406
P A R T 4
Drugs acting on the central and peripheral nervous systems
Clinically important drug–drug interactions
When opioid agonists are given with barbiturate
general anaesthetics or with some phenothiazines and
MAO inhibitors, the likelihood of respiratory depres-
sion, hypotension and sedation or coma is increased. If
these drug combinations cannot be avoided, individuals
should be monitored closely and appropriate supportive
measures taken.
opioids. These drugs have three functions: (1) relief of
moderate to severe pain; (2) adjuncts to general anaes-
thesia; and (3) relief of pain during labour and delivery.
See Table 26.1 for usual indications for each opioid
agonist-antagonist agent.
Pharmacokinetics
Opioid agonists–antagonists are readily absorbed after
IM administration and reach peak levels rapidly when
given IV. They are metabolised in the liver and excreted
in urine or faeces. They are known to cross the placenta
and enter breast milk.
Buprenorphine is available for use in IM and IV
forms.
Contraindications and cautions
Opioid agonists–antagonists are contraindicated in the
presence of any known allergy to any opioid agonist-
antagonist
to avoid hypersensitivity reactions.
Caution should be used in cases of physical depend-
ence on an opioid
because a withdrawal syndrome may
be precipitated
; the opioid antagonistic properties can
block the analgesic effect and intensify the pain. Opioid
agonists–antagonists may be desirable for relieving
chronic pain in people who are susceptible to opioid
dependence, but extreme care must be used if they are
switched directly from an opioid agonist to one of these
drugs.
Caution should also be exercised in the following
conditions: chronic obstructive pulmonary disease or
other respiratory dysfunction,
which could be exac-
erbated by respiratory depression
; acute myocardial
infarction (MI), documented coronary artery disease
(CAD) or hypertension,
which could be exacerbated by
the cardiac stimulatory effects of these drugs
; and renal
or hepatic dysfunction,
which could interfere with the
metabolism and excretion of the drug.
There are no adequate studies regarding their effects
during pregnancy. They should be used during preg-
nancy only if the benefit to the mother clearly outweighs
the risk to the fetus
because of potential adverse effects
on the neonate, including respiratory depression.
They
can be used to relieve pain during labour and delivery,
which provides a short-term exposure to the fetus. They
are known to enter breast milk and should be used with
caution during breastfeeding
because of the potential
for adverse effects on the baby
.
Adverse effects
The most frequently seen adverse effects associated with
opioid agonists–antagonists relate to their effects on
various opioid receptors. Respiratory depression with
apnoea and suppression of the cough reflex is associated
with the respiratory centre depression. Nausea, vomiting,
Prototype summary: Morphine
Indications:
Relief of moderate to severe acute or
chronic pain; preoperative medication; component
of combination therapy for severe chronic pain;
intraspinal to reduce intractable pain.
Actions:
Acts as an agonist at specific opioid
receptors in the CNS to produce analgesia,
euphoria and sedation.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
60 mins
5–7 hours
SC Rapid
50–90 mins 5–7 hours
IM Rapid
30–60 mins 5–6 hours
IV Immediate 20 mins
5–6 hours
T
1/2
:
1.5 to 2 hours; metabolised in the liver,
excreted in the urine and bile.
Adverse effects:
Light-headedness, dizziness,
sedation, nausea, vomiting, dry mouth,
constipation, ureteral spasm, respiratory
depression, apnoea, circulatory depression,
respiratory arrest, shock, cardiac arrest.
O
pioid agonists
–
antagonists
The
opioid agonists–antagonists
(Table 26.1) stimulate
certain opioid receptors but block other such receptors.
These drugs, which have less abuse potential than the
pure opioid agonists, exert a similar analgesic effect as
morphine. Like morphine, they may cause sedation, res-
piratory depression and constipation. They have also
been associated with more psychotic-like reactions, and
they may even induce a withdrawal syndrome in people
who have been taking opioids for a long period.
The available opioid agonist-antagonist is buprenor-
phine (
Norspan
,
Norgesic
).
Therapeutic actions and indications
The opioid agonists–antagonists act at specific opioid
receptor sites in the CNS to produce analgesia, sedation,
euphoria and hallucinations. In addition, they block
opioid receptors that may be stimulated by other
