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9 Analgesics(14–21 hours) than pethidine and accumulates in renal failure. It has been associated
with hallucinations and grand mal seizures following its accumulation. Its effects
are not reversed by naloxone. Norpethidine and pethidinic acid are excreted in the
urine along with small amounts of unchanged pethidine. The duration of action of
pethidine is 120–150 minutes.Fentanyl
Fentanyl is a synthetic phenylpiperidine derivative with a rapid onset of action. It is
aμ-receptor agonist and as such shares morphine’s effects. However, it is less likely
to precipitate histamine release. High doses (50–150μg.kg−^1 )significantly reduce
or even eliminate the metabolic stress response to surgery but are associated with
bradycardia and chest wall rigidity.Presentation
Fentanyl is prepared as a colourless solution for injection containing 50μg.ml−^1 ,as
transdermal patches that release between 25 and 100μgper hour for 72 hours and
as lozenges releasing 200μg–1.6 mg over 15 minutes.Uses
Doses vary enormously depending on the duration of analgesia and sedation
required. For pain associated with minor surgery, 1–2μg.kg−^1 is used intravenously
and has a duration of about 30 minutes. Higher doses are generally required to obtund
the stimulation of laryngoscopy. High doses (50–100μg.kg−^1 )areused for an opioid-
based anaesthetic (although a hypnotic is also required), and here its duration of
action is extended to about 6 hours. Following prolonged administration by contin-
uous infusion only its elimination half-life is apparent, leading to a more prolonged
duration of action.
Fentanyl has also been used to augment the effects of local anaesthetics in spinal
and epidural anaesthesia at 10–25μgand 25–100μg, respectively. Its high lipid sol-
ubility ensures that a typical intrathecal dose does not cause delayed respiratory
depression as it diffuses rapidly from cerebrospinal fluid (CSF) into the spinal cord.
This contrasts with morphine, which enters the spinal cord slowly leaving some to be
transported in the CSF by bulk flow up to the midbrain. However, respiratory depres-
sion is observed when epidural fentanyl is administered by continuous infusion or
as repeated boluses.Kinetics
Itsonset of action is rapid following intravenous administration due to its high lipid
solubility (nearly 600 times more lipid-soluble than morphine). However, follow-
ing the application of a transdermal patch, plasma levels take 12 hours to reach
equilibrium. At low doses (<3μg.kg−^1 intravenous) its short duration of action is
due solely to distribution. However, following prolonged administration or with