The document discusses drugs that act on the gastrointestinal tract to treat nausea and vomiting. It describes the vomiting reflex and centers in the brain that control it, including the chemoreceptor trigger zone. It then covers various classes of antiemetics that work by different mechanisms, such as inhibiting cholinergic pathways, blocking dopamine receptors in the chemoreceptor trigger zone, and antagonizing 5-HT3 receptors. These drugs include antihistamines, phenothiazines, butyrophenones, 5-HT3 antagonists, cannabinoids, glucocorticoids, and benzodiazepines. The document also briefly discusses emetics like ipecac that induce vomiting.

1. Drugs Acting on the
Gastrointestinal Tract

2. 1. Emetics and Antiemetics

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

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

11. Histamine1 (H1)-receptor antagonists

12. Histamine1 (H1)-receptor antagonists
• diphenhydramine [Benadryl]
• meclizine [Antivert, Bonine]
• dimenhydrinate [Dramamine]
• promethazine [Phenergan]

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.

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.

17. 2. Phenothiazines and butyrophenones
• Phenothiazine: prochlorperazine [Compazine]
• Butyrophenone: droperidol [Inapsine].

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.