaan Barnard Memorial Hospital
said at the recent FCPSA congress.
In his presentation, Dr Raff dealt with
the basics of the physiology of pain,
stressing the transmission mechanism of
pre-synaptic neurons releasing neuro-
transmitters, reaching the receptor on
the post-synaptic neuron in onward
transmission to the spinal cord, cortex and
the limbic brain, which integrates pain
awareness with subjective factors such as
fear, anxiety and sleep disturbance. ‘At
each physiological level, we have agents
to target the pain mechanism (Table 1)
but we must appreciate that one aetiology
does not cause one symptom but causes a
cluster of symptoms that are shared with
other aetiologies, requiring more than one
therapeutic approach’, Dr Raff noted.
With regard to neuropathic pain, there
are four main drug classes that can be
used: carbamazepine as a sodium channel
blocker plus anti-depressants; the alpha-2
delta-ligands (pregabalin and gabapentin);
SNRIs; and opioids. ‘The difficulty is that
there are no predictors to guide choice
and no head-to-head studies to compare
agents’, Dr Raff pointed out. This has
led to the development of a stepwise
pharmacological approach of using
agents, first developed by Dickenson,
1
and latterly followed by international
agencies such as the European Federation
of Neuroscience guidelines.
2
Recent South African guidelines
have been published,
3
with input from
an expert panel consisting of specialists
from the fields of psychiatry, neurology,
neurosurgery, anaesthesiology, family
medicine and basic science (Table 2).
The expert panel makes the following
recommendations:
•
First-line therapy is the alpha-2 delta-
ligands (pregabalin or gabapentin),
TCAs (tricyclic antidepressants) or the
SNRIs (duloxetine and venlafaxine).
•
Second-line therapy consists of a
combination of these drugs.
•
Third-line therapy involves the use of
tramadol and the opioids (morphine,
oxycodone, fentanyl).
‘Interestingly, our so-called proven
use of tricyclic antidepressants with their
known wide spectrum of side effects is
based on a very small study of 79 cases’,
Dr Raff said.
TABLE 1. PATHOPHYSIOLOGICAL TARGETS IN PAIN MANAGEMENT
Peripheral activation (mainly prostaglandin
mediated)
NSAIDS, COXibs
Factors affecting transmission
e.g. increased sodium channels
Carbamazepine, lignocaine
Conduction via afferent neurons to dorsal horn
(alpha-2 delta subunit)
Pregabalin, gabapentin
Dorsal horn receptors
(NMDA receptors)
Ketamine (anaesthesia)
Gabapentinoids
Spinal cord (COX-3 mediated and other
mediators)
NSAIDS, paracetamol
Brain (
µ, κ, δ
receptors)
Opioids
Modulation of the feedback mechanism
(serotonin and noradrenaline mediated)
Tramadol
SNRIs (selective noradrenaline reuptake inhibitors)
SSRIs (selective serotonin reuptake inhibitors)
