Emetics & Anti-emetics are used to induce or treat nausea and vomiting. There are various classifications and mechanisms of action. Emetics like apomorphine and ipecacuanha act on the chemoreceptor trigger zone to induce vomiting. Anti-emetics from different classes like antihistamines, antimuscarinics, dopamine antagonists, 5-HT3 receptor antagonists, cannabinoids, benzodiazepines and glucocorticoids are used to treat nausea and vomiting through various receptor mechanisms with some adverse effects. Combination therapy provides better efficacy with lower adverse effects.

1. Emetics & Anti-emetics
Sanjaya Mani Dixit
Assistant Prof of Pharmacology

2. Therapy of nausea and vomiting
Classification
Mechanism of action
Uses
Adverse effects and
Drug interactions

3. Definitions
Nausea
Term derived from Nautia (Gr: sea sickness)
Unpleasant feeling that often precedes vomiting
Emesis (vomiting/puking)
Forcible emptying of gastric, and occasionally, intestinal
contents
Antiemetic agents
Used to relieve nausea and vomiting

4. Vomiting
Two major cerebral centers:
1.Chemoreceptor trigger
zone (CTZ)
2.Vomiting center
•Both located near floor of 4th
ventricle, close to the vital
centers
•EC is within the blood brain
barrier (BBB)-Drugs act
•CTZ outside in the area
postrema
•They are connected together

5. Mechanism of Vomiting
The CTZ receives most of the impulses from drugs,
toxins, and the vestibular center.
The neurotransmitter dopamine stimulates the
CTZ, which in-turn stimulates the vomiting center,
when triggered, motor neuron responds 
contraction of diaphragm, anterior abdominal
muscles, & the stomach.
The glottis closes, the abdominal wall moves,
upward & vomiting occurs.

7. Emetic- Reflexes
Rational reflex
prevention of ingestion of noxious substances (sight,
smell, taste, texture)
local gut reflexes stimulate vomiting e.g. toxins
Irrational reflexes
labyrinth
pregnancy
‘visual nasties’!

8. Causes of vomiting
The cause of the vomiting needs to be identified, before using
drugs.
Causes
•Food intolerance
•Surgery, PG, pain, shock
•Effects of some drugs, radiation
•Disturbances of middle ear affecting equilibrium
•Motion sickness & morning sickness
•Viral & bacterial infection

13. Emetics
Drugs that cause emesis.
l. Act on CTZ : Apomorphine
1. Act reflexly and on CTZ : Ipecacuanha
Powdered mustard suspension or strong salts
solution may be used in emergency. They irritate
the stomach and reflexly cause vomiting.
Used to reduce absorption, following ingestion of
toxic substances .

14. Apomorphine
Semisynthetic derivative of morphine
Dopaminergic agonist @ CTZ.
Dose of 6 mg injected IM/SC, produces vomiting
within 5-15 mins.
Oral dose is larger and hence not recommended,
slow to act and rather inconsistent action.
Known to have therapeutic effect in parkinsonism
but not used owing to S/Es.
Not to be used when respiration in depressed, since
it depresses respiration & CNS.

15. Apomorphine
Cardiotoxic if absorbed and can cause cardiac
conduction disturbances, atrial fibrillation, or
fatal myocarditis.
If emesis does not occur, gastric lavage using a
nasogastric tube must be performed.
Opioid antagonists such as naloxone usually
reverse the depressant actions of apomorphine.
Because of the possibility of respiratory
depression, apomorphine is infrequently used as an
emetic.

16. Ipecac(Ipecacuanha)
Ipecac (Cephaelis ipecacuanha - root) contains
alkaloid emetine.
Dose- Ipecac syrup 15-30ml
Less dependable in emergency situations but is
safer.
M/A
Stimulates the CTZ in the medulla & acts directly
on the gastric mucosa.

17. Ipecac(Ipecacuanha)
Take with water (not milk or carbonated drinks) -
onset of action in 15 to 30 min.
Repeat treatment if needed.
Toxic if absorbed 
Give charcoal- Decreases toxicity  hypotension,
tachycardia, chest pain
S/E
Diarrhoea, sedation, lethargy

18. Emesis Contraindications
1.CNS Stimulant drug- Convulsions may occur
2.Kerosene/ Petroleum poisoning
Aspiration (low viscosity)-chemical pneumonia
3. Corrosive substances poisoning -Risk of perforation &
injury to esophagus
4. Unconscious patient- aspiration
5. Morphine or phenothiazine
Emetics are ineffective
Activated charcoal is given when emesis is C/I or ineffective.

19. Antiemetics

20. Clinical use of anti-emetic drugs:
H1-receptor antagonists:
cylizine - motion sickness
cinnarizine - motion sickness, vestibular disorders (e.g.
Meniére´s disease)
promethazine - severe morning sickness of pregnancy
(only if absolutely essential)
5-HT3receptor antagonists:
ondansetron - vomiting caused by cytotoxic
anticancer drugs (drug of choice), postoperative
vomiting; radiation- induced vomiting

21. D2-receptor antagonists:
phenothiazines (e.g. thiethylperazine) - vomiting caused
by uraemia, radiation, viral gastroenteritis (drugs of choice);
severe morning sickness of pregnancy (if absolutely essential)
metoclopramide - vomiting caused by uraemia, radiation,
gastrointestinal disorders, cytotoxic drugs
Muscarinic-receptor antagonists:
hyoscine - motion sickness (drug of choice)
Cannabinoids:
nabilone - for vomiting caused by cytotoxic anticancer drugs
Clinical use of anti-emetic drugs:

22. Antihistamines & Anti-cholinergics
Hydroxyzine, Promethazine & Scopolamine
Act primarily on the vomiting center,
decrease stimulation of CTZ
S/E
Drowsiness, dry mouth, constipation
Blurred vision (pupil dilation), tachycardia
Do not use in clients with glaucoma d/t dilation of
pupils

23. ANTI-HISTAMINICS
Prevention of motion sickness; use may be limited by
S/Es--dizziness, sedation, confusion, dry mouth,
cycloplegia, and urinary retention.
Diphenhydramine and Dimenhydrinate, 1st-gen H1
antagonists have anticholinergic properties.
Diphenhydramine (sedative) is commonly used in
conjunction with other antiemetics for treatment of emesis
due to chemotherapy.
Meclizine is an H1 antihistaminic agent with minimal
anticholinergic properties that also causes less sedation.
It is used for the prevention of motion sickness and
treatment of vertigo due to labyrinth dysfunction.

24. ANTIMUSCARINICS
Hyoscine (scopolamine), a prototypic muscarinic
receptor antagonist.
One of the best agents for the prevention of motion
sickness.
However, it has a very high incidence of
anticholinergic effects when given orally or
parenterally.
It is better tolerated as a transdermal patch.
Superiority to dimenhydrinate has not been proved.

25. Centrally acting
D2- receptor antagonists
Prochlorperazine, Promethazine, Thiethylperazine
Block dopamine-2 receptors in the CTZ, thus decrease CTZ
stimulation of the vomiting center.
Can be used for their potent antiemetic and sedative
properties(H1 blocking effects).
Antiemetic properties are mediated through inhibition of
dopamine and muscarinic receptors.
Use
Severe N & V from surgery, anesthetics, chemo & radiation
sickness
S/E
Extrapyramidal symptoms (tremors, mask face, rigidity,
shuffling gait)

26. Centrally acting
D2- receptor antagonists
Metoclopramide --1970s (gastric hurrying agent)
M/A
Blocks both dopamine & serotonin receptors in the CTZ
D2 antagonism
Blocks D2 receptors (inhibitory) in GIT– hastens gastric emptying and
enhances LES tone increasing Ach release.
D2 blockade- antagonism of apomorphine induced vomiting
5HT4 agonism —Gastric hurrying action
Activation of 5HT4 receptors in primary afferent neurones of ENS &
enhances Ach release from myenteric motor neurones in GIT
5HT3 antagonism- Large doses in chemotherapy blocks serotonin
receptors in inhibitory myenteric interneurones and in CTZ.

27. Centrally acting
D2- receptor antagonists
Use
Prevention and treatment of nausea and vomiting of different
kinds
Drug induced, disease associated (especially migraine), Post-
operative emesis, chemotherapy & radiation therapy
Metoclopramide may be given in the relatively high dosage of
10–20 mg orally or intravenously q 6 hours.
Less effective in motion sickness.
Stopping persistent hiccups.
S/E
Sedation & diarrhea in high dose
Extrapyrimidal effects--restlessness, dystonias, and parkinsonian
symptoms.

28. Butyrophenones
Haloperidol, droperidol
M/A
Block dopamine-2 receptors in the CTZ
Use
Treatment of post-operative nausea and vomiting associated
with toxins, chemo & radiation therapy
S/E
EPS if used over extended time, hypotension

29. 5-HT3 RECEPTOR ANTAGONISTS
Ondansetron, granisetron, palonosetron
Potent antiemetic properties mediated mainly through:
•Central 5-HT3-receptor blockade in VC and CTZ
•Blockade of peripheral 5-HT3 receptors on extrinsic
intestinal vagal & spinal afferent nerves.
Action of these agents is restricted to emesis attributable to
vagal stimulation (eg, postoperative) and chemotherapy.
These agents do not inhibit dopamine or muscarinic receptors.

30. 5-HT3 RECEPTOR ANTAGONISTS
P/K
T1/2 of 4–9 h and administered once daily PO/IV
All drugs have comparable efficacy and tolerability
when administered at equipotent doses.
Palonosetron is a newer I/V agent that has greater
affinity for the 5-HT3 receptor and a long serum t1/2 of 40 h.
All drugs undergo extensive hepatic metabolism and
are eliminated by renal and hepatic excretion.
Ondansetron- dose reduction required in hepatic
insufficiency.

31. 5-HT3 RECEPTOR ANTAGONISTS
Uses
•Chemotherapy induced emesis - PO & IV
•Post operative and post-radiation induced nausea
and vomiting

32. 5-HT3 ANTAGONISTS
Adverse Effects
Most common:
•Headache, dizziness
•Constipation.
•Small prolongation of the QT interval (Dola..)
Although cardiac arrhythmias have not been linked to use of
dolasetron, it should not be administered to patients with
prolonged QT or in conjunction with other medications that
may prolong the QT interval.

33. Cannabinoids
Dronabinol-Derivative of THC, major psychoactive
chemical in marijuana.
For those unable to use or respond to other anti-emetics.
After oral ingestion, the drug is almost completely
absorbed but undergoes significant 1st-pass effect;
metabolites are excreted slowly over days to weeks in the
feces and urine.
Dronabinol-psychoactive agent,used as appetite
stimulant and as an antiemetic, but mechanisms are not
understood.
Now uncommonly used for the prevention of chemotherapy-
induced nausea and vomiting.

34. Cannabinoids
Combination therapy with phenothiazines provides
synergistic antiemetic action and appears to attenuate the
A/E of both agents.
A/E
Euphoria, dysphoria, sedation, hallucinations,
Dry mouth, and increased appetite.
Autonomic effects -tachycardia, orthostatic hypotension.
Nabilone is a closely related THC approved for use in the
USA.

35. BENZODIAZEPINES
Lorazepam or diazepam are used prior to the
initiation of chemotherapy to reduce anticipatory
vomiting or vomiting caused by anxiety.
Lorazepam
For nausea and vomiting d/t chemotherapy - May be
given with an antiemetic such as metoclopramide

36. Glucocorticoids
Dexamethasone, methylprednisolone –IV dosing
They are individually effective against mildly to
moderately emetogenic chemotherapy Most
frequently, however, they are used in combination
with other agents.
Their antiemetic mechanism is not known, but it
may involve blockade of prostaglandins.
These drugs can cause insomnia as well as
hyperglycemia in patients with DM.

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