Page 46 Guide to Pain Management in Low-Resource Settings

34 Kay Brune

neuron and thus facilitates transmission of nociception- • Some of these compounds are absorbed quickly
related inputs to the central nervous system, resulting in and others slowly. Th is diff erence is important if
pain sensation. Inhibition of prostaglandin production acute pain relief is required.
by the induced COX-2 reduces (normalizes) excitability • Some compounds are eliminated quickly, others
of the second neuron for glutamate-mediated transmis- slowly. Th ose that are eliminated quickly have a
sion and thus exerts an antihyperalgesic eff ect. short duration of action, and these are often less
Similarly, in the periphery, at the site of trauma toxic at low doses. Slow elimination goes along
or infl ammation COX-2 is induced as well. It produces with prolonged analgesic action but may lead to
prostaglandin E and increases the sensitivity of TRPV1 unwanted side eff ects, including water and fl uid
2
receptors, allowing for the activation of multimodal re- retention, increased blood pressure, and worsen-
ceptors (nociceptors) by temperature, pressure, and ing of cardiac insuffi ciency.
proteins. Again, blockade of prostaglandin production
reduces peripheral hyperalgesia. So, why did I recommend diclofenac
to my friend in case report 1?
Going back to the case report, the acute trauma
caused peripheral and central hyperalgesia within half Th e reasons I recommended diclofenac to my friend
an hour. Th is pain can be reduced eff ectively by inhibi- were:
tors of COXs. Th e widespread use of COX inhibitors 1) Fast absorption
shows the importance of this class of analgesic com- 2) Very potent inhibition of COX, with greater inhi-
pounds. In contrast to what was believed in the past, bition of COX-2 than COX-1
this group of drugs comprises old and new substances, Th e fast onset of absorption of diclofenac resin-
including acetaminophen/paracetamol (formerly be- ate is preferable to the “normal” diclofenac preparations
lieved to have a unique mode of action), aspirin, dipy- in which the active ingredient is often given in an acid-
rone, ibuprofen, indomethacin, and piroxicam. In other resistant coating. Th is may lead to delayed absorption,
words, this group comprises relatively weak compounds and consequently, lack of fast pain relief. On the other
as well as highly eff ective ones. Th ey diff er in their phar- hand, diclofenac, once absorbed, is eliminated quickly
macokinetic behavior and some of their unwanted drug by metabolism. Consequently, to have a prolonged ef-
eff ects that are not related to their mode of action. Acet- fect, slow absorption is necessary.
aminophen overdose, for example, leads to serious liver
failure, which is almost never seen with ibuprofen. Case report 2: Choosing

the right combination
How do the various COX inhibitors available
diff er pharmacokinetically?
A man, aged 71, complained about excruciating pain in
Th is group of drugs exerts analgesia via inhibition of his spine. Th e reason was metastasis of a prostate car-
prostaglandin production. Th e diff erences, however, re- cinoma, the growth of which was not completely con-
sult from their pharmacokinetic characteristics (Table 1). trolled. Every evening the patient took liquid tramadol
• Some (nonacidic) agents such as acetaminophen, in a dose of 100 mg, which did not reduce his pain suf-
dipyrone, and metamizol are distributed homoge- fi ciently. In his desperation he added 3 g (6 tablets) of
neously throughout the body. Th ey are analgesic aspirin, and despite GI discomfort, he found rest. Th e
but not anti-infl ammatory. treating physician changed this combination and pre-
• Other (acidic) agents achieve high concentrations scribed morphine (sustained-release) and naproxen to-
in infl amed tissue, but also in the kidney, stomach gether with a proton pump inhibitor (PPI). Th e patient
wall, bloodstream, and liver. Th ey have an analge- was satisfi ed with this therapy.
sic and anti-infl ammatory eff ect, but gastrointes-
tinal (GI) and kidney toxicity is pronounced (for Why was morphine plus naproxen
all except acetaminophen and dipyrone). the better choice?
• Selective COX inhibitors demonstrate less GI Tumor metastases are surrounded by an infl ammatory tis-
toxicity, no interference with blood coagulation, sue capsule containing many activated nociceptors. Th is
and less aspirin-induced asthma. Examples are layer of infl ammatory cells produces many prostaglandins,
acetaminophen, celecoxib, and etoricoxib. which lead to peripheral and central hyperalgesia. By