Pharmacology 15 – Anti-Emetics
Anil Chopra
1. To describe, in broad terms, the control of vomiting
2. To state the receptor specificity, the main sites of action and the specific
antiemetic uses of promethazine, metoclopramide, hyoscine and ondansetreon (see
Fig.).
3. To list the main pharmacokinetic features and unwanted actions of specific drugs.
Anti emetics are used only when the cause of nausea/vomiting is known. Stimuli
include:
- Peripheral organs
o Pharynx
o Stomach
o Duodenum
o Heart
o Bladder
o Uterus
o Viscera
o Testicles
- Endogenous Toxins
o Infections
o Cancer
o Chemotherapeutic agents
o Radiation damage
o Morphine
o Cardiac glycosides,
o Estrogen (early pregnancy)
o Recovery from general anaesthesia
- Motion sickness
- Emotional
-
There are 4 main stimuli for the vomiting pathway:
Peripheral Organs – e.g. pharynx, stomach, duodenum, heart, testicles,
bladder, uterus etc
Endogenous Toxins – e.g. drugs, infections, cancer, radiation damage,
morphine, chemotherapeutic agents, cardiac glycosides, estrogen (early
pregnancy) and recovery from general anaesthesia
Motion Sickness
Pain etc - repulsive sights and smells, and emotional factors
All of these inputs feed to the vomiting centre (lower medulla, reticular formation,
dorsal Vagal nucleus) which gives a co-ordinated response to nerves supplying
somatic and visceral receptors (e.g. respiratory and abdominal muscles) to allow for
vomiting
-
Receptors and neurotransmitters involved:
o AChM = Muscarinic ACh receptor
o H1 = Histamine receptors
o 5-HT3 = Serotonin receptors
o D2 = Dopamine Receptor
Inducing Vomiting
Stimuli
from
peripheral
organs
VISCERAL
AFFERENTS
Endogenous toxins,
drugs
Release of
emetogenic
agents
5-HT3 R
Blood
AchM,
H1 R
STIMULI
Labyrinth
Vestibular nuclei
AchM, H1
R
CSF?
Nucleus of the
solitary tract
Pain, repulsive
sights & smells,
emotional factors.
Motion
sickness
CHEMORECEPTOR TRIGGER ZONE
Floor V, IV, medulla, area postrema
INPUT
to CNS
SENSORY AFFERENTS
& CNS PATHWAYS
HIGHER CENTRES
D2, 5-HT3,
R
AchM, H1 R
VOMITING CENTRE
Lower medulla, reticular
formation,
dorsal vagal nucleus
INTE GRATION
AchM, H1 R
NERVES TO SOMATIC AND VISCERAL RECEPTORS
Co-ordination of somatic respiratory & abdominal muscles & g.i.t. smooth muscle
OUTPUT
Name:
Promethazine
Uses
-
Motion sickness
Disorders of labyrinth e.g. Meniere’s disease
Hyperemesis gravidarium (morning sickness in pregnancy)
Pre and post operatively (sedative and anti muscarinic actions useful)
Relief of allergic symptoms
Anaphylactiv emergency
Night Sedation (in insomnia)
Mode of Action
It acts as a competitive antagonist at histaminergic (H1) cholinergic (muscarinic, M)
and dopaminergic (D2). Potency H1 > M > D2 receptors. It also acts on the labyrinth,
NTS (nucleus of the solitary tract), vomit centre to block its activation.
Side-Effects
 Dizziness
 Tinnitus
 Fatigue
 Sedation (‘do not drive or operate machinery')
 Excitation in excess
 Convulsions (children more susceptible)
 Antimuscarininc side-effects
Pharmacokinetics
 Administer orally
 Onset of action 1-2 hours
 Maximum effect circa 4 hours
 Duration of action 24 hours
Name
Metoclopramide
Uses
Used to treat nausea and vomiting associated with:
 uraemia (severe renal failure)
 radiation sickness
 gastrointestinal disorders
 cancer chemotherapy (high doses) eg. cisplatin (intractable vomiting)
Mode of Action
It is also a dopamine receptor antagonists. Order of antagonistic potency: D2 > H1 >
Muscarinic receptors. It acts centrally at the chemoreceptor trigger zone and on the
gastrointestinal tract by increasing smooth muscle motility (from oesophagus to small
intestine), accelerating gastric emptying and accelerating transit of intestinal contents
(from duodenum to ileo-coecal valve).
Side Effects
As it increases GI motility, it can cause reduce nutrient supply and effectiveness of
certain drugs such as digoxin.
In CNS
 drowsiness
 dizziness
 anxiety
 extrapyramidal reactions; children more susceptible than adults (Parkinsonian-like
syndrome: rigidity, tremor, motor restlessness)
NOTE: No anti-psychotic actions
In the endocrine system
 hyperprolactinaemia
 galactorrhoea
 disorders of menstruation
Pharmacokinetics
 may be administered orally; rapidly absorbed; extensive first pass metabolism
 may also be given i.v.
 crosses Blood brain barrier
 crosses placenta
Name
Hyoscine
Uses
 Prevention of motion sickness
 Has little effects once nausea/emesis is established
 In operative pre-medication
NOTE: Atropine is less effective
 Also has sedative properties unlike atropine which is exctiatory
Mode of Action
It is an anti-muscarinic drug but also acts in the vestibular nuclei, nucleus of the
solitary tract, and vomiting centre to block activation.
Side Effects
Typical anti-muscarinic side-effects:
 drowsiness
 dry mouth,
 cycloplegia
 mydriasis
 constipation (not usually at anti-emetic doses)
Other
Can be administered orally (peak effect in 1-2 hours), i.v., transdermally
Name
Ondansetron
Uses
 main use in preventing anticancer drug-induced vomiting, especially cisplatin
 radiotherapy-induced sickness
 post-operative nausea and vomiting
Mode of Action
Acts to block transmission in visceral afferents and chemoreceptor trigger zone.
Side Effects
 headache
 sensation of flushing and warmth
 increased large bowel transit time (constipation)
Other
Administer orally; well absorbed, excreted in urine.