Page 365 Guide to Pain Management in Low-Resource Settings

Drug Profi les, Doses, and Side Eff ects 353

the side eff ects of NSAIDs. Rapid intravenous application in HIV/AIDS patients. Unfortunately, chronic noncan-
may be associated with hypotension, which should not cer pain, like chronic nonspecifi c back pain or head-
be mistaken for a allergic response, which in fact occurs ache, is only rarely a good indication for opioids. In pal-
only rarely. Contraindications include porphyria, glucose- liative care, opioids may also be used to control dyspnea
6-phosphate dehydrogenase defi ciency, pregnancy (espe- very eff ectively.
cially the last trimester), and breastfeeding. Drug abuse with opioids is extremely rare in pa-
The standard dose of dipyrone is 500–1000 tients who do not have a history of alcohol, benzodiaze-
mg q.i.d. pine, or opioid abuse! Th e reason is that when opioids are
used for control of pain, the regular dosing avoids major
Opioid analgesics changes in serum levels, therefore preventing the activa-
tion of our dopaminergic reward system (as opposed to
For legal reasons, opioids may be classifi ed into weak drug addicts experiencing a “high” after sudden blood
and strong ones. Th e World Health Organization level increases after the intravenous push-injection of an
(WHO) three-step ladder for cancer pain management opioid and a “craving” in the time interval before the next
also follows this distinction, advocating fi rst the use of a injection). Do not confuse drug addiction with physical
“weak” opioid (e.g., tramadol or codeine) followed by a dependence. As a matter of fact, all opioids cause physical
“strong” opioid (e.g., morphine or hydromorphone). For dependence (as with a number of other classes of drugs,
clinical practice, this distinction is probably irrelevant, such as beta blockers or anticonvulsants), and patients
because there are no data indicating that equianalgesic will develop symptoms of withdrawal if they discontinue
doses of “weak” and “strong” opioids have a diff erent opioids without tapering down the dose.
side-eff ect or eff ectivity profi le. Th erefore, opioid thera-
“Weak” opioids
py may be started with low doses of a “strong” opioid, if
“weak” opioids are not available. According to the three-step ladder of the WHO for can-
Opioids may also be classifi ed according to their cer pain, weak opioids should be used fi rst, if nonopioid
receptor affi nity. Th e analgesic eff ect of opioids is me- analgesics are insuffi cient to control the pain. Tramadol,
diated through binding to μ, κ, and δ receptors. With codeine, and dihydrocodeine are examples of this group.
the exception of pentazocine, tramadol, and buprenor- Tramadol has affi nity to the μ-opioid-receptor, as well
phine, all commonly available opioids are more or less as reuptake inhibiting activities for norepinephrine and
pure μ-agonists with a linear dose-eff ect function. Tra- serotonin in the descending inhibitory nervous system.
madol, pentazocine, and buprenorphine on the other Tramadol is also thought to have some NMDA-receptor
hand have a ceiling eff ect, and they bind to diff erent or antagonist eff ects. Weak opioids are sometimes avail-
additional receptors. Opioid receptors are found in sev- able in fi xed combinations with NSAIDs or acetamino-
eral areas of the brain, the spinal cord and—contrary to phen/paracetamol.
common belief—in the peripheral tissues, especially if Weak opioids, unlike strong opioids, have a ceil-
infl ammation is present. Th e analgesic eff ect is a result ing eff ect, meaning that there is a maximum dose above
of the reduced presynaptic opening of calcium channels which there is no further increase of analgesia. Th e risk
and glutamate liberation as well as the increase of post- for respiratory depression is very low with weak opioids.
synaptic potassium outfl ow and hyperpolarization of Depending on the region of the world where tramadol
the cell membrane, which reduces excitability. or codeine are used, certain genetic polymorphisms
Treatment with opioids involves a balance be- may exist that can result in the need for unexpectedly
tween suffi cient analgesia and the typical side eff ects. high or low doses. For example, in Eastern Asia and
Luckily, the most frequent side eff ects—nausea, respira- Northern Africa, hepatic metabolism of codeine and
tory depression, and sedation—diminish over time be- tramadol may be impaired in a considerable proportion
cause of tolerance, and constipation may be prophylac- of the population. Otherwise, the drugs are considered
tically treated with good results. very safe, even in patients with impaired organ function.
Th e best clinical indications for opioids are the Th e standard dose for tramadol is 50 to 100 mg
symptomatic treatment of moderate to severe acute t.i.d., which is suffi cient for postoperative analgesia after
pain, especially postoperative pain and cancer pain. most surgical interventions. Tramadol is also available
Neuropathic pain may be an indication, too, especially in an intravenous application formulation.