2. Learning objectives
Classify the main different classes of antiemetic drugs according to
their mechanism of action.
Know the characteristic pharmacokinetics & dynamics of different
classes of antiemetic drugs.
Identify the selective drugs that can be used according to the cause
of vomiting.
Learn the adjuvant antiemetics.
Describe the major side effects for the different classes of
antiemetics.
3. Vomiting
Is a complex series of integrated events
culminating in the forceful expulsion of gastric
contents through the mouth.
4. Causes of nausea and vomiting
a useful abbreviation for remembering causes of
nausea and vomiting is VOMIT.
Vestibular
Obstruction or drugs like opiates
Mind (dysmotility)
Infection (irritation of gut)
Toxins (taste and other senses)
5. Causes of Vomiting
Nausea and vomiting may be manifestations
of many conditions and may occur due to
stimulation of vomiting center that respond to
inputs from:
• Higher cortical centers stimulation (CNS)
• Chemoreceptor trigger zone (CTZ)
stimulation
• Disturbance of vestibular system
• The periphery (Pharynx, GIT) via sensory
nerves
6. 1. Stimulation of chemoreceptor trigger zone (CTZ)
CTZ is an area of medulla that communicate
with vomiting center to initiate vomiting.
CTZ is physiologically outside BBB.
CTZ Contains D2 receptors , 5 HT3
receptors, opioid receptors
stimulated by the following in blood or CSF. :
Drugs (chemotherapy, opioids, general
anesthetics, digitalis, L-dopa,).
Chemicals
Toxins
Radiation.
7. 2. The periphery via sensory nerves
GIT irritation, myocardial infarction, renal or
biliay stones.
3. Disturbance of vestibular system
by motion sickness (H1 & M1 receptors)
4. Higher cortical centers stimulation:
emotional factors, nauseating smells or sights.
14. Serotonin (5-HT3) antagonists
• Drugs as
– Ondansetron (zofran)
– Granisetron (Kytril)
• Orally or parenterally, have long duration of
action
• The most potent antiemetic drugs
• Act by blocking 5-HT3 receptor centrally (in
vomiting center, CTZ) and peripherally
(5HT3 receptors on GI vagal afferents).
15. Uses of 5-HT3 antagonists
• First choice for prevention and treatment of
moderate to severe emesis:
–Chemotherapy-induced nausea and
vomiting (CINV) especially cisplatin (highly
emetogenic anticancer).
–Post-radiation NV& Post-operative NV
– Their effects is augmented by combination
with corticosteroids or NK1 antagonists.
19. Uses
Antiemetics (blocking D2 receptors in CTZ)
Effective against vomiting due to cytotoxic
drugs, gastroenteritis, surgery, toxins,
uremia, radiation
Prokinetic
Gastroesophageal reflux disease (GERD)
Gastroparesis (impaired gastric emptying
after surgery).
20. Metoclopramide crosses BBB but domperidone
cannot (both have antiemetic effects as CTZ is
outside BBB).
Side effects (only for metoclopramide):
Dyskinesia (extra-pyramidal side effects),
Galactorrhea, menstrual disorders, impotence
Postural hypotension (α-blocking action).
Sedation, drowsiness
21. Other D2 receptor antagonists
Neuroleptics (Antipsychotics)
Chlorpromazine (CPZ), droperidol
Acts centrally to block D2 receptors in CTZ
used for postoperative vomiting and
chemotherapy-induced emesis.
Side effects:
Extra pyramidal symptoms
Sedation
Postural hypotension
22. Neurokinin1 (NK1) receptor antagonists
Aprepitant
Acts centrally as substance P antagonist by
blocking neurokinin 1 receptors in vagal
afferent fibers in STN and area postrema.
Orally
Usually combined with 5-HT3 antagonists and
corticosteroids in chemotherapy-induced
nausea and vomiting and post- operative NV.
N.B. STN is Solitary Tract Nucleus
23. H1-receptor antagonists
• Include drugs as
– diphenhydramine, promethazine
– meclizine, cyclizine
• Used for
– Motion sickness
– Morning sickness in pregnancy
– Promethazine: severe morning sickness of
pregnancy (if only essential).
Side effects:
– Prominent sedation, hypotension,
– Anticholinergic effects (dry mouth, dilated
pupils, urinary retention, constipation).
24. Muscarinic receptor antagonists
• Hyoscine (scopolamine)
• Orally, injection, patches
• Used as transdermal patches for prevention of
motion sickness (applied behind the external
ear before an insult).
• Acts centrally by reduce impulses from
vestibular nuclei
• Not in chemotherapy-induced vomiting
26. Glucocorticoids
• Dexamethasone - methylprednisolone
• Used in chemotherapy-induced vomiting
• combined with 5-HT3 antagonists or NK1
receptor antagonists.
28. Cannabinoids
• Nabilone, dronabinol
• mechanism of action not understood.
• act at central cannabinoid receptors.
• Used in vomiting due to cytotoxic drugs
(adjuvant therapy).
• Limited use due to side effects
Side effects:
Euphoria, dysphoria, sedation, hallucination.
29. Summary
The choice of antiemetic drug depends on the etiology
Motion sickness
Muscarinic antagonists
Antihistaminics
Vomiting with pregnancy (morning sickness)
avoid all drugs in the first trimester
Pyridoxine (B6)
Promethazine (only if absolutely essential in late
pregnancy.
30. Post operative nausea & vomiting
D2- antagonists
5-HT3 antagonists
Vomiting due to cytotoxic drugs.
5-HT3 antagonists
D2- antagonists
NK1 antagonists
Glucocorticoids
Cannabinoids (rare)
