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P A R T 4
Drugs acting on the central and peripheral nervous systems
O
pioid antagonists
The
opioid antagonists
(Table 26.1) are drugs that bind
strongly to opioid receptors but do not activate them.
They block the effects of the opioid receptors and are
often used to block the effects of too many opioids in the
system. The opioid antagonists in use include naloxone
(
Narcan
) and naltrexone (
Naltraccord
,
ReVia
).
Therapeutic actions and indications
The opioid antagonists block opioid receptors and reverse
the effects of opioids, including respiratory depression,
sedation, psychomimetic effects and hypotension.
These agents are indicated for reversal of the adverse
effects of opioid use, including respiratory depression
and sedation, and for treatment of opioid overdose. (See
Table 26.1 for usual indications for each opioid antag-
onist agent.) The opioid antagonists do not have an
appreciable effect in most people, but individuals who are
addicted to opioids experience the signs and symptoms
of withdrawal when receiving these drugs rapidly.
Pharmacokinetics
Opioid antagonists may be administered parenterally
(SC, IM or IV) or orally. These drugs are well absorbed
after injection and are widely distributed in the body.
They undergo hepatic metabolism and are excreted pri-
marily in the urine.
Contraindications and cautions
Opioid antagonists are contraindicated in the presence
of any known allergy to any opioid antagonist
to avoid
hypersensitivity reactions
. Caution should be used in
the following circumstances: during pregnancy and
breastfeeding
because of potential adverse effects on
the fetus and neonate
; with opioid addiction
because
of the precipitation of a withdrawal syndrome
; and
with cardiovascular (CV) disease,
which could be
exacerbated by the reversal of the depressive effects of
opioids.
Adverse effects
The most frequently seen adverse effects associated with
these drugs relate to the blocking effects of the opioid
receptors. The most common effect is an acute opioid
abstinence syndrome that is characterised by nausea,
vomiting, sweating, tachycardia, hypertension, tremu-
lousness and feelings of anxiety. A naloxone challenge
should be administered before giving naltrexone to help
to avoid acute reactions.
CNS excitement and reversal of analgesia are espe-
cially common after surgery. Cardiovascular (CV)
effects related to the reversal of the opioid depression
can include tachycardia, blood pressure changes, dys-
rhythmias and pulmonary oedema.
Drug–drug interactions
To reverse the effects of buprenorphine or dextropro-
poxyphene, larger doses of opioid antagonists may be
needed.
■
■
Provide thorough teaching, including drug name,
prescribed dose and schedule of administration;
measures for avoidance of adverse effects; warning
signs that may indicate possible problems; safety
measures such as avoiding driving, getting
assistance with ambulation, avoiding making
important decisions or signing important papers;
and the need for monitoring and evaluation
to
enhance the person’s knowledge about drug
therapy and to promote compliance.
Evaluation
■
■
Monitor the person’s response to the drug (relief of
pain, sedation).
■
■
Monitor for adverse effects (CNS changes, GI
depression, respiratory depression, arrhythmias,
hypertension).
■
■
Evaluate the effectiveness of the teaching plan
(person can give the drug name and dosage and
describe possible adverse effects to watch for,
specific measures to prevent them and warning
signs to report).
■
■
Monitor the effectiveness of comfort measures and
compliance with the regimen.
Prototype summary: Naloxone
Indications:
Complete or partial reversal of
opioid depression; diagnosis of suspected opioid
overdose.
Actions:
Pure opioid antagonist; reverses the effects
of the opioids, including respiratory depression,
sedation and hypotension.
Pharmacokinetics:
Route
Peak
Onset
Duration
IV
Unknown 2 mins
4–6 hours
IM, SC Unknown 3–5 mins
4–6 hours
T
1/2
:
30 to 81 minutes; metabolised in the liver,
excreted in the urine.
Adverse effects:
Acute opioid abstinence syndrome
(nausea, vomiting, sweating, tachycardia, fall
in blood pressure), hypotension, hypertension,
pulmonary oedema.
