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9780521704632c18 CUFX213A/Peck 9780521618168 December 28, 2007 13:51
18 Antiemetics and related drugsMechanism of action
Metoclopramide exerts its antiemetic actions primarily through dopamine (D 2 )
receptor antagonism at the CTZ, although it does have prokinetic effects on the
stomach (cf. Chapter 19 ). It also blocks 5-HT 3 receptors, which may account for
some of its antiemetic properties.Effects
Central nervous system – metoclopramide crosses the blood–brain barrier and
may precipitate extrapyramidal effects up to 72 hours after administration. Such
effects are more common in young females (1 in 5000). Rarely it may precipitate
the neuroleptic malignant syndrome. Sedation is seen more commonly during
long-term administration. Agitation is occasionally seen following intramuscular
premedication with 10–20 mg.
Cardiovascular – hypotension, tachy- and bradycardias have been reported fol-
lowing rapid intravenous administration.Kinetics
Metoclopramide is well absorbed from the gut although first-pass metabolism varies
significantly producing a wide range in oral bioavailability (30–90%). It may be given
intravenously. It is conjugated in the liver and excreted along with unchanged drug
in the urine.Anticholinergics
While so-called ‘anticholinergic’ agents are effective antagonists at muscarinic recep-
tors, they have very little activity at nicotinic receptors and may therefore be thought
of as essentially selective agents at normal doses.
The naturally occurring tertiary amines, atropine and hyoscine, are esters formed
bythe combination of tropic acid and an organic base (tropine or scopine) and are
able to cross the blood–brain barrier. Their central effects include sedation, amnesia,
anti-emesis and the central anticholinergic syndrome. Glycopyrrolate is a synthetic
quaternary amine (therefore charged) with no central effects as it is unable to cross
the blood–brain barrier.Hyoscine
Hyoscine is a racemic mixture, but onlyl-hyoscine is active.Uses
Hyoscine has traditionally been given with an intramuscular opioid as premedica-
tion, and in this setting has been shown to reduce PONV. It has also been used as a
sedative and amnesic agent.