Page 172 Guide to Pain Management in Low-Resource Settings

160 Rainer Sabatowski and Hans J. Gerbershagen

Transdermal fentanyl, a synthetic mu-receptor grapefruit juice are responsible for magnifi ed metha-
agonist, delivers fentanyl via a self-adhesive patch with done eff ects, whereas corticosteroids, St. John’s wort,
a rate-limiting membrane. Due to the slow delivery, the carbamazepine, and rifampin might lower the eff ect.
patches have to be changed every 72 hours (in 20% of Methadone might cause prolongation of the QT-inter-
patients a new patch has to be applied every 48 hours val and may cause torsades de pointes ventricular tachy-
due to end-of-dose failure). Th e conversion ratio to cardia. Th erefore in patients at risk of hypokalemia, car-
morphine is 100:1 (e.g., 120 mg morphine/day equals diac diseases, or cocaine abuse, methadone should be
50 μg fentanyl/hour). Advantages over morphine are used carefully, and an electrocardiogram should be per-
the absence of active metabolites. However, in the pres- formed, if available.
ence of renal dysfunction, sensitivity to the drug’s eff ect
is increased. Liver cirrhosis does not seem to aff ect the Corticosteroids
pharmacology of fentanyl, but impaired liver blood fl ow Corticosteroids, especially dexamethasone, are helpful
or liver failure does so. Constipation is less pronounced when there is clinical evidence of nerve structure com-
as compared to morphine. Disadvantages include adhe- pression or pain due to edema surrounding the metas-
sive problems and the slow onset of action (when the tases. In cases of severe pain, doses of 16–24 mg a day
patch is applied for the fi rst time, a 12-hour gap before should be prescribed initially. In cases of an emergency
the onset of action has to be taken into account). (spinal cord compression) initial intravenous doses of
Methadone might be considered an important up to 100 mg, followed by 60 mg in three divided doses
alternative and, in cases of severe plexopathy, even as should be used. Steroids should be continued until oth-
a fi rst-line opioid. Methadone is a synthetic opioid act- er treatment approaches (radiotherapy, drug therapy)
ing as a μ-receptor agonist, an NMDA-receptor block- are initiated, after which dexamethasone can be tapered
er, and a presynaptic serotonin reuptake inhibitor. Due off gradually. Dexamethasone has two other “side ef-
to its long elimination half-life of 24 hours (up to 130 fects” that might be helpful for palliative treatment. It
hours), titration is sometimes diffi cult, but methadone has an antiemetic eff ect and might increase the appetite.
can also be regarded as a long-acting opioid, which ne- To increase appetite, dexamethasone can be prescribed
cessitates only three to four daily dosages. Th e usual continuously in a daily dose of 2 mg.
dose begin with 5 mg q.i.d. for 2–3 days. For inadequate
NMDA-receptor antagonists
pain relief or breakthrough pain, an additional 5 mg
might be administered. Switching to or starting with Excitatory neurotransmitters, such as glutamate, play a
methadone might be diffi cult. For this reason an algo- major role in pain transmission at the spinal cord level.
rithm is recommended. On day 1 treatment with pre- Glutamate activates the NMDA receptor, which is as-
existing opioids should be stopped. Oral methadone sociated with phenomenon such as central sensitiza-
2.5–5 mg should be administered every 4 hours. For tion. Ketamine, an NMDA-receptor antagonist and a
breakthrough pain 2.5–5 mg methadone might be used drug used extensively in anesthesia, should be consid-
additionally (with a dosage interval of 1 hour). On days ered, especially in situations when opioid analgesia is
2–3, a dose maximal increment of 30% might be neces- not eff ective enough. Th e addition of oral ketamine ap-
sary, if pain relief on day 1 was not suffi cient. On day proximately 10–25 mg t.i.d. should be combined with
4, 72 hours after initiating methadone therapy, the dos- diazepam in low doses (e.g., 5 mg) to avoid psychotic
ing interval should be changed to t.i.d. (every 8 hours), symptoms associated with the use of ketamine.
and the intervals for breakthrough medication should
Cannabinoids
be prolonged to 3 hours as well. If pain relief is still not
adequate or if pain increases due to cancer progression, Newer classes of drugs to treat neuropathic pain are
dose adjustments might be performed. Patients on very cannabinoids. Th ere is evidence that oral delta-9-tetra-
high oral morphine doses (>1000 mg/day) should start hydrocannabinol (THC) and other cannabinoids might
on day 1 with 50 mg methadone q.i.d. Over the follow- provide relief from neuropathic pain, improve appetite,
ing days, dose adjustments should be performed as de- and reduce nausea and vomiting. However, these drugs
scribed above. Due to its metabolism via cytochrome cannot be recommended in general, due to the lack of
P-450, precautions have to be taken to prevent drug in- well-designed studies in the area of cancer-related neu-
teractions. Ketoconazole, HIV protease inhibitors, and ropathic pain.