C H A P T E R 2 6
Opioids, opioid antagonists and antimigraine agents
405
Pharmacokinetics
Intravenous (IV) administration is the most reliable
way to achieve therapeutic levels of opioids. Intramus-
cular (IM) and subcutaneous (SC) administration offer
varying rates of absorption, and absorption is slower in
females than in males because of the normal fat content
of female muscles and tissue. These drugs undergo
hepatic metabolism and are generally excreted in the
urine and bile. Half-life periods vary widely, depending
on the drug being used. These agents cross the placenta
and are known to enter breast milk.
Contraindications and cautions
The opioid agonists are contraindicated in the follow-
ing conditions: presence of any known allergy to any
opioid agonist
to avoid hypersensitivity reactions
; diar-
rhoea caused by toxic poisons
because depression of GI
activity could lead to increased absorption and toxicity
;
and after biliary surgery or surgical anastomoses
because of the adverse effects associated with slowed GI
activity due to opioids.
Oxycodone is classified as pregnancy category B,
whereas all of the other opioids agonists are in
category C, so it might be the drug of choice if one is
needed during pregnancy. Extended-release oxycodone
(
OxyContin
) has been associated with abuse because
when the tablet is cut, crushed or chewed, the entire
dose of the drug is released at once. Pregnant women
must be cautioned not to cut, crush or chew these tablets
if they are prescribed this drug. Many sources recom-
mend waiting 4 to 6 hours after receiving an opioid
before breastfeeding the baby if an opioid is needed for
pain control.
Caution should be used in people with respira-
tory dysfunction,
which could be exacerbated by the
respiratory depression caused by these drugs
; recent
GI or genitourinary (GU) surgery, acute abdomen or
ulcerative colitis,
which could become worse with the
depressive effects of the opioids
; head injuries, alco-
holism, delirium tremens or cerebral vascular disease,
which could be exacerbated by the CNS effects of the
drugs
; liver or renal dysfunction,
which could alter the
metabolism and excretion of the drugs
; and during
pregnancy, labour or breastfeeding
because of potential
adverse effects on the fetus or neonate, including res-
piratory depression.
Adverse effects
The most frequently seen adverse effects associated with
opioid agonists relate to their effects on various opioid
receptors. Respiratory depression with apnoea, cardiac
arrest and shock may result from opioid-induced res-
piratory centre depression. Orthostatic hypotension
is commonly seen with some opioids. Gastrointesti-
nal effects such as nausea, vomiting, constipation and
biliary spasm may occur as a result of CTZ stimulation
and negative effects on GI motility. Box 26.3 discusses
a drug approved to treat opioid-induced constipation.
Neurological effects such as light-headedness, dizziness,
psychoses, anxiety, fear, hallucinations, pupil constric-
tion and impaired mental processes may occur as a
result of the stimulation of CNS opioid receptors in the
cerebrum, limbic system and hypothalamus. GU effects,
including ureteral spasm, urinary retention, hesitancy
and loss of libido, may be related to direct receptor stim-
ulation or to CNS activation of sympathetic pathways.
In addition, sweating and dependence (both physical
and psychological) are possible, more so with some
agents than with others.
• Keep this drug and all medications out of the reach of
children.
• Do not take any leftover medication for other disorders
and do not let anyone else take your medication.
• Take this drug exactly as prescribed. Regular medical
follow-up is necessary to evaluate the effects of this drug
on your body.
One of the most uncomfortable side effects of opioid
use is constipation. Frequently, when ordering a opioid
for pain, a prescriber will also order a laxative to avert
serious constipation discomfort. When a person is on
long-term opioids for controlling pain in cases of cancer
or in hospice settings where palliative care uses opioids
to make people comfortable, constipation can be a real
problem. In 2008, methylnaltrexone bromide (
Relistor
)
was approved for the treatment of opioid-induced
constipation in people who are receiving palliative care
and who no longer respond to traditional laxatives.
Relistor
is a peripherally acting, mu-specific opioid
antagonist. It blocks the mu-receptors responsible for
constipation related to opioid use.
Relistor
is given
by subcutaneous injection once each day. It is rapidly
absorbed from the tissues, reaching peak levels in
30 minutes. It is excreted primarily unchanged in the
urine with a half-life of 8 hours. The adverse effects
associated with the drug are related to the increase in
GI activity that occurs—diarrhoea, abdominal pain,
flatulence and nausea.
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BOX 26.3
Laxative for dealing with
opioid-induced constipation
