Page 48 Guide to Pain Management in Low-Resource Settings

36 Kay Brune

neuron is also regulated by N-type calcium channels. Nevertheless, low-dose ketamine (<0.2 mg/kg/h S-
Th e blockade of these channels blocks the infl ow of ketamine or <0.4 mg/kg/h ketamine) maybe helpful as
calcium into glutamate cells, thus reducing glutamate a “rescue medication” in uncontrolled pain, e.g., due to
release and activation of NMDA receptors. However, nerve plexus infi ltration in cancer. Unfortunately, as oral
as these N-type channels are present in most neuronal bioavailability is unpredictable, only the intravenous
cells, a general blockade would be incompatible with route can be used.
life. But recently ziconotide, a toxin from a sea snail, has
been found to block these channels when administered Pearls of wisdom
directly into the spinal column, with tolerable side ef-
fects. Unfortunately, intrathecal administration of drugs • Th e drugs discussed in this chapter allow for suc-
is quite a sophisticated and expensive option for pain cessful treatment of most pain conditions, but
control, and presently it is done only at a few highly spe- not all.
cialized pain centers for exceptional cases. • It should be kept in mind that the most impor-
tant prototypes of the nonopioid analgesics are
What other—more practical—options are the COX inhibitors, which comprise the most
available, when antiepileptic drugs fail to help?
widely used drugs worldwide because they are
Another option for treating pain in the clinical setting also given against fever, infl ammation, and many
is the use of ketamine, which blocks use-dependent so- states of discomfort, including migraine. Due to
dium channels of the glutamate NMDA receptor. Such their mode of action, their eff ect plateaus. In oth-
receptors are not limited to the pain pathway, but are er words, the normalization of hyperalgesia ends
ubiquitously involved in neuronal communication. when prostaglandin E production is completely
2
Consequently, the blockade of this sodium channel can- suppressed. Increasing the dose will not increase
not be limited to pain pathways, but a certain degree of the eff ect any further.
selectivity is achieved by the use dependence. In other • Constant inhibition of COXs in the vascular wall
words, painful stimuli lead to a higher probability of (selectively or nonselectively) leads to a constant
opening of this channel, which can be accessed only in blockade of the production of the vasoprotective
the open position by ketamine, which can then block it. factor prostacyclin (PGI ). Th is appears to be the
2
Still, the relatively low specifi city of ketamine’s action main reason for the increased incidence of car-
causes many unwanted drug eff ects, ranging from “bad diovascular events (heart attack, stroke, athero-
trips” (dysphoria) to lack of coherent thinking and at- sclerosis), seen with the use of COX inhibitors,
tention. Consequently, the use of ketamine is restricted including acetaminophen (paracetamol).
to the clinical setting, in particular analgesic sedation.

Table 2
Physicochemical and pharmacological data of nonselective COX-2 inhibitors
COX-1/ Binding Primary Metabolism Single Dose (Max.
Pharmacokinetic/ COX-2 to Plasma Oral Bio- (Cytochrome Daily Dose) for
Chemical Subclass Ratio Protein VD availability t t P-450 Enzymes) Adults
max 50
Acetaminophen ~ 20% ~70 L ~ 90% 1 h 1–3 h Oxidation (direct sul- 1 g (4 g)
(paracetamol) fation)
Celecoxib 30 91% 400 L 20–60% 2–4 h 6–12 h Oxidation (CYP2C9, 100–200 mg (400
CYP3A4) mg) for osteoarthro-
sis and rheumatoid
arthritis
Etoricoxib 344 92% 120 L 100% 1 h 20–26 h Oxidation to 6’-hydroxy- 60 mg (60 mg) for
methyl-etoricoxib (major osteoarthrosis, 90
role: CYP3A4; ancillary mg (90 mg) for
role: CYP2C9, CYP2D6, rheumatoid arthri-
CYP1A2) tis, 120 mg (120
mg for acute gouty
arthritis