Page 53 Guide to Pain Management in Low-Resource Settings

Opioids in Pain Medicine 41

abdomen, and larynx. Th is problem is fi rst recognized to 3 × 40 mg/day orally), which is mandatory during
by the impairment of adequate ventilation followed by chronic opioid use.
hypoxia and hypercarbia. Th e mechanism is not well
Pruritus
understood. Life-threatening diffi culty in assisted venti-
lation can be treated with muscle relaxants (e.g., succi- Opioid-induced pruritus (itch) commonly occurs fol-
nylcholine 50–100 mg i.v., i.m.). lowing systemic administration and even more com-
monly following intrathecal/epidural opioid adminis-
Respiratory depression
tration. Although pruritus may be due to a generalized
Respiratory depression is a common phenomenon histamine release following the application of morphine,
of all μ-opioid agonists in clinical use. Th ese drugs it is also evoked by fentanyl, a poor histamine liberator.
reduce the breathing rate, delay exhalation, and pro- Th e main mechanism is thought to be centrally medi-
mote an irregular breathing rhythm. Opioids reduce ated in that inhibition of pain may unmask underlying
the responsiveness to increasing CO by elevating activity of pruritoreceptive neurons. Opioid-induced
2
the end-tidal pCO threshold and attenuating the hy- pruritus can be successfully attenuated by naltrexone (6
2
poxic ventilation response. Th e fundamental drive mg orally) or with less impact on the analgesic eff ect by
for respiration is located in respiratory centers of the mixed agonists such as nalbuphine (e.g., 4 mg i.v.).
brainstem that consist of diff erent groups of neuronal
networks with a high density of μ-opioid receptors. Routes of opioid administration
Life-threatening respiratory arrest can be reversed by
titration with the i.v. opioid antagonist naloxone (e.g.,
Oral
0.4–0.8–1.2 mg).
Th e majority of opioids are easily absorbed from the
Antitussive eff ects gastrointestinal tract with an oral bioavailability of 35%
In addition to respiratory depression, opioids suppress (e.g., morphine) to 80% (e.g., oxycodone) entering the
the coughing refl ex, which is therapeutically produced circulation. However, they undergo to a high degree
by antitussive drugs like codeine, noscapine, and dex- (40–80%) immediate fi rst-pass metabolism in the liver,
tromethorphan (e.g., codeine 5–10–30 mg orally). Th e where glucuronic acid binding makes the drug inactive
main antitussive eff ect of opioids is regulated by opioid and ready for renal excretion. Exceptions are metabo-
receptors within the medulla. lites of morphine, e.g., morphine-6-glucuronide, which
is itself analgesic, or morphine-3-glucuronide, which
Gastrointestinal eff ects is neurotoxic and can accumulate during renal impair-
Opioid side eff ects on the gastrointestinal system are ment as well as cause serious side eff ects such as re-
well known. In general, opioids evoke nausea and spiratory depression or neurotoxicity. Oral opioids are
vomiting, reduce gastrointestinal motility, increase commonly available in two galenic preparations, an
circular contractions, decrease gastrointestinal mu- immediate-release formula (onset: within 30 min, du-
cus secretion, and increase fl uid absorption, which ration: 4–6 hours) and an extended-release formula
eventually results in constipation. In addition, they (onset: 30–60 min, duration: 8–12 hours). Th ere is pre-
cause smooth muscle spasms of the gallbladder, bili- liminary evidence for ethnic diff erences, e.g., between
ary tract, and urinary bladder, resulting in increased Caucasians and Africans, with regard to the hepatic me-
pressure and bile retention or urinary retention. Th ese tabolism of opioids, i.e., opioids exert a longer duration
gastrointestinal eff ects of opioids are mainly due to of action in Africans. Th is may be due in part to specifi c
the involvement of peripheral opioid receptors in the genetic subtypes of the hepatic enzyme cytochrome
mesenteric and submucous plexus, and are due to a P-450, and in part due to the individual patient’s lifestyle
lesser extent to central opioid receptors. Th erefore, ti- and habits.
tration with methylnaltrexone (100–150–300 mg oral-
ly), which does not penetrate into the central nervous Intravenous/intramuscular/subcutaneous
system, successfully attenuates opioid-induced consti- Th ese diff erent forms of parenteral opioid application
pation. More common practice, however, is the coad- follow the same goals: a convenient and reliable way of
ministration of laxatives such as lactulose (3 × 10 mg application, a fast onset of analgesic eff ect, and bypass