3. Vomiting reflex
– The vomiting reflex is a coordinated reflex controlled
by a bilateral vomiting center in the dorsal portion of
the lateral reticular formation in the medulla.
– Pharmacologic intervention relies on inhibition of
inputs or depression of the vomiting center.
4. – The vomiting center receives inputs from several
sources:
1. Chemoreceptor trigger zone (CTZ)
2. Vestibular nucleus
3. Peripheral afferents from the pharynx,
gastrointestinal tract, and genitals
4. Psychologic input from the central nervous
system (CNS)
– Serotonin (5-HT3)-receptors, which are the
predominant mediators of the reflex, are present in:
– vomiting center
– CTZ
– periphery
5.
6.
7. Antiemetics
• Def.: Agents to treat nausea and vomiting
• Useful in the treatment of vomiting associated
with:
• motion sickness
• chemotherapy
8. 1.Cholinergic antagonists
– They reduce the excitability of labyrinthine
receptors and depress conduction from the
vestibular apparatus to the vomiting center.
9. • Cholinergic antagonists are used to:
– treat motion sickness
– in preoperative situations.
• They are not useful in treating nausea caused
by chemotherapy.
10. Scopolamine
Inhibit cholinergic and muscarinic CNS receptors.
Crosses the blood-brain barrier.
More effective against motion-induced emesis.
SIDE EFFECTS: sedation, CNS excitation, dry mouth,
urinary retention, blurred vision, confusion, disorientation,
hallucinations
13. • These agents most likely act by inhibiting
cholinergic pathways of the vestibular apparatus
by receptor “crossover.”
• H1-receptor antagonists are used to treat motion
sickness and vertigo.
• These agents produce sedation and dry mouth.
• Meclizine and promethazine have minimal
anticholinergic side effects and are used most
often.
14. Dopamine antagonists
1. Metoclopramide [Reglan]
– blocks receptors within the CTZ.
– increases the sensitivity of the gastrointestinal tract to
the action of acetylcholine (ACh)
– this enhances gastrointestinal motility and gastric
emptying and increases lower esophageal sphincter
tone.
– High doses of metoclopramide antagonize serotonin
(5-HT3)-receptors in the vomiting center and
gastrointestinal tract.
15.
16. • Metoclopramide is used to treat:
• nausea due to chemotherapy (caused by agents
such as cisplatin and doxorubicin)
• narcotic-induced vomiting.
• Metoclopramide produces sedation, diarrhea,
extrapyramidal effects, and elevated prolactin
secretion.
18. • Phenothiazines and butyrophenones:
– block dopaminergic receptors in the CTZ
– inhibit peripheral transmission to the vomiting center.
• These agents are used to:
– treat nausea due to chemotherapy and radiation therapy
– control postoperative nausea.
• Adverse effects (less pronounced with butyrophenones)
include:
• Anticholinergic effects (drowsiness, dry mouth, and blurred
vision),
• Extrapyramidal effects
• Orthostatic hypotension.
19. 5-HT3 antagonists
• Ondansetron [Zofran]
– not effective for motion-sickness-induced nausea.
– more effective against nausea induced by
chemotherapy.
– used in postoperative nausea.
– can be administered intravenously or orally.
– Side effects may include mild constipation.
20. Granisetron [Kytril]
• has a greater affinity for 5-HT3 receptors.
• Granisetron is longer acting and more potent
than ondansetron or metoclopramide.
• administered by intravenous infusion or orally.
• The most common adverse effect of granisetron is
headache.
21. Cannabinoids
– The most commonly used in the USA is dronabinol
(Δ-9-tetrahydrocannabinol) [Marinol].
– Acts by inhibiting the vomiting center, but the
mechanism is unclear.
– used to control nausea induced by chemotherapy.
– administered as oral preparations.
– adverse effect : produce sedation, psychoactive
effects (“high”), dry mouth, orthostatic hypotension,
and increased appetite.
22. Glucocorticoids
• Dexamethasone [Decadron]
• Methylprednisolone [Solu-Medrol].
• These agents can be effective as a treatment of
vomiting caused by highly emetic agents.
• High doses are given as an intravenous (IV) bolus or
orally for delayed nausea, often combined with
metoclopramide, haloperidol, diphenhydramine, or
ondansetron.
23. Benzodiazepines
• Lorazepam [Ativan]
• Diazepam [Valium]
• act as anxiolytic agents to reduce anticipatory
emesis.
• Diazepam is useful as a treatment of vertigo.
24. – Emetrol
• Emetrol is an over-the-counter (OTC)
preparation containing a mixture of fructose,
dextrose, and buffered orthophosphoric acid.
• Emetrol is used to treat vomiting in morning
sickness and in infants.
25. Neurokinin 1 (NK1) antagonist
• Aprepitant [Emend]
• (substance P receptor antagonist) used in
delayed nausea caused by chemotherapy.
• It can be used in a combination with
benzodiazepines and 5-HT3 antagonists, or alone.
26. Emetics: agents that induce reflex vomiting.
• Ipecac
• Ipecac is a mixture of alkaloids, derived from the
ipecacuanha plant.
27. • Ipecac induces vomiting by stimulating the CTZ
and by causing gastrointestinal irritation.
• Ipecac is administered orally and is fast acting,
causing vomiting in 85% of patients within 20
minutes.
• Ipecac is rarely used anymore because of its low
effectiveness and high side effect profile.
• Cardiac toxicity caused by the emetine in ipecac
is noted in abusers such as bulimics.
