entity, 4 and that a number of
neuronal areas within the medulla
interact to coordinate the emetic
reflex.
Mechanisms of CINV
Neurons that coordinate the
bodily functions associated with
emesis are spread throughout the
medulla, which supports the idea
that a ‘central pattern generator’
coordinates the sequence of
behaviours during emesis. The
central pattern generator receives
indirect input from both the area
postrema (chemoreceptor trigger
zone) and the abdominal vagus
by means of the nucleus tractus
solitarius.
Chemotherapy agents might
cause emesis through effects at a
number of sites. The mechanism
that is best evidenced involves
an effect on the upper small
intestine. After the administration
of chemotherapy, free radicals
are generated, leading to localised
exocytotic release of serotonin
(5-HT) from the enterochromaffin
cells; serotonin then interacts
with 5-HT 3 receptors on vagal
afferent terminals in the wall of
the bowel. Vagal afferent fibres
project to the dorsal brainstem,
primarily to the nucleus tractus
solitarius, and, to a lesser extent,
the area postrema and the dorsal
vagal complex.
Receptors for a number of
neurotransmitters with potentially
important roles in the emetic
8 | 2019 | hospitalpharmacyeurope.com
response are present in the dorsal
vagal complex. These include
neurokinin-1 (NK 1 ), 5-HT 3 and
dopamine D 2 receptors, which
bind to substance P, serotonin, and
dopamine, respectively.
Serotonin is believed to play
the most important role in the
process of acute CINV, as 90% of
the body’s stores are located in the
enterochromaffin cells.
Efferent fibres project from
the dorsal vagal complex to the
central pattern generator, which
is an anatomically indistinct
area occupying a more ventral
location in the brainstem.
Receptors for other locally
released mediators, such as
substance P, cholecystokinin, and
prostaglandins, are also present
on the vagal afferent terminals.
However, the extent to which
these mediators are involved at
this peripheral site is unknown.
Chemotherapy agents might
also induce emesis through
an interaction with the area
postrema within the dorsal vagal
complex. Other potential sources
of efferent input that result
in emesis after chemotherapy
include a number of structures
in the temporal lobe, such as
the amygdala. Evidence for this
pathway is less well established
than for other proposed sites of
chemotherapeutic action. 3 Other
mechanisms implicated in CINV
include activation of the cortical
pathway (psychogenic causes or